SPaCE Swab: Point-of-Care Sensor for Simple and Rapid Detection of Acute Wound Infection.

Wound infection is commonly observed after surgery and trauma but is difficult to diagnose and poorly defined in terms of objective clinical parameters. The assumption that bacteria in a wound correlate with infection is false; all wounds contain microorganisms, but not all wounds are clinically infected. This makes it difficult for clinicians to determine true wound infection, especially in wounds with pathogenic biofilms. If an infection is not properly treated, pathogenic virulence factors, such as rhamnolipids from Pseudomonas aeruginosa, can modulate the host immune response and cause tissue breakdown. Life-threatening sepsis can result if the organisms penetrate deep into host tissue. This communication describes the sensor development for five important clinical microbial pathogens commonly found in wounds: Staphylococcus aureus, P. aeruginosa, Candida albicans/auris, and Enterococcus faecalis (the SPaCE pathogens). The sensor contains liposomes encapsulating a self-quenched fluorescent dye. Toxins, expressed by SPaCE infecting pathogens in early-stage infected wounds, break down the liposomes, triggering dye release, thus changing the sensor color from yellow to green, an indication of infection. Five clinical species of bacteria and fungi, up to 20 strains each (totaling 83), were grown as early-stage biofilms in ex vivo porcine burn wounds. The biofilms were then swabbed, and the swab placed in the liposome suspension. The population density of selected pathogens in a porcine wound biofilm was quantified and correlated with colorimetric response. Over 88% of swabs switched the sensor on (107-108 CFU/swab). A pilot clinical study demonstrated a good correlation between sensor switch-on and early-stage wound infection.

Operating at the extreme: estimating the upper yield boundary of winter wheat production in commercial practice.

Wheat farming provides 28.5% of global cereal production. After steady growth in average crop yield from 1950 to 1990, wheat yields have generally stagnated, which prompts the question of whether further improvements are possible. Statistical studies of agronomic parameters such as crop yield have so far exclusively focused on estimating parameters describing the whole of the data, rather than the highest yields specifically. These indicators include the mean or median yield of a crop, or finding the combinations of agronomic traits that are correlated with increasing average yields. In this paper, we take an alternative approach and consider high yields only. We carry out an extreme value analysis of winter wheat yield data collected in England and Wales between 2006 and 2015. This analysis suggests that, under current climate and growing conditions, there is indeed a finite upper bound for winter wheat yield, whose value we estimate to be 17.60 tonnes per hectare. We then refine the analysis for strata defined by either location or level of use of agricultural inputs. We find that there is no statistical evidence for variation of maximal yield depending on location, and neither is there statistical evidence that maximum yield levels are improved by high levels of crop protection and fertilizer use.

Linear discriminant analysis reveals differences in root architecture in wheat seedlings related to nitrogen uptake efficiency.

Root architecture impacts water and nutrient uptake efficiency. Identifying exactly which root architectural properties influence these agronomic traits can prove challenging. In this paper, approximately 300 wheat (Triticum aestivum) plants were divided into four groups using two binary classifications, high versus low nitrogen uptake efficiency (NUpE), and high versus low nitrate in the growth medium. The root system architecture for each wheat plant was captured using 16 quantitative variables. The multivariate analysis tool, linear discriminant analysis, was used to construct composite variables, each a linear combination of the original variables, such that the score of the plants on the new variables showed the maximum between-group variability. The results show that the distribution of root-system architecture traits differs between low- and high-NUpE plants and, less strongly, between low-NUpE plants grown on low versus high nitrate media.

Digital Single-Cell Analysis of Plant Organ Development Using 3DCellAtlas.

Diverse molecular networks underlying plant growth and development are rapidly being uncovered. Integrating these data into the spatial and temporal context of dynamic organ growth remains a technical challenge. We developed 3DCellAtlas, an integrative computational pipeline that semiautomatically identifies cell types and quantifies both 3D cellular anisotropy and reporter abundance at single-cell resolution across whole plant organs. Cell identification is no less than 97.8% accurate and does not require transgenic lineage markers or reference atlases. Cell positions within organs are defined using an internal indexing system generating cellular level organ atlases where data from multiple samples can be integrated. Using this approach, we quantified the organ-wide cell-type-specific 3D cellular anisotropy driving Arabidopsis thaliana hypocotyl elongation. The impact ethylene has on hypocotyl 3D cell anisotropy identified the preferential growth of endodermis in response to this hormone. The spatiotemporal dynamics of the endogenous DELLA protein RGA, expansin gene EXPA3, and cell expansion was quantified within distinct cell types of Arabidopsis roots. A significant regulatory relationship between RGA, EXPA3, and growth was present in the epidermis and endodermis. The use of single-cell analyses of plant development enables the dynamics of diverse regulatory networks to be integrated with 3D organ growth.

Integrative epigenetic profiling analysis identifies DNA methylation changes associated with chronic alcohol consumption.

Alcoholism has always been a major public health concern in Taiwan, especially in the aboriginal communities. Emerging evidence supports the association between DNA methylation and alcoholism, though very few studies have examined the effect of chronic alcohol consumption on the epignome. Since 1986, we have been following up on the mental health conditions of four major aboriginal peoples of Taiwan. The 993 aboriginal people who underwent the phase 1 (1986) clinical interviews were followed up through phase 2 (1990-1992), and phase 3 (2003-2009). Selected individuals for the current study included 10 males from the phase 1 normal cohort who remained normal at phase 2 and became dependent on alcohol by phase 3 and 10 control subjects who have not had any drinking problems throughout the study. We profiled the DNA methylation changes in the blood samples collected at phases 2 and 3. Enrichment analyses have identified several biological processes related to immune system responses and aging in the control group. In contrast, differentially methylated genes in the case group were mostly associated with susceptibility to infections, as well as pathways related to muscular contraction and neural degeneration. The methylation levels of six genes were found to correlate with alcohol consumption. These include genes involved in neurogenesis (NPDC1) and inflammation (HERC5), as well as alcoholism-associated genes ADCY9, CKM, and PHOX2A. Given the limited sample size, our approach uncovered genes and disease pathways associated with chronic alcohol consumption at the epigenetic level. The results offer a preliminary methylome map that enhances our understanding of alcohol-induced damages and offers new targets for alcohol injury research.

Promotion of testa rupture during garden cress germination involves seed compartment-specific expression and activity of pectin methylesterases.

Pectin methylesterase (PME) controls the methylesterification status of pectins and thereby determines the biophysical properties of plant cell walls, which are important for tissue growth and weakening processes. We demonstrate here that tissue-specific and spatiotemporal alterations in cell wall pectin methylesterification occur during the germination of garden cress (Lepidium sativum). These cell wall changes are associated with characteristic expression patterns of PME genes and resultant enzyme activities in the key seed compartments CAP (micropylar endosperm) and RAD (radicle plus lower hypocotyl). Transcriptome and quantitative real-time reverse transcription-polymerase chain reaction analysis as well as PME enzyme activity measurements of separated seed compartments, including CAP and RAD, revealed distinct phases during germination. These were associated with hormonal and compartment-specific regulation of PME group 1, PME group 2, and PME inhibitor transcript expression and total PME activity. The regulatory patterns indicated a role for PME activity in testa rupture (TR). Consistent with a role for cell wall pectin methylesterification in TR, treatment of seeds with PME resulted in enhanced testa permeability and promoted TR. Mathematical modeling of transcript expression changes in germinating garden cress and Arabidopsis (Arabidopsis thaliana) seeds suggested that group 2 PMEs make a major contribution to the overall PME activity rather than acting as PME inhibitors. It is concluded that regulated changes in the degree of pectin methylesterification through CAP- and RAD-specific PME and PME inhibitor expression play a crucial role during Brassicaceae seed germination.

Transcriptional dynamics of two seed compartments with opposing roles in Arabidopsis seed germination.

Seed germination is a critical stage in the plant life cycle and the first step toward successful plant establishment. Therefore, understanding germination is of important ecological and agronomical relevance. Previous research revealed that different seed compartments (testa, endosperm, and embryo) control germination, but little is known about the underlying spatial and temporal transcriptome changes that lead to seed germination. We analyzed genome-wide expression in germinating Arabidopsis (Arabidopsis thaliana) seeds with both temporal and spatial detail and provide Web-accessible visualizations of the data reported (vseed.nottingham.ac.uk). We show the potential of this high-resolution data set for the construction of meaningful coexpression networks, which provide insight into the genetic control of germination. The data set reveals two transcriptional phases during germination that are separated by testa rupture. The first phase is marked by large transcriptome changes as the seed switches from a dry, quiescent state to a hydrated and active state. At the end of this first transcriptional phase, the number of differentially expressed genes between consecutive time points drops. This increases again at testa rupture, the start of the second transcriptional phase. Transcriptome data indicate a role for mechano-induced signaling at this stage and subsequently highlight the fates of the endosperm and radicle: senescence and growth, respectively. Finally, using a phylotranscriptomic approach, we show that expression levels of evolutionarily young genes drop during the first transcriptional phase and increase during the second phase. Evolutionarily old genes show an opposite pattern, suggesting a more conserved transcriptome prior to the completion of germination.

A novel method testing the ability to imitate composite emotional expressions reveals an association with empathy.

Social communication relies on intentional control of emotional expression. Its variability across cultures suggests important roles for imitation in developing control over enactment of subtly different facial expressions and therefore skills in emotional communication. Both empathy and the imitation of an emotionally communicative expression may rely on a capacity to share both the experience of an emotion and the intention or motor plan associated with its expression. Therefore, we predicted that facial imitation ability would correlate with empathic traits. We built arrays of visual stimuli by systematically blending three basic emotional expressions in controlled proportions. Raters then assessed accuracy of imitation by reconstructing the same arrays using photographs of participants' attempts at imitations of the stimuli. Accuracy was measured as the mean proximity of the participant photographs to the target stimuli in the array. Levels of performance were high, and rating was highly reliable. More empathic participants, as measured by the empathy quotient (EQ), were better facial imitators and, in particular, performed better on the more complex, blended stimuli. This preliminary study offers a simple method for the measurement of facial imitation accuracy and supports the hypothesis that empathic functioning may utilise motor control mechanisms which are also used for emotional expression.

Transcriptional bursting diversifies the behaviour of a toggle switch: hybrid simulation of stochastic gene expression.

Hybrid models for gene expression combine stochastic and deterministic representations of the underlying biophysical mechanisms. According to one of the simplest hybrid formalisms, protein molecules are produced in randomly occurring bursts of a randomly distributed size while they are degraded deterministically. Here, we use this particular formalism to study two key regulatory motifs-the autoregulation loop and the toggle switch. The distribution of burst times is determined and used as a basis for the development of exact simulation algorithms for gene expression dynamics. For the autoregulation loop, the simulations are compared to an analytic solution of a master equation. Simulations of the toggle switch reveal a number of qualitatively distinct scenarios with implications for the modelling of cell-fate selection.

Incidence of first onset alcohol use disorder: a 16-year follow-up in the Taiwanese aborigines.

PURPOSE: To investigate the incidence and cumulative risk of first onset alcohol use disorder (AUD) in a 16-year follow-up among Taiwanese aboriginal populations. METHODS: Participants included in this study were cohort subjects free from any AUD at phase 1 survey (n = 428 for DSM-3-R and 451 for DSM-4) of the Taiwan aboriginal study project conducted in 1986-1988. They were reassessed approximately 16 years later, with a response rate of 98.8 %. A Chinese version of the WHO schedules for clinical assessment in neuropsychiatry was employed to assess the lifetime drinking history and AUD. RESULTS: Age-standardized annual incidence rates of AUD in all groups were 2.26 and 1.75 % according to DSM-3-R and DSM-4, respectively. The overall incidence rates of AUD were comparable to most of other studies in Caucasian populations, but the sex ratios of women to men were higher in this study (1:2-3) than in the latter (1:6). The incidence of AUD was higher with DSM-3-R than with DSM-4 criteria in this study, attributable to the exclusion of physical/psychological harm in DSM-4 alcohol abuse. The cumulative risks of DSM-4 AUD in this study were very high, being 72.2 ± 19.8 for men and 48.7 ± 8.2 for women up to the age of 65 years. CONCLUSIONS: High incidence rates and cumulative risks of AUD in Taiwanese aborigines demand effective prevention strategy.

Exact and approximate distributions of protein and mRNA levels in the low-copy regime of gene expression.

Gene expression at the single-cell level incorporates reaction mechanisms which are intrinsically stochastic as they involve molecular species present at low copy numbers. The dynamics of these mechanisms can be described quantitatively using stochastic master-equation modelling; in this paper we study a generic gene-expression model of this kind which explicitly includes the representations of the processes of transcription and translation. For this model we determine the generating function of the steady-state distribution of mRNA and protein counts and characterise the underlying probability law using a combination of analytic, asymptotic and numerical approaches, finding that the distribution may assume a number of qualitatively distinct forms. The results of the analysis are suitable for comparison with single-molecule resolution gene-expression data emerging from recent experimental studies.

Multiscale stochastic modelling of gene expression.

Stochastic phenomena in gene regulatory networks can be modelled by the chemical master equation for gene products such as mRNA and proteins. If some of these elements are present in significantly higher amounts than the rest, or if some of the reactions between these elements are substantially faster than others, it is often possible to reduce the master equation to a simpler problem using asymptotic methods. We present examples of such a procedure and analyse the relationship between the reduced models and the original.

A guideline to family-wide comparative state-of-the-art quantitative RT-PCR analysis exemplified with a Brassicaceae cross-species seed germination case study.

Comparative biology includes the comparison of transcriptome and quantitative real-time RT-PCR (qRT-PCR) data sets in a range of species to detect evolutionarily conserved and divergent processes. Transcript abundance analysis of target genes by qRT-PCR requires a highly accurate and robust workflow. This includes reference genes with high expression stability (i.e., low intersample transcript abundance variation) for correct target gene normalization. Cross-species qRT-PCR for proper comparative transcript quantification requires reference genes suitable for different species. We addressed this issue using tissue-specific transcriptome data sets of germinating Lepidium sativum seeds to identify new candidate reference genes. We investigated their expression stability in germinating seeds of L. sativum and Arabidopsis thaliana by qRT-PCR, combined with in silico analysis of Arabidopsis and Brassica napus microarray data sets. This revealed that reference gene expression stability is higher for a given developmental process between distinct species than for distinct developmental processes within a given single species. The identified superior cross-species reference genes may be used for family-wide comparative qRT-PCR analysis of Brassicaceae seed germination. Furthermore, using germinating seeds, we exemplify optimization of the qRT-PCR workflow for challenging tissues regarding RNA quality, transcript stability, and tissue abundance. Our work therefore can serve as a guideline for moving beyond Arabidopsis by establishing high-quality cross-species qRT-PCR.

Mortality and suicide after self-harm: community cohort study in Taiwan.

BACKGROUND: Little is known about outcomes after self-harm in East Asia. AIMS: To investigate mortality after self-harm in a Taiwanese population. METHOD: Between 2000 and 2003, 1083 individuals who self-harmed were identified through a population self-harm register in Nantou County, Taiwan, and followed until 2007 for date and cause of death on a national mortality database. RESULTS: In total, 145 individuals died, 48 through suicide. The risks of all-cause and suicide mortality in the first year were 4.7% and 2.1% respectively, representing 8- and 131-fold age- and gender-standardised increases. Male gender and older age were independent risk factors for both suicide and non-suicide mortality. Use of more lethal methods in the index episode was associated with higher mortality but this was accounted for by gender. CONCLUSIONS: Results in this sample support the recommendation that people with a history of recent self-harm should be a major target for suicide prevention programmes.

Non-fatal repetition of self-harm: population-based prospective cohort study in Taiwan.

BACKGROUND: Repeated self-harm is relatively common and is linked with an elevated risk of eventual suicide. There has been no study of this involving a large sample from the Far East. AIMS: To estimate the risk over the medium term of non-fatal repetition of self-harm and identify predictive factors in those carrying out self-harm. METHOD: A total of 970 individuals who had self-harmed were recruited from a community-based suicide behaviour register system in Nantou, Taiwan from July 2000 to February 2003. Information regarding demography and suicide methods was collected. Individuals were followed-up until December 2005 to examine the risk of repeated self-harm and independent predictive factors. RESULTS: Ninety cohort members had repeated self-harm during the follow-up period (accounting for 131 repeated self-harm episodes in all). The cumulative risks were 5.7% for the first year, 7.8% for the second year and 9.5% for the fourth year. The risk was highest within the first year after the self-harm event. Independent risk factors included female gender and self-cutting as well as self-poisoning with drugs. Effect of younger age was mediated through the choice of methods. CONCLUSIONS: Individuals with self-harm have a high risk of repetition, especially within the first year. Suicide prevention strategies need to focus on intervening with this population to reduce their repetition.

Effect of media reporting of the suicide of a singer in Taiwan: the case of Ivy Li.

BACKGROUND: Suicide attempters are known to be vulnerable to the influence of media reporting of suicide events. This study investigates possible influences of media reporting of a celebrity suicide on subsequent suicide attempts and associated risk factors among suicide attempters. METHODS: Sixty-three suicide attempters registered in a surveillance system of Taipei City Suicide Prevention Center were assessed using a structured interview soon after media reporting of the suicide of a young female singing star. RESULTS: Forty-three (68%) respondents had encountered with the suicide news. Among them, 37% reported being influenced by the media reporting on their subsequent suicide attempts. Men (adjusted OR 6.36, 95% CI 1.29-31.44) and younger age groups (adjusted OR 4.93, 95% CI 1.04-23.45) were more susceptible to the media reporting. There was a positive modeling effect in method of suicide (charcoal burning) (adjusted OR 7.27, 95% CI 6.31-168.66). CONCLUSIONS: This study has provided further evidence for suicide imitation among vulnerable people encountered with media reporting of celebrity suicide, and for the need to actively restrain reporting of suicides to decrease the imitation effect.

Development of a Chinese version of the Suicide Intent Scale.

This study established the psychometric properties of the Chinese version of the Suicide Intent Scale (SIS) in a clinic- and community-based sample of 36 patients and 592 respondents, respectively. Results showed that the Chinese SIS demonstrated good inter-rater and test-retest reliability. Factor analysis generated three factors (Precautions, Planning, and Seriousness) explaining 92.9% of the total variance with high internal consistency. It was moderately correlated with depressive symptoms. Results suggest that the Chinese SIS is a reliable and valid instrument for use in assessing the extent of suicidal intention among subjects with deliberate self-harm in ethnic Chinese populations.

Psychiatric consultation for post-liver-transplantation patients.

AIM: This report describes the clinical characteristics of referral inpatients who received liver transplantation and the surgeon's concordance with the psychiatric consultation. METHODS: During a 4-year period, psychiatric consultation was arranged for 30 post-liver-transplantation inpatients at Kaohsiung Chang Gung Memorial Hospital. A psychiatrist assessed these patients and made psychiatric diagnoses according to the Diagnostic and Statistical Manual, 4th edition. The clinical data were routinely collected via modified MICRO-CARES software. At the end of the 4-year study period, all the medical records of these 30 inpatients were reviewed. RESULTS: Psychiatric diagnosis was made in 70% of the patients (n = 21) in three major categories, including delirious state (n = 8), depressive disorder (n = 5), and anxiety/dyssomnia (n = 8). All these conditions were improved by psychiatric management. We found that the consultee's concordance with recommended drug prescriptions was high with antidepressants in depressive patients and low with antipsychotics in patients with delirium. Moreover, anxiolytics were frequently prescribed in post-transplant inpatients before psychiatric consultation. CONCLUSION: These findings suggest that psychiatric consultation is beneficial to inpatients after liver transplantation, especially those with depression and delirium.