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Circulating tumor DNA (ctDNA) analysis can identify patients with residual disease before it is clinically or radiologically evident. Minimal residual disease (MRD) is an advancing area in the management of radically treated solid tumors. Which MRD assay is optimum and when it should be used is still not defined. Whilst promising, the clinical utility of this technology to guide patient care is still investigational in non-small cell lung cancer (NSCLC) and has not entered routine care. Once technically and clinically optimized, MRD may be utilized to personalize adjuvant therapy, detect disease relapse earlier and improve cure rates. In this review, we discuss the current status of MRD monitoring in NSCLC by summarizing frequently used MRD assays and their associated evidence in NSCLC. We discuss the potential applications of these technologies and the challenge of demonstrating MRD clinical utility in trials. [ABSTRACT FROM AUTHOR]

Background: There is evidence that antipsychotic drugs differ in their effect on the cognitive symptoms of schizophrenia. So far, there is no comprehensive systematic review available that would enable providers and patients to make informed choices regarding this important aspect of treatment. With a large number of substances available, conventional pairwise meta-analyses will not be sufficient to inform this choice. To fill this gap, we will conduct a network meta-analysis (NMA), integrating direct and indirect comparisons from randomized controlled trials (RCTs) to rank antipsychotics according to their effect on cognitive functioning. Methods: In our NMA, we will include RCTs in patients with schizophrenia or schizophrenia-like psychoses comparing one antipsychotic agent with another antipsychotic agent or placebo that measures cognitive function. We will include studies on patients of every age group, in any phase of illness (e.g., acute or stable, first episode or chronic schizophrenia, in- or outpatients) with an intervention time of at least 3 weeks. The primary outcome will be the composite score of cognitive functioning, preferentially measured with the test battery developed by the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative. The secondary outcomes include the seven cognitive domains that the composite score is composed of, as well as functioning and quality of life. Study selection and data extraction will be conducted by at least two independent reviewers. We will use the Cochrane Risk of Bias tool 2 to determine the risk of bias in studies, and we will evaluate the confidence in the results using Confidence in Network Meta-Analysis (CINeMA). We will perform NMA using R (package netmeta). We will conduct subgroup and sensitivity analyses to explore the heterogeneity and assess the robustness of our findings. Discussion: This systematic review and network meta-analysis aims to inform evidence-based antipsychotic treatment choice for cognitive deficits in schizophrenia patients by analyzing existing RCTs on this subject. The results have the potential to support patients' and physicians' decision-making processes based on the latest available evidence. Systematic review registration: PROSPERO CRD42022312483 [ABSTRACT FROM AUTHOR]

Arterial hypertension in renal transplant recipients warrants antihypertensive treatment. The preferable choice of antihypertensives that should be used in patients after kidney transplantation remains a matter of debate; however, calcium channel blockers (CCB) and angiotensin-converting enzyme inhibitors (ACEI) are currently the most commonly used antihypertensives. This educational review summarizes the current evidence about the effects of these two classes of medications in transplant recipients. Several studies have demonstrated that both classes of drugs can reduce blood pressure (BP) to similar extents. Meta-analyses of adult randomized controlled trials have shown that graft survival is improved in patients treated with ACEIs and CCBs, and that CCBs increase, yet ACEIs decrease, graft function. Proteinuria is usually decreased by ACEIs but remains unchanged with CCBs. In children, no randomized controlled study has ever been performed to compare BP or graft survival between CCBs and ACEIs. Post-transplant proteinuria could be reduced in children along with BP by ACEIs. The results of the most current meta-analyses recommend that due to their positive effects on graft function and survival, along with their lack of negative effects on serum potassium, CCBs could be the preferred first-line antihypertensive agent in renal transplant recipients. However, antihypertensive therapy should be individually tailored based on other factors, such as time after transplantation, presence of proteinuria/albuminuria, or hyperkalemia. Furthermore, due to the difficulty in controlling hypertension, combination therapy containing both CCBs and ACEIs could be a reasonable first-step therapy in treating children with severe post-transplantation hypertension. [ABSTRACT FROM AUTHOR]

Background: The clinical significance of isolated systolic hypertension with normal central blood pressure known as spurious hypertension (sHT) in adolescents and its evolution over time is not known. Methods: The aim of this study was to analyze changes in office, ambulatory blood pressure (ABPM), central systolic blood pressure (cSBP), hemodynamic parameters, and target organ damage (TOD) over a 1-year follow-up in a group of non-obese children with sHT. Results: Of 294 patients referred for primary hypertension, 138 patients (31 girls; 22%) had hypertension confirmed by ABPM. 48/138 (35%) patients (7 girls; 15%) were diagnosed with sHT (elevated office and ambulatory systolic BP, but normal cSBP); 43 of them (6 girls; 14%) were followed for 12 ± 3 months during non-pharmacological therapy. At baseline 7 (16%) patients had borderline values of cIMT or LVMi indicating mild TOD. After 12 months, 10/43 (3 girls; 23%) patients developed sustained HT (elevated office, ambulatory BP and cSBP), 11/43 (1 girl; 26%) maintained sHT, and 22/43 (2 girls; 51%) evolved to white coat hypertension or normotension. The cSBP values increased in 27 patients (4 girls; 63%), but the group average remained in the normal range. Prevalence of TOD did not change during observation. The multivariate regression analysis showed that the only predictor of cSBP change over time was a change in serum uric acid level. Conclusions: In conclusion, after 1 year of non-pharmacological treatment, 23% of adolescents with sHT developed sustained hypertension, with the main predictor of cSBP change being the change in serum uric acid. [ABSTRACT FROM AUTHOR]

Will sensor-based exposure assessment be the future in workplace settings? Static instruments with embedded sensors are already applied to monitor levels of dangerous substances—in the context of acute health effects—at critical locations. However, with wearable, lightweight, miniaturized (low-cost) sensors developing quickly, much more is possible with sensors in relation to exposure assessment. Sensors can be applied in the work environment, on machines, or on employees and may include sensors that measure chemical exposures, but also sensors or other technologies that collect contextual information to support the exposure measurements. Like every technology it also has downsides. Sensors collect data on individuals that, depending on the purpose, need to be shared with others (e.g. health, safety and environment manager). One can imagine that people are afraid of misuse. To explore possible ethical and privacy issues that may come along with the introduction of sensors in the workplace, we organized a workshop with stakeholders (n = 32) to discuss three possible sensor-based scenarios in a structured way around five themes: purpose, efficacy, intrusiveness, proportionality, and fairness. The main conclusion of the discussions was that stakeholders currently see benefits in using sensors for applied targeted studies (short periods, clear reasons). In order to find acceptance for the implementation of sensors, all individuals affected by the sensors or its data need to be involved in the decisions on the purpose and application of sensors. Possible negative side effects need to be discussed and addressed. Continuous sensor-based monitoring of workers currently appears to be a bridge too far for the participants of this workshop. [ABSTRACT FROM AUTHOR]

There remains a lack of consensus among guideline relating to which patients require investigation for haematuria. We determined the incidence of urinary tract cancer in a prospective observational study of 3556 patients referred for investigation of haematuria across 40 hospitals between March 2016 and June 2017 (DETECT 1; ClinicalTrials.gov: NCT02676180 ) and the appropriateness of age at presentation in cases with visible (VH) and nonvisible (NVH) haematuria. The overall incidence of urinary tract cancer was 10.0% (bladder cancer 8.0%, renal parenchymal cancer 1.0%, upper tract transitional cell carcinoma 0.7%, and prostate cancer 0.3%). Patients with VH were more likely to have a diagnosis of urinary tract cancer compared with NVH patients (13.8% vs 3.1%). Older patients, male gender, and smoking history were independently associated with urinary tract cancer diagnosis. Of bladder cancers diagnosed following NVH, 59.4% were high-risk cancers, with 31.3% being muscle invasive. The incidence of cancer in VH patients <45 yr of age was 3.5% ( n = 7) and 1.0% ( n = 4) in NVH patients <60 yr old. Our results suggest that patients with VH should be investigated regardless of age. Although the risk of urinary tract cancer in NVH patients is low, clinically significant cancers are detected below the age threshold for referral for investigation. Patient summary This study highlights the requirement to investigate all patients with visible blood in the urine and an age threshold of ≥60 yr, as recommended in some guidelines, as the investigation of nonvisible blood in the urine will miss a significant number of urinary tract cancers. Patient preference is important, and evidence that patients are willing to submit to investigation should be considered in reaching a consensus recommendation for the investigation of haematuria. International consensus to guide that patients will benefit from investigation should be developed. [ABSTRACT FROM AUTHOR]

To improve the photophysical performance of colloidal quantum dots for laser applications, sophisticated core/shell geometries have been developed. Typically, a wider bandgap semiconductor is added as a shell to enhance the gain from the quantum-dot core. This shell is designed to electronically isolate the core, funnel excitons to it, and reduce nonradiative Auger recombination. However, the shell could also potentially provide a secondary source of gain, leading to further versatility in these materials. Here we develop high-quality quantum-dot ring lasers that not only exhibit lasing from both the core and the shell but also the ability to switch between them. We fabricate ring resonators (with quality factors up to ~2500) consisting only of CdSe/CdS/ZnS core/shell/shell quantum dots using a simple template-stripping process. We then examine lasing as a function of the optical excitation power and ring radius. In resonators with quality factors >1000, excitons in the CdSe cores lead to red lasing with thresholds at ~25 µJ/cm². With increasing power, green lasing from the CdS shell emerges (>100 µJ/cm²) and then the red lasing begins to disappear (>250 µJ/cm²). We present a rate-equation model that can explain this color switching as a competition between exciton localization into the core and stimulated emission from excitons in the shell. Moreover, by lowering the quality factor of the cavity we can engineer the device to exhibit only green lasing. The mechanism demonstrated here provides a potential route toward color-switchable quantum-dot lasers. [ABSTRACT FROM AUTHOR]

Background: Haematuria is a common finding in general practice which requires visual inspection of the bladder by cystoscopy as well as upper tract imaging. In addition, patients with non-muscle invasive bladder cancer (NMIBC) often require surveillance cystoscopy as often as three monthly depending on disease risk. However, cystoscopy is an invasive procedure which is uncomfortable, requires hospital attendance and is associated with a risk of urinary tract infection. We have developed the UroMark assay, which can detect 150 methylation specific alteration specific to bladder cancer using DNA from urinary sediment cells.Methods: DETECT I and DETECT II are two multi-centre prospective observational studies designed to conduct a robust validation of the UroMark assay. DETECT I will recruit patients having diagnostic investigations for haematuria to determine the negative predictive value of the UroMark to rule out the presence of bladder cancer. DETECT II will recruit patients with new or recurrent bladder cancer to determine the sensitivity of the UroMark in detecting low, intermediate and high grade bladder cancer. NMIBC patients in DETECT II will be followed up with three monthly urine sample collection for 24 months while having surveillance cystoscopy. DETECT II will include a qualitative analysis of semi-structured interviews to explore patients' experience of being diagnosed with bladder cancer and having cystoscopy and a urinary test for bladder cancer surveillance. Results of the UroMark will be compared to cystoscopy findings and histopathological results in patients with bladder cancer.Discussion: A sensitive and specific urinary biomarker will revolutionise the haematuria diagnostic pathway and surveillance strategies for NMIBC patients. None of the six approved US Food and Drug Administration urinary test are recommended as a standalone test. The UroMark assay is based on next generation sequencing technology which interrogates 150 loci and represents a step change compared to other biomarker panels. This enhances the sensitivity of the test and by using a random forest classifier approach, where the UroMark results are derived from a cut off generated from known outcomes of previous samples, addresses many shortcomings of previous assays.Trial Registration: Both trails are registered on clinicaltrials.gov.DetectI: NCT02676180 (18th December 2015).Detect Ii: NCT02781428 (11th May 2016). [ABSTRACT FROM AUTHOR]

Background: Epigenetic heterogeneity within a tumour can play an important role in tumour evolution and the emergence of resistance to treatment. It is increasingly recognised that the study of DNA methylation (DNAm) patterns along the genome - so-called 'epialleles' - offers greater insight into epigenetic dynamics than conventional analyses which examine DNAm marks individually. Results: We have developed a Bayesian model to infer which epialleles are present in multiple regions of the same tumour. We apply our method to reduced representation bisulfite sequencing (RRBS) data from multiple regions of one lung cancer tumour and a matched normal sample. The model borrows information from all tumour regions to leverage greater statistical power. The total number of epialleles, the epiallele DNAm patterns, and a noise hyperparameter are all automatically inferred from the data. Uncertainty as to which epiallele an observed sequencing read originated from is explicitly incorporated by marginalising over the appropriate posterior densities. The degree to which tumour samples are contaminated with normal tissue can be estimated and corrected for. By tracing the distribution of epialleles throughout the tumour we can infer the phylogenetic history of the tumour, identify epialleles that differ between normal and cancer tissue, and define a measure of global epigenetic disorder. Conclusions: Detection and comparison of epialleles within multiple tumour regions enables phylogenetic analyses, identification of differentially expressed epialleles, and provides a measure of epigenetic heterogeneity. R code is available at github.com/james-e-barrett. [ABSTRACT FROM AUTHOR]

In the core of a brain infarct, loss of neuronal function is followed by neuronal death within minutes. In an area surrounding the core (penumbra), some perfusion remains. Here, neurons initially remain structurally intact, but massive synaptic failure strongly reduces neural activity. Activity in the penumbra may eventually recover or further deteriorate toward massive cell death. Besides activity recovery, return of brain functioning requires restoration of connectivity. However, low activity has been shown to initiate compensatory mechanisms that affect network connectivity. We investigated the effect of transient hypoxia and compensatory mechanisms on activity and functional connectivity using cultured cortical networks on multielectrode arrays. Networks were exposed to hypoxia of controlled depth (10–90% of normoxia) and duration (6–48 h). First, we determined how hypoxic depth and duration govern activity recovery. Then, we investigated connectivity changes during and after hypoxic incidents, mild enough for activity to recover. Shortly after hypoxia onset, activity and connectivity decreased. Following 4–6 h of ongoing hypoxia, we observed partial recovery. Only if the hypoxic burden was limited did connectivity show further recovery upon return to normoxia. Partial recovery during hypoxia was dominated by restored baseline connections, rather than newly formed ones. Baseline strengths of surviving (persisting or recovered) and lost connections did not differ nor did baseline activity at their “presynaptic” electrodes. However, “postsynaptic” electrodes of surviving connections were significantly more active during baseline than those of lost connections. This implies that recovery during hypoxia reflects an effective mechanism to restore network activity, which does not necessarily conserve prehypoxia connectivity. NEW & NOTEWORTHY Hypoxia reduced the firing rates of cultured neurons. Depending on hypoxic depth and duration, activity recovered during hypoxia and upon return to normoxia. Recovery (partial) during hypoxia was associated with restored baseline connections rather than newly formed ones. Predominantly, baseline connections with most active postsynaptic electrodes recovered, supporting the notion of effective activity homeostasis. This compensatory mechanism remained effective during ~20 h of hypoxia. Beyond 20 h of compensation, loss of activity and connectivity became irreversible. [ABSTRACT FROM AUTHOR]

Background: Bladder cancer (BC) is one of the most common cancers in the western world and ranks as the most expensive to manage, due to the need for cystoscopic examination. BC shows frequent changes in DNA methylation, and several studies have shown the potential utility of urinary biomarkers by detecting epigenetic alterations in voided urine. The aim of this study is to develop a targeted bisulfite next-generation sequencing assay to diagnose BC from urine with high sensitivity and specificity. Results: We defined a 150 CpG loci biomarker panel from a cohort of 86 muscle-invasive bladder cancers and 30 normal urothelium. Based on this panel, we developed the UroMark assay, a next-generation bisulphite sequencing assay and analysis pipeline for the detection of bladder cancer from urinary sediment DNA. The 150 loci UroMark assay was validated in an independent cohort (n = 274, non-cancer (n = 167) and bladder cancer (n = 107)) voided urine samples with an AUC of 97%. The UroMark classifier sensitivity of 98%, specificity of 97% and NPV of 97% for the detection of primary BC was compared to non-BC urine. Conclusions: Epigenetic urinary biomarkers for detection of BC have the potential to revolutionise the management of this disease. In this proof of concept study, we show the development and utility of a novel high-throughput, next-generation sequencing-based biomarker for the detection of BC-specific epigenetic alterations in urine. [ABSTRACT FROM AUTHOR]

The media can reflect social opinion and influence debate and policy. Wild vertebrate welfare issues are regularly reported in the media, but there has been no study of the type and frequency of their coverage. We compiled a list of potential wild vertebrate welfare issues in the United Kingdom, recording how often each issue was mentioned in the media during 2014. Lethal wildlife management issues were most frequently reported, whereas issues that received little coverage included marine debris, commercial fishing, and pollution. Overall, the media tended more frequently to report welfare issues that involved intent to harm an animal, were illegal, or occurred in the terrestrial environment. Insofar as media reporting may lead to improvements in the welfare of wild animals, greater effort may be required to provoke media interest in welfare issues that do not involve intent to harm, are legal, or occur in marine environments. [ABSTRACT FROM AUTHOR]

We present a conceptual framework that can be used to assign risk bands to inhaled low aspect ratio nanoparticles starting from exposure bands assigned to a specific exposure situation. The framework mimics a basic physiological scheme that captures the essential mechanisms of fate and toxicity of inhaled nanoparticles and is composed of several models and rules that estimate the result of the following processes: the deposition of particles in the respiratory tract, their (de-)agglomeration, lung burden and clearance, their diffusion through the lung mucus layer, translocation and cellular uptake and local and systemic toxicity. Each model is based on a set of particle’s physicochemical properties, including the size and size distribution(s), the zeta potential (or net charge at a specific pH), the surface hydrophobicity or hydrophilicity, the conduction band energy (for metals, metal oxides, quantum dots, etc.) and the solubility at a specific pH. The framework takes the exposure bands as input and predicts, using the above-mentioned models, an internal dose band (module 1). Module 2 assigns a relative hazard ranking depending on the region of particle deposition in the respiratory tract, the likelihood of uptake and whether the toxicological effects are assumed to be local and/or systemic. By combining the results of Module 1 and 2, the framework provides a relative risk ranking. [ABSTRACT FROM AUTHOR]

The assessment of blood pressure (BP) can be challenging in children, especially in very young individuals, due to their variable body size and lack of cooperation. In the absence of data relating BP with cardiovascular outcomes in children, there is a need to convert absolute BP values (in mmHg) into age-, gender- and height appropriate BP percentiles or Z-scores in order to compare a patient's BP with the BP of healthy children of the same age, but also of children of different ages. Traditionally, the interpretation of BP has been based mainly on the assessment of the BP level obtained by office, home or 24-h BP monitoring. Recent studies suggest that it is not only BP level (i.e. average BP) but also BP variability that is clinically important for the development of target organ damage, including the progression of chronic kidney disease. In this review we describe current methods to evaluate of BP level, outline available methods for BP variability assessment and discuss the clinical consequences of BP variability, including its potential role in the management of hypertension. [ABSTRACT FROM AUTHOR]

Improvement of neuronal recovery in the ischemic penumbra around a brain infarct has a large potential to advance clinical recovery of patients with acute ischemic stroke. However, pathophysiological mechanisms leading to either recovery or secondary damage in the penumbra are not completely understood. We studied neuronal dynamics in a model system of the penumbra consisting of networks of cultured cortical neurons exposed to controlled levels and durations of hypoxia. Short periods of hypoxia (pO2≈20mmHg) reduced spontaneous activity, due to impeded synaptic function. After ≈6 hours, activity and connectivity partially recovered, even during continuing hypoxia. If the oxygen supply was restored within 12 hours, changes in network connectivity were completely reversible. For longer periods of hypoxia (12–30 h), activity levels initially increased, but eventually decreased and connectivity changes became partially irreversible. After ≈30 hours, all functional connections disappeared and no activity remained. Since this complete silence seemed unrelated to hypoxic depths, but always followed an extended period of low activity, we speculate that irreversible damage (at least partly) results from insufficient neuronal activation. This opens avenues for therapies to improve recovery by neuronal activation. [ABSTRACT FROM AUTHOR]

There is an increasing amount of data indicating that primary hypertension (PH) is not only a hemodynamic phenomenon but also a complex syndrome involving abnormal fat tissue distribution, over-activity of the sympathetic nervous system (SNS), metabolic abnormalities, and activation of the immune system. In children, PH usually presents with a typical phenotype of disturbed body composition, accelerated biological maturity, and subtle immunological and metabolic abnormalities. This stage of the disease is potentially reversible. However, long-lasting over-activity of the SNS and immuno-metabolic alterations usually lead to an irreversible stage of cardiovascular disease. We describe an intermediate phenotype of children with PH, showing that PH is associated with accelerated development, i.e., early premature aging of the immune, metabolic, and vascular systems. The associations and determinants of hypertensive organ damage, the principles of treatment, and the possibility of rejuvenation of the cardiovascular system are discussed. [ABSTRACT FROM AUTHOR]

Arterial hypertension (HTN) in children after kidney transplantation is an important risk factor not only for graft loss but also for cardiovascular morbidity and mortality. The prevalence of posttransplant HTN ranges between 60% and 90%. The etiology of posttransplant HTN is multifactorial and includes residual chronic native kidney disease, immunosuppressive therapy, and chronic allograft dysfunction among other causes. Clinic blood pressure (BP) should be measured at each outpatient visit. However, ambulatory blood pressure monitoring (ABPM) is the gold standard method for BP evaluation in children after kidney transplantation, as it often reveals masked and nocturnal HTN; given this, it should be regularly performed in each transplanted child. All classes of antihypertensive drugs are used in the treatment of posttransplant HTN because it has never been proven that one class is better than another. However, in several retrospective studies, the use of calcium channel blockers is associated with better graft function. The optimal target BP for transplanted children is still a matter of debate; it is recommended to target the same BP as for healthy children, that is, <95th percentile. Control of HTN in transplanted children remains poor – only 20%–50% of treated children have normal BP. There is a great potential for improvement of antihypertensive treatment that could potentially result in improvement of both graft and patient survival in children after kidney transplantation. [ABSTRACT FROM AUTHOR]

Background: Long non-coding RNAs (lncRNAs) have been claimed as key molecular players in gene expression regulation, being involved in diverse epigenetic processes. They are aberrantly expressed in various tumors, but their exact role in bladder cancer is still obscure. We have recently found a major role of the Polycomb repression complex in recurrence of non-muscle-invasive bladder cancer. Here, we report the xpression of Polycomb-related lncRNAs:antisense noncoding RNA in the INK4 locus (ANRIL) and HOX antisense intergenic RNA (HOTAIR) in these tumors. Findings: We studied a dataset of non-invasive bladder cancer samples by quantitative reverse transcription PCR (RT-qPCR) and analyzed also invasive bladder cancer samples using TCGA data. Our results showed that, while ANRIL seemed not to have a determining role, an increased HOTAIR expression appeared in recurrent and high-graded tumors associated with poor prognosis. In addition, through genome-wide transcriptome analyses, we observed that HOTAIR-EZH2-complex-regulated genes can efficiently discriminate between non-tumoral, recurrent, and non-recurrent bladder cancer samples. We also observed a significant correlation between EZH2 and HOTAIR expression levels. Using overexpression, knockdown, and pharmacological approaches in bladder cancer cell lines, we also observed that EZH2 regulates HOTAIR expression. Conclusions: Our findings indicate that HOTAIR expression has prognostic value for bladder cancer progression, recurrence, and survival and suggest that HOTAIR plays active roles in modulating the cancer epigenome, becoming an interesting candidate as a target for cancer diagnosis and therapy. The observed HOTAIR regulation by EZH2 and the possibility of modulating EZH2 activity with specific inhibitors open new possible paths to be explored in bladder cancer therapy. [ABSTRACT FROM AUTHOR]

Organic farming, a low intensity system, may offer benefits for a range of taxa, but what affects the extent of those benefits is imperfectly understood. We explored the effects of organic farming and landscape on the activity density and species density of spiders and carabid beetles, using a large sample of paired organic and conventional farms in the UK. Spider activity density and species density were influenced by both farming system and surrounding landscape. Hunting spiders, which tend to have lower dispersal capabilities, had higher activity density, and more species were captured, on organic compared to conventional farms. There was also evidence for an interaction, as the farming system effect was particularly marked in the cropped area before harvest and was more pronounced in complex landscapes (those with little arable land). There was no evidence for any effect of farming system or landscape on web-building spiders (which include the linyphiids, many of which have high dispersal capabilities). For carabid beetles, the farming system effects were inconsistent. Before harvest, higher activity densities were observed in the crops on organic farms compared with conventional farms. After harvest, no difference was detected in the cropped area, but more carabids were captured on conventional compared to organic boundaries. Carabids were more species-dense in complex landscapes, and farming system did not affect this. There was little evidence that non-cropped habitat differences explained the farming system effects for either spiders or carabid beetles. For spiders, the farming system effects in the cropped area were probably largely attributable to differences in crop management; reduced inputs of pesticides (herbicides and insecticides) and fertilisers are possible influences, and there was some evidence for an effect of non-crop plant species richness on hunting spider activity density. The benefits of organic farming may be greatest for taxa with lower dispersal abilities generally. The evidence for interactions among landscape and farming system in their effects on spiders highlights the importance of developing strategies for managing farmland at the landscape-scale for most effective conservation of biodiversity. [ABSTRACT FROM AUTHOR]

Background While ghrelin was initially related to appetite stimulation and growth hormone secretion, it also has a neuroprotective effect in neurodegenerative diseases and regulates cognitive function. The cellular basis of those processes is related to synaptic efficacy and plasticity. Previous studies have shown that ghrelin not only stimulates synapse formation in cultured cortical neurons and hippocampal slices, but also alters some of the electrophysiological properties of neurons in the hypothalamus, amygdala and other subcortical areas. However, direct evidence for ghrelin's ability to modulate the activity in cortical neurons is not available yet. In this study, we investigated the effect of acylated ghrelin on the development of the activity level and activity patterns in cortical neurons, in relation to its effect on synaptogenesis. Additionally, we quantitatively evaluated the expression of the receptor for acylated ghrelin - growth hormone secretagogue receptor-1a (GHSR-1a) during development. Results We performed electrophysiology and immunohistochemistry on dissociated cortical cultures from neonates, treated chronically with acylated ghrelin. On average 76 ± 4.6% of the cortical neurons expressed GHSR-1a. Synapse density was found to be much higher in ghrelin treated cultures than in controls across all age groups (1, 2 or 3 weeks). In all cultures (control and ghrelin treated), network activity gradually increased until it reached a maximum after approximately 3 weeks, followed by a slight decrease towards a plateau. During early developmental stages (1-2 weeks), the activity was much higher in ghrelin treated cultures and consequently, they reached the plateau value almost a week earlier than controls. Conclusions Acylated ghrelin leads to earlier network formation and activation in cultured cortical neuronal networks, the latter being a possibly consequence of accelerated synaptogenesis. [ABSTRACT FROM AUTHOR]

Control of light-matter interactions at the nanoscale has advanced fields such as quantum optics, photovoltaics and telecommunications. These advances are driven by an improved understanding of the nanoscale behaviour of light, enabled by direct observations of the local electric fields near photonic nanostructures. With the advent of metamaterials that respond to the magnetic component of light, schemes have been developed to measure the nanoscale magnetic field. However, these structures interact not only with the magnetic field, but also with the electric field of light. Here, we demonstrate the essential simultaneous detection of both electric and magnetic fields with subwavelength resolution. By explaining our measurements through reciprocal considerations, we create a route towards designing probes sensitive to specific desired combinations of electric and magnetic field components. Simultaneous access to nanoscale electric and magnetic fields will pave the way for new designs of optical nanostructures and metamaterials. [ABSTRACT FROM AUTHOR]

BACKGROUND: The diagnosis of hypertension is often unrecognized in the general paediatric and type 1 diabetes populations. Reference to a simple blood pressure table has been proposed as a screening tool for the identification of abnormal paediatric blood pressure. This simple table lists one cut-off blood pressure value for each sex and year of age, compared with the standard blood pressure tables, which list 476 abnormal and normal blood pressure values. OBJECTIVE: To determine the sensitivity and specificity of the simple blood pressure table in identifying hypertensive and abnormal (hypertensive or prehypertensive) blood pressure values in children with type 1 diabetes. METHODS: A retrospective cohort study was conducted. Data regarding baseline characteristics and blood pressure measurements were collected. Blood pressure values were categorized as nonhypertensive, prehypertensive or hypertensive using the standard and simple blood pressure tables. Sensitivity and specificity of the simple blood pressure table was determined for the identification of hypertensive and abnormal (hypertensive or prehypertensive) blood pressure values using a generalized estimating equation approach. RESULTS: The simple blood pressure table had sensitivities of 100% (95% CI 95.7% to 100%) and 100% (95% CI 97.6% to 100%), and specificities of 61.1% (95% CI 54.0% to 67.8%) and 81.3% (95% CI 74.4% to 86.6%), for the identification of hypertensive and abnormal blood pressure values, respectively. CONCLUSION: The simple blood pressure table is an effective screening tool that may enable earlier detection and timely treatment of abnormal blood pressure. [ABSTRACT FROM AUTHOR]

Abstract: Ghrelin was initially related to appetite stimulation and growth hormone secretion. However, it also has a neuroprotective effect in neurodegenerative diseases and regulates cognitive function. The cellular basis of these processes is related to synaptic efficacy and plasticity. Previous studies indicated that ghrelin has an excitatory effect on neuronal activity, and stimulates synaptic plasticity in vivo. Plasticity in the adult brain occurs in many different ways, including changes in synapse morphology and number. Therefore, we used in vitro neuronal cultures to investigate how ghrelin affects synaptogenesis. We used dissociated cortical cultures of newborn rats, chronically treated with different doses of ghrelin (0.5, 1, 1.5 and 2μM). After one-, two-, three- or four weeks cultures were immunostained for the presynaptic marker synaptophysin. In parallel, additional groups of non-treated cultures were immunostained for detection of ghrelin receptor (GHSR1). During development, GHSR1was increasingly expressed in all type of neurons, as well as the synaptophysin. Synaptic density depended on ghrelin concentration, and was much higher than in controls in all age groups. In conclusion, ghrelin leads to earlier network formation in dissociated cortical networks and an increase in number of synapses. The effect is probably mediated by GHSR1. These findings suggest that ghrelin may provide a novel therapeutic strategy for the treatment of disorders related to synaptic impairment. [Copyright &y& Elsevier]

Background: The diagnosis of hypertension (HTN)/normotension (NT) on ambulatory blood pressure monitoring (ABPM) is usually based on systolic (SBP) or diastolic blood pressure (DBP). The goal of this study was to analyze whether inclusion of mean arterial pressure (MAP) improves the detection of HTN on ABPM. Methods: We retrospectively studied ABPM records in 229 children (116 boys, median age = 15.3 years) who were referred for evaluation of HTN. A diagnosis of HTN was made if: (A) MAP or SBP or DBP was ≥1.65 SDS (95th percentile); (B) SBP or DBP was ≥1.65 SDS (95th percentile), during 24-h or daytime or night-time in both definitions. Results: Using definition A, 46/229 patients had HTN compared to definition B by which only 37/229 patients had HTN ( p = 0.001). The level of agreement between the two definitions was very good (kappa = 0.86 ± 0.04), however nine patients (19.5 %) were missed by not using MAP in the definition of HTN. These nine patients had only mild HTN with a median Z score of 1.69. Conclusions: The inclusion of MAP in the definition of ambulatory HTN significantly increased the number of hypertensive patients. MAP may be very helpful in detecting mild HTN in patients with normal/borderline SBP and DBP. [ABSTRACT FROM AUTHOR]

Epigenetic changes are frequently observed in cancer. However, their role in establishing or sustaining the malignant state has been difficult to determine due to the lack of experimental tools that enable resetting of epigenetic abnormalities. To address this, we applied induced pluripotent stem cell (iPSC) reprogramming techniques to invoke widespread epigenetic resetting of glioblastoma (GBM)-derived neural stem (GNS) cells. GBM iPSCs (GiPSCs) were subsequently redifferentiated to the neural lineage to assess the impact of cancer-specific epigenetic abnormalities on tumorigenicity. GiPSCs and their differentiating derivatives display widespread resetting of common GBM-associated changes, such as DNA hypermethylation of promoter regions of the cell motility regulator TES (testis-derived transcript), the tumor suppressor cyclin-dependent kinase inhibitor 1C (CDKN1C; p57KIP2), and many polycomb-repressive complex 2 (PRC2) target genes (e.g., SFRP2). Surprisingly, despite such global epigenetic reconfiguration, GiPSC-derived neural progenitors remained highly malignant upon xenotransplantation. Only when GiPSCs were directed to nonneural cell types did we observe sustained expression of reactivated tumor suppressors and reduced infiltrative behavior. These data suggest that imposing an epigenome associated with an alternative developmental lineage can suppress malignant behavior. However, in the context of the neural lineage, widespread resetting of GBM-associated epigenetic abnormalities is not sufficient to override the cancer genome. [ABSTRACT FROM AUTHOR]

A typical property of isolated cultured neuronal networks of dissociated rat cortical cells is synchronized spiking, called bursting, starting about one week after plating, when the dissociated cells have sufficiently sent out their neurites and formed enough synaptic connections. This paper is the third in a series of three on simulation models of cultured networks. Our two previous studies [26, 27] have shown that random recurrent network activity models generate intra- and interbursting patterns similar to experimental data. The networks were noise or pacemaker-driven and had Izhikevich-neuronal elements with only short-term plastic (STP) synapses (so, no long-term potentiation, LTP, or depression, LTD, was included). However, elevated pre-phases (burst leaders) and after-phases of burst main shapes, that usually arise during the development of the network, were not yet simulated in sufficient detail. This lack of detail may be due to the fact that the random models completely missed network topology .and a growth model. Therefore, the present paper adds, for the first time, a growth model to the activity model, to give the network a time dependent topology and to explain burst shapes in more detail. Again, without LTP or LTD mechanisms. The integrated growth-activity model yielded realistic bursting patterns. The automatic adjustment of various mutually interdependent network parameters is one of the major advantages of our current approach. Spatio-temporal bursting activity was validated against experiment. Depending on network size, wave reverberation mechanisms were seen along the network boundaries, which may explain the generation of phases of elevated firing before and after the main phase of the burst shape. In summary, the results show that adding topology and growth explain burst shapes in great detail and suggest that young networks still lack/do not need LTP or LTD mechanisms. [ABSTRACT FROM AUTHOR]

Abstract: Although intensive forestry practices have greatly reduced the biodiversity of native woodland, sympathetic management offers much potential to reverse these negative trends. We tested, using a species-rich group, whether woodland conservation management practices could be of overall benefit, for threatened generalists and specialists alike. Our landscape-scale light-trap experiment compared presence/absence, abundance and species richness of macro-moths at 36 repeatedly sampled sites from six experimental ‘woodland management’ treatments. We recorded 11,670 individuals from 265 species. Our results show that the sheltered, dark, humid, late-successional, high deciduous forest biotope is characterised by high numbers of both individuals and species of moth, and is especially important for some scarce and specialist species of conservation concern. Coppicing and ride widening, which open up dense forest structures, are also valuable woodland conservation tools for macro-moths. Specifically, we show that the mechanism behind the pattern of increased species richness at the woodland-scale involved an increased structural and hence increased micro-climatic and resource diversity for species with an affinity for more open biotopes. This benefits generalist species of conservation concern. Additionally, we show that woodland area is an important factor affecting both moth abundance and species richness in coppiced plots, especially so for nationally declining and severely declining species, suggesting that larger woodlands offer the best opportunities to increase biodiversity through active coppice management. Based on these complementary findings we recommend zoning woodland conservation management practices to take into account the differential value of successional stages for different ecological groups of Lepidoptera. [Copyright &y& Elsevier]

Summary: Eighty children with nephrotic syndrome underwent lumbar spine densitometry and vertebral morphometry soon after glucocorticoid initiation. We found an inverse relationship between glucocorticoid exposure and spine areal bone mineral density (BMD) Z-score and a low rate of vertebral deformities (8%). Introduction: Vertebral fractures are an under-recognized complication of childhood glucocorticoid-treated illnesses. Our goal was to study the relationships among glucocorticoid exposure, lumbar spine areal BMD (LS BMD), and vertebral shape in glucocorticoid-treated children with new-onset nephrotic syndrome. Methods: Lateral thoracolumbar spine radiography and LS BMD were performed in 80 children with nephrotic syndrome (median age 4.4 years; 46 boys) within the first 37 days of glucocorticoid therapy. Genant semiquantitative grading was used as the primary method for vertebral morphometry; the algorithm-based qualitative (ABQ) method was used for secondary vertebral deformity analysis. Results: Six of the 78 children with usable radiographs (8%; 95% confidence interval 4 to 16%) manifested a single Genant grade 1 deformity each. All deformities were mild anterior wedging (two at each of T6, T7, and T8). Four of the 78 children (5%; 95% confidence interval 2 to 13%) showed one ABQ sign of fracture each (loss of endplate parallelism; two children at T6 and two at T8). Two of the children with ABQ signs also had a Genant grade 1 deformity in the same vertebral body. None of the children with a Genant or ABQ deformity reported back pain. An inverse relationship was identified between LS BMD Z-score and glucocorticoid exposure. Conclusions: Although we identified an inverse relationship between steroid exposure and LS BMD soon after glucocorticoid initiation for childhood nephrotic syndrome, there was only a low rate of vertebral deformities. The clinical significance of these findings requires further study. [ABSTRACT FROM AUTHOR]

BMC Research Notes recently published a research article regarding the use of ligated DNA extracted from formalin-fixed paraffin embedded (FFPE) tissue on the Illumina Infinium methylation platform--"Interpretation of genome-wide infinium methylation data from ligated DNA in formalin-fixed, paraffin-embedded paired tumor and normal tissue" Jasmine et al. BMC Research Notes 2012, 5:117. This article repeatedly refers to our previous work and concludes that methylation data obtained from ligated FFPE extracted DNA should be used with great caution. In this Discussion we review the data analysis performed in Jasmine et al's paper and suggest limitations which subsequently lead the authors to draw what we believe are incorrect conclusions. Moreover, we continue to analyse genome-wide methylation data from DNA extracted from FFPE tissue successfully on both the HumMeth27 and 450 K arrays. [ABSTRACT FROM AUTHOR]

Rhythmic bursting is the most striking behavior of cultured cortical networks and may start in the second week after plating. In this study, we focus on the intervals between spontaneously occurring bursts, and compare experimentally recorded values with model simulations. In the models, we use standard neurons and synapses, with physiologically plausible parameters taken from literature. All networks had a random recurrent architecture with sparsely connected neurons. The number of neurons varied between 500 and 5,000. We find that network models with homogeneous synaptic strengths produce asynchronous spiking or stable regular bursts. The latter, however, are in a range not seen in recordings. By increasing the synaptic strength in a (randomly chosen) subset of neurons, our simulations show interburst intervals (IBIs) that agree better with in vitro experiments. In this regime, called weakly synchronized, the models produce irregular network bursts, which are initiated by neurons with relatively stronger synapses. In some noise-driven networks, a subthreshold, deterministic, input is applied to neurons with strong synapses, to mimic pacemaker network drive. We show that models with such 'intrinsically active neurons' (pacemaker-driven models) tend to generate IBIs that are determined by the frequency of the fastest pacemaker and do not resemble experimental data. Alternatively, noise-driven models yield realistic IBIs. Generally, we found that large-scale noise-driven neuronal network models required synaptic strengths with a bimodal distribution to reproduce the experimentally observed IBI range. Our results imply that the results obtained from small network models cannot simply be extrapolated to models of more realistic size. Synaptic strengths in large-scale neuronal network simulations need readjustment to a bimodal distribution, whereas small networks do not require such changes. [ABSTRACT FROM AUTHOR]

Abstract: Agri-environment schemes are the main policy instruments for reversing declines in farmland biodiversity, but there is scope for improvement. Within an intensive agricultural landscape, a mark-release-recapture experiment was used to investigate the relative effects on the number of adults of 23 moth species of two landscape features (wide field margins and hedgerow trees) that may feature within agri-environment schemes. Species belonged to either the grass/herb- or shrub/tree-feeders’ guild. Margin width did not affect the number of individuals, in either guild. Numbers of shrub/tree-feeding individuals were higher at sites with hedgerow trees, but not so for this guild''s two most mobile species, nor for the grass/herb-feeders, which were 30% more mobile. The results show that hedgerow trees increase adult moth numbers because they are shelter-providing resources in typically exposed agricultural landscapes, rather than due to being larval food resources. Hedgerow tree retention and establishment options should be part of efficient general agri-environment schemes, while grassy wide field margins may not always deliver gains, at least not when implemented at the field-scale. [Copyright &y& Elsevier]

Childhood HTN (hypertension) has become a widely investigated topic within the last decade due to its increasing prevalence. In the present review, we examine new developments and trends that have significantly contributed to aetiology, diagnosis, evaluation and management of childhood HTN. Many recent reports document an increasing prevalence of HTN, mainly essential HTN, in children worldwide. This is probably related to the increase of childhood obesity, although obesity is not the only factor. Evidence has been accumulating to suggest a rather complex interplay between obesity, uric acid level, dietary sodium intake, inflammation, inheritance and other factors, which lead to increased risk of developing HTN in childhood and adulthood. The detection and monitoring of HTN has significantly improved with the use of ABPM (ambulatory blood pressure monitoring), which allows not only for a more accurate classification and staging of HTN, but also for the calculation of more sophisticated parameters such as the AASI (ambulatory arterial stiffness index). Measurement of arterial stiffness enables assessment of arterial dysfunction, which may precede structural vascular changes evaluated by carotid intima media thickness. Sustained HTN eventually leads to end-organ damage [LVH (left ventricular hypertrophy), central nervous system], which in turn increases the risk of cardiovascular morbidity and mortality. New developments in childhood HTN, as outlined in the present review, will hopefully contribute to better screening and management of HTN in children. [ABSTRACT FROM AUTHOR]

One of the most specific and exhibited features in the electrical activity of dissociated cultured neural networks (NNs) is the phenomenon of synchronized bursts, whose profiles vary widely in shape, width and firing rate. On the way to understanding the organization and behavior of biological NNs, we reproduced those features with random connectivity network models with 5,000 neurons. While the common approach to induce bursting behavior in neuronal network models is noise injection, there is experimental evidence suggesting the existence of pacemaker-like neurons. In our simulations noise did evoke bursts, but with an unrealistically gentle rising slope. We show that a small subset of ‘pacemaker’ neurons can trigger bursts with a more realistic profile. We found that adding pacemaker-like neurons as well as adaptive synapses yield burst features (shape, width, and height of the main phase) in the same ranges as obtained experimentally. Finally, we demonstrate how changes in network connectivity, transmission delays, and excitatory fraction influence network burst features quantitatively. [ABSTRACT FROM AUTHOR]

Abstract: Field margins have been widely advocated as a means of integrating agronomic and biodiversity objectives and are included in agri-environment schemes across Europe. However, information on the long-term development of field margin plant communities remains limited. We describe a long-term experiment on the effects of field margin management on biodiversity and weed species. Swards were established by natural regeneration or sowing a grass and wildflower seed mixture, and treatments manipulated the frequency and timing of mowing, application of herbicide and leaving of hay. Vegetation was monitored to evaluate the extent to which early conclusions remained valid after 13years. Although early successional trends suggested that naturally regenerated swards would rapidly become dominated by pernicious perennial weeds, and that sown swards would exclude such species, neither was true in the longer term. Sown swards were eventually invaded by unsown perennials, but they remained distinct from naturally regenerated swards. Plant species richness declined throughout the experiment. Annuals were lost most rapidly from sown swards but, under natural regeneration, loss could be modified by mowing. Perennial species initially increased during natural regeneration before stabilising. In sown swards they declined under all treatments. Species richness in naturally regenerating swards was promoted initially by mowing twice annually. After 13years, timing and frequency of mowing had no significant effect on species richness although it still influenced sward composition. Leaving cut hay lying produced species-poor swards. We conclude that the choice of establishment and management methods for arable field margins significantly affects the long-term conservation value of the swards. [Copyright &y& Elsevier]

Learning, or more generally, plasticity may be studied using cultured networks of rat cortical neurons on multi electrode arrays. Several protocols have been proposed to affect connectivity in such networks. One of these protocols, proposed by Shahaf and Marom, aimed to train the input-output relationship of a selected connection in a network using slow electrical stimuli. Although the results were quite promising, the experiments appeared difficult to repeat and the training protocol did not serve as a basis for wider investigation yet. Here, we repeated their protocol, and compared our 'learning curves' to the original results. Although in some experiments the protocol did not seem to work, we found that on average, the protocol showed a significantly improved stimulus response indeed. Furthermore, the protocol always induced functional connectivity changes that were much larger than changes that occurred after a comparable period of random or no stimulation. Finally, our data shows that stimulation at a fixed electrode induces functional connectivity changes of similar magnitude as stimulation through randomly varied sites; both larger than spontaneous connectivity fluctuations. We concluded that slow electrical stimulation always induced functional connectivity changes, although uncontrolled. The magnitude of change increased when we applied the adaptive (closed-loop) training protocol. We hypothesize that networks develop an equilibrium between connectivity and activity. Induced connectivity changes depend on the combination of applied stimulus and initial connectivity. Plain stimuli may drive networks to the nearest equilibrium that accommodates this input, whereas adaptive stimulation may direct the space for exploration and force networks to a new balance, at a larger distance from the initial state. [ABSTRACT FROM AUTHOR]

The article discusses an atypical case of acute kidney injury. Topics discussed include Hemolytic uremic syndrome (HUS) as an acute kidney injury associated with irreversible renal and central nervous system (CNS) complications, HUS caused by regulation, of defective complement alternative pathway (CAP) and investigating Coombs test and low C3 complement level as diagnostic criteria for HUS.

The article focuses on study related to multiple myeloma and role of global hypomethylation in myeloma which is associated with poor prognosis. Topics discussed include methylation patterns which include global hypomethylation in asymptomatic myeloma and hypermethylation in symptomatic myeloma; role of transcription start site in regulation of gene expression; and relevance of gene promoter hypomethylation to survival outcomes in myeloma patients.

UTI are common in renal Tx recipients and may significantly impact on the graft function. The aim of our study was to evaluate the prevalence, risk factors, and significance of UTI in Tx children. We performed a retrospective cross-sectional study of 76 Tx patients, median age at Tx was 13.4 yr. Twenty-one of 76 (28%) patients developed at least one UTI during the mean follow-up time of 3.3 ± 2.0 yr post-Tx. The first UTI occurred at a median of 160 days post-Tx. The RR of having UTI was significantly higher in patients with the primary diagnosis of obstructive uropathy (RR = 2.6, 95th CI = 1.1–6.0, p = 0.032), history of PN pre Tx (RR = 2.7, 95th CI = 1.3–5.4, p = 0.009) and pre Tx VUR (RR = 2.2, 95th CI = 1.1–4.5, p = 0.045). These three factors also significantly decreased the infection-free survival time to the first UTI. Most UTI caused reversible acute allograft dysfunction, but the long-term graft function could not be reliably assessed with SCr. In conclusion, UTI occurred in 28% of pediatric Tx recipients, mostly during the first year post-Tx despite antibiotic prophylaxis. The diagnosis of obstructive uropathy, history of UTI and VUR prior to Tx were significant risk factors. [ABSTRACT FROM AUTHOR]

Abstract: Most arable field margins are sown grass strips which are limited in the avian food resources they offer but potentially supply grass seeds and, depending on the complexity of the sward structure, a range of arthropods. Adding perennial forbs to a grass mixture provides more diverse plant and invertebrate food resources for birds. The availability of seeds and invertebrates on uncropped margins is strongly influenced by management, particularly cutting, cultivation and herbicide use. Cropped margins with reduced chemical inputs and wild bird cover crops can provide relatively high food resources compared with a conventionally managed crop. However, resources are only present until harvest, their plant communities are relatively poor and arthropod abundance is usually lower than in uncropped margins. The best winter food supplies for birds will be provided by options that create seed-rich habitats in winter. The best summer food supplies will be provided by options that create a structurally and floristically diverse sward. The least valuable margin in terms of food resources is a grass-only strip. On an area-for-area basis, field margins will potentially produce food resources for birds more cost-effectively than whole farm practices such as organic farming, though the value of margins will depend on their management and the diversity of margin types at a farm scale. Because no single margin type can provide the optimum year-round food supply, different types of margins should be incorporated at the farm level, but appropriate management (and further innovation in margin design) is needed to deliver their benefits. Field margins should be managed in conjunction with adjacent boundary features, especially hedgerows, to create complex structures that maximise nesting opportunities for birds and create habitats for a range of invertebrates. [Copyright &y& Elsevier]

The current guidelines recommend a dosage of prednisone of 60 mg/m2 body surface area per day (BSA PRED) for the initial therapy of nephrotic syndrome (NS). Alternatively, a dosage of 2 mg/kg body weight per day (W PRED) can be used. We hypothesized that the BSA PRED and W PRED are not equivalent and analyzed the differences between BSA PRED calculated with various formulas for body surface area (BSA), W PRED and the dose of prednisone prescribed for our patients. We performed a retrospective chart review of the patients at their initial presentation of NS. Thirty-three children were included, of median age 3.34 years at presentation. The W PRED was significantly lower than BSA PRED ( P < 0.05), with a median W PRED:BSA PRED ratio of 0.85 [interquartile range (IQR) 0.8 to 0.9]. The difference between W PRED and BSA PRED decreased proportionally to patients’ weights up to 30 kg. No differences were noted between the various BSA formulas using both weight and height for the calculation of BSA. The Bland–Altman analysis showed a proportional error between W PRED and BSA PRED up to the average daily dose of 60 mg, with a mean bias of 0.86 (95% limits of agreement = 0.68 to 1.05). Ten out of the 33 patients (30%) were given a lower than recommended BSA PRED dose by more than 5 mg/day. In conclusion, the dosage of prednisone at 2 mg/kg per day versus 60 mg/m2 per day is not equivalent for patients with weights <30 kg and/or dose <60 mg/day. [ABSTRACT FROM AUTHOR]

We have studied the effect that learning a new stimulus-response (SR) relationship had within a neuronal network cultured on a multielectrode array. For training, we applied repetitive focal electrical stimulation delivered at a low rate ((us). Stimulation was withdrawn when a desired SR success ratio was achieved. It has been shown elsewhere, and we verified that this training algorithm, named conditional repetitive stimulation (CRS), can be used to strengthen an initially weak SR. So far, it remained unclear what the role of the rest of the network during learning was. We therefore studied the effect of CRS on spontaneously occurring network bursts. To this end, we made profiles of the firing rates within network bursts. We have earlier shown that these profiles change shape on a time base of several hours during spontaneous development. The show here that profiles of summed activity, called burst profiles, changed shape at an increased rate during CRS. This suggests that the whole network was involved in making the changes necessary to incorporate the desired SR relationship. However, a local (path-specific) component to learning was also found by analyzing profiles of single-electrode-activity phase profiles. Phase profiles that were not part of the SR relationship changed far less during CRS than the phase profiles of the electrodes that were part of the SR relationship. Finally, the manner in which phase profiles changed shape varied and could not be linked to the SR relationship. [ABSTRACT FROM AUTHOR]

How best to optimize the biodiversity gain from agri-environment schemes (AES) has recently been identified as a key policy-relevant question. Here, the effects of two features of lowland agricultural landscapes on the abundance and diversity of larger moths are contrasted. Although both features bring about positive effects, hedgerow trees have a larger impact than 6m wide grassy field margins. Whilst AES payments are given to create and maintain grass margins, no financial reward is currently offered for the retention of hedgerow trees. Furthermore, it was only in areas where the amount of land under AES was experimentally increased, by targeting farmers, that the presence of hedgerow trees resulted in a substantially higher abundance (+60%) and diversity (+38%) of moths. Thus, by using larger moths as bio-indicators of landscape-scale quality, it is demonstrated that improvements to the cost-effectiveness of AES could be achieved, firstly, by providing more appropriate financial rewards to farmers for different landscape features, and secondly, through landscape-scale targeting of farmers to encourage participation in AES. [Copyright &y& Elsevier]

Agri-environment schemes (AES) are widely used policy instruments intended to combat widespread biodiversity declines across agricultural landscapes. Here, using a light trapping and mark-release-recapture study at a field-scale on nine common and widespread larger moth species, we investigate the effect of wide field margins (a popular current scheme option) and the presence of hedgerow trees (a potential scheme option in England) on moth abundance. Of these, we show that wide field margins positively affected abundances, although species did not all respond in the same way. We demonstrate that this variation can be attributed to species-specific mobility characteristics. Those species for which the effect of wide margins was strongest covered shorter distances, and were more frequently recaptured at their site of first capture. This demonstrates that the standard, field-scale uptake of AES may be effective only for less mobile species. We discuss that a landscape-scale approach, in contrast, could deliver significant biodiversity gains, as our results indicate that such an approach (perhaps delivered through targeting farmers to join AES) would be effective for the majority of wider countryside species, irrespective of their mobility level. [Copyright &y& Elsevier]