Modeling the effects of stressors on the performance of populations of pigs.
A simulation model that predicts the effect of the social, physical, and nutritional environments on pig food intake and performance was extended to deal with individual variation. The aim was to investigate the effect of between-animal variation on the performance of a population of growing pigs. Variation was generated in initial state, growth potential, and ability to cope when exposed to social "stressors" (EX). Variation in initial state is described by initial body weight (BW0), from which the chemical composition of the pig is calculated. Variation in growth potential is described by creating variation in the genetic growth descriptors. Variation in EX exists between genotypes, where it has been suggested that leaner, more modern genotype pigs tend to be less able to cope. It is expected that within a population or group that the social environment (i.e., position within the social hierarchy) also affects an individual's ability to cope. In the model, it is assumed that the larger, more dominant individuals are better able to cope when exposed to social stressors. Consequently, within a population, EX is correlated with body weight around the genotype mean. Model predictions showed that increasing the variation in BW0 and EX increased the variation in pig performance. This is an important practical consideration in commercial pig production, where the heterogeneity of the population at slaughter may affect the profitability of an enterprise. The way a stressor constrains performance determines whether the mean population response to a given stressor is the same as the average individual response. If all pigs in a group are affected at the same stressor intensity (e.g., all are either mixed or not), then the predicted average individual and mean population responses will be the same. If, however, the intensity of stressor at which performance becomes limiting differs between individuals (such as space allowance or temperature), differences between the individual and mean population responses will be predicted. Variation in the growth response of a population was determined to a greater extent by variation in EX and BW0 than by variation in growth potential, when pigs were housed in simulated conditions likely to be encountered in commercial environments. Consequently, decreasing the variation in initial body weight and improving ability of pigs to cope may be a better way of improving pig performance than selecting only for increased growth potential.


Vitamin D receptor deletion leads to increased hematopoietic stem and progenitor cells residing in the spleen.
Bone components participate in the regulation of hematopoietic stem cells in the adult mammal. Vitamin D regulates bone mineralization and is associated with pleiotropic effects in many cell types, including putative roles in hematopoietic differentiation. We report that deletion of the vitamin D receptor (VDR) in hematopoietic cells did not result in cell autonomous perturbation of hematopoietic stem cell or progenitor function. However, deletion of VDR in the microenvironment resulted in a marked accumulation of hematopoietic stem cells in the spleen that could be reversed by calcium dietary supplementation. These data suggest that VDR participates in restricting splenic hematopoiesis through maintenance of bone calcium homeostasis and are consistent with the concept that calcium regulation through VDR is a central participant in localizing adult hematopoiesis preferentially to bone marrow.


Methodichlorophen as anti-tumor drug.
Methodichlorophen was given to 26 patients with terminal malignant disease. Eight patients received adequate doses, and five of them showed objective evidence of tumour regression while three failed to respond. Those who responded included four out of five patients with lung cancer (three with squamous-cell carcinoma and one with oat-cell carcinoma) and a patient with hypernephroma. Two patients with testicular teratomas and one with acute myeloid leukemia failed to respond. The drug may be given safely by mouth to outpatients if certain precautions are taken.


Sex differences in toddlers with autism spectrum disorders.
Although autism spectrum disorders (ASD) prevalence is higher in males than females, few studies address sex differences in developmental functioning or clinical manifestations. Participants in this study of sex differences in developmental profiles and clinical symptoms were 22 girls and 68 boys with ASD (mean age = 28 months). All children achieved strongest performance in visual reception and fine motor followed by gross motor and language functioning. Sex differences emerged in developmental profiles. Controlling for language, girls achieved higher visual reception scores than boys; boys attained higher language and motor scores and higher social-competence ratings than girls, particularly when controlling for visual reception. Longitudinal, representative studies are needed to elucidate the developmental and etiological significance of the observed sex differences.


Tai Chi Improves Cognition and Plasma BDNF in Older Adults With Mild Cognitive Impairment: A Randomized Controlled Trial.
Effects of Tai Chi (TC) on specific cognitive function and mechanisms by which TC may improve cognition in older adults with amnestic mild cognitive impairment (a-MCI) remain unknown. To examine the effects of TC on cognitive functions and plasma biomarkers (brain-derived neurotrophic factor [BDNF], tumor necrosis factor-α [TNF-α], and interleukin-10 [IL-10]) in a-MCI. A total of 66 older adults with a-MCI (mean age = 67.9 years) were randomized to either a TC (n = 33) or a control group (n = 33). Participants in the TC group learned TC with a certified instructor and then practiced at home for 50 min/session, 3 times/wk for 6 months. The control group received educational material that covered information related to cognition. The primary outcome was cognitive performance, including Logical Memory (LM) delayed recall, Block Design, Digit Span, and Trail Making Test B minus A (TMT B-A). The secondary outcomes were plasma biomarkers, including BDNF, TNF-α, and IL-10. At the end of the trial, performance on the LM and TMT B-A was significantly better in the TC group compared with the control group after adjusting for age, gender, and education ( P < .05). Plasma BDNF level was significantly increased for the TC group, whereas the other outcome measures were similar between the 2 groups after adjusting for age and gender ( P < .05). TC training significantly improved memory and the mental switching component of executive function in older adults with a-MCI, possibly via an upregulation of BDNF.


Comparison of two fat-suppressed magnetic resonance imaging pulse sequences to standard t2-weighted images for brain parenchymal contrast and lesion detection in dogs with inflammatory intracranial disease.
T2-weighted (T2w) sequences are commonly relied upon in magnetic resonance imaging protocols for the detection of brain lesions in dogs. Previously, the effect of fluid suppression via fluid-attenuated inversion recovery (FLAIR) has been compared to T2-weighting with mixed results. Short tau inversion recovery (STIR) has been reported to increase the detection of some CNS lesions in people. The purpose of the current study was to evaluate the effect of fat suppression on brain parenchymal contrast resolution and lesion detection in dogs. We compared three sequences: T2w images, STIR, and T2w FLAIR with chemical fat suppression (T2-FLAIR-FS) in dogs with meningoencephalitis. Dogs with meningoencephalitis and dogs with idiopathic epilepsy were retrospectively identified and anonymized. Evaluators recorded the presence or absence of lesions within 12 predetermined brain regions on randomized sequences, viewing and scoring each sequence individually. Additionally, signal-to-noise ratios, contrast-to-noise ratios, and relative contrast (RC) were measured in a reference population. Short tau inversion recovery sequences had the highest RC between gray and white matter. While descriptively more lesions were identified by evaluators on T2-FLAIR-FS images, there was no statistical difference in the relative sensitivity of lesion detection between the sequences. Nor was there a statistical difference in false lesion detection within our reference population. Short tau inversion recovery may be favored for enhanced anatomic contrast depiction in brain imaging. No benefit of the inclusion of a fat-suppressed T2-FLAIR sequence was found.


Memory CD8+ T Cell Protection From Viral Reinfection Depends on Interleukin-33 Alarmin Signals.
Memory CD8+ cytotoxic T lymphocytes (CTLs) can protect against viral reinfection. However, the signals driving rapid memory CTL reactivation have remained ill-defined. Viral infections can trigger the release of the alarmin interleukin-33 (IL-33) from non-hematopoietic cells. IL-33 signals through its unique receptor ST2 to promote primary effector expansion and activation of CTLs. Here, we show that the transcription factor STAT4 regulated the expression of ST2 on CTLs in vitro and in vivo in primary infections with lymphocytic choriomeningitis virus (LCMV). In the primary antiviral response, IL-33 enhanced effector differentiation and antiviral cytokine production in a CTL-intrinsic manner. Further, using sequential adoptive transfers of LCMV-specific CD8+ T cells, we deciphered the IL-33 dependence of circulating memory CTLs at various stages of their development. IL-33 was found dispensable for the formation and maintenance of memory CTLs, and its absence during priming did not affect their recall response. However, in line with the CTL-boosting role of IL-33 in primary LCMV infections, circulating memory CTLs required IL-33 for efficient secondary expansion, enhanced effector functions, and virus control upon challenge infection. Thus, beyond their effector-promoting activity in primary immune reactions, innate alarmin signals also drive memory T cell recall responses, which has implications for immunity to recurrent diseases.


Continuing reductions in HPV 16/18 in a population with high coverage of bivalent HPV vaccination in England: an ongoing cross-sectional study.
The human papillomavirus (HPV) immunisation programme in England was introduced in 2008. Monitoring changes in type-specific HPV prevalence allows assessment of the population impact of this vaccination programme. Residual vulva-vaginal swab specimens were collected from young sexually active women (aged 16-24 years) attending for chlamydia screening across England. Specimens were collected between 2010 and 2013 for type-specific HPV-DNA testing. HPV prevalence was compared to a similar survey conducted in 2008 prior to the introduction of HPV vaccination. A total of 7321 specimens collected in the postvaccination period, and 2354 specimens from the prevaccination period were included in this analysis. Among the individuals aged 16-18 years, with an estimated vaccination coverage of 67%, the prevalence of HPV16/18 infection decreased from 17.6% in 2008 to 6.1% in the postvaccination period. Within the postvaccination period, there was a trend towards lower HPV16/18 prevalence with higher vaccination coverage and increasing time since vaccine introduction from 8.5% in the period 2-3 years postvaccination to 4.0% in the period 4-5 years postvaccination. The prevalence of HPV31 reduced from 3.7% in the prevaccination period to 0.9% after vaccine introduction, although this no longer reached statistical significance after additional consideration of the uncertainty due to the assay change. Smaller reductions were seen in the individuals aged 19-21 years with lower estimated vaccination coverage, but there was no evidence of a reduction in the older unvaccinated women. Some overall increase in non-vaccine types was seen in the youngest age groups (ORs (95% CI); 1.3 (1.0 to 1.7) and 1.5 (1.1 to 2.0) for individuals aged 16-18 and 19-21 years, respectively, when adjusted for known population changes and the change in assay) although this should be interpreted with caution given the potential unmasking effect. These data demonstrate a reduction in the HPV vaccine types in the age group with the highest HPV vaccination coverage.


Elementary Excitations of Superfluid Helium Droplets Probed by Ion Spectroscopy.
Electronic spectra of molecules in helium droplets reveal spectral features that are related to the elementary excitations of the superfluid helium environment. In order to determine to what extent the interaction strength of the molecule with the helium affects these excitations, the spectrum corresponding to the B̃(2)A″ ← X̃ (2)A″ transition of 2,5-difluorophenol cations in helium droplets has been recorded. The vibronic resonances reveal a sharp zero-phonon line whose width is largely determined by the rotational band contour, followed by a broad structureless phonon wing at higher frequencies. The splitting between the zero-phonon line and phonon wing is approximately half of that found for neutral 2,5-difluorophenol. This difference is attributed to the increased helium density around the ion due to its strong interaction with the helium.


A new reducing agent to prepare single-layer, high-quality reduced graphene oxide for device applications.
We report on a novel, efficient, and one-step approach to prepare single-layer reduced graphene oxide (RGO) suspensions and films using hydroxylamine hydrochloride. The effective chemical reduction of GO was evidenced by a significant increase in the C/O ratio and five orders of magnitude decrease in the GO resistance. Field-effect transistor gas sensors were fabricated using as-produced RGO sheets and the resulting sensor exhibited a fast response and a high sensitivity to low-concentration target gases at room temperature.


Neuroimaging findings in treatment-resistant schizophrenia: A systematic review: Lack of neuroimaging correlates of treatment-resistant schizophrenia.
Recent developments in neuroimaging have advanced the understanding of biological mechanisms underlying schizophrenia. However, neuroimaging correlates of treatment-resistant schizophrenia (TRS) and superior effects of clozapine on TRS remain unclear. Systematic search was performed to identify neuroimaging characteristics unique to TRS and ultra-resistant schizophrenia (i.e. clozapine-resistant [URS]), and clozapine's efficacy in TRS using Embase, Medline, and PsychInfo. Search terms included (schizophreni*) and (resistan* OR refractory OR clozapine) and (ASL OR CT OR DTI OR FMRI OR MRI OR MRS OR NIRS OR PET OR SPECT). 25 neuroimaging studies have investigated TRS and effects of clozapine. Only 5 studies have compared TRS and non-TRS, collectively providing no replicated neuroimaging finding specific to TRS. Studies comparing TRS and healthy controls suggest that hypometabolism in the prefrontal cortex, hypermetabolism in the basal ganglia, and structural anomalies in the corpus callosum contribute to TRS. Clozapine may increase prefrontal hypoactivation in TRS although this was not related to clinical improvement; in contrast, evidence has suggested a link between clozapine efficacy and decreased metabolism in the basal ganglia and thalamus. Existing literature does not elucidate neuroimaging correlates specific to TRS or URS, which, if present, might also shed light on clozapine's efficacy in TRS. This said, leads from other lines of investigation, including the glutamatergic system can prove useful in guiding future neuroimaging studies focused on, in particular, the frontocortical-basal ganglia-thalamic circuits. Critical to the success of this work will be precise subtyping of study subjects based on treatment response/nonresponse and the use of multimodal neuroimaging.


Age and ethnic differences in the onset, persistence and recurrence of alcohol use disorder.
To estimate ethnic differences in three components of alcohol use disorder and alcohol dependence course (onset, persistence and recurrence) in a developmental framework. Longitudinal data from The National Epidemiologic Survey of Alcohol and Related Conditions (NESARC), collected using face-to-face interviews. Civilian non-institutionalized US population aged 18 years and older, with oversampling of Hispanics, blacks and those aged 18-24 years. Individuals who completed both NESARC assessments, were not life-long abstainers and were either white (n = 17,458), black (n = 4995), US-born Hispanic (n = 2810) or Hispanic-born outside the United States (n = 2389). Alcohol dependence (AD) and alcohol use disorder (AUD; abuse or dependence) onset, persistence and recurrence were examined using the Alcohol Use Disorders and Associated Disabilities Interview Schedule, DSM-IV version. Among men: relative to whites aged 18-29, AUD onset and persistence were elevated only in US-born Hispanics aged 40 years and older; odds were reduced for all non-US-born Hispanics, older whites, most blacks and US-born Hispanics aged 30-39. For AD, onset risk was elevated for all younger minority men and only reduced among non-US-born aged Hispanics 40 or older. For women: compared to young whites, non-US-born Hispanics were at decreased AUD and AD onset risk; AUD and AD onset and persistence were increased for older blacks and US-born Hispanics. In the United States, ethnic differences in alcohol disorder transitions (onset, persistence, and recurrence) vary across age, gender and whether a broad (alcohol use disorder) or narrow (alcohol dependence) alcohol definition is used. Evidence of increased risk for some transitions in minority groups suggests that attention should be paid to the course of alcohol use disorders, and that differences in prevalence should not be assumed to reflect differences in specific transitions.


The challenge of cultural competence in the workplace: perspectives of healthcare providers.
Cross-cultural educational initiatives for professionals are now commonplace across a variety of sectors including health care. A growing number of studies have attempted to explore the utility of such initiatives on workplace behaviors and client outcomes. Yet few studies have explored how professionals perceive cross-cultural educational models (e.g., cultural awareness, cultural competence) and the extent to which they (and their organizations) execute the principles in practice. In response, this study aimed to explore the general perspectives of health care professionals on culturally competent care, their experiences working with multi-cultural patients, their own levels of cultural competence and the extent to which they believe their workplaces address cross-cultural challenges. The perspectives and experiences of a sample of 56 health care professionals across several health care systems from a Mid-Western state in the United States were sourced via a 19-item questionnaire. The questionnaire comprised both open-ended questions and multiple choice items. Percentages across participant responses were calculated for multiple choice items. A thematic analysis of open-ended responses was undertaken to identify dominant themes. Participants largely expressed confidence in their ability to meet the needs of multi-cultural clientele despite almost half the sample not having undergone formal cross-cultural training. The majority of the sample appeared to view cross-cultural education from a 'cultural awareness' perspective - effective cross-cultural care was often defined in terms of possessing useful cultural knowledge (e.g., norms and customs) and facilitating communication (the use of interpreters); in other words, from an immediate practical standpoint. The principles of systemic cross-cultural approaches (e.g., cultural competence, cultural safety) such as a recognition of racism, power imbalances, entrenched majority culture biases and the need for self-reflexivity (awareness of one's own prejudices) were scarcely acknowledged by study participants. Findings indicate a need for interventions that acknowledge the value of cultural awareness-based approaches, while also exploring the utility of more comprehensive cultural competence and safety approaches.


High prevalence of the 999del5 mutation in icelandic breast and ovarian cancer patients.
Studies on Icelandic breast cancer families have shown that most of them segregate a 999del5 BRCA2 mutation. Here, we report the frequency of the 999del5 BRCA2 mutation in an Icelandic control population and four different groups of cancer patients diagnosed with (a) breast cancer; (b) ovarian cancer; (c) prostate cancer (patients younger than 65 years); and (d) other cancer types. The proportions of individuals carrying the mutation were 0.4% in the control population and in the patient groups 8.5%, 7.9%, 2.7%, and 1.0%, respectively. Our results indicate that BRCA2 confers a very high risk of breast cancer and is responsible for a substantial fraction of breast and ovarian cancer in Iceland, but only a small proportion of other cancers.


Kelp forests at the end of the earth: 45 years later.
The kelp forests of southern South America are some of the least disturbed on the planet. The remoteness of this region has, until recently, spared it from many of the direct anthropogenic stressors that have negatively affected these ecosystems elsewhere. Re-surveys of 11 locations at the easternmost extent of Tierra del Fuego originally conducted in 1973 showed no significant differences in the densities of adult and juvenile Macrocystis pyrifera kelp or kelp holdfast diameter between the two survey periods. Additionally, sea urchin assemblage structure at the same sites were not significantly different between the two time periods, with the dominant species Loxechinus albus accounting for 66.3% of total sea urchin abundance in 2018 and 61.1% in 1973. Time series of Landsat imagery of the region from 1998 to 2018 showed no long-term trends in kelp canopy over the past 20 years. However, ~ 4-year oscillations in canopy fraction were observed and were strongly and negatively correlated with the NOAA Multivariate ENSO index and sea surface temperature. More extensive surveying in 2018 showed significant differences in benthic community structure between exposed and sheltered locations. Fish species endemic to the Magellanic Province accounted for 73% of all nearshore species observed and from 98-100% of the numerical abundance enumerated at sites. Fish assemblage structure varied significantly among locations and wave exposures. The recent creation of the Yaganes Marine Park is an important step in protecting this unique and biologically rich region; however, the nearshore waters of the region are currently not included in this protection. There is a general lack of information on changes in kelp forests over long time periods, making a global assessment difficult. A complete picture of how these ecosystems are responding to human pressures must also include remote locations and locations with little to no impact.


Oral administration of fluoride in pregnant women, and the relation between concentration in maternal plasma and in amniotic fluid.
The aim was to measure the ionic fluoride concentration in maternal plasma and in amniotic fluid after oral administration of different doses of sodium fluoride (NaF) to 121 pregnant women. They were divided into six groups, according to the dose administered; 0 for the control group and 0.25, 0.50, 0.75, 1.00 or 1.25 mg of F- for the others. The subjects were instructed to take the corresponding NaF dose both 24 and 3 h before amniocentesis. Amniotic fluid (5 ml) and venous blood (5 ml) were obtained from each subject. Ionic fluoride concentration was measured with an expanded-scale potentiometer and a selective fluoride electrode. The results showed that F- concentration in amniotic fluid and, presumably, in fetal circulation, was not significantly different in groups taking 0.25, 0.50, 0.75 or 1.00 mg/day of F-. The F- concentration in amniotic fluid of the 1.25 mg/day group was, however, significantly higher than in all the other groups.


Outcome measures for assessing the effectiveness of non-pharmacological interventions in frequent episodic or chronic migraine: a Delphi study.
The aim of this Delphi survey was to establish an international consensus on the most useful outcome measures for research on the effectiveness of non-pharmacological interventions for migraine. This is important, since guidelines for pharmacological trials recommend measuring the frequency of headaches with 50% reduction considered a clinically meaningful effect. It is unclear whether the same recommendations apply to complementary (or adjunct) non-pharmacological approaches, whether the same cut-off levels need to be considered for effectiveness when used as an adjunct or stand-alone intervention, and what is meaningful to patients. University-initiated international survey. The expert panel was chosen based on publications on non-pharmacological interventions in migraine populations and from personal contacts. 35 eligible researchers were contacted, 12 agreed to participate and 10 completed all 3 rounds of the survey. To further explore how migraine patients viewed potential outcome measures, four migraine patients were interviewed and presented with the same measurement tools as the researchers. The initial Delphi round was based on a systematic search of the literature for outcome measures used in non-pharmacological interventions for headache. Suggested outcome measures were rated by each expert, blinded towards the other members of the panel, for its usefulness on a 5-point Likert scale ranging from definitely not useful to extremely useful. Results were combined using median values and IQRs. Tools rated overall as definitely or probably not useful were excluded from subsequent rounds. Experts further suggested additional outcome measures that were presented to the panel in subsequent rounds. Additionally, experts were asked to rank the most useful tools and provide information on feasible cut-off levels for effectiveness for the three highest ranked tools. Results suggest the use of the Migraine Disability Assessment (MIDAS), Headache Impact Test (HIT-6) and headache frequency as primary outcome measures. Patient experts suggested the inclusion of a measure of quality of life and evaluation of associated symptoms and fear of attacks. Recommendations are for the use of the MIDAS, the HIT-6 and headache frequency, in combination with an outcome measure for quality of life. Associated symptoms and fear of attacks should also be considered as secondary outcomes, if relevant for the individual target population. The cut-off level for effectiveness should be lower for non-pharmacological interventions, especially when used as an adjunct to medication. German Register of Clinical Trials (DRKS00011777).


A universal method for automated gene mapping.
Small insertions or deletions (InDels) constitute a ubiquituous class of sequence polymorphisms found in eukaryotic genomes. Here, we present an automated high-throughput genotyping method that relies on the detection of fragment-length polymorphisms (FLPs) caused by InDels. The protocol utilizes standard sequencers and genotyping software. We have established genome-wide FLP maps for both Caenorhabditis elegans and Drosophila melanogaster that facilitate genetic mapping with a minimum of manual input and at comparatively low cost.


Checkpoint failure and chromosomal instability without lymphomagenesis in Mre11(ATLD1/ATLD1) mice.
In this study, mice expressing one of the two Mre11 alleles inherited in the human ataxia-telangiectasia like disorder (A-TLD) were derived. The mutation had a profound maternal effect on embryonic viability, revealing an acute requirement for Mre11 complex function in early embryogenesis. Mre11(ATLD1/ATLD1) mice exhibited several indices of impaired ATM function. The mice also exhibited pronounced chromosomal instability. Despite this phenotypic spectrum, the animals were not prone to malignancy. These data indicate that defective cell cycle checkpoints and chromosomal instability are insufficient to significantly enhance the initiation of tumorigenesis. In contrast, the latency of malignancy in p53(+/-) mice was dramatically reduced. We propose that in Mre11(ATLD1/ATLD1) mice, genome instability and cell cycle checkpoint defects reduce viability in early embryos and in proliferating cells, while promoting malignancy in the context of an initiating lesion.


A novel cytochrome c peroxidase from Neisseria gonorrhoeae: a lipoprotein from a Gram-negative bacterium.
A cytochrome c peroxidase (CCP) produced by Neisseria gonorrhoeae has been shown to have novel characteristics by investigating its location, expression and role in Neisseria gonorrhoeae and by expression in Escherichia coli. Analysis of the N-terminus of CCP indicated that it is a lipoprotein with a signal peptide for cleavage by signal peptidase II. Expression of the gonococcal CCP in E. coli revealed that it is first synthesized as a pro-apo-cytochrome that is translocated across the cytoplasmic membrane. The signal peptide is cleaved and haem is attached in the periplasm. The gonococcal CCP was associated with the membrane of both E. coli and N. gonorrhoeae. The expression of a MalE-CCP fusion protein has allowed characterization of CCP in vitro. Evidence is presented that CCP protects gonococci from hydrogen peroxide, presumably in the periplasmic compartment of the cell. The expression of CCP is dependent on the transcription factor FNR, but is repressed by nitrite, indicating that it could be most important in the stationary-phase response. These data support the hypothesis that the gonococcal lipoprotein CCP is anchored to the membrane in the periplasm, where it might be responsible for the reduction of hydrogen peroxide. Other putative CCP lipoproteins have been identified, representing a new subclass of bacterial CCP proteins.


Dietary inflammatory index is positively associated with serum high-sensitivity C-reactive protein in a Korean adult population.
To our knowledge, only a few studies have explored the relationship between the inflammatory potential of diet and serum inflammatory markers in Korean adults. The likely novel aim of this study was to examine the association between the dietary inflammatory index (DII) and serum high-sensitivity C-reactive protein (hs-CRP) in a Korean adult population. A cross-sectional study was conducted using the data set from the Korea National Health and Nutrition Examination Survey (KNHANES) 2015. Korean adults ≥19 y of age with hs-CRP values were included in this study. After excluding individuals with missing variables for covariates, the final analytic sample for the study was 3014 adults (1295 men and 1719 women). DII scores were calculated from a 1-d 24-h dietary recall, and hs-CRP was measured using the immunoturbidimetric method. Multivariable logistic regression analyses were performed to calculate adjusted odds ratios (AORs) and 95% confidence intervals (CIs) to test the effect of the DII score on serum hs-CRP as dichotomous (>2 versus ≤2 mg/L). A significant association was observed between increasing DII scores and elevated hs-CRP. Korean adults in the highest quintile of the DII (indicating the most proinflammatory diet), compared with the lowest quintile of the DII (indicating the most anti-inflammatory diet), had increased odds of having elevated hs-CRP concentrations (>2 mg/L; AOR, 1.70; 95% CI, 1.07-2.69; Ptrend < 0.0001) after controlling for age, sex, education, marital status, alcohol consumption, smoking status, body mass index, high-density lipoprotein cholesterol, and physical activity. Higher DII scores were positively associated with elevated hs-CRP levels in Korean adults. Because inflammation affects the risk for cancer, cardiovascular disease, and other inflammation-related conditions, future studies are warranted to examine the effect of the DII on other inflammatory biomarkers and chronic disease outcomes among the Korean population.


voomDDA: discovery of diagnostic biomarkers and classification of RNA-seq data.
RNA-Seq is a recent and efficient technique that uses the capabilities of next-generation sequencing technology for characterizing and quantifying transcriptomes. One important task using gene-expression data is to identify a small subset of genes that can be used to build diagnostic classifiers particularly for cancer diseases. Microarray based classifiers are not directly applicable to RNA-Seq data due to its discrete nature. Overdispersion is another problem that requires careful modeling of mean and variance relationship of the RNA-Seq data. In this study, we present voomDDA classifiers: variance modeling at the observational level (voom) extensions of the nearest shrunken centroids (NSC) and the diagonal discriminant classifiers. VoomNSC is one of these classifiers and brings voom and NSC approaches together for the purpose of gene-expression based classification. For this purpose, we propose weighted statistics and put these weighted statistics into the NSC algorithm. The VoomNSC is a sparse classifier that models the mean-variance relationship using the voom method and incorporates voom's precision weights into the NSC classifier via weighted statistics. A comprehensive simulation study was designed and four real datasets are used for performance assessment. The overall results indicate that voomNSC performs as the sparsest classifier. It also provides the most accurate results together with power-transformed Poisson linear discriminant analysis, rlog transformed support vector machines and random forests algorithms. In addition to prediction purposes, the voomNSC classifier can be used to identify the potential diagnostic biomarkers for a condition of interest. Through this work, statistical learning methods proposed for microarrays can be reused for RNA-Seq data. An interactive web application is freely available at http://www.biosoft.hacettepe.edu.tr/voomDDA/.


[Description of psychosocial risk factors in four companies].
To describe the distribution of work-related psychosocial risk factor scores in four companies according to the personal and occupational characteristics of the workers. Cross-sectional study of a sample of 890 workers in four companies who participated in this study voluntarily. The overall response rate was 34.5%. A self-administrated questionnaire was used to measure the presence of demand, control and social support according to the workers' perceptions. Statistical analyses were performed using median and dispersion measures of psychosocial risk factors for each company separately, as well as description of their distribution according to personal and occupational variables. The median score for social support was almost always equal to 5 for all four companies. However, there was greater variability in psychological demand (between 13 and 16), and for control (between 20 and 26). Comparison of the scores for social and occupational variables revealed similar values for social support but not for control and demand, which showed greater variation according to sex (men), age group (less than 40 years) and occupation (clerks). Although the low response rate could limit the validity of our results, this is the first study to value the distribution of work-related psychosocial risk factor scores in four companies in Spain. Variability among companies for different groups of workers was found. This study could be useful for future studies exploring the feasibility of defining reference values for use in preventive measures.


Updated Priorities Among Effective Clinical Preventive Services.
The Patient Protection and Affordable Care Act's provisions for first-dollar coverage of evidence-based preventive services have reduced an important barrier to receipt of preventive care. Safety-net providers, however, still serve a substantial uninsured population, and clinician and patient time remain limited in all primary care settings. As a consequence, decision makers continue to set priorities to help focus their efforts. This report updates estimates of relative health impact and cost-effectiveness for evidence-based preventive services. We assessed the potential impact of 28 evidence-based clinical preventive services in terms of their cost-effectiveness and clinically preventable burden, as measured by quality-adjusted life years (QALYs) saved. Each service received 1 to 5 points on each of the 2 measures-cost-effectiveness and clinically preventable burden-for a total score ranging from 2 to 10. New microsimulation models were used to provide updated estimates of 12 of these services. Priorities for improving delivery rates were established by comparing the ranking with what is known of current delivery rates nationally. The 3 highest-ranking services, each with a total score of 10, are immunizing children, counseling to prevent tobacco initiation among youth, and tobacco-use screening and brief intervention to encourage cessation among adults. Greatest population health improvement could be obtained from increasing utilization of clinical preventive services that address tobacco use, obesity-related behaviors, and alcohol misuse, as well as colorectal cancer screening and influenza vaccinations. This study identifies high-priority preventive services and should help decision makers select which services to emphasize in quality-improvement initiatives.


Is subclinical thyroid dysfunction in the elderly associated with depression or cognitive dysfunction?
Widespread use of automated sensitive assays for thyroid hormones and thyroid-stimulating hormone (TSH) has increased identification of mild thyroid dysfunction, especially in elderly patients. The clinical significance of this dysfunction, however, remains uncertain, and associations with cognitive impairment, depression, and anxiety are unconfirmed. To determine the association between mild thyroid dysfunction and cognition, depression, and anxiety in elderly persons. Cross-sectional study. Associations were explored through mixed-model analyses. Primary care practices in central England. 5865 patients 65 years of age or older with no known thyroid disease who were recruited from primary care registers. Serum TSH and free thyroxine (T4) were measured. Depression and anxiety were assessed by using the Hospital Anxiety and Depression Scale (HADS), and cognitive functioning was established by using the Middlesex Elderly Assessment of Mental State and the Folstein Mini-Mental State Examination. Comorbid conditions, medication use, and sociodemographic profiles were recorded. 295 patients met the criteria for subclinical thyroid dysfunction (127 were hyperthyroid, and 168 were hypothyroid). After confounding variables were controlled for, statistically significant associations were seen between anxiety (HADS score) and TSH level (P = 0.013) and between cognition and both TSH and free T4 levels. The magnitude of these associations lacked clinical relevance: A 50-mIU/L increase in the TSH level was associated with a 1-point reduction in the HADS anxiety score, and a 1-point increase in the Mini-Mental State Examination score was associated with an increase of 50 mIU/L in the TSH level or 25 pmol/L in the free T4 level. Because of the low participation rate, low prevalence of subclinical thyroid dysfunction, and other unidentified recruitment biases, participants may not be representative of the elderly population. After the confounding effects of comorbid conditions and use of medication were controlled for, subclinical thyroid dysfunction was not associated with depression, anxiety, or cognition.


Multidimensional examination of impulsivity in relation to disordered gambling.
Impulsivity has been consistently associated with pathological gambling (PG), but the diversity of definitions and measures of impulsivity has led to ambiguity with regard to which indices are independently relevant. Toward clarifying this relationship, the current study examined indices from an array of commonly used impulsivity measures in relation to PG severity in an adult community sample of frequent gamblers (N = 353). These included both survey assessments and behavioral tasks. Using a factor analytic approach, 4 latent factors were identified among 19 indices and were designated reward sensitivity, punishment sensitivity, delay discounting, and cognitive impulsivity. All 4 latent variables were positively and independently related to PG severity, albeit at a trend level for cognitive impulsivity in a combined model. These findings reveal 4 generally independent domains of impulsivity that are related to PG severity, clarify which assessment measures aggregate in each domain, and illustrate the importance of measurement specificity in studying impulsivity in relation to PG and other psychiatric disorders.


PRN: a preprint service for catalyzing R-fMRI and neuroscience related studies.
Sharing drafts of scientific manuscripts on preprint hosting services for early exposure and pre-publication feedback is a well-accepted practice in fields such as physics, astronomy, or mathematics. The field of neuroscience, however, has yet to adopt the preprint model. A reason for this reluctance might partly be the lack of central preprint services for the field of neuroscience. To address this issue, we announce the launch of Preprints of the R-fMRI Network (PRN), a community funded preprint hosting service. PRN provides free-submission and free hosting of manuscripts for resting state functional magnetic resonance imaging (R-fMRI) and neuroscience related studies. Submissions will be peer viewed and receive feedback from readers and a panel of invited consultants of the R-fMRI Network. All manuscripts and feedback will be freely available online with citable permanent URL for open-access. The goal of PRN is to supplement the "peer reviewed" journal publication system - by more rapidly communicating the latest research achievements throughout the world. We hope PRN will help the field to embrace the preprint model and thus further accelerate R-fMRI and neuroscience related studies, eventually enhancing human mental health.


Management of acute kidney injury in the intensive care unit: a cost-effectiveness analysis of daily vs alternate-day hemodialysis.
Although evidence suggests that a higher hemodialysis dose and/or frequency may be associated with improved outcomes, the cost-effectiveness of a daily hemodialysis strategy for critically ill patients with acute kidney injury (AKI) is unknown. We developed a Markov model of the cost, quality of life, survival, and incremental cost-effectiveness of daily hemodialysis, compared with alternate-day hemodialysis, for patients with AKI in the intensive care unit (ICU). We employed a societal perspective with a lifetime analytic time horizon. We modeled the efficacy of daily hemodialysis as a reduction in the relative risk of death on the basis of data reported in the 2004 clinical trial published by Schiffl et al. We performed 1- and 2-way sensitivity analyses across cost, efficacy, and utility input variables. The main outcome measure was cost per quality-adjusted life-year (QALY). In the base case for a 60-year-old man, daily hemodialysis was projected to add 2.14 QALYs and $10,924 in cost. We found that the cost-effectiveness of daily hemodialysis compared with alternate-day hemodialysis was $5084 per QALY gained. The incremental cost-effectiveness ratio became less favorable (>$50,000 per QALY gained) when the maintenance hemodialysis rate of the daily hemodialysis group was varied to more than 27% and when the difference in 14-day postdischarge mortality between the alternatives was varied to less than 0.5%. Daily hemodialysis is a cost-effective strategy compared with alternate-day hemodialysis for patients with severe AKI in the ICU.


Attention, spatial representation, and visual neglect: simulating emergent attention and spatial memory in the selective attention for identification model (SAIM).
The selective attention for identification model (SAIM) is presented. This uses a spatial window to select visual information for recognition, binding parts to objects and generating translation-invariant recognition. The model provides a qualitative account of both normal and disordered attention. Simulations of normal attention demonstrate 2-object costs and effects of object familiarity on selection, global precedence, spatial cueing, and inhibition of return. When lesioned, SAIM demonstrated either view- or object-centered neglect or spatial extinction, depending on the type and extent of lesion. The model provides a framework to unify (a) object- and space-based theories of normal selection, (b) dissociations within the syndrome of unilateral neglect, and (c) attentional and representational accounts of neglect.


Surface tension of ionic liquids and ionic liquid solutions.
Some of the most active scientific research fronts of the past decade are centered on ionic liquids. These fluids present characteristic surface behavior and distinctive trends of their surface tension versus temperature. One way to explore and understand their unique nature is to study their surface properties. This critical review analyses most of the surface tension data reported between 2001 and 2010 (187 references).


Sense and self-regulation checklist, a measure of comorbid autism symptoms: initial psychometric evidence.
Sensory and self-regulatory symptoms make up most of the comorbid symptoms in autism and are associated with increased autism severity. We validated a parent-caregiver measure of comorbid symptoms in autism, the Sense and Self-Regulation Checklist (SSC), in 265 children <6 yr with typical development (n = 138), autism (n = 99), or other developmental delay (n = 28); Cronbach's α was .87. We report two new findings discriminating autism from other groups: (1) multifocal tactile sensory impairment, characterized by hyporeactivity to injurious stimuli and hyperreactivity to noninjurious stimuli (F[2, 262] = 86.8, p < .001) and (2) global self-regulatory delay (F[2, 262] = 122, p < .001). Both findings suggest an explanation for social delay in children with autism. The SSC reports a prevalence of sensory and self-regulatory findings approaching 100% in the autism group (96% and 98%, respectively), raising the possibility that sensory and self-regulatory difficulties represent a core part of autism.


Penetration and biological effects of topically applied cyclosporin A nanoparticles in a human skin organ culture inflammatory model.
Systemic antipsoriatic therapies have potentially life-threatening, long-term side effects. The efficacy of topical drugs is poor, but may be improved by the use of delivery systems based on drug nanoparticles. To produce nanoparticles (NP) composed of cyclosporin A, a classical antipsoriatic drug, and to investigate their penetration and biological effects in human skin affected by psoriatic symptoms, poly-ε-caprolactone (PCL) and cyclosporin A (CsA) NP were prepared by the solvent evaporation method. Skin penetration was followed using fluorescently labeled NP in human skin organ cultures (hSOC). Psoriatic symptoms were mimicked in hSOC by the treatment with epidermal growth factor (EGF) and bacterial lipopolysaccharide (LPS). Cell viability in hSOC was evaluated by the resazurin test, and cytokine secretion into the growth medium was measured by immunodetection. We showed that topically applied NP diffused throughout the epidermis within two hours and through the dermis within the following day. They significantly reduced the secretion of inflammatory cytokines IL-1β, IL-6, IL-8, IL-20 and IL-23. At active doses, no cytotoxicity was detected. This type of NP display relevant properties for the use as topical anti-inflammatory agents and may help to resorb psoriatic lesions.


Quality of Frozen Hake Fillets in the Portuguese Retail Market: A Case Study of Inadequate Practices in the European Frozen White Fish Market.
The overall quality of frozen hake fillets in the Portuguese market was evaluated. Physical, biochemical, microbiological, and sensory analysis in 20 brands revealed several non-conformities. Hake was identified in 19 brands, although two mislabeled the species. Lower net weight than labeled was evidenced in ca. one-third of brands. TVB-N in ca. one-third of the samples presented high values, although within legal limit. Almost all brands presented excessive amount of ice glaze, low levels of WHC (raw/cooked), low levels of soluble protein, and undue thaw-drip loss, thus reflecting the poor quality of fillets. Added phosphates were below the legal limit in all samples; however, they were used in glaze ice in three brands, and only labeled in one. Overall microbiological quality of frozen fillets was good, though yeasts and molds detected in six samples indicate poor hygienic conditions in some facilities. Labels comply with legal requisites, however, need improvement, namely the 'best before' periods. In general, packaging was efficient regarding presence of ice crystals and dehydration signs. Concerning sensory analysis of cooked fillets, 63% of the brands had bad to poor quality and 37% fair quality. Merluccius productus revealed the worst quality, namely regarding thaw drip loss, thaw drip loss protein, M/P ratio, pH and sensory evaluation. Overall results show that a significant part of the hake fillets business operators are still failing in relation with best practices.


A systematic review and evaluation of measures for suicidal ideation and behaviors in population-based research.
The use of measures of suicidal ideation and behavior with sound measurement properties is critical in identifying people most at risk of suicide. In particular, brief self-report measures of suicidal ideation and behaviors are needed for use in large-scale population-based research and in the development and evaluation of suicide prevention programs in the community. This review aimed to identify and recommend psychometrically sound self-report measures of suicidal ideation and behaviors that could be used in population-based research of adults. To identify existing self-report measures for adult use, a systematic search was conducted using MEDLINE (Medical Literature Analysis and Retrieval System Online) and PsycINFO (Psychological Information Database) databases. Abstracts, reference lists, and previous review papers were screened. Once measures were identified, we used a hierarchical criterion-based approach to assess their utility, psychometric properties, and appropriateness for population-based research. Nineteen measures were evaluated against 6 criteria. Three brief measures that met all criteria of the evaluation and demonstrated adequate psychometric properties were the Depressive Symptom Index Suicidality Subscale (DSI-SS), Suicidal Behaviors Questionnaire-Revised (SBQ-R), and Suicidal Ideation Attributes Scale (SIDAS). None of the comprehensive measures met all criteria for use in population-based studies, due to financial costs imposed on use, although the Beck Scale for Suicide Ideation (BSSI) and the Adult Suicidal Ideation Questionnaire (ASIQ) had considerable evidence of psychometric robustness. Suicide researchers are encouraged to further establish the validity of scores on these measures across diverse adult populations.


Uptake of interventions, outcomes and challenges in caring for HIV-exposed infants in Kingston, Jamaica.
In a few Caribbean islands, prevention of mother-to-child transmission (pMTCT) of HIV with zidovudine prophylaxis has reduced transmission rates from 27 - 44% to 5.5 - 9 %. To highlight the uptake of interventions, preliminary outcomes and challenges in caring for HIV-exposed infants in a pMTCT HIVprogramme in a resource-limited setting. A cohort of HIV-infected pregnant women were identified at the leading maternity centres in Greater Kingston through HIV counselling and testing and enrolled in the Kingston Paediatric and Perinatal HIV/AIDS Programme. Antiretroviralprophylaxis with zidovudine or nevirapine was given to the HIV-positive women and their newborns along with formula feeding. Some infants were enrolled retrospectively and followed irrespective of whether they had or had not received antiretroviral prophylaxis. A multidisciplinary team at the paediatric centres supervised protocol-driven management of the infants. Infants were followed for clinical progress and definitive HIV-infection status was to be confirmed at 18 months of age by ELISA or the Determine Rapid Test. During September 1, 2002 through August 31, 2003, 132 HIV-exposed infants were identified. For those infants prospectively enrolled (78), 97% received antiretroviral prophylaxis and 90% were not breastfed For all HIV-exposed children, 90% received cotrimoxazole prophylaxis and 88% continued follow-up care. Ninety-two per cent of all the infants remained asymptomatic and five died; of these deaths one is possibly HIV-related (severe sepsis at 11 weeks). This infant was retrospectively identified, had received no antiretroviral prophylaxis and was breastfed The main programme challenges, which were overcome, included the impact of stigma, compliance with antiretroviral chemoprophylaxis, breast-milk substitution and follow-up care. Financial constraints and laboratory quality assurance issues limited early diagnosis of HIV infection. Despite the challenges, the expected outcome is to prevent 50 new cases of HIV/AIDS in children living in Greater Kingston per year (300 over six years).


Detection of interfacial phenomena with osteoblast-like cell adhesion on hydroxyapatite and oxidized polystyrene by the quartz crystal microbalance with dissipation.
The adhesion process of osteoblast-like cells on hydroxyapatite (HAp) and oxidized polystyrene (PSox) was investigated using a quartz crystal microbalance with dissipation (QCM-D), confocal laser scanning microscope (CLSM), and atomic force microscope (AFM) techniques in order to clarify the interfacial phenomena between the surfaces and cells. The interfacial viscoelastic properties (shear viscosity (η(ad)), elastic shear modulus (μ(ad)), and tan δ) of the preadsorbed protein layer and the interface layer between the surfaces and cells were estimated using a Voigt-based viscoelastic model from the measured frequency (Δf) and dissipation shift (ΔD) curves. In the ΔD-Δf plots, the cell adhesion process on HAp was classified as (1) a mass increase only, (2) increases in both mass and ΔD, and (3) slight decreases in mass and ΔD. On PSox, only ΔD increases were observed, indicating that the adhesion behavior depended on the surface properties. The interfacial μ(ad) value between the material surfaces and cells increased with the number of adherent cells, whereas η(ad) and tanδ decreased slightly, irrespective of the surface. Thus, the interfacial layer changed the elasticity to viscosity with an increase in the number. The tan δ values on HAp were higher than those on PSox and exceeded 1.0. Furthermore, the pseudopod-like structures of the cells on HAp had periodic stripe patterns stained with a type I collagen antibody, whereas those on PSox had cell-membrane-like structures unstained with type I collagen. These results indicate that the interfacial layers on PSox and HAp exhibit elasticity and viscosity, respectively, indicating that the rearrangements of the extracellular matrix and cytoskeleton changes cause different cell-surface interactions. Therefore, the different cell adhesion process, interfacial viscoelasticity, and morphology depending on the surfaces were successfully monitored in situ and evaluated by the QCM-D technique combined with other techniques.


A seasonal periodicity in relapses of multiple sclerosis? A single-center, population-based, preliminary study conducted in Bologna, Italy.
Temporal, i.e., 24-hour, weekly, and seasonal patterns in the occurrence of acute cardiovascular and cerebrovascular events are well documented; however, little is known about temporal, especially seasonal, variation in multiple sclerosis (MS) and its relapses. This study investigated, by means of a validated chronobiological method, whether severe relapses of MS, ones requiring medical specialty consultation, display seasonal differences, and whether they are linked with seasonal differences in local meteorological variables. We considered 96 consecutive patients with severe MS relapse (29 men, 67 women, mean age 38.5 ± 8.8 years), referred to the Multiple Sclerosis Center, Bellaria Hospital, Bologna, Italy, between January 1, 2007 and December 31, 2008. Overall, we analyzed 164 relapses (56 in men, 108 in women; 115 in patients aged < 40 years, 49 in patients ≥40 years). Relapses were more frequent in May and June (12.2% each) and the least frequent in September (3.7%). Chronobiological analysis showed a biphasic pattern (major peak in May-June, secondary peak in November-December, p = 0.030). Analysis of monthly mean meteorological data showed a significant seasonal pattern in ambient temperature (peak in July, p < 0.001), relative humidity (peak in January, p < 0.001), and wind speed (peak in June, p = 0.011). In this Italian setting, we found a biphasic pattern (peaks in spring and autumn) in severe MS relapses requiring medical consultation by doctors of the MS specialty center, apparently unrelated to meteorological variables. Confirmations of the findings on larger multi-center populations residing in different climatic conditions are needed to further explore the potential seasonality of MS relapses and associated environmental triggers.


SARS-CoV-2 spike protein dictates syncytium-mediated lymphocyte elimination.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is highly contagious and causes lymphocytopenia, but the underlying mechanisms are poorly understood. We demonstrate here that heterotypic cell-in-cell structures with lymphocytes inside multinucleate syncytia are prevalent in the lung tissues of coronavirus disease 2019 (COVID-19) patients. These unique cellular structures are a direct result of SARS-CoV-2 infection, as the expression of the SARS-CoV-2 spike glycoprotein is sufficient to induce a rapid (~45.1 nm/s) membrane fusion to produce syncytium, which could readily internalize multiple lines of lymphocytes to form typical cell-in-cell structures, remarkably leading to the death of internalized cells. This membrane fusion is dictated by a bi-arginine motif within the polybasic S1/S2 cleavage site, which is frequently present in the surface glycoprotein of most highly contagious viruses. Moreover, candidate anti-viral drugs could efficiently inhibit spike glycoprotein processing, membrane fusion, and cell-in-cell formation. Together, we delineate a molecular and cellular rationale for SARS-CoV-2 pathogenesis and identify novel targets for COVID-19 therapy.


Pre-pregnancy body mass index and the risk of antenatal depression and anxiety.
While the physical health risks of obesity during pregnancy for women are well understood, little is known about the mental health implications. The aim of this study was to investigate the relationship between pre-pregnancy body mass index (BMI) and symptoms of antenatal depression and anxiety. Secondary analysis of cross-sectional data contributed by the younger cohort (born 1973-78) of the Australian Longitudinal Study of Women's Health who were pregnant at the time of the survey (Waves 4-6: aged 28-39years). Primary outcomes were symptoms of depression (Center for Epidemiologic Studies Depression Scale 10 score≥10) and anxiety (Goldberg Anxiety Scale score≥6). BMI was assessed using self-reported pre-pregnancy weight and height. Demographic characteristics, psychosocial factors, health behaviors and reproductive history were assessed using study-specific and standardized measures. Multivariable regression models were used to examine the associations between predictors and outcome scores. The mean pre-pregnancy BMI of the 1621 women included in the analysis was 24.9kg/m2; more than a third (39.8%) were overweight or obese. More than one in ten (15.4%) had depressive symptoms, and a quarter (25.0%) had anxiety symptoms. Higher pre-pregnancy BMI and certain sociodemographic characteristics including not having a paid job were significantly related to higher antenatal depression and anxiety scores. High pre-pregnancy BMI is significantly associated with an increased risk of antenatal depression and anxiety. Consistent with clinical practice guidelines, women with high pre-pregnancy BMI should be screened and assessed for depression and anxiety, and where appropriate provided with clinical referral pathways and support.


Storage/Turnover rate of inorganic carbon and its dissolvable part in the profile of saline/alkaline soils.
Soil inorganic carbon is the most common form of carbon in arid and semiarid regions, and has a very long turnover time. However, little is known about dissolved inorganic carbon storage and its turnover time in these soils. With 81 soil samples taken from 6 profiles in the southern Gurbantongute Desert, China, we investigated the soil inorganic carbon (SIC) and the soil dissolved inorganic carbon (SDIC) in whole profiles of saline and alkaline soils by analyzing their contents and ages with radiocarbon dating. The results showed that there is considerable SDIC content in SIC, and the variations of SDIC and SIC contents in the saline soil profile were much larger than that in the alkaline profile. SDIC storage accounted for more than 20% of SIC storage, indicating that more than 1/5 of the inorganic carbon in both saline and alkaline soil is not in non-leachable forms. Deep layer soil contains considerable inorganic carbon, with more than 80% of the soil carbon stored below 1 m, whether for SDIC or SIC. More importantly, SDIC ages were much younger than SIC in both saline soil and alkaline soil. The input rate of SDIC and SIC ranged from 7.58 to 29.54 g C m(-2) yr(-1) and 1.34 to 5.33 g C m(-2) yr(-1) respectively for saline soil, and from 1.43 to 4.9 g C m(-2) yr(-1) and 0.79 to 1.27 g C m(-2) yr(-1)respectively for alkaline soil. The comparison of SDIC and SIC residence time showed that using soil inorganic carbon to estimate soil carbon turnover would obscure an important fraction that contributes to the modern carbon cycle: namely the shorter residence and higher input rate of SDIC. This is especially true for SDIC in deep layers of the soil profile.


Preliminary results with the Clarion cochlear implant.
A new cochlear implant has become available. This device, called the Clarion Multichannel Cochlear Implant, is the result of collaborative efforts between the University of California, San Francisco (UCSF), the Research Triangle Institute (RTI), Research Triangle Park, North Carolina, and the device manufacturer and sponsor, MiniMed Technologies of Sylmar, California. The Clarion represents a new generation of multi-programmable cochlear implant systems. Options in waveform, the stimulation mode, and the temporal distribution of the signal permit the device to be optimally customized for each individual patient. The speech coding scheme offering the greatest opportunity for speech recognition can be selected. The first Clarion recipient has recently been implanted at UCSF, initiating the Clarion's investigational clinical trials. A description of the device and preliminary patient results are presented.


Optimising patient discharge management after transfemoral transcatheter aortic valve implantation: the multicentre European FAST-TAVI trial.
Treatment pathway optimisation in TAVI should include timely patient discharge with a minimised risk for out-of-hospital adverse events. The aim of this study was to define a standardised set of risk criteria that allows a safe and timely discharge, to validate their appropriateness prospectively in different centres and multiple European countries, and to assess post-discharge outcomes. We defined and validated the adequacy of a set of discharge criteria and its ability to predict timely and safe discharge properly after the intervention in a prospective, European, multicentre registry. A total of 502 unselected patients were enrolled at 10 sites in three countries. The primary endpoint, defined as a composite of all-cause mortality, vascular access-related complications, permanent pacemaker implantation, stroke, re-hospitalisation due to cardiac reasons, kidney failure and major bleeding at 30 days, was reached in 12.9% of patients (95% CI: 11.3-16.5). The overall 30-day mortality was 1.1% (95% CI: 0.2-2.0), and the rates of stroke/TIA 1.7% (95% CI: -0.6 to 4.0), PPI 7.3% (95% CI: 5.8-8.9), major vascular complications 1.9% (95% CI: 0.7-3.1), major/life-threatening bleeding 2.4% (95% CI: 1.0-3.8) and cardiac re-hospitalisation 3.7% (95% CI: 1.4-6.0). Patients appropriately discharged early had a significantly lower risk of the primary endpoint (7.0 vs. 26.4%; p<0.001) which was reflected in some of its relevant components: stroke (0.0 vs. 2.8%; p=0.015), PPI (4.3 vs. 15.9%; p<0.001), major vascular complications (0.3 vs. 4.7%; p=0.004) and major/life-threatening bleeding (0.3 vs. 6.5%; p<0.001). We validated the appropriateness of a pre-specified set of risk criteria that allows a safe and timely discharge. The rate of 30-day complications did not reveal any risk increase with this strategy compared with the reported outcomes in major TAVI trials and registries. ClinicalTrials.gov Identifier: NCT02404467.


Oscillations of cyclic nucleotide concentrations in relation to the excitability of Dictyostelium cells.
Aggregating cells of Dictyostelium discoideum are able to release cyclic AMP periodically. The oscillations of cAMP generation are associated with changes in adenylate cyclase activity. Cyclic AMP receptors on the cell surface are functionally coupled to the oscillating system as evidenced by phase shifts that are induced by small pulses of extracellular cAMP. An important element of the oscillating system is the signal processing from surface receptors to the adenylate cyclase. This pathway exhibits adaptation resulting in the suppression of responses to constant, elevated concentrations of cAMP. The signal input for adenylate cyclase activation is, therefore, a change in the extracellular cAMP concentration with time. Oscillations in the absence of detectable changes of intra- or extracellular cAMP concentrations suggest the possibility that there is a metabolic network in D. discoideum cells that undergoes oscillations without coupling to adenylate cyclase. Cyclic GMP concentrations oscillate with a slight phase difference in advance of that of cAMP, suggesting that the two nucleotide cyclases might not be activated by the same mechanism. Elevation of extracellular calcium exerts an inhibitory effect on the accumulation of cAMP and on the second of the two cGMP peaks.


Music improves social communication and auditory-motor connectivity in children with autism.
Music has been identified as a strength in people with Autism Spectrum Disorder; however, there is currently no neuroscientific evidence supporting its benefits. Given its universal appeal, intrinsic reward value and ability to modify brain and behaviour, music may be a potential therapeutic aid in autism. Here we evaluated the neurobehavioural outcomes of a music intervention, compared to a non-music control intervention, on social communication and brain connectivity in school-age children (ISRCTN26821793). Fifty-one children aged 6-12 years with autism were randomized to receive 8-12 weeks of music (n = 26) or non-music intervention (n = 25). The music intervention involved use of improvisational approaches through song and rhythm to target social communication. The non-music control was a structurally matched behavioural intervention implemented in a non-musical context. Groups were assessed before and after intervention on social communication and resting-state functional connectivity of fronto-temporal brain networks. Communication scores were higher in the music group post-intervention (difference score = 4.84, P = .01). Associated post-intervention resting-state brain functional connectivity was greater in music vs. non-music groups between auditory and subcortical regions (z = 3.94, P < .0001) and auditory and fronto-motor regions (z = 3.16, P < .0001). Post-intervention brain connectivity was lower between auditory and visual regions in the music compared to the non-music groups, known to be over-connected in autism (z = 4.01, P < .00001). Post-intervention brain connectivity in the music group was related to communication improvement (z = 3.57, P < .0001). This study provides the first evidence that 8-12 weeks of individual music intervention can indeed improve social communication and functional brain connectivity, lending support to further investigations of neurobiologically motivated models of music interventions in autism.


Development of a Fungicide-Based Management Strategy for Foliar Disease Caused by Phoma ligulicola in Tasmanian Pyrethrum Fields.
The efficacy of a range of fungicides were assessed under in vitro conditions in four field trials over three seasons for the management of ray blight of pyrethrum, caused by the fungus Phoma ligulicola in Tasmania. Fungicides belonging to the demethylation inhibitor group, including prochloraz, tebuconazole, difenoconazole, and cyproconazole, produced the most significant reduction in mycelial growth in vitro compared with unamended controls. Significant reductions in germination of conidia resulted from low concentrations of azoxystrobin. In the field, azox-ystrobin (as Amistar) at a rate of 300 g of product/ha significantly decreased disease intensity and increased pyrethrin yield (kg/ha) in all seasons. Applications of either azoxystrobin or difenoconazole (as Score) at a rate of 250 ml of product/ha in early spring were the most effective, whereas no significant benefit was demonstrated from applications in autumn. Over all seasons, azoxystrobin applications resulted in double the weight of flowers produced compared with nontreated areas, whereas increases in pyrethrin content within the flowers were season and location specific. Application of azoxystrobin and chlorothalonil (as Bravo 720) at a rate of 1.4 liters of product/ha resulted in a 45 to 48% increase in flowers, reduced defoliation, and increased stem diameter. The weight of individual flowers and flower maturity was not significantly affected by fungicide application. These data provide the basis for cost-effective management of this disease.


Characterization of common virulence plasmids in Yersinia species and their role in the expression of outer membrane proteins.
The virulence plasmids pYV019, pYV8081, and pIB1 from Yersinia pestis, Yersinia enterocolitica, and Yersinia pseudotuberculosis, respectively, were characterized by restriction endonuclease analysis. The three plasmids exhibited a region of common DNA previously shown to encode determinants which confer Ca2+ dependence. The plasmids from Y. pestis and Y. pseudotuberculosis were similar throughout their genomes. In contrast, a region of the plasmid from Y. enterocolitica which contained an origin of replication differed from the other two plasmids as determined by DNA homology and replication properties. Plasmid-associated outer membrane proteins from all three species of Yersinia were characterized by polyacrylamide gel electrophoresis. There were no differences in the outer membrane protein profiles between plasmid-containing and homogenic strains lacking the plasmid after growth at 28 degrees C. After growth at 37 degrees C, both Y. enterocolitica and Y. pseudotuberculosis showed at least four major plasmid-associated outer membrane proteins. Y. pestis did not show any discernible changes after growth at 37 degrees C. It was shown by using E. coli minicell analysis that the plasmid DNA from all three species of Yersinia contained the coding capacity for production of the novel outer membrane proteins.


New identification of proanthocyanidins in cinnamon (Cinnamomum zeylanicum L.) using MALDI-TOF/TOF mass spectrometry.
The inner bark of Ceylon cinnamon (Cinnamomum zeylanicum L.) is commonly used as a spice and has also been widely employed in the treatment and prevention of disease. The positive health effects associated with the consumption of cinnamon could in part be due to its phenolic composition; proanthocyanidins (PA) are the major polyphenolic component in commercial cinnamon. We present a thorough study of the PA profile of cinnamon obtained using matrix-assisted laser desorption/ionization tandem time-of-flight (MALDI-TOF/TOF) mass spectrometry. In addition to the advantages of MALDI-TOF as a sensitive technique for the analysis of high-molecular-weight compounds, the tandem arrangement allows the identification of the compounds through their fragmentation patterns from MS/MS experiments. This is the first time that this technique has been used to analyze polymeric PA. The results show that cinnamon PA are more complex than was previously thought. We show here for the first time that they contain (epi)gallocatechin and (epi)catechingallate units. As gallates (galloyl moieties) and the pyrogallol group in gallocatechins have been related to the biological activity of grape and tea polyphenols, the presence of these substructures may explain some of the properties of cinnamon extracts. MALDI-TOF/TOF reveals that cinnamon bark PA include combinations of (epi)catechin, (epi)catechingallate, (epi)gallocatechin, and (epi)afzelechin, which results in a highly heterogeneous mixture of procyanidins, prodelphinidins, and propelargonidins.


Accurate temperature model for absorptance determination of optical components with laser calorimetry.
In the international standard (International Organization for Standardization 11551) for measuring the absorptance of optical components (i.e., laser calorimetry), the absorptance is obtained by fitting the temporal behavior of laser irradiation-induced temperature rise to a homogeneous temperature model in which the infinite thermal conductivity of the sample is assumed. In this paper, an accurate temperature model, in which both the finite thermal conductivity and size of the sample are taken into account, is developed to fit the experimental temperature data for a more precise determination of the absorptance. The difference and repeatability of the results fitted with the two theoretical models for the same experimental data are compared. The optimum detection position when the homogeneous model is employed in the data-fitting procedure is also analyzed with the accurate temperature model. The results show that the optimum detection location optimized for a wide thermal conductivity range of 0.2-50W/m·K moves toward the center of the sample as the sample thickness increases and deviates from the center as the radius and irradiation time increase. However, if the detection position is optimized for an individual sample with known sample size and thermal conductivity by applying the accurate temperature model, the influence of the finite thermal conductivity and sample size on the absorptance determination can be fully compensated for by fitting the temperature data recorded at the optimum detection position to the homogeneous temperature model.


Contagious yawning in domestic dog puppies (Canis lupus familiaris): the effect of ontogeny and emotional closeness on low-level imitation in dogs.
Contagious yawning is a well-documented phenomenon in humans and has recently attracted much attention from developmental and comparative sciences. The function, development and underlying mechanisms of the phenomenon, however, remain largely unclear. Contagious yawning has been demonstrated in dogs and several non-human primate species, and theoretically and empirically associated with empathy in humans and non-human primates. Evidence of emotional closeness modulating contagious yawning in dogs has, nonetheless, been contradictory. Humans show a developmental increase in susceptibility to yawn contagion, with typically developing children displaying a substantial increase at the age of four, when a number of cognitive abilities (e.g. accurate identification of others' emotions) begin to clearly manifest. Explicit tests of yawn contagion in non-human animals have, however, thus far only involved adult individuals. Here, we report a study of the ontogeny of domestic dogs' (Canis lupus familiaris) susceptibility to yawn contagion, and whether emotional closeness to the yawning model affects this. Thirty-five dogs, aged 4-14 months, observed a familiar and unfamiliar human repeatedly yawn or gape. The dogs yawned contagiously, but emotional closeness with the model did not affect the strength of contagion, raising questions as to recent evidence of emotionally modulated auditory contagious yawning in dogs. The dogs showed a developmental effect, with only dogs above 7 months evidencing contagion. The results support the notion of a developmental increase in dogs' attention to others and identification of others' emotional states and suggest that yawn contagion is underpinned by developmental processes shared by humans and other animals.


Approximate entropy detects the effect of a secondary cognitive task on postural control in healthy young adults: a methodological report.
Biomechanical measures of postural stability, while generally useful in neuroscience and physical rehabilitation research, may be limited in their ability to detect more subtle influences of attention on postural control. Approximate entropy (ApEn), a regularity statistic from nonlinear dynamics, recently has demonstrated relatively good measurement precision and shown promise for detecting subtle change in postural control after cerebral concussion. Our purpose was to further explore the responsiveness of ApEn by using it to evaluate the immediate, short-term effect of secondary cognitive task performance on postural control in healthy, young adults. Thirty healthy, young adults performed a modified version of the Sensory Organization Test featuring single (posture only) and dual (posture plus cognitive) task trials. ApEn values, root mean square (RMS) displacement, and equilibrium scores (ES) were calculated from anterior-posterior (AP) and medial-lateral (ML) center of pressure (COP) component time series. For each sensory condition, we compared the ability of the postural control parameters to detect an effect of cognitive task performance. COP AP time series generally became more random (higher ApEn value) during dual task performance, resulting in a main effect of cognitive task (p = 0.004). In contrast, there was no significant effect of cognitive task for ApEn values of COP ML time series, RMS displacement (AP or ML) or ES. During dual task performance, ApEn revealed a change in the randomness of COP oscillations that occurred in a variety of sensory conditions, independent of changes in the amplitude of COP oscillations. The finding expands current support for the potential of ApEn to detect subtle changes in postural control. Implications for future studies of attention in neuroscience and physical rehabilitation are discussed.


Comparison of procedural and clinical outcomes with Evolut R versus Medtronic CoreValve: a Swiss TAVI registry analysis.
Data on procedural and clinical outcomes after transcatheter aortic valve implantation (TAVI) with the new-generation self-expanding Medtronic Evolut R prosthesis in comparison with its predecessor, the Medtronic CoreValve, are scarce. The aim of this study was to assess the safety and efficacy of the Evolut R device compared with the former-generation CoreValve. In a nationwide, prospective, multicentre cohort study, outcomes of consecutive transfemoral TAVI patients treated with the new-generation Medtronic Evolut R (September 2014 - February 2016) and the Medtronic CoreValve (February 2011 - February 2016) were investigated. Events were reported according to VARC-2 and adjudicated by a clinical events committee. During the study period, 317 and 678 consecutive patients underwent TAVI with the Evolut R and the CoreValve bioprosthesis, respectively. Baseline clinical characteristics between the groups were comparable, although Evolut R patients were lower risk according to the STS score (4.8±3.4% vs. 6.9±5.0%, p<0.001) and logistic EuroSCORE (17.3±13% vs. 20.1±13%, p=0.009). Implantation of the Evolut R was associated with a lower use of predilatation (48.1% vs. 72.4%, p<0.001), a shorter procedure time (67.9±36 min vs. 76.7±42 min, p=0.002), and less contrast dye use during the procedure (155.2±98 ml vs. 208.0±117 ml, p<0.001). Post-procedural mean gradient was comparable (7.4±4.7 mmHg vs. 7.5±5.0 mmHg), as were the 30-day rates of moderate to severe aortic regurgitation (8.5% vs. 10.5%), major vascular (9.8% vs. 10.3%) and life-threatening bleeding complications (5.4% vs. 5.3%), disabling stroke (1.9% vs. 1.6%), all-cause mortality (3.2% vs. 3.4%) as well as permanent pacemaker implantation (22.1% vs. 23.4%). Thirty-day clinical outcomes were favourable and comparable between the Evolut R and the CoreValve bioprosthesis.


Reorienting adolescent sexual and reproductive health research: reflections from an international conference.
On December 4th 2014, the International Centre for Reproductive Health (ICRH) at Ghent University organized an international conference on adolescent sexual and reproductive health (ASRH) and well-being. This viewpoint highlights two key messages of the conference--(1) ASRH promotion is broadening on different levels and (2) this broadening has important implications for research and interventions--that can guide this research field into the next decade. Adolescent sexuality has long been equated with risk and danger. However, throughout the presentations, it became clear that ASRH and related promotion efforts are broadening on different levels: from risk to well-being, from targeted and individual to comprehensive and structural, from knowledge transfer to innovative tools. However, indicators to measure adolescent sexuality that should accompany this broadening trend, are lacking. While public health related indicators (HIV/STIs, pregnancies) and their behavioral proxies (e.g., condom use, number of partners) are well developed and documented, there is a lack of consensus on indicators for the broader construct of adolescent sexuality, including sexual well-being and aspects of positive sexuality. Furthermore, the debate during the conference clearly indicated that experimental designs may not be the only appropriate study design to measure effectiveness of comprehensive, context-specific and long-term ASRH programmes, and that alternatives need to be identified and applied. Presenters at the conference clearly expressed the need to develop validated tools to measure different sub-constructs of adolescent sexuality and environmental factors. There was a plea to combine (quasi-)experimental effectiveness studies with evaluations of the development and implementation of ASRH promotion initiatives.


Epistemological erasure: The subject of abuse in the problematization of 'elder abuse'.
The academic field of literature pertaining to elder abuse emerges largely from gerontology with contributions from a variety of disciplines including geriatric medicine, nursing, public health, law, psychology, sociology and social work. This paper presents a critical review of articles drawn from this literature to identify current directions leading the development of empirical research in this field. The objective measurement of prevalence, the identification and correlation of psycho-social risk factors and practice-based research oriented to intervention and prevention are identified as privileged sites for scientific investigation. These sites are critically analysed in terms of their underpinning rationalities to reveal the operation of a hegemonic post-positivist epistemological framework. This framework enables an expert professional discourse to structure knowledge and the field of inquiry through constructions of the 'subject of abuse' as a statistical figure, a factorial subject of risk and universally vulnerable. These modes of representation preclude subjective lived experience and, in doing so, inaugurate an 'epistemological erasure' of the embodied subject of abuse. The review attends to the limited body of qualitative research in the field, some of which claims a politicized empiricism of 'voice'. However, whilst the findings produced by this research suggest theoretically and conceptually fertile lines of inquiry, these have not disrupted or extended the dominant discourses in the field. This paper argues that an epistemological gulf, riven through a politics of evidence, ensures the reproduction of dominant discourses and their attendant limitations in ways that forestall the conceptual and theoretical advancement of the field.


Direct molecular imaging of Lymnaea stagnalis nervous tissue at subcellular spatial resolution by mass spectrometry.
The imaging capabilities of time-of-flight secondary ion mass spectrometry (ToF-SIMS) and MALDI-MS sample preparation methods were combined. We used this method, named matrix-enhanced (ME) SIMS, for direct molecular imaging of nervous tissue at micrometer spatial resolution. Cryosections of the cerebral ganglia of the freshwater snail Lymnaea stagnalis were placed on indium-tin-oxide (ITO)-coated conductive glass slides and covered with a thin layer of 2,5-dihydroxybenzoic acid by electrospray deposition. High-resolution molecular ion maps of cholesterol and the neuropeptide APGWamide were constructed. APGWamide was predominantly localized in the cluster of neurons that regulate male copulation behavior of Lymnaea. ME-SIMS imaging allows direct molecule-specific imaging from tissue sections without labeling and opens a complementary mass window (<2500 Da) to MALDI imaging mass spectrometry at an order of magnitude higher spatial resolution (<3 microm).


Osteoporosis therapies in 2014.
Osteoporosis is a systemic disorder characterized by low bone mass and microarchitectural deterioration of bone tissue with a consequent increase in bone fragility and susceptibility to fracture. It has a significant impact on public health through the increased morbidity, mortality, and economic costs associated with fractures. Despite the severe medical and socioeconomic consequences of fragility fractures, relatively few adults with fractures are evaluated and/or treated for osteoporosis. In this review, we summarize the existing treatment options and promising new therapies for the prevention and treatment of osteoporosis.


Analysis of Heritability and Genetic Architecture of Pancreatic Cancer: A PanC4 Study.
Pancreatic cancer is the fourth-leading cause of cancer death in both men and women in the United States. The currently identified common susceptibility loci account for a small fraction of estimated heritability. We sought to estimate overall heritability of pancreatic cancer and partition the heritability by variant frequencies and functional annotations. Analysis using the genome-based restricted maximum likelihood method (GREML) was conducted on Pancreatic Cancer Case-Control Consortium (PanC4) genome-wide association study (GWAS) data from 3,568 pancreatic cancer cases and 3,363 controls of European Ancestry. Applying linkage disequilibrium- and minor allele frequency-stratified GREML (GREML-LDMS) method to imputed GWAS data, we estimated the overall heritability of pancreatic cancer to be 21.2% (SE = 4.8%). Across the functional groups (intronic, intergenic, coding, and regulatory variants), intronic variants account for most of the estimated heritability (12.4%). Previously identified GWAS loci explained 4.1% of the total phenotypic variation of pancreatic cancer. Mutations in hereditary pancreatic cancer susceptibility genes are present in 4% to 10% of patients with pancreatic cancer, yet our GREML-LDMS results suggested these regions explain only 0.4% of total phenotypic variance for pancreatic cancer. Although higher than previous studies, our estimated 21.2% overall heritability may still be downwardly biased due to the inherent limitation that the contribution of rare variants in genes with a substantive overall impact on disease are not captured when applying these commonly used methods to imputed GWAS data. Our work demonstrated the importance of rare and common variants in pancreatic cancer risk.


Proton secretion by the gastric parietal cell.
The parietal cell occupies a unique niche among eukaryotic cells in that it develops a proton gradient of more than 4 million-fold across the membrane of the secretory canaliculus. At rest, the cell is still able to develop a proton gradient across intracellular membranes, such that the acid compartment has a pH of less than 4. Acidification depends on the simultaneous presence of ATP, K+ and Cl- as demonstrated in permeabilized cells. With acidification of the luminal side of the proton pump, there is a corresponding alkalinization of the cytosolic face as revealed by carboxyfluorescein fluorescence enhancement. Disposal of the resultant alkali depends on carbonic anhydrase activity and the functioning of a coupled Na+:H+ and Cl-:OH-antiport across the basal lateral membrane. Accordingly, with secretion there is an increased cellular Cl- level, which is exported across the apical membrane in association with K+. The Na+ pump dependent secretion of KCl across this membrane is one of the major sites of the gastric ATPase. Membranes isolated from secreting tissue contain a KCl permeation pathway largely absent from membranes isolated from resting tissue. The pump itself acts as an H+ for K+ exchange ATPase which is most probably composed of at least two peptides of 100 000 Mr. That catalytic cycle consists of formation and breakdown of a covalent aspartyl phosphate. Formation of the intermediate depends on loss of K+ from cytosolic binding sites, and breakdown of the intermediate depends on K+ binding to the luminal face of the enzyme. During breakdown, an acid labile E . P is formed, and, at high ATP concentrations, loss of this form of the enzyme is probably the rate limiting step.


International evolution of fat, oil and grease (FOG) waste management - A review.
In recent years, issues relating to fat, oil and grease (FOG) in sewer systems have intensified. In the media, sewer blockages caused by FOG waste deposits, commonly referred to as 'fatbergs', are becoming a reminder of the problems that FOG waste can cause when left untreated. These FOG blockages lead to sanitary sewer overflows, property flooding and contamination of water bodies with sewage. Despite these financial and environmentally detrimental effects, a homogenous FOG waste management method has not been developed internationally. However, some successful enduring FOG management programmes have been established, such as in Dublin city and in Scandinavian countries. The aim of this paper is to carry out a review on existing FOG research and management approaches. FOG management involves comprehending: (1) FOG deposition factors in the sewer, (2) FOG prevention and awareness tactics undertaken internationally and (3) potential utilisation methods for FOG waste. This review will highlight that preventing FOG from entering the sewer is the most common approach, often through simple awareness campaigns. The diverted FOG is rarely valorised to bioenergy or biomaterials, despite its potential. Thus, all facets of the FOG waste lifecycle must be identified and managed. Advancements in processes and techniques must be assessed to best determine the future evolution of FOG waste management to assist in achieving a sustainable urban environment.


Growth characteristics of the chimeric Japanese encephalitis virus vaccine candidate, ChimeriVax-JE (YF/JE SA14--14--2), in Culex tritaeniorhynchus, Aedes albopictus, and Aedes aegypti mosquitoes.
The Japanese encephalitis (JE) virus vaccine candidate, ChimeriVax-JE, which consists of a yellow fever (YF) 17D virus backbone containing the prM and E genes from the JE vaccine strain JE SA14--14--2, exhibits restricted replication in non-human primates, producing only a low-level viremia following peripheral inoculation. Although this reduces the likelihood that hematophagous insects could become infected by feeding on a vaccinated host, it is prudent to investigate the replication kinetics of the vaccine virus in mosquito species that are known to vector the viruses from which the chimera is derived. In this study ChimeriVax-JE virus was compared to its parent viruses, as well as to wild-type JE virus, for its ability to replicate in Culex tritaeniorhynchus, Aedes albopictus, and Aedes aegypti mosquitoes. Individual mosquitoes were exposed to the viruses by oral ingestion of a virus-laden blood meal or by intrathoracic (IT) virus inoculation. ChimeriVax-JE virus did not replicate following ingestion by any of the three mosquito species. Additionally, replication was not detected after IT inoculation of ChimeriVax-JE in the primary JE virus vector, Cx. tritaeniorhynchus. ChimeriVax-JE exhibited moderate growth following IT inoculation into Ae. aegypti and Ae. albopictus, reaching titers of 3.6-5.0 log(10) PFU/mosquito. There was no change in the virus genotype associated with replication in mosquitoes. Similar results were observed in mosquitoes of all three species that were IT inoculated or had orally ingested the YF 17D vaccine virus. In contrast, all mosquitoes either IT inoculated with or orally fed wild-type and vaccine JE viruses became infected, reaching maximum titers of 5.4-7.3 log(10) PFU/mosquito. These results indicate that ChimeriVax-JE virus is restricted in its ability to infect and replicate in these mosquito vectors. The low viremia caused by ChimeriVax-JE in primates and poor infectivity for mosquitoes are safeguards against secondary spread of the vaccine virus.


Snail promotes resistance to enzalutamide through regulation of androgen receptor activity in prostate cancer.
Treatment with androgen-targeted therapies can induce upregulation of epithelial plasticity pathways. Epithelial plasticity is known to be important for metastatic dissemination and therapeutic resistance. The goal of this study is to elucidate the functional consequence of induced epithelial plasticity on AR regulation during disease progression to identify factors important for treatment-resistant and metastatic prostate cancer. We pinpoint the epithelial plasticity transcription factor, Snail, at the nexus of enzalutamide resistance and prostate cancer metastasis both in preclinical models of prostate cancer and in patients. In patients, Snail expression is associated with Gleason 9-10 high-risk disease and is strongly overexpressed in metastases as compared to localized prostate cancer. Snail expression is also elevated in enzalutamide-resistant prostate cancer cells compared to enzalutamide-sensitive cells, and downregulation of Snail re-sensitizes enzalutamide-resistant cells to enzalutamide. While activation of Snail increases migration and invasion, it is also capable of promoting enzalutamide resistance in enzalutamide-sensitive cells. This Snail-mediated enzalutamide resistance is a consequence of increased full-length AR and AR-V7 expression and nuclear localization. Downregulation of either full-length AR or AR-V7 re-sensitizes cells to enzalutamide in the presence of Snail, thus connecting Snail-induced enzalutamide resistance directly to AR biology. Finally, we demonstrate that Snail is capable of mediating-resistance through AR even in the absence of AR-V7. These findings imply that increased Snail expression during progression to metastatic disease may prime cells for resistance to AR-targeted therapies by promoting AR activity in prostate cancer.


Replication study of four keloid-associated polymorphisms in patients of European descent - a single centre study.
Keloid is defined as a benign dermal fibro-proliferative growth that extends outside the original wound and invades adjacent dermal tissue. Its pathogenesis is complex and much evidence suggests the influence of genetic factors, including the rs873549, rs1511412, rs940187 and rs8032158 polymorphisms associated with keloid risk in Japanese patients. The aim of our study was to investigate possible associations between rs873549, rs1511412, rs940187 and rs8032158 variants and the risk of keloid in Polish patients of European descent. The genetic polymorphisms were identified by sequencing genomic DNA extracted from peripheral blood leukocytes from 86 keloid patients and from newborn cord blood leukocytes from 100 newborns as a control group. No significant differences (p > 0.05) in the distributions of rs873549, rs1511412, rs940187 and rs8032158 alleles were found between keloid patients and newborn controls (26.7% vs. 25.5%, 9.9% vs.7.0%, 19.8% vs. 12.5%, and 41.9% vs. 33.5%, respectively). Logistic regression with adjustment for gender revealed that only the CC homozygous genotype of rs8032158 polymorphism was significantly more frequent in keloid patients as compared with controls (19.8% vs. 11.0%, respectively). Our results suggest that in contrast to Asian populations only the rs8032158 polymorphism at locus 15q21.3 is associated with the susceptibility to keloid scarring in patients of European descent.


Lung cancer in women: role of estrogens.
The incidence of lung cancer in females is increasing, in contrast to that seen in males. In addition, the proportion of lung cancer cases in women attributable to smoking is approximately half of that seen in males. Female sex hormones, especially estrogen, may play a key role in this. Estrogen receptors ERalpha and ERbeta have been detected on lung cancer cells and there is new evidence suggesting that hormone-replacement therapy may increase both the incidence of, and mortality from, lung cancer in women. Laboratory evidence lends credence to the carcinogenic effects of estrogens in lung cancer. This article summarizes the current evidence on their role in lung cancer.