Multiple polynomial regression method for determination of biomedical optical properties from integrating sphere measurements.
We present a new, to our knowledge, method for extracting optical properties from integrating sphere measurements on thin biological samples. The method is based on multivariate calibration techniques involving Monte Carlo simulations, multiple polynomial regression, and a Newton-Raphson algorithm for solving nonlinear equation systems. Prediction tests with simulated data showed that the mean relative prediction error of the absorption and the reduced scattering coefficients within typical biological ranges were less than 0.3%. Similar tests with data from integrating sphere measurements on 20 dye-polystyrene microsphere phantoms led to mean errors less than 1.7% between predicted and theoretically calculated values. Comparisons showed that our method was more robust and typically 5-10 times as fast and accurate as two other established methods, i.e., the inverse adding-doubling method and the Monte Carlo spline interpolation method.


Microarray analysis of transcriptional responses to abscisic acid and osmotic, salt, and drought stress in the moss, Physcomitrella patens.
Dehydration tolerance was an adaptive trait necessary for the colonization of land by plants, and remains widespread among bryophytes: the nearest extant relatives of the first land plants. A genome-wide analysis was undertaken of water-stress responses in the model moss Physcomitrella patens to identify stress-responsive genes. An oligonucleotide microarray was used for transcriptomic analysis of Physcomitrella treated with abscisic acid (ABA), or subjected to osmotic, salt and drought stress. Bioinformatic analysis of the Physcomitrella genome identified the responsive genes, and a number of putative stress-related cis-regulatory elements. In protonemal tissue, 130 genes were induced by dehydration, 56 genes by ABA, but only 10 and eight genes, respectively, by osmotic and salt stress. Fifty-one genes were induced by more than one treatment. Seventy-six genes, principally encoding chloroplast proteins, were drought down-regulated. Many ABA- and drought-responsive genes are homologues of angiosperm genes expressed during drought stress and seed development. These ABA- and drought-responsive genes include those encoding a number of late embryogenesis abundant (LEA) proteins, a 'DREB' transcription factor and a Snf-related kinase homologous with the Arabidopsis ABA signal transduction component 'OPEN STOMATA 1'. Evolutionary capture of conserved stress-regulatory transcription factors by the seed developmental pathway probably accounts for the seed-specificity of desiccation tolerance among angiosperms.


The acceptability, knowledge and perceptions of pregnant women toward HIV testing in pregnancy at Ilembe District.
This research study aimed to investigate the acceptability, knowledge and perceptions of pregnant women toward HIV testing in pregnancy in Ilembe District. An exploratory research design guided the study. A systematic random sampling was used to select pregnant women who were attending the ante-natal clinic for the first time in their current pregnancy. Self-administered questionnaires with close-ended questions were used in the collection of data. The questions included the women's demographic details, their views of HIV testing, knowledge and as well as their acceptability of HIV testing. Forty questionnaires were distributed and they were all returned. A quantitative method was used to analyse the data. The findings of the study revealed that 45 % of the women in the sample were relatively young (18-25 years) and most of them (90%) were unmarried .The majority of women (92.5%) said testing was a good idea and 85% said it was necessary. However only 52.5% said they would opt for HIV testing. The uptake of HIV testing was found to be low. Eighty-seven and a half percent (87.5%) of the women in the sample were of the opinion that HIV testing in pregnancy was of benefit to the mother and her baby. Women in the study were generally found to have a good understanding and good perceptions towards HIV testing in pregnancy, but this was not consistent with their behaviour.


Efficient degenerate four-wave mixing in a diode-pumped microchip Nd:YVO(4) amplifier.
The process of saturable-gain degenerate four-wave mixing in a diode-pumped microchip Nd:YVO(4) amplifier is investigated. To enhance the efficiency of the interaction, multipass geometries are employed in which the weak signal beam and therefore the conjugate beam experience several passes in the gain medium. Degenerate fourwave mixing reflectivities as high as R = 10% and R = 170% have been obtained experimentally for 130-W diode pumping with two-pass and four-pass geometries, respectively. Finally, the imaging capabilities of the volume population hologram written in the Nd:YVO(4) amplifier are demonstrated.


Crossed beams and theoretical studies of the dynamics of hyperthermal collisions between Ar and ethane.
Crossed molecular beams experiments and classical trajectory calculations have been used to study the dynamics of Ar+ethane collisions at hyperthermal collision energies. Experimental time-of-flight and angular distributions of ethane molecules that scatter into the backward hemisphere (with respect to their original direction in the center-of-mass frame) have been collected. Translational energy distributions, derived from the time-of-flight distributions, reveal that a substantial fraction of the collisions transfer abnormally large amounts of energy to internal excitation of ethane. The flux of the scattered ethane molecules increased only slightly from directly backward scattering to sideways scattering. Theoretical calculations show angular and translational energy distributions which are in reasonable agreement with the experimental results. These calculations have been used to examine the microscopic mechanism for large energy transfer collisions ("supercollisions"). Collinear ("head-on") or perpendicular ("side-on") approaches of Ar to the C-C axis of ethane do not promote energy transfer as much as bent approaches, and collisions in which the H atom is "sandwiched" in a bent Ar...H-C configuration lead to the largest energy transfer. The sensitivity of collisional energy transfer to the intramolecular potential energy of ethane has also been examined.


Results of a phase II placebo-controlled randomized trial of minocycline in acute spinal cord injury.
Preclinical studies have attributed neuroprotective properties to the antibiotic minocycline. Animal studies and early clinical trials support its use in several neurological diseases. In animal spinal cord injury models, minocycline improved neurological and histological outcomes, reduced neuronal and oligodendroglial apoptosis, decreased microglial activation and reduced inflammation. A single-centre, human, double-blind, randomized, placebo-controlled study of minocycline administration after spinal cord injury was undertaken for the purposes of dose optimization, safety assessment and to estimate outcome changes and variance. Neurological, functional, pharmacological and adverse event outcomes were compared between subjects administered 7 days of intravenous minocycline (n = 27) or placebo (n = 25) after acute traumatic spinal cord injury. The secondary outcome used to assess neurological differences between groups that may warrant further investigation was motor recovery over 1 year using the American Spinal Cord Injury Association examination. Recruitment and analyses were stratified by injury severity and injury location a priori given the expected influence of these on the sensitivity of the motor exam. Minocycline administered at higher than previously reported human doses produced steady-state concentrations of 12.7 µg/ml (95% confidence interval 11.6-13.8) in serum and 2.3 µg/ml (95% confidence interval 2.1-2.5) in cerebrospinal fluid, mimicking efficacious serum levels measured in animal studies. Transient elevation of serum liver enzymes in one patient was the only adverse event likely related to the study drug. Overall, patients treated with minocycline experienced six points greater motor recovery than those receiving placebo (95% confidence interval -3 to 14; P = 0.20, n = 44). No difference in recovery was observed for thoracic spinal cord injury (n = 16). A difference of 14 motor points that approached significance was observed in patients with cervical injury (95% confidence interval 0-28; P = 0.05, n = 25). Patients with cervical motor-incomplete injury may have experienced a larger difference (results not statistically significant, n = 9). Functional outcomes exhibited differences that lacked statistical significance but that may be suggestive of improvement in patients receiving the study drug. The minocycline regimen established in this study proved feasible, safe and was associated with a tendency towards improvement across several outcome measures. Although this study does not establish the efficacy of minocycline in spinal cord injury the findings are encouraging and warrant further investigation in a multi-centre phase III trial. ClinicalTrials.gov number NCT00559494.


The effectiveness of preemptive sphenopalatine ganglion block on postoperative pain and functional outcomes after functional endoscopic sinus surgery.
The sphenopalatine ganglion block (SPGB) with local anesthetic is used to treat facial pain and headache of various etiologies; it has been widely used during functional endoscopic sinus surgery (FESS). The purpose of this study was to investigate whether preemptive SPGB may positively impact postoperative pain and functional outcomes after FESS. A prospective, double-blind, randomized, placebo-controlled study was performed. A total of 60 patients (18-70 years), undergoing general anesthesia for bilateral FESS, were randomly assigned to receive SPGB with either 2 mL 0.25% bupivacaine with epinephrine 1:100,000 (BP, treatment group) or normal saline (NS, control group). SPGB was performed preemptively 10 minutes before the start of surgery. Preoperative and postoperative (day 0, day 7, and day 30) visual analog pain scale, Sino-Nasal Outcome Test (SNOT-20), computed tomography (CT) and endoscopic scores were compared between the 2 groups. A total of 29 patients were enrolled in BP, and 27 were enrolled in NS. Three patients withdrew from the study, and 1 was withdrawn by the investigator due to severe hypertension after induction of anesthesia. There were no differences in patient demographic characteristics between the study groups. On day 7, the mean visual analog pain scales were 1.12 ± 0.3 in NS and 0.48 ± 0.23 in BP (p = 0.053). There were no statistical differences in other outcome measures (SNOT-20, CT and endoscopic scores) between the 2 groups. A limited trend toward reduced postoperative pain after FESS was noted with bupivacaine compared to saline, but statistical significance was not achieved. Preemptive SPGB may offer sinonasal symptomatic benefits for patients undergoing FESS, but larger studies are warranted.


Mortality attributable to Plasmodium vivax malaria: a clinical audit from Papua, Indonesia.
Plasmodium vivax causes almost half of all malaria cases in Asia and is recognised as a significant cause of morbidity. In recent years it has been associated with severe and fatal disease. The extent to which P. vivax contributes to death is not known. To define the epidemiology of mortality attributable to vivax malaria in southern Papua, Indonesia, a retrospective clinical records-based audit was conducted of all deaths in patients with vivax malaria at a tertiary referral hospital. Between January 2004 and September 2009, hospital surveillance identified 3,495 inpatients with P. vivax monoinfection and 65 (1.9%) patients who subsequently died. Charts for 54 of these 65 patients could be reviewed, 40 (74%) of whom had pure P. vivax infections on cross-checking. Using pre-defined conservative criteria, vivax malaria was the primary cause of death in 6 cases, a major contributor in 17 cases and a minor contributor in a further 13 cases. Extreme anaemia was the most common primary cause of death. Malnutrition, sepsis with respiratory and gastrointestinal manifestations, and chronic diseases were the commonest attributed causes of death for patients in the latter two categories. There were an estimated 293,763 cases of pure P. vivax infection in the community during the study period giving an overall minimum case fatality of 0.12 per 1,000 infections. The corresponding case fatality in hospitalised patients was 10.3 per 1,000 infections. Although uncommonly directly fatal, vivax malaria is an important indirect cause of death in southern Papua in patients with malnutrition, sepsis syndrome and chronic diseases, including HIV infection.


Experiencing the failing dentition: what dentists do.
The heavily restored, failing dentition, often associated with older patients, is one of the clinical challenges of our time. Patients tend to have high hopes for definitive, comfortable solutions and dentists may struggle to meet those expectations. In his autobiographical work, Experience, Martin Amis describes his failing dentition and its emotional consequences. His reflections have much to teach us as a profession.


Comparison of the effects of desflurane and sevoflurane on middle ear pressure: a randomized controlled clinical trial.
The aim of the present study was to compare the effects of two inhalation anesthetics, desflurane and sevoflurane, on middle ear pressure. After we obtained written consent from the patients and the approval from our institutional ethical committee, we included 56 ASA I-II patients aged between 18 and 60 years in this study. They were randomly divided into two groups of 28 patients each. Desflurane 4-6% (Group D) or sevoflurane 1-2% (Group S) were used for anesthesia management in patients. Baseline tympanometry was carried out and recorded before the induction of anesthesia on both ears, and 3 more measurements were done and recorded 5, 15 and 30 min after induction. In both groups, middle ear pressure values were found to be significantly elevated when compared to baseline measurements (p < 0.05). When middle ear pressure was compared between the groups, no difference was found between the values obtained at baseline and at 5 min in Group S, while especially the values obtained at 15 min revealed significantly higher middle ear pressures in Group D. It was observed that the increase in middle ear pressure caused by sevoflurane was significantly lower than that caused by desflurane.


Ligand-accelerated Cu-catalyzed azide-alkyne cycloaddition: a mechanistic report.
The experimental rate law for the Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction was found to vary in complex ways with concentration, the presence of chloride ion, and the presence of accelerating ligands. Several examples of discontinuous ("threshold behavior") kinetics were observed, along with a decidedly nonlinear correlation of electronic substituent parameter with the rate of CuAAC reaction with p-substituted arylazides. The previously observed tendency of the CuAAC reaction to provide ditriazoles from a conformationally constrained 1,3-diazide was found to be affected by a class of polybenzimidazole ligands introduced in the accompanying article. Various lines of evidence suggest that the standard tris(triazolylmethyl)amine ligand binds less strongly to Cu(I) than its benzimidazole analogues. On the basis of these observations, it is proposed that (a) a central nitrogen donor provides electron density at Cu(I) that assists the cycloaddition reaction, (b) the three-armed motif bearing relatively weakly coordinating heterocyclic ligands serves to bind the metal with sufficient strength while providing access to necessary coordination site(s), (c) at least two active catalysts or mechanisms are operative under the conditions studied, and (d) pendant acid or ester arms in the proper position can assist the reaction by speeding the protiolysis step that cleaves the Cu-C bond of a Cu.triazolyl intermediate.


Innate stimuli accentuate end-organ damage by nephrotoxic antibodies via Fc receptor and TLR stimulation and IL-1/TNF-alpha production.
Innate stimuli are well recognized as adjuvants of the systemic immune response. However, their role in driving end-organ disease is less well understood. Whereas the passive transfer of glomerular-targeting Abs alone elicited minimal renal disease, the concomitant delivery of innate stimuli triggered severe nephritis, characterized by proliferative glomerulonephritis with crescent formation, and tubulointerstitial disease. Specifically, stimulating TLR2, TLR3, TLR4, and TLR5 by using peptidoglycan, poly(I:C), LPS, and flagellin, respectively, all could facilitate anti-glomerular Ab-elicited nephritis. In this model, innate and immune triggers synergistically activated several cytokines and chemokines, including IL-1, IL-6, TNF-alpha, and MCP-1, some of which were demonstrated to be absolutely essential for the development of renal disease. Genetic studies revealed that, whereas the innate trigger is dependent on TLR/IL-1R-associated kinase-mediated signaling, the immune component was contingent on FcR-mediated signals. Importantly, infiltrating leukocytes as well as intrinsic glomerular cells may both serve to integrate these diverse signals. Extrapolating to spontaneous immune-mediated nephritis, although the adaptive immune system may be important in generating end-organ targeting Abs, the extent of damage inflicted by these Abs may be heavily dependent on cues from the innate immune system.


What a difference your e-mail makes: effects of informal e-mail addresses in online résumé screening.
Résumés are screened rapidly, with some reports stating that recruiters form their impressions within 10 seconds. Certain résumé characteristics can have a significant impact on the snap judgments these recruiters make. The main goal of the present study was to examine the effect of the e-mail address (formal vs. informal) used in a résumé on the hirability perceptions formed by professional recruiters (N=73). In addition, the effect of the e-mail address on hirability perceptions was compared to the effects of spelling errors and typeface. Participants assessed the cognitive ability, personality, and the hirability of six fictitious applicants for the job of an HR specialist. The hirability ratings for the résumés with informal e-mail addresses were significantly lower than the hirability ratings for résumés that featured a formal e-mail address. The effect of e-mail address was as strong as the effect of spelling errors and stronger than that of typeface. The effect of e-mail address on hirability was mediated by perceptions of conscientiousness and honesty-humility. This study among actual recruiters shows for the first time that the choice of the e-mail address used on a résumé might make a real difference.


Dosing of Ceftriaxone and Metronidazole for Children With Severe Acute Malnutrition.
Infants and young children with severe acute malnutrition (SAM) are treated with empiric broad-spectrum antimicrobials. Parenteral ceftriaxone is currently a second-line agent for invasive infection. Oral metronidazole principally targets small intestinal bacterial overgrowth. Children with SAM may have altered drug absorption, distribution, metabolism, and elimination. Population pharmacokinetics of ceftriaxone and metronidazole were studied, with the aim of recommending optimal dosing. Eighty-one patients with SAM (aged 2-45 months) provided 234 postdose pharmacokinetic samples for total ceftriaxone, metronidazole, and hydroxymetronidazole. Ceftriaxone protein binding was also measured in 190 of these samples. A three-compartment model adequately described free ceftriaxone, with a Michaelis-Menten model for concentration and albumin-dependent protein binding. A one-compartment model was used for both metronidazole and hydroxymetronidazole, with only 1% of hydroxymetronidazole predicted to be formed during first-pass. Simulations showed 80 mg/kg once daily of ceftriaxone and 12.5 mg/kg twice daily of metronidazole were sufficient to reach therapeutic targets.


Effect of high intensity focused ultrasound (HIFU) in conjunction with a nanomedicines-microbubble complex for enhanced drug delivery.
Although nanomedicines have been intensively investigated for cancer therapy in the past, poor accumulation of nanomedicines in tumor sites remains a serious problem. Therefore, a novel drug delivery system is required to enhance accumulation and penetration of nanomedicines at the tumor site. Recently, high-intensity focused ultrasound (HIFU) has been highlighted as a non-invasive therapeutic modality, and showed enhanced therapeutic efficacy in combination with nanomedicines. Cavitation effect induced by the combination of HIFU and microbubbles results in transiently enhanced cell membrane permeability, facilitating improved drug delivery efficiency into tumor sites. Therefore, we introduce the acoustic cavitation and thermal/mechanical effects of HIFU in conjunction with microbubble to overcome the limitation of conventional drug delivery. The cavitation effect maximized by the strong acoustic energy of HIFU induced the preferential accumulation of nanomedicine locally released from the nanomedicines-microbubble complex in the tumor. In addition, the mechanical effect of HIFU allowed the accumulated nanomedicines to penetrate into deeper tumor region. The preferential accumulation and deeper penetration of nanomedicines by HIFU showed enhanced therapeutic efficacy, compared to low frequency ultrasound (US). These overall results demonstrate that the strategy combined nanomedicines-microbubble complex with HIFU is a promising tools for cancer therapy.


Visual differentiation and recognition memory of look-alike drug names: effects of disfluent format, text enhancement and exposure time.
Three computer-based experiments were conducted to examine whether disfluent format, enhanced text, and increased exposure time improve the accuracy of visual differentiation and recognition memory of look-alike drug names. A three-way, repeated-measures look-alike drug name differentiation test assessed the visual differentiation accuracy of 30 nursing students (Experiment 1) and 15 nurses (Experiment 2). A two-way, repeated-measures recognition memory test examined the recognition memory accuracy of 15 nurses for look-alike drug names (Experiment 3). We found that making drug names disfluent did not significantly improve differentiation (Experiment 2) or memory accuracy (Experiment 3), but even impaired differentiation accuracy (Experiment 1). Enhanced text and longer exposure time significantly improved differentiation accuracy (Experiments 1 and 2). However, the enhanced text did not improve recognition memory (Experiment 3). We suggest that making look-alike drug names disfluent is not favourable. Enhanced text and longer exposure times are effective in supporting visual differentiation of look-alike drug names. Practitioner Summary: Confusion arising from look-alike drug names may compromise patient safety. Three experiments examined the effects of disfluent format, text enhancement and increased exposure time on visual and memory performances. Making drug names more difficult to read did not improve performance. Enhancing text design and increasing exposure (i.e. reading) time improved visual differentiation between medications, but did not improve the recognition of medications from memory. Abbreviations: SEEV: Salience-effort-expectancy-value; FDA: Food and Drug Administration; ANOVA: analysis of variance; SD: standard deviation, DF: disfluent format; TE: text enhancement; ET: exposure time.


Overexpression of alternative oxidase gene confers aluminum tolerance by altering the respiratory capacity and the response to oxidative stress in tobacco cells.
Aluminum (Al) stress represses mitochondrial respiration and produces reactive oxygen species (ROS) in plants. Mitochondrial alternative oxidase (AOX) uncouples respiration from mitochondrial ATP production and may improve plant performance under Al stress by preventing excess accumulation of ROS. We tested respiratory changes and ROS production in isolated mitochondria and whole cell of tobacco (SL, ALT 301) under Al stress. Higher capacities of AOX pathways relative to cytochrome pathways were observed in both isolated mitochondria and whole cells of ALT301 under Al stress. AOX1 when studied showed higher AOX1 expression in ALT 301 than SL cells under stress. In order to study the function of tobacco AOX gene under Al stress, we produced transformed tobacco cell lines by introducing NtAOX1 expressed under the control of the cauliflower mosaic virus (CaMV) 35 S promoter in sensitive (SL) Nicotiana tabacum L. cell lines. The enhancement of endogenous AOX1 expression and AOX protein with or without Al stress was in the order of transformed tobacco cell lines > ALT301 > wild type (SL). A decreased respiratory inhibition and reduced ROS production with a better growth capability were the significant features that characterized AOX1 transformed cell lines under Al stress. These results demonstrated that AOX plays a critical role in Al stress tolerance with an enhanced respiratory capacity, reducing mitochondrial oxidative stress burden and improving the growth capability in tobacco cells.


TGF-β-activated kinase 1 promotes cell cycle arrest and cell survival of X-ray irradiated HeLa cells dependent on p21 induction but independent of NF-κB, p38 MAPK and ERK phosphorylations.
Transforming growth factor-β-activated kinase 1 (TAK1) appears to play a role in inhibiting apoptotic death in response to multiple stresses. To assess the role of TAK1 in X-ray induced apoptosis and cell death, we irradiated parental and siRNA-TAK1-knockdown HeLa cells. Changes in gene expression levels with and without TAK1-knockdown were also examined after irradiation to elucidate the molecular mechanisms involved. After X-ray irradiation, cell death estimated by the colony formation assay increased in the TAK1-knockdown cells. Apoptosis induction, determined by caspase-3 cleavage, suggested that the increased radiosensitivity of the TAK1-knockdown cells could be partially explained by the induction of apoptosis. However, cell cycle analysis revealed that the percentage of irradiated cells in the G(2)/M-phase decreased, and those in the S- and SubG(1)-phases increased due to TAK1 depletion, suggesting that the loss of cell cycle checkpoint regulation may also be involved in the observed increased radiosensitivity. Interestingly, significant differences in the induction of NF-κB, p38 MAPK and ERK phosphorylation, the major downstream molecules of TAK1, were not observed in TAK1 knockdown cells compared to their parental control cells after irradiation. Instead, global gene expression analysis revealed differentially expressed genes after irradiation that bioinformatics analysis suggested are associated with cell cycle regulatory networks. In particular, CDKN1A (coding p21(WAF1)), which plays a central role in the identified network, was up-regulated in control cells but not in TAK1 knockdown cells after X-ray irradiation. Si-RNA knockdown of p21 decreased the percentage of cells in the G(2)/M phase and increased the percentage of cells in the S- and SubG(1)-phases after X-ray irradiation in a similar manner as TAK-1 knockdown. Taken together, these findings suggest that the role of TAK1 in cell death, cell cycle regulation and apoptosis after X irradiation is independent of NF-κB, p38 MAPK, and ERK phosphorylation, and dependent, in part, on p21 induction.


Towards UNAIDS Fast-Track goals: targeting priority geographic areas for HIV prevention and care in Zimbabwe.
Zimbabwe has made substantial progress towards the Joint United Nations Programme on HIV/AIDS (UNAIDS) targets of 90-90-90 by 2020, with 73% of people living with HIV diagnosed, 87% of those diagnosed on antiretroviral therapy (ART) and 86% of those on ART virally suppressed. Despite this exceptional response, more effort is needed to completely achieve the UNAIDS targets. Here, we conducted a detailed spatial analysis of the geographical structure of the HIV epidemic in Zimbabwe to include geographical prioritization as a key component of their overall HIV intervention strategy. Data were obtained from Zimbabwe Demographic and Health Survey (ZDHS) conducted in 2015 as well as estimations from the Zimbabwe Population-Based HIV Impact Assessment (ZIMPHIA) 2016 report, and other published literature. Data were used to produce high-resolution maps of HIV prevalence. Using these maps combined with the population density maps, we mapped the HIV-infected population lacking ART coverage and viral suppression. HIV maps for both sexes illustrated similar geographical variation of HIV prevalence within the country. HIV-infected populations lacking ART coverage and viral suppression were concentrated in the main cities and urban settlements such as Bulawayo, Harare, Ruwa and Chitungwiza. Our study showed extensive local variation in HIV disease burden across Zimbabwe for both women and men. The high-resolution maps generated here identified areas wherein high density of HIV-infected individuals are lacking ART coverage and viral suppression. These results suggest that there is need to tailor HIV programmes to address specific local needs to efficiently achieve epidemic control in Zimbabwe.


Assessing Antibody Strength: Comparison of MFI, C1q, and Titer Information.
The presence of donor-specific HLA antibodies before or after transplantation may have different implications based on the antibody strength. Yet, current approaches do not provide information regarding the true antibody strength as defined by antigen-antibody dissociation rate. To assess currently available methods, we compared between neat mean fluorescence intensity (MFI) values, C1q MFI values, ethylenediaminetetraacetic acid (EDTA)-treated samples, as well as titration studies and peak MFI values of over 7000 Luminex-based single-antigen HLA antibody data points. Our results indicate that neat MFI values do not always accurately depict antibody strength. We further showed that EDTA treatment (6%) does not always remove all inhibitory factors compared with C1q or titration studies. In this study of patients presenting with multiple antibody specificities, a prozone effect was observed in 71% of the cohort (usually not affecting all antibody specificities within a single serum sample, though). Similar to titration studies, the C1q assay was able to address the issue of potential inhibition; however, its limitation is its low sensitivity and inability to detect the presence of weak antibodies. Titration studies are the only method among the approaches used in this study to provide information suggesting antigen-antibody dissociation rates and are, therefore, likely to provide better indication of true antibody strength.


ONC201: Stressing tumors to death.
The small molecule ONC201 was identified in a screen for compounds that would induce expression of the gene encoding tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in tumors and thus cause an autocrine- or paracrine-induced death in tumor cells. Two Research Articles in this issue of Science Signaling by Ishizawa et al. and Kline et al. describe how ONC201 can also trigger cytotoxicity by inducing a stress response. The mechanisms of the stress response induced differ between hematological malignancies and solid tumors, highlighting the complexity of ONC201-induced toxicity and raising intriguing issues of tissue-specific pathways activated by the drug.


Identifying good group homes: qualitative indicators using a quality of life framework.
Abstract Despite change toward more individualized support, group homes are likely to remain for people with severe intellectual disability. As such, the search continues for ways to determine and maintain the quality of these settings. This article draws on in-depth qualitative analysis of participant observations conducted over 9-12 months in seven group homes for 21 people with a severe and profound level of intellectual disability. It explores the conceptualization of good outcomes and support for this group in terms of their quality of life and staff practices. The qualitative indicators of good outcomes for this group using quality of life domains can be used by auditors, community visitors, funders, advocates, or family members to guide observation and judgements about group homes.


Do differences in food web structure between organic and conventional farms affect the ecosystem service of pest control?
While many studies have demonstrated that organic farms support greater levels of biodiversity, it is not known whether this translates into better provision of ecosystem services. Here we use a food-web approach to analyse the community structure and function at the whole-farm scale. Quantitative food webs from 10 replicate pairs of organic and conventional farms showed that organic farms have significantly more species at three trophic levels (plant, herbivore and parasitoid) and significantly different network structure. Herbivores on organic farms were attacked by more parasitoid species on organic farms than on conventional farms. However, differences in network structure did not translate into differences in robustness to simulated species loss and we found no difference in percentage parasitism (natural pest control) across a variety of host species. Furthermore, a manipulative field experiment demonstrated that the higher species richness of parasitoids on the organic farms did not increase mortality of a novel herbivore used to bioassay ecosystem service. The explanation for these differences is likely to include inherent differences in management strategies and landscape structure between the two farming systems.


Lessons from models of murine erythroleukemia to acute myeloid leukemia (AML): proof-of-principle of co-operativity in AML.
The models of acute erythroleukemia caused in mice by the Friend retrovirus SFFV (spleen focus forming virus) and the Spi-1/PU.1 transgenesis provide considerable information to help to understand the molecular mechanisms underlying the multi-stage nature of leukemia. Leukemogenesis in these murine models is initiated from an acute hyperplasia of erythroid progenitor cells followed later on by a blastic crisis. This review highlights recent findings demonstrating the key roles of the co-operation of two mutations occurring during leukemic progression, a mutation interfering with differentiation and a mutation conferring a proliferative advantage to cells. Through their multi-step evolution, these mouse erythroleukemia models resemble the two phases of human acute myeloid leukemia (AML). The findings we discuss provide evidence for similar molecular mechanisms involved in the evolution of leukemia in mice and men.


Effects of long-term, moderate-intensity oral anticoagulation in addition to aspirin in unstable angina. The Organization to Assess Strategies for Ischemic Syndromes (OASIS) Investigators.
We sought to evaluate whether oral anticoagulant (AC) therapy given for five months was superior to standard (control) therapy in patients with unstable angina receiving aspirin. The long-term risk of myocardial infarction (MI) or death remains high in patients with unstable angina, despite the use of aspirin. Therefore, additional treatments are necessary. Of the 10,141 patients entering the main trial, 3,712 were randomized 12 to 48 h later to receive oral AC therapy (n = 1,848) or standard therapy (n = 1,864). One-hundred forty patients (7.6%) suffered from cardiovascular death, MI or stroke while receiving oral AC, compared with 155 patients (8.3%) on standard therapy (relative risk [RR] 0.90, 95% confidence interval [CI] 0.72 to 1.14; p = 0.40). The rates of the primary outcomes plus refractory angina were 16.7% (n = 308) versus 17.5% (n = 327) (RR 0.95, 95% CI 0.81 to 1.11; p = 0.53). Countries were divided into good or poor compliers (based on the use of oral AC above or below 70% at 35 days), without knowledge of results by country. In good-complier countries, oral AC was discontinued in only 10.4% of patients at seven days and in 23.6% by five months, compared with 27.6% and 44.9%, respectively, in poor complier countries. There were significant reductions in the risks of both the primary (6.1% vs. 8.9%; RR 0.68, 95% CI 0.48 to 0.95; p = 0.02) and secondary outcomes (11.9% vs. 16.5%; RR 0.70, 95% CI 0.55 to 0.90; p = 0.005) with oral AC in the good-complier countries. There was little difference in the poor-complier countries (9.0% vs. 7.8% for the primary and 21.3% vs. 18.5% for the secondary outcomes, tests for interactions comparing the RRs for the primary and secondary outcomes were p < 0.02 and p = 0.002, respectively, between the two sets of countries). In the overall study, there was an excess of major bleeding (2.7% vs. 1.3%; p = 0.004), which was larger in the good-complier countries (RR 2.71) compared with the poor-complier countries (RR 1.58). There were also reductions in cardiac catheterization (RR 0.80; p = 0.004) and coronary revascularization procedures (RR 0.82; p = 0.06) in the good-complier countries, but not in the poor-complier countries (RR 0.98 and 1.06, respectively, p for interaction of 0.06 and 0.04, respectively). Overall, oral AC led to a small, nonsignificant reduction in the risk of the primary and secondary outcomes. Stratifying the countries or centers by their rates of compliance to oral AC suggested that good compliance to oral AC could potentially lead to clinically important reductions in major ischemic cardiovascular events.


Structural and Thermodynamic Characterization of Protein-Ligand Interactions Formed between Lipoprotein-Associated Phospholipase A2 and Inhibitors.
Lipoprotein-associated phospholipase A2 (Lp-PLA2) represents a promising therapeutic target for atherosclerosis and Alzheimer's disease. Here we reported the first crystal structures of Lp-PLA2 bound with reversible inhibitors and the thermodynamic characterization of complexes. High rigidity of Lp-PLA2 structure and similar binding modes of inhibitors with completely different scaffolds are revealed. It not only provides the molecular basis for inhibitory activity but also sheds light on the essential features of Lp-PLA2 recognition with reversible inhibitors.


Bivalirudin versus heparin monotherapy in non-ST-segment elevation myocardial infarction.
The optimal anti-coagulation strategy for patients with non-ST-elevation myocardial infarction treated with percutaneous coronary intervention is unclear in contemporary clinical practice of radial access and potent P2Y12-inhibitors. The aim of this study was to investigate whether bivalirudin was superior to heparin monotherapy in patients with non-ST-elevation myocardial infarction without routine glycoprotein IIb/IIIa inhibitor use. In a large pre-specified subgroup of the multicentre, prospective, randomised, registry-based, open-label clinical VALIDATE-SWEDEHEART trial we randomised patients with non-ST-elevation myocardial infarction undergoing percutaneous coronary intervention, treated with ticagrelor or prasugrel, to bivalirudin or heparin monotherapy with no planned use of glycoprotein IIb/IIIa inhibitors during percutaneous coronary intervention. The primary endpoint was the rate of a composite of all-cause death, myocardial infarction or major bleeding within 180 days. A total of 3001 patients with non-ST-elevation myocardial infarction, were enrolled. The primary endpoint occurred in 12.1% (182 of 1503) and 12.5% (187 of 1498) of patients in the bivalirudin and heparin groups, respectively (hazard ratio of bivalirudin compared to heparin treatment 0.96, 95% confidence interval 0.78-1.18, p=0.69). The results were consistent in all major subgroups. All-cause death occurred in 2.0% versus 1.7% (hazard ratio 1.15, 0.68-1.94, p=0.61), myocardial infarction in 2.3% versus 2.5% (hazard ratio 0.91, 0.58-1.45, p=0.70), major bleeding in 8.9% versus 9.1% (hazard ratio 0.97, 0.77-1.24, p=0.82) and definite stent thrombosis in 0.3% versus 0.2% (hazard ratio 1.33, 0.30-5.93, p=0.82). Bivalirudin as compared to heparin during percutaneous coronary intervention for non-ST-elevation myocardial infarction did not reduce the composite of all-cause death, myocardial infarction or major bleeding in non-ST-elevation myocardial infarction patients receiving current recommended treatments with modern P2Y12-inhibitors and predominantly radial access.


Mutations in the N terminus of the oX174 DNA pilot protein H confer defects in both assembly and host cell attachment.
The øX174 DNA pilot protein H forms an oligomeric DNA-translocating tube during penetration. However, monomers are incorporated into 12 pentameric assembly intermediates, which become the capsid's icosahedral vertices. The protein's N terminus, a predicted transmembrane helix, is not represented in the crystal structure. To investigate its functions, a series of absolute and conditional lethal mutations were generated. The absolute lethal proteins, a deletion and a triple substitution, were efficiently incorporated into virus-like particles lacking infectivity. The conditional lethal mutants, bearing cold-sensitive (cs) and temperature-sensitive (ts) point mutations, were more amenable to further analyses. Viable particles containing the mutant protein can be generated at the permissive temperature and subsequently analyzed at the restrictive temperature. The characterized cs defect directly affected host cell attachment. In contrast, ts defects were manifested during morphogenesis. Particles synthesized at permissive temperature were indistinguishable from wild-type particles in their ability to recognize host cells and deliver DNA. One mutation conferred an atypical ts synthesis phenotype. Although the mutant protein was efficiently incorporated into virus-like particles at elevated temperature, the progeny appeared to be kinetically trapped in a temperature-independent, uninfectious state. Thus, substitutions in the N terminus can lead to H protein misincorporation, albeit at wild-type levels, and subsequently affect particle function. All mutants exhibited recessive phenotypes, i.e., rescued by the presence of the wild-type H protein. Thus, mixed H protein oligomers are functional during DNA delivery. Recessive and dominant phenotypes may temporally approximate H protein functions, occurring before or after oligomerization has gone to completion.


Role of adjuvant or salvage radiosurgery in the management of unresected residual or progressive glioblastoma multiforme in the pre-bevacizumab era.
After initial standard of care management of glioblastoma multiforme (GBM), relatively few proven options remain for patients with unresected progressive tumor. Numerous reports describe the value of radiosurgery, yet this modality appears to remain underutilized. The authors analyzed the outcomes of early adjuvant stereotactic radiosurgery (SRS) for unresected tumor or later salvage SRS for progressive GBM. Radiosurgery was performed as part of the multimodality management and was combined with other therapies. Patients continued to receive additional chemotherapy after SRS and prior to progression being documented. In this retrospective analysis, the authors evaluated factors that affected patient overall survival (OS) and progression-free survival. Between 1987 and 2008 the authors performed Gamma Knife SRS in 297 patients with histologically proven GBMs. All patients had received prior fractionated radiation therapy, and 66% had undergone one or more chemotherapy regimens. Ninety-six patients with deep-seated unresectable GBMs underwent biopsy only. Of those in whom excision had been possible, resection was considered to be gross total in 68 and subtotal in 133. The median patient age was 58 years (range 23-89 years) and the median tumor volume was 14 cm(3) (range 0.26-84.2 cm(3)). The median prescription dose delivered to the imaging-defined tumor margin was 15 Gy (range 9-25 Gy). The median follow-up duration was 8.6 months (range 1.1-173 months). Cox regression models were used to analyze survival outcomes. Variables examined included age, residual versus recurrent tumor, prior chemotherapy, time to first recurrence, SRS dose, and gross tumor volume. The median survival times after radiosurgery and after diagnosis were 9.03 and 18.1 months, respectively. The 1-year and 2-year OS after SRS were 37.9% and 16.7%, respectively. The 1-year and 2-year OS after diagnosis were 76.2% and 30.8%, respectively. Using multivariate analysis, factors associated with improved OS after diagnosis were younger age (< 60 years) at diagnosis (p < 0.0001), tumor volume < 14 cm(3) (p < 0.001), use of prior chemotherapy (p = 0.001), and radiosurgery at the time of recurrence (p < 0.0001). Multivariate analysis showed that younger age (p < 0.0001) and smaller tumor volume (< 14 cm(3)) (p = 0.001) were significantly associated with increased OS after SRS. Adverse radiation effects were seen in 69 patients (23%). Fifty-eight patients (19.5%) underwent additional resection after SRS. The median survivals after diagnosis for recursive partitioning analysis Classes III, IV and V+VI were 31.6, 20.8, and 16.7 months, respectively. In this analysis 30% of a heterogeneous cohort of GBM patients eligible for SRS had an OS of 2 years. Radiosurgery at the time of tumor progression was associated with a median survival of 21.8 months. The role of radiosurgery for GBMs remains controversial. The findings in this study support the need for a funded and appropriately designed clinical trial that will provide a higher level of evidence regarding the future role of SRS for glioblastoma patients in whom disease has progressed despite standard management.


The medical complications of anorexia nervosa.
The physical complications of anorexia nervosa are common and can be life threatening, but psychiatrists and the increasing number of non-medical therapists involved in treatment programmes often overlook these complications. Cardiovascular complications are the most common, and the most likely to result in fatalities, particularly in those patients who vomit, purge or abuse diuretics, because of the electrolyte abnormalities induced. Osteoporosis is an early and perhaps irreversible consequence of severe weight loss. Further, there are dangers in rapid intravenous hyperalimentation.


[French ccAFU guidelines - Update 2018-2020: Penile cancer].
To update French oncology guidelines concerning penile cancer. Comprehensive Medline search between 2016 and 2018 upon diagnosis, treatment and follow-up of testicular germ cell cancer to update 2016-2018 guidelines. Level of evidence was evaluated according to AGREE-II. Epidermoid carcinoma is the most common penile cancer histology. Physical examination is mandatory to define local and inguinal nodal cancer stage. MRI with artificial erection can help to assess deep infiltration in cases of organ-sparing intention. Node negative patients (defined by palpation and imaging) will present micro nodal metastases in up to 25% of cases. Invasive lymph node assessment is thus advocated except for low risk patients. Sentinel node dynamic biopsy is the first line technique. Modified bilateral inguinal lymphadenectomy is an option with higher morbidity. 18-FDG-PET is recommended in patients with palpable nodes. Chest, abdominal and pelvis computerized tomography is an option. Fine needle aspiration (when positive) is an easy way to assess inguinal palpable node pathological involvement. Treatment is mostly surgical. Free margins status is essential, but it also has to be organ-sparing when possible. Brachytherapy and topic agents can cure in selected cases. Lymph node assessment should be synchronous to the removal of the tumour when possible. Limited inguinal lymph node involvement (pN1 stage) can be cured with the only lymphadenectomy. In case of larger lymph node stage, one should consider multidisciplinary treatment including chemotherapy and inclusion in a trial. Penile cancer needs demanding surgery to be cured, surrounded by chemotherapy in node positive patients. Lymph nodes involvement is a major prognostic factor. Thus, inguinal node assessment cannot be neglected.


Biases in the interpretation and use of research results.
The latter half of this century has seen an erosion in the perceived legitimacy of science as an impartial means of finding truth. Many research topics are the subject of highly politicized dispute; indeed, the objectivity of the entire discipline of psychology has been called into question. This essay examines attempts to use science to study science: specifically, bias in the interpretation and use of empirical research findings. I examine theory and research on a range of cognitive and motivational mechanisms for bias. Interestingly, not all biases are normatively proscribed; biased interpretations are defensible under some conditions, so long as those conditions are made explicit. I consider a variety of potentially corrective mechanisms, evaluate prospects for collective rationality, and compare inquisitorial and adversarial models of science.


Long-term outcome and impact of surgery on adults with coronary arteries originating from the opposite coronary cusp.
An anomalous coronary artery from the opposite sinus of Valsalva may increase sudden death risk in children and young adults, and surgical intervention is often recommended. The impact of this lesion when recognized in the adult and its management are ill defined. We reviewed 210 700 cardiac catheterizations performed over a 35-year period at a single institution and identified 301 adults with an anomalous coronary artery from the opposite sinus of Valsalva, either anomalous right coronary artery from the left cusp or anomalous left main coronary artery from the right cusp. Patients were stratified by the pathway of the anomalous artery and the chosen treatment. Among the 301 patients with anomalous coronary artery from the opposite sinus of Valsalva (0.14% of the cohort), 79% had anomalous right coronary artery from the left cusp, and 18% had an interarterial course (IAC). Patients with IAC were younger (52±13 versus 59±13 years; P=0.001) and more likely to undergo surgical intervention (52% versus 27%; P<0.001), but mortality was not increased with IAC. Among the 54 patients with IAC, 28 underwent surgical repair with no perioperative deaths. Patients evaluated since 2000 were significantly more likely to be referred for surgery (P=0.004). Surgical patients were more likely to have abnormal stress tests (90% versus 43%; P=0.01) and had more extensive atherosclerosis but less diabetes mellitus (0% versus 23%; P=0.01). Long-term survival at 10 years appeared similar in both groups. In this single-center cohort study of patients with an anomalous coronary artery from the opposite sinus of Valsalva, surgical management appears to have been favored recently. Despite no perioperative mortality, a positive impact on long-term survival was not observed. The impact of surgery in older adults with anomalous coronary arteries arising from the opposite coronary sinus with IAC deserves further study.


A new family of mobilizable suicide plasmids based on broad host range R388 plasmid (IncW) and RP4 plasmid (IncPalpha) conjugative machineries and their cognate Escherichia coli host strains.
We describe the construction of the pSW family of conditionally replicating plasmids which are based on the IncX oriV origin (oriV(R6Kgamma)) of replication that is dependent on the pir-encoded protein. We constructed several Escherichia coli derivatives expressing pir from different chromosomal loci, and the pir gene could be transduced by phage P1 to any E. coli strain. These chromosomal constructions generate dapA and thyA knockouts, which lead to diaminopimelate or thymidine auxotrophies, respectively, and they serve to provide absolute counterselection even in rich media. These strains can be easily counterselected if used in plasmid transfer experiments into markerless recipients, and they have been demonstrated to work efficiently in E. coli xVibrio or E. coli xBartonella matings. We constructed different pSW plasmids carrying either the oriT(RP4) or the oriT(R388), and we demonstrated that these derivatives can be efficiently transferred using RP4 and R388 conjugation machineries, respectively. We also constructed two plasmids expressing the R388 conjugation machinery, but lacking the oriT(R388). We demonstrated that these plasmids enabled efficient and exclusive transfer of a pSW-oriT(R388) derivative from E. coli to V. cholerae, and we offer an alternative to the popular RP4-based delivery system.


The syntaxin homolog AtPEP12p resides on a late post-Golgi compartment in plants.
Soluble proteins are transported to the plant vacuole through the secretory pathway via membrane-bound vesicles. Targeting of vesicles to appropriate organelles requires several membrane-bound and soluble factors that have been characterized in yeast and mammalian systems. For example, the yeast PEP12 protein is a syntaxin homolog that is involved in protein transport to the yeast vacuole. Previously, we isolated an Arabidopsis thaliana homolog of PEP12 by functional complementation of the yeast pep12 mutant. Antibodies raised against the cytoplasmic portion of AtPEP12 have been prepared and used for intracellular localization of this protein. Biochemical analysis indicates that AtPEP12 does not localize to the endoplasmic reticulum, Golgi apparatus, plasma membrane, or tonoplast in Arabidopsis plants; furthermore, based on biochemical and electron microscopy immunogold labeling analyses, AtPEP12 is likely to be localized to a post-Golgi compartment in the vacuolar pathway.


"Suboptimal" kidney donors: the experience with tacrolimus-based immunosuppression.
Female, pediatric, and older donors have been associated with inferior graft survival after renal transplantation. We analyzed these three subgroups in 397 patients receiving tacrolimus-based immunosuppression. There were no differences in recipient age, incidence of retransplantation, or percentage of sensitized patients. Female donors, compared with male donors, were associated with comparable 1- and 3-year patient survival rates (96% and 93% vs. 95% and 92%, respectively) and comparable 1- and 3-year graft survival rates (90% and 80% vs. 88% and 81%, respectively). Renal function was also similar. Recipients of pediatric en bloc kidneys, when compared with recipients of other cadaveric kidneys, also had comparable 1- and 3-year patient survival rates (94% and 94% vs. 95% and 91%, respectively) and comparable 1- and 3-year graft survival rates (84% and 84% vs. 89% and 79%, respectively). Renal function was better in recipients of en bloc kidneys, with a mean serum creatinine level of 1.4+/-1.8 mg/dl vs. 2.0+/-1.5 mg/dl (P=0.01). In contrast to the first two subgroups, donors over 60 years of age, when compared with donors under 60 years of age, were associated with worse 1- and 3-year patient survival rates (88% and 80% vs. 96% and 94%, respectively; P<0.03) and worse 1- and 3-year graft survival rates (74% and 62% vs. 91% and 83%, respectively; P<0.0001). Renal function was worse in the older donor group, with a serum creatinine level of 2.7+/-1.2 mg/ml vs. 1.9+/-1.5 mg/dl (P=0.01). We conclude that, under tacrolimus-based immunosuppression, kidneys from female or very young pediatric donors are not associated with adverse outcomes, whereas kidneys from donors over 60 years of age are associated with inferior outcomes.


Outcomes of Atrial Arrhythmia Surgery in Patients With Congenital Heart Disease: A Systematic Review.
Background The improved life expectancy of patients with congenital heart disease is often accompanied by the development of atrial tachyarrhythmias. Similarly, the number of patients requiring redo operations is expected to continue to rise as these patients are aging. Consequently, the role of arrhythmia surgery in the treatment of atrial arrhythmias is likely to become more important in this population. Although atrial arrhythmia surgery is a well-established part of Fontan conversion procedures, evidence-based recommendations for arrhythmia surgery for macroreentrant atrial tachycardia and atrial fibrillation in other patients with congenital heart disease are still lacking. Methods and Results Twenty-eight studies were included in this systematic review. The median reported arrhythmia recurrence was 13% (interquartile range, 4%-26%) during follow-up ranging from 3 months to 15.2 years. A large variation in surgical techniques was observed. Based on the acquired data, biatrial lesions are more effective in the treatment of atrial fibrillation than exclusive right-sided lesions. Right-sided lesions may be more appropriate in the treatment of macroreentrant atrial tachycardia; evidence for the superiority of additional left-sided lesions is lacking. There are not enough data to support the use of exclusive left-sided lesions. Theoretically, prophylactic atrial arrhythmia surgery may be beneficial in this population, but evidence is currently limited. Conclusions To be able to provide recommendations for arrhythmia surgery in patients with congenital heart disease, future studies should report outcomes according to the type of preoperative arrhythmia, underlying congenital heart disease, lesion set, and energy source. This is essential for determining which surgical techniques should ideally be applied under which circumstances.


Nanoparticles Can Wrap Epithelial Cell Membranes and Relocate Them Across the Epithelial Cell Layer.
Although the link between the inhalation of nanoparticles and cardiovascular disease is well established, the causal pathway between nanoparticle exposure and increased activity of blood coagulation factors remains unexplained. To initiate coagulation tissue factor bearing epithelial cell membranes should be exposed to blood, on the other side of the less than a micrometre thin air-blood barrier. For the inhaled nanoparticles to promote coagulation, they need to bind lung epithelial-cell membrane parts and relocate them into the blood. To assess this hypothesis, we use advanced microscopy and spectroscopy techniques to show that the nanoparticles wrap themselves with epithelial-cell membranes, leading to the membrane's disruption. The membrane-wrapped nanoparticles are then observed to freely diffuse across the damaged epithelial cell layer relocating epithelial cell membrane parts over the epithelial layer. Proteomic analysis of the protein content in the nanoparticles wraps/corona finally reveals the presence of the coagulation-initiating factors, supporting the proposed causal link between the inhalation of nanoparticles and cardiovascular disease.


Facet-selective group-III incorporation in InGaAs template assisted selective epitaxy.
InGaAs is a potential candidate for Si replacement in upcoming advanced technological nodes because of its excellent electron transport properties and relatively low interface defect density in dielectric gate stacks. Therefore, integrating InGaAs devices with the established Si platforms is highly important. Using template-assisted selective epitaxy (TASE), InGaAs nanowires can be monolithically integrated with high crystal quality, although the mechanisms of group III incorporation in this ternary material have not been thoroughly investigated. Here we present a detailed study of the compositional variations of InGaAs nanostructures epitaxially grown on Si(111) and Silicon-on-insulator substrates by TASE. We present a combination of XRD data and detailed EELS maps and find that the final Ga/In chemical composition depends strongly on both growth parameters and the growth facet type, leading to complex compositional sub-structures throughout the crystals. We can further conclude that the composition is governed by the facet-dependent chemical reaction rates at low temperature and low V/III ratio, while at higher temperature and V/III ratio, the incorporation is transport limited. In this case we see indications that the transport is a competition between Knudsen flow and surface diffusion.


Changes in ultrasound-assessed carotid intima-media thickness and plaque with a Mediterranean diet: a substudy of the PREDIMED trial.
The Prevención con Dieta Mediterránea (PREDIMED) trial showed that a Mediterranean diet (MedDiet) supplemented with either extra virgin olive oil or 30 g/d of mixed nuts reduced incident cardiovascular events compared with a control (low fat) diet. The mechanisms of cardiovascular protection afforded by MedDiets remain to be uncovered. We assessed the effect of both supplemented MedDiets on internal carotid intima-media thickness (ICA-IMT) and plaque height, the ultrasound features that best predict future cardiovascular events, in subjects at high cardiovascular risk. In a PREDIMED subcohort (n=175), plaque height and carotid IMT of 3 prespecified segments (ICA, bifurcation, and common) were sonographically assessed at baseline and after intervention for a mean of 2.4 years. We evaluated 164 subjects with complete data. In a multivariate model, mean ICA-IMT progressed in the control diet group (mean [95% confidence interval], 0.052 mm [-0.014 to 0.118 mm]), whereas it regressed in the MedDiet+nuts group (-0.084 mm [-0.158 to -0.010 mm]; P=0.024 versus control). Similar results were observed for maximum ICA-IMT (control, 0.188 mm [0.077 to 0.299 mm]; MedDiet+nuts, -0.030 mm [-0.153 to 0.093 mm]; P=0.034) and maximum plaque height (control, 0.106 mm [0.001 to 0.210 mm]; MedDiet+nuts, -0.091 mm [-0.206 to 0.023 mm]; P=0.047). There were no changes in ICA-IMT or plaque after the MedDiet+extra virgin olive oil. Compared with a control diet, consumption of a MedDiet supplemented with nuts is associated with delayed progression of ICA-IMT and plaque. The results contribute mechanistic evidence for the reduction of cardiovascular events observed in the PREDIMED trial. http://www.controlled-trials.com. Unique identifier: ISRCTN35739639.


Monitoring the Decade of Action for Global Road Safety 2011-2020: An update.
The United Nations Road Safety Collaboration (UNRSC) was set up in 2004 in response to the recognised need for the United Nations (UN) system to encourage efforts to address the global road safety crisis. In 2010, the UN General Assembly Resolution 64/255 declared 2011-2020 the Decade of Action for Road Safety with the overarching goal of stabilising and reducing the forecasted number of road traffic deaths by increasing activities at national, regional and global levels. In 2011, a Plan of Action for the Decade of Action, a tool to support the development of national and local plans of action, was launched. Countries are encouraged to implement activities according to the five pillars set out by the Plan of Action. The UNRSC, tasked to evaluate the overall impact of the Decade, developed and populated indicators for each pillar. Currently, 36 of 38 proposed indicators are populated by baseline data for 2010 from the second Global status report for road safety. However, gaps exist in data quality and availability on a global level. Therefore, there is an urgent need for improving data quality and availability to measure the progress of the Decade of Action.


Factors influencing individual variability in high fat diet-induced weight gain in out-bred MF1 mice.
Easy access to high-energy palatable foods has been suggested to have contributed to the world-wide obesity epidemic. However, within these 'obesogenic' environments many people manage to remain lean. Mice also show variability in their weight gain responses to high-fat diet (HFD) feeding and their weight loss responses to calorically restricted (CR) feeding. In this study we investigated which factors contribute to determining susceptibility to HFD-induced obesity in mice, and whether the responses in weight gain on HFD are correlated with the responses to CR. One-hundred twenty four mice were exposed to 30% CR for 28days followed by a 14day recovery period, and subsequent exposure to 60% HFD for 28days. Responses in various metabolic factors were measured before and after each exposure (body mass; BM, body composition, food intake; FI, resting metabolic rate; RMR, physical activity, body temperature and glucose tolerance; GT). Weight changes on HFD ranged from -1 to 26%, equivalent to -0.2g to 10.5g in absolute mass. Multiple regression models showed that fat free mass (FFM) of the mice before exposure to HFD predicted 12% of the variability in weight gain on HFD (p<0.001). Also, FI during the first week of HFD feeding predicted 20% of the variability in BM and fat mass (FM) gain 4weeks later. These data may point to a role for the reward system in driving individual differences in FI and weight gain. Weight gain on the HFD was significantly negatively correlated to weight loss on CR, indicating that animals that are poor at defending against weight gain on HFD, were also poor at defending against CR-induced weight loss. Changes in FM and FFM in response to HFD or CR were not correlated however.


The beneficial effect of melatonin in brain endothelial cells against oxygen-glucose deprivation followed by reperfusion-induced injury.
Melatonin has a cellular protective effect in cerebrovascular and neurodegenerative diseases. Protection of brain endothelial cells against hypoxia and oxidative stress is important for treatment of central nervous system (CNS) diseases, since brain endothelial cells constitute the blood brain barrier (BBB). In the present study, we investigated the protective effect of melatonin against oxygen-glucose deprivation, followed by reperfusion- (OGD/R-) induced injury, in bEnd.3 cells. The effect of melatonin was examined by western blot analysis, cell viability assays, measurement of intracellular reactive oxygen species (ROS), and immunocytochemistry (ICC). Our results showed that treatment with melatonin prevents cell death and degradation of tight junction protein in the setting of OGD/R-induced injury. In response to OGD/R injury of bEnd.3 cells, melatonin activates Akt, which promotes cell survival, and attenuates phosphorylation of JNK, which triggers apoptosis. Thus, melatonin protects bEnd.3 cells against OGD/R-induced injury.


Follicular lymphoma, a B cell malignancy addicted to epigenetic mutations.
While follicular lymphoma (FL) is exquisitely responsive to immuno-chemotherapy, many patients follow a relapsing remitting clinical course driven in part by a common precursor cell (CPC) population. Advances in next generation sequencing have provided valuable insights into the genetic landscape of FL and its clonal evolution in response to therapy, implicating perturbations of epigenetic regulators as a hallmark of the disease. Recurrent mutations of histone modifiers KMT2D, CREBBP, EP300, EZH2, ARIDIA, and linker histones are likely early events arising in the CPC pool, rendering epigenetic based therapies conceptually attractive for treatment of indolent and transformed FL. This review provides a synopsis of the main epigenetic aberrations and the current efforts in development and testing of epigenetic therapies in this B cell malignancy.


Control of the diffracted response of wire arrays with double periods.
The possibility of controlling the diffracted response of a periodic structure is investigated by using dual-period arrays, i.e., periodic arrays with a compound unit cell. We consider wire gratings in which each period comprises several cylinders with circular cross sections and all the cylinder axes are contained in the same plane. It is shown that this kind of structure permits one to control the diffracted response, regardless of the cylinder material and the incident polarization. Our numerical results suggest that the effect produced by wire gratings with dual-period characteristics is basically a geometric effect, and it can be present for other shapes of individual scatterers within each subarray.


Rigorous expressions for the Fresnel equations at interfaces between absorbing media.
When conventional Fresnel theory is applied to absorbing multilayer systems, a slight discrepancy with respect to the principle of conservation of energy arises. Here we solve this long-perceived problem and present rigorous expressions for the Fresnel equations generally applicable to interfaces between isotropic absorbing media. These equations satisfy the conservation law automatically and coincide naturally with the conventional ones in reflection by simple mirrors placed in a vacuum.


A study of medical students' specialty-choice pathways: trying on possible selves.
To describe the decision-making processes reported by graduating medical students in choosing primary care (PC) or non-primary-care (NPC) specialties. Members of the University of Washington School of Medicine's graduating class of 1995 were invited to participate in focus groups. Six specialty-choice pathways were defined based on a previously administered survey of recalled preferences at matriculation and stated choice at the time of the National Resident Matching Program. Students were assigned to focus groups based on specialty-choice pathway. Transcribed discussions and summaries were thematically coded and analyzed using grounded theory and quantitative comparisons. Of 157 students, 140 (89%) completed the initial survey, and 133 (85%) provided enough information to be classified by pathway. In all, 47 students participated in the focus group discussions. The PC students cited PC orientation, diversity of patients and activities, role models and mentors, interaction with patients, and overall medical school culture as having influenced their choice. The NPC students cited lifestyle, controllable hours, opportunities to do procedures, therapeutic urgency and effect, active tempo, exciting settings, and intellectual challenge. Role models influenced PC career choice much more than NPC career choice, and often served to refute negative stereotypes. The sense of personal fit between themselves and specialties was important to the students in all groups, but differed in emphasis according to career-choice pathways. Those whose preferences did not change experienced a confirmation of pre-existing beliefs, while those who switched specialty areas developed a sense of fit through the inclusion or elimination of different practice aspects. Those who switched specialty areas reported more negative influences and misunderstanding of their initially preferred specialties. The process of specialty choice can be described usefully as a socially constructed process of "trying on possible selves" (i.e., projecting oneself into hypothetical career and personal roles). This may explain role models' exceptional influence in disproving negative stereotypes. Medical students' choices can best be facilitated by recognizing their needs to gain knowledge not only about specialty content, but also about practitioners' lives and the students' own present and possible selves.


Lichen sclerosus et atrophicus causing phimosis in boys: a prospective study with 5-year followup after complete circumcision.
We prospectively investigated 100 pediatric patients suffering from phimosis and found a 10% incidence of lichen sclerosus et atrophicus. This condition usually can be diagnosed preoperatively because of its classic manifestation of severe phimosis due to a sclerotic, whitish ring at the tip of the prepuce, which in our cases was accompanied by sclerogenous glanular lesions. To our knowledge our study represents the first evidence that the development of secondary phimosis with no apparent reason in school-age boys is highly suggestive for lichen sclerosus et atrophicus. Complete circumcision is the therapy of choice because it completely removes all affected tissue and it allows spontaneous regression or resolution of glanular lesions. There has been no recurrence after 5 years of followup.


The Role of Familiarity for Representations in Norm-Based Face Space.
According to the norm-based version of the multidimensional face space model (nMDFS, Valentine, 1991), any given face and its corresponding anti-face (which deviates from the norm in exactly opposite direction as the original face) should be equidistant to a hypothetical prototype face (norm), such that by definition face and anti-face should bear the same level of perceived typicality. However, it has been argued that familiarity affects perceived typicality and that representations of familiar faces are qualitatively different (e.g., more robust and image-independent) from those for unfamiliar faces. Here we investigated the role of face familiarity for rated typicality, using two frequently used operationalisations of typicality (deviation-based: DEV), and distinctiveness (face in the crowd: FITC) for faces of celebrities and their corresponding anti-faces. We further assessed attractiveness, likeability and trustworthiness ratings of the stimuli, which are potentially related to typicality. For unfamiliar faces and their corresponding anti-faces, in line with the predictions of the nMDFS, our results demonstrate comparable levels of perceived typicality (DEV). In contrast, familiar faces were perceived much less typical than their anti-faces. Furthermore, familiar faces were rated higher than their anti-faces in distinctiveness, attractiveness, likability and trustworthiness. These findings suggest that familiarity strongly affects the distribution of facial representations in norm-based face space. Overall, our study suggests (1) that familiarity needs to be considered in studies of mental representations of faces, and (2) that familiarity, general distance-to-norm and more specific vector directions in face space make different and interactive contributions to different types of facial evaluations.


Cold-priming of chloroplast ROS signalling is developmentally regulated and is locally controlled at the thylakoid membrane.
24 h exposure to 4 °C primes Arabidopsis thaliana in the pre-bolting rosette stage for several days against full cold activation of the ROS responsive genes ZAT10 and BAP1 and causes stronger cold-induction of pleiotropically stress-regulated genes. Transient over-expression of thylakoid ascorbate peroxidase (tAPX) at 20 °C mimicked and tAPX transcript silencing antagonized cold-priming of ZAT10 expression. The tAPX effect could not be replaced by over-expression of stromal ascorbate peroxidase (sAPX) demonstrating that priming is specific to regulation of tAPX availability and, consequently, regulated locally at the thylakoid membrane. Arabidopsis acquired cold primability in the early rosette stage between 2 and 4 weeks. During further rosette development, primability was widely maintained in the oldest leaves. Later formed and later maturing leaves were not primable demonstrating that priming is stronger regulated with plant age than with leaf age. In 4-week-old plants, which were strongest primable, the memory was fully erasable and lost seven days after priming. In summary, we conclude that cold-priming of chloroplast-to-nucleus ROS signalling by transient post-stress induction of tAPX transcription is a strategy to modify cell signalling for some time without affecting the alertness for activation of cold acclimation responses.


The effects of protocolized use of recombinant factor VIIa within a massive transfusion protocol in a civilian level I trauma center.
Despite conflicting data regarding its effectiveness, many massive transfusion protocols (MTPs) include recombinant Factor VIIa (rFVIIa) as an adjunct to hemorrhage control. Over a 3-year period, outcome data for massively transfused patients was compared based on administration of rFVIIa as part of a mature MTP. Of 228 MTP activations, 117 patients were candidates for rFVIIa, and, of these, 39 patients received rFVIIa under the MTP. Comparing patients who received rFVIIa with those who did not based on initial packed red blood cell (PRBC) transfusion requirements, there was no difference in mortality for transfusions ≤ 20 units (25 vs 24%, 24-hour; 25 vs 42%, 30-day) or 21 to 30 units (33 vs 47%, 24-hour; 55 vs 50%, 30-day). For initial requirement ≥ 30 units of PRBCs, 24-hour mortality (26 vs 64%, P = 0.02) was significantly decreased in patients that received rFVIIa (n = 19) compared with those who did not (n = 17). These mortality differences were not maintained at 30 days (68 vs 71%). rFVIIa had minimal clinical impact on outcomes for patients requiring less than 30 units of PRBCs. For patients transfused more than 30 units of PRBCs, differences in 24-hour and 30-day mortality suggest that rFVIIa converted early deaths from exsanguination to late deaths from multiorgan failure.


Hemolytic uremic syndrome after renal transplantation.
Hemolytic Uremic Syndrome after kidney transplantation affects an increasing number of patients. It is characterized as recurrent and de novo. Older age at onset of HUS, shorter mean interval between HUS and transplantation or ESRD, living related donor and treatment with CNI have been associated with an increased risk of recurrence. Patients who lost the first transplant because of HUS recurrence should not receive a second transplant. The outcome of recurring HUS after transplantation is worse in familial forms leading invariably to graft loss and for this reason doctors should discourage the use of living related donors in this setting. De novo HUS is not a rare complication after kidney transplantation and may be associated with infection, CNI or mTOR inhibitor toxicity, antibody use (OKT3), or acute vascular rejection. The clinical picture is obscure and treatment rests on removal of inciting factor with or without plasma exchange/FFP infusion.


The leucine zipper putative tumor suppressor 2 protein LZTS2 regulates kidney development.
Members of the leucine zipper putative tumor suppressor (LZTS) family play crucial roles in transcription modulation and cell cycle control. We previously demonstrated that LZTS2 functions as a novel β-catenin-interacting protein and represses β-catenin-mediated transcription on T-cell factor/lymphoid enhancing factor. Here, we investigate the biological role of LZTS2 using newly established Lzts2 KO mice. Homozygosity for loss-of-function of the Lzts2-targeted allele resulted in severe kidney and urinary tract developmental defects, including renal/ureteral duplication, hydroureter, and hydronephrosis, which were visible prenatally. Altered ureteric bud outgrowth was identified in Lzts2 null embryos. Further analysis indicated that β-catenin subcellular localization was altered in fibroblasts isolated from Lzts2 null embryos. In addition, Wnt growth factor-induced β-catenin-mediated transcriptional activity was increased in Lzts2 null fibroblasts, suggesting a direct role for Lzts2 in the Wnt signaling pathway. These data demonstrate a critical role of LZTS2 in renal development and implicate LZTS2 as a critical regulator of β-catenin-mediated nephrogenesis.


Mouth occlusion pressure, CO2 response and hypercapnia in severe chronic obstructive pulmonary disease.
The resting mouth occlusion pressure 0.1 s after onset of inspiration (P0.1) and minute ventilation (V'E) and their response to CO2 in patients with chronic obstructive pulmonary disease (COPD) remain controversial. The ventilatory drive and the factors that predict resting arterial CO2 tension (Pa,CO2) were studied in 19 eucapnic and 14 hypercapnic severe COPD patients, and 20 controls. The CO2 response was evaluated by the Read technique. The V'E, and P0.1 as a function of end-tidal CO2 tension (Pet,CO2) was used to study the ventilatory (deltaV'E/deltaPet,CO2) and P0.1 response (deltaP0.1/deltaPet,CO2). In the patients, respiratory muscle function and pleural occlusion pressure 0.1 s after onset of inspiration (Ppl,0.1) were evaluated with simultaneous measurement of pleural (Ppl) and gastric (Pga) pressures. Hypercapnic patients had lower forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and arterial O2 tension (Pa,O2). Resting P0.1 was higher in patients than in controls, whereas deltaP0.1/deltaPet,CO2 was similar in the three groups. There was no difference in resting P0.1 (3.6+/-2.0 versus 4.3+/-2.8 kPa (2.7+/-1.5 versus 3.2+/-2.1 cmH2O), p=0.2) and Ppl,0.1 (1.4+/-2.3 versus 5.2+/-3.3 kPa (4.08+/-1.7 versus 3.9+/-2.5 cmH2O), p=0.22) between eucapnic and hypercapnic COPD, whereas deltaV'E/deltaPet,CO2 was lower in the hypercapnic group (0.29+/-0.24 versus 0.66+/-0.5 L x min(-1) x kPa, p<0.001). By logistic regression only FEVI and increased diaphragmatic load, and not respiratory drive, predicted resting Pa,CO2. Irrespective of CO2 level, baseline central drive (represented by the mouth occlusion and pleural pressures) and CO2 response are preserved in most patients with severe chronic obstructive pulmonary disease. Effective ventilation is inadequate in the more severely obstructed patients and this results in hypercapnia. Neuroventilatory coupling failure is an attractive explanation for chronic hypercapnia in these patients.


The gastroprotective effect of obestatin on indomethacin-induced acute ulcer is mediated by a vagovagal mechanism.
In order to investigate the role of the vagus nerve in the possible gastroprotective effect of obestatin on the indomethacin-induced acute oxidative gastric injury, Sprague-Dawley rats of both sexes were injected subcutaneously with indomethacin (25 mg/kg, 5% NaHCO3) followed by obestatin (10, 30 or 100 μg/kg). In other sets of rats, surgical vagotomy (Vx) or selective degeneration of vagal afferent fibers by perivagal capsaicin was performed before the injections of indomethacin or indomethacin + obestatin (30 μg/kg). Gastric serosal blood flow was measured, and 4 h after ulcer induction gastric tissue samples were taken for histological and biochemical assays. Obestatin reduced the severity of indomethacin-induced acute ulcer via the reversal of reactive hyperemia, by inhibiting ulcer-induced neutrophil infiltration and lipid peroxidation along with the replenishment of glutathione (GSH) stores, whereas Vx abolished the inhibitory effect of obestatin on blood flow and lipid peroxidation, and worsened the severity of ulcer. On the other hand, serosal blood flow was even amplified by the selective denervation of the capsaicin-sensitive vagal afferent fibers, but obestatin-induced reduction in ulcer severity was not altered. In conclusion, the gastroprotective effect of obestatin on indomethacin-induced ulcer appears to involve the activation of the vagovagal pathway.


Invisible Stories: A Phenomenological Study of Bi and Trans Parent Experiences Within Elementary Schools in the Southwestern United States.
Heteronormativity, family hegemony, and gender biases in K-12 education threaten child safety, parental dignity, and identity among queer families. While prior research examined the experiences of queer parents-specifically those of lesbian and gay parents-empirical attention to school-related experiences of trans and bi parents is lacking. Hence, this phenomenological study focuses on the PK-12 school-related experiences of bi and trans parents. Using queer theory as a theoretical framework, we review relevant literature on family hegemony, gender biases, and heteronormativity within school settings and its impact on children with queer families. Then, we discuss the methods and analysis used to understand the experiences of bi and trans parent participants. Analysis revealed four themes: (a) concern for the child; (b) value for diversity; (c) heteronormative nature of schools; and (d) importance of inclusivity. Finally, we provide recommendations on ways school personnel can better support trans and bi parents and their children.


Analysis of plastid and mitochondrial DNA insertions in the nucleus (NUPTs and NUMTs) of six plant species: size, relative age and chromosomal localization.
We analysed the size, relative age and chromosomal localization of nuclear sequences of plastid and mitochondrial origin (NUPTs-nuclear plastid DNA and NUMTs-nuclear mitochondrial DNA) in six completely sequenced plant species. We found that the largest insertions showed lower divergence from organelle DNA than shorter insertions in all species, indicating their recent origin. The largest NUPT and NUMT insertions were localized in the vicinity of the centromeres in the small genomes of Arabidopsis and rice. They were also present in other chromosomal regions in the large genomes of soybean and maize. Localization of NUPTs and NUMTs correlated positively with distribution of transposable elements (TEs) in Arabidopsis and sorghum, negatively in grapevine and soybean, and did not correlate in rice or maize. We propose a model where new plastid and mitochondrial DNA sequences are inserted close to centromeres and are later fragmented by TE insertions and reshuffled away from the centromere or removed by ectopic recombination. The mode and tempo of TE dynamism determines the turnover of NUPTs and NUMTs resulting in their species-specific chromosomal distributions.


Reducing the risk of noncontact anterior cruciate ligament injuries in the female athlete.
High school and collegiate female athletes have a significantly increased risk of sustaining a noncontact anterior cruciate ligament injury compared with male athletes participating in the same sport. This review summarizes the current knowledge of the risk factors hypothesized to influence this problem, and the neuromuscular training programs designed to correct certain biomechanical problems noted in female athletes. The risk factors include a genetic predisposition for sustaining a knee ligament injury, environmental factors, anatomical indices, hormonal influences, and neuromuscular factors. The greatest amount of research in this area has studied differences between female and male athletes in movement patterns during athletic tasks; muscle strength, activation, and recruitment patterns; and knee joint stiffness under controlled, preplanned, and reactive conditions in the laboratory. Neuromuscular retraining programs have been developed in an attempt to reduce these differences. The successful programs teach athletes to control the upper body, trunk, and lower body position; lower the center of gravity by increasing hip and knee flexion during activities; and develop muscular strength and techniques to land with decreased ground reaction forces. In addition, athletes are taught to preposition the body and lower extremity prior to initial ground contact to obtain the position of greatest knee joint stability and stiffness. Two published programs have significantly reduced the incidence of noncontact anterior cruciate ligament injuries in female athletes participating in basketball, soccer, and volleyball. Other programs were ineffective, had a poor study design, or had an insufficient number of participants, which precluded a true reduction in the risk of this injury. In order to determine which risk factors for noncontact anterior cruciate ligament ruptures are significant, future investigations should include larger cohorts of athletes in multiple sports, analyze factors from all of the major risk categories, and follow athletes for at least one full athletic season. Future risk assessment studies should incorporate reactive tasks under more realistic sports conditions.


An Exploration of the Mechanism of Action of an Equine-Assisted Intervention.
Though long alluded to, there is now an accumulation of evidence of the vital contribution that emotion makes to learning. Within this broad advance in understanding is a growing body of research emphasising the embodied nature of this emotion-based learning. The study presented here is a pilot study using a mixed-method approach (combining both physiological and experiential methodologies) to give a picture of the "emotional landscape" of people's learning through the intervention under study. This has allowed researchers to examine mediating pathways that may underlie any effects of an equine-assisted intervention. This study specifically focuses on examining the role of emotion. The intervention under study was used with young people with chronic mental health and behavioural problems for whom talk-based interventions were not working. Nine healthy participants aged 18-24 undertook the equine intervention, with an initial group having emotion-related psycho-physiological changes (skin conductance responses) measured while viewing their experience on video, and a further two participants experiencing a development of the methodology as their physiological responses were captured in real time during the intervention. The sessions were analysed by a group of five cross-disciplinary researchers to determine when significant learning episodes occurred, and the findings were that this learning was associated with powerful skin conductance responses. The qualitative element of the research entailed the participants watching themselves on video undertaking the equine intervention. They were asked to stop the video and share any changes in emotion at any point while watching. All participants experienced a positive temporal change in mood as the intervention progressed. All results supported the findings that emotional arousal occurred in relation to the participants asking the horse to perform a task. This paper will offer two novel contributions: (1) description of a new methodology for investigating the mechanism of action occurring in this type of intervention and (2) findings from the exploration of the intervention via psycho-physiological and experiential mechanisms.


Genotype-Specific Growth and Proteomic Responses of Maize Toward Salt Stress.
Salt stress in plants triggers complex physiological responses that are genotype specific. Many of these responses are either not yet described or not fully understood or both. In this work, we phenotyped three maize genotypes of the CIMMYT gene bank alongside the reference B73 genotype (NCRPIS - United States) under both control and salt-stressed conditions. We have ranked their growth potential and we observed significant differences in Na+ and Cl- ion accumulation. Genotype CML421 showed the slowest growth, while CML451 had the lowest accumulation of ions in its leaves. The phenotyping defined the right timing for the proteomics analysis, allowing us to compare the contrasting genotypes. In general 1,747 proteins were identified, of which 209 were significantly more abundant in response to salt stress. The five most significantly enriched annotations that positively correlated with stress were oxidation reduction, catabolic process, response to chemical stimulus, translational elongation and response to water. We observed a higher abundance of proteins involved in reactions to oxidative stress, dehydration, respiration, and translation. The five most significantly enriched annotations negatively correlated with stress were nucleosome organization, chromatin assembly, protein-DNA complex assembly, DNA packaging and nucleosome assembly. The genotypic analysis revealed 52 proteins that were correlated to the slow-growing genotype CML421. Their annotations point toward cellular dehydration and oxidative stress. Three root proteins correlated to the CML451 genotype were annotated to protein synthesis and ion compartmentalization. In conclusion, our results highlight the importance of the anti-oxidative system for acclimatization to salt stress and identify potential genotypic marker proteins involved in salt-stress responses.


DNA structure-induced recruitment and activation of the Fanconi anemia pathway protein FANCD2.
The Fanconi anemia (FA) pathway proteins are thought to be involved in the repair of irregular DNA structures including those encountered by the moving replication fork. However, the nature of the DNA structures that recruit and activate the FA proteins is not known. Because FA proteins function within an extended network of proteins, some of which are still unknown, we recently established cell-free assays in Xenopus laevis egg extracts to deconstruct the FA pathway in a fully replication-competent context. Here we show that the central FA pathway protein, xFANCD2, is monoubiquitinated (xFANCD2-L) rapidly in the presence of linear and branched double-stranded DNA (dsDNA) structures but not single-stranded or Y-shaped DNA. xFANCD2-L associates with dsDNA structures in an FA core complex-dependent manner but independently of xATRIP, the regulatory subunit of xATR. Formation of xFANCD2-L is also triggered in response to circular dsDNA, suggesting that dsDNA ends are not required to trigger monoubiquitination of FANCD2. The induction of xFANCD2-L in response to circular dsDNA is replication and checkpoint independent. Our results provide new evidence that the FA pathway discriminates among DNA structures and demonstrate that triggering the FA pathway can be uncoupled from DNA replication and ATRIP-dependent activation.


Inductively coupled plasma-mass spectrometry (ICP-MS) for quantitative analysis in environmental and life sciences: a review of challenges, solutions, and trends.
This focal point review provides an overview of recent developments and capabilities of inductively coupled plasma mass spectrometry (ICP-MS) coupled with different separation techniques for applications in the fields of quantitative environmental and bio-analysis. Over the past years numerous technical improvements, which are highlighted in this review, have helped to promote the evolution of ICP-MS to one of the most versatile tools for elemental quantification. In particular, the benefits and possibilities of using state-of-the-art hyphenated ICP-MS approaches for quantitative analysis are demonstrated with a focus on environmental and bio-analytical applications.


Characterization of the woody biomass feedstock potential resulting from California's drought.
Regional tree die-off events generate large quantities of standing dead wood, raising concern over catastrophic wildfire and other hazards. Governmental responses to tree die-off have often focused on incentivizing biomass energy production that utilizes standing dead trees removed for safety concerns. However, the full distribution of potential woody bioenergy feedstock after tree die-off has not been evaluated due to the complexities of surveying and precisely measuring large forested areas. In this paper, we present a novel method for estimating standing dead biomass at a fine spatial resolution that combines aerial survey data with forest structure maps. Using this method, we quantify biomass generated by the unprecedented tree die-off that occurred in California following a 4-year drought and widespread pest outbreaks. The results are used to estimate feasibly recoverable feedstock for energy production. We find that approximately 95.1 million bone-dry tons (BDT) of dead biomass resulted from 2012-2017 mortality, with a lower bound of 26.2 million BDT. In other words, of the aboveground live tree biomass in 2012, ~1.3-4.8% died by 2017. Of the standing dead biomass, 29% meets minimum constraints for potential cost-effective bioenergy feedstock. This proportion drops to as low as 15% in the most affected areas due to terrain slope, wilderness status, and other factors, highlighting the need to complement disposal via biomass energy with other strategies to mitigate the risks of the tree mortality crisis, which is likely to only become more severe over time due to climate change.


Inhalation exposure to white spirit causes region-dependent alterations in the levels of glial fibrillary acidic protein.
Enhanced expression of glial fibrillary acidic protein (GFAP) is known to be associated with toxicant-induced gliosis, a homotypic response of the central nervous system to neural injury. A variety of neurochemical and neurophysiological effects have been observed in experimental animals exposed to white spirit, but a linkage of such effects to neural damage has not been established. Here we evaluated the regional levels of GFAP to assess potential sites of CNS damage in the rat, following exposure to dearomatized and aromatic white spirit. Samples from rats exposed to dearomatized white spirit were assayed for GFAP levels in the United States and Denmark. The results were remarkably similar between countries. Small region-dependent increases and decreases in GFAP were observed with the cerebellum showing the most consistent effects (increases). In contrast, samples from rats exposed to aromatic white spirit showed large (as much as 150% of control) increases in regional levels of GFAP; again, the cerebellum showed the most consistent effects. The data are indicative of an aromatic white-spirit-induced astrogliosis in several regions of the rat CNS and suggest that chronic exposure to this solvent may be associated with underlying neural damage.


The absolute configurations of hydroxy fatty acids from the royal jelly of honeybees (Apis mellifera).
9-Hydroxy-2E-decenoic acid (9-HDA) is a precursor of the queen-produced substance, 9-oxo-2E-decenoic acid (9-ODA), which has various important functions and roles for caste maintenance in honeybee colonies (Apis mellifera). 9-HDA in royal jelly is considered to be a metabolite of 9-ODA produced by worker bees, and it is fed back to the queen who then transforms it into 9-ODA. Recently we found that 9-HDA is present in royal jelly as a mixture of optical isomers (R:S, 2:1). The finding leads us to suspect that chiral fatty acids in royal jelly are precursors of semiochemicals. Rather than looking for semiochemicals in the mandibular glands of the queen bee, this study involves the search for precursors of pheromones from large quantities of royal jelly. Seven chiral hydroxy fatty acids, 9,10-dihydroxy-2E-decenoic, 4,10-dihydroxy-2E-decenoic, 4,9-dihydroxy-2E-decenoic, 3-hydroxydecanoic, 3,9-dihydroxydecanoic, 3,11-dihydroxydodecanoic, and 3,10-dihydroxydecanoic acids were isolated. The absolute configurations of these acids were determined using the modified Mosher's method, and it was revealed that, similar to 9-HDA, five acids are present in royal jelly as mixtures of optical isomers.