Failure of a patient-centered intervention to substantially increase the identification and referral for-treatment of ambulatory emergency department patients with occult psychiatric conditions: a randomized trial [ISRCTN61514736]

BACKGROUND: We previously demonstrated that a computerized psychiatric screening interview (the PRIME-MD) can be used in the Emergency Department (ED) waiting room to identify patients with mental illness. In that trial, however, informing the ED physician of the PRIME-MD results did not increase the frequency of psychiatric diagnosis, consultation or referral. We conducted this study to determine whether telling the patient and physician the PRIME-MD result would result in the majority of PRIME-MD-diagnosed patients being directed toward treatment for their mental illness. METHODS: In this single-site RCT, consenting patients with non-specific somatic chief complaints (e.g., fatigue, back pain, etc.) completed the computerized PRIME-MD in the waiting room and were randomly assigned to one of three groups: patient and physician told PRIME-MD results, patient told PRIME-MD results, and neither told PRIME-MD results. The main outcome measure was the percentage of patients with a PRIME-MD diagnosis who received a psychiatric consultation or referral from the ED. RESULTS: 183 (5% of all ED patients) were approached. 123 eligible patients consented to participate, completed the PRIME-MD and were randomized. 95 patients had outcomes recorded. 51 (54%) had a PRIME-MD diagnosis and 8 (16%) of them were given a psychiatric consultation or referral in the ED. While the frequency of consultation or referral increased as the intervention's intensity increased (tell neither = 11% (1/9), tell patient 15% (3/20), tell patient and physician 18% (4/22)), no group came close to the 50% threshold we sought. For this reason, we stopped the trial after an interim analysis. CONCLUSION: Patients willingly completed the PRIME-MD and 54% had a PRIME-MD diagnosis. Unfortunately, at our institution, informing the patient (and physician) of the PRIME-MD results infrequently led to the patient being directed toward care for their psychiatric condition

X-ray emission from isolated neutron stars

X-ray emission is a common feature of all varieties of isolated neutron stars (INS) and, thanks to the advent of sensitive instruments with good spectroscopic, timing, and imaging capabilities, X-ray observations have become an essential tool in the study of these objects. Non-thermal X-rays from young, energetic radio pulsars have been detected since the beginning of X-ray astronomy, and the long-sought thermal emission from cooling neutron star's surfaces can now be studied in detail in many pulsars spanning different ages, magnetic fields, and, possibly, surface compositions. In addition, other different manifestations of INS have been discovered with X-ray observations. These new classes of high-energy sources, comprising the nearby X-ray Dim Isolated Neutron Stars, the Central Compact Objects in supernova remnants, the Anomalous X-ray Pulsars, and the Soft Gamma-ray Repeaters, now add up to several tens of confirmed members, plus many candidates, and allow us to study a variety of phenomena unobservable in "standard'' radio pulsars.Comment: Chapter to be published in the book of proceedings of the 1st Sant Cugat Forum on Astrophysics, "ICREA Workshop on the high-energy emission from pulsars and their systems", held in April, 201

Information Transmission in Cercal Giant Interneurons Is Unaffected by Axonal Conduction Noise

What are the fundamental constraints on the precision and accuracy with which nervous systems can process information? One constraint must reflect the intrinsic “noisiness” of the mechanisms that transmit information between nerve cells. Most neurons transmit information through the probabilistic generation and propagation of spikes along axons, and recent modeling studies suggest that noise from spike propagation might pose a significant constraint on the rate at which information could be transmitted between neurons. However, the magnitude and functional significance of this noise source in actual cells remains poorly understood. We measured variability in conduction time along the axons of identified neurons in the cercal sensory system of the cricket Acheta domesticus, and used information theory to calculate the effects of this variability on sensory coding. We found that the variability in spike propagation speed is not large enough to constrain the accuracy of neural encoding in this system

Genome-wide survey and analysis of microsatellites in nematodes, with a focus on the plant-parasitic species Meloidogyne incognita

<p>Abstract</p> <p>Background</p> <p>Microsatellites are the most popular source of molecular markers for studying population genetic variation in eukaryotes. However, few data are currently available about their genomic distribution and abundance across the phylum Nematoda. The recent completion of the genomes of several nematode species, including <it>Meloidogyne incognita</it>, a major agricultural pest worldwide, now opens the way for a comparative survey and analysis of microsatellites in these organisms.</p> <p>Results</p> <p>Using MsatFinder, the total numbers of 1-6 bp perfect microsatellites detected in the complete genomes of five nematode species (<it>Brugia malayi</it>, <it>Caenorhabditis elegans</it>, <it>M. hapla</it>, <it>M. incognita</it>, <it>Pristionchus pacificus</it>) ranged from 2,842 to 61,547, and covered from 0.09 to 1.20% of the nematode genomes. Under our search criteria, the most common repeat motifs for each length class varied according to the different nematode species considered, with no obvious relation to the AT-richness of their genomes. Overall, (AT)_<it>n</it>, (AG)_{<it>n </it>}and (CT)_{<it>n </it>}were the three most frequent dinucleotide microsatellite motifs found in the five genomes considered. Except for two motifs in <it>P. pacificus</it>, all the most frequent trinucleotide motifs were AT-rich, with (AAT)_{<it>n </it>}and (ATT)_{<it>n </it>}being the only common to the five nematode species. A particular attention was paid to the microsatellite content of the plant-parasitic species <it>M. incognita</it>. In this species, a repertoire of 4,880 microsatellite loci was identified, from which 2,183 appeared suitable to design markers for population genetic studies. Interestingly, 1,094 microsatellites were identified in 801 predicted protein-coding regions, 99% of them being trinucleotides. When compared against the InterPro domain database, 497 of these CDS were successfully annotated, and further assigned to Gene Ontology terms.</p> <p>Conclusions</p> <p>Contrasted patterns of microsatellite abundance and diversity were characterized in five nematode genomes, even in the case of two closely related <it>Meloidogyne </it>species. 2,245 di- to hexanucleotide loci were identified in the genome of <it>M. incognita</it>, providing adequate material for the future development of a wide range of microsatellite markers in this major plant parasite.</p

Designing Products for the Circular Economy

Until recent years, apparel product design has been undertaken with very little reference to environmental sustainability. However, the legislative framework has increasingly constrained design decisions relating to the use of hazardous chemicals, especially with the advent of REACH regulations within the EU. Most companies now recognise a large number of chemical substances that are prohibited in the dyeing and finishing of textiles. This dominates thinking about design for the environment. The increasing adoption of environmental management systems has expanded the vision for initiatives promoting sustainability, including laundering and care. Principles are recognised for product design and development that lead to more sustainable goods and services. In some industries, regulations require producer to take responsibility for the disposal of products companies release to the market. This obligation has triggered thinking about design for disassembly and design for disposal. This development has accelerated the adoption of circular economy concepts. The EU has not implemented producer responsibility in apparel, although some companies have voluntarily championed circular economy initiatives. However, the business models of most apparel companies have nothing to say about end-of-life issues. This chapter is concerned with new product development processes that incorporate Design for Environment and Design for Disassembly and Disposal. As there are numerous technical issues to address, a team-based product development process has many advantages, whereby garment designers work alongside specialists from other disciplines. This process requires culture change to be embraced by most brand owners, and a departure from the practice of separating the design process from the product development process. In most cases, changes of this nature bring disruption to a globalised industrial sector. Case studies will be considered that illustrate the concepts developed in this chapter. In particular, the French experience of adopting producer responsibility for apparel goods is considered. The accredited organisation ECO TLC exhibits strength in the promotion of sustainability projects, but there is a fundamental weakness in that culture change in the design process of brand owners is hard to discern

Obesity Takes Its Toll on Visceral Pain: High-Fat Diet Induces Toll-Like Receptor 4- Dependent Visceral Hypersensitivity

Exposure to high-fat diet induces both, peripheral and central alterations in TLR4 expression. Moreover, functional TLR4 is required for the development of high-fat diet-induced obesity. Recently, central alterations in TLR4 expression have been associated with the modulation of visceral pain. However, it remains unknown whether there is a functional interaction between the role of TLR4 in diet-induced obesity and in visceral pain. In the present study we investigated the impact of long-term exposure to high-fat diet on visceral pain perception and on the levels of TLR4 and Cd11b (a microglial cell marker) protein expression in the prefrontal cortex (PFC) and hippocampus. Peripheral alterations in TLR4 were assessed following the stimulation of spleenocytes with the TLR4-agonist LPS. Finally, we evaluated the effect of blocking TLR4 on visceral nociception, by administering TAK-242, a selective TLR4-antagonist. Our results demonstrated that exposure to high-fat diet induced visceral hypersensitivity. In parallel, enhanced TLR4 expression and microglia activation were found in brain areas related to visceral pain, the PFC and the hippocampus. Likewise, peripheral TLR4 activity was increased following long-term exposure to high-fat diet, resulting in an increased level of pro-inflammatory cytokines. Finally, TLR4 blockage counteracted the hyperalgesic phenotype present in mice fed on high-fat diet. Our data reveal a role for TLR4 in visceral pain modulation in a model of diet-induced obesity, and point to TLR4 as a potential therapeutic target for the development of drugs to treat visceral hypersensitivity present in pathologies associated to fat diet consumption

The evidence base for circulating tumour DNA blood-based biomarkers for the early detection of cancer: a systematic mapping review

Background: The presence of circulating cell-free DNA from tumours in blood (ctDNA) is of major importance to those interested in early cancer detection, as well as to those wishing to monitor tumour progression or diagnose the presence of activating mutations to guide treatment. In 2014, the UK Early Cancer Detection Consortium undertook a systematic mapping review of the literature to identify blood-based biomarkers with potential for the development of a non-invasive blood test for cancer screening, and which identified this as a major area of interest. This review builds on the mapping review to expand the ctDNA dataset to examine the best options for the detection of multiple cancer types. Methods: The original mapping review was based on comprehensive searches of the electronic databases Medline, Embase, CINAHL, the Cochrane library, and Biosis to obtain relevant literature on blood-based biomarkers for cancer detection in humans (PROSPERO no. CRD42014010827). The abstracts for each paper were reviewed to determine whether validation data were reported, and then examined in full. Publications concentrating on monitoring of disease burden or mutations were excluded. Results: The search identified 94 ctDNA studies meeting the criteria for review. All but 5 studies examined one cancer type, with breast, colorectal and lung cancers representing 60% of studies. The size and design of the studies varied widely. Controls were included in 77% of publications. The largest study included 640 patients, but the median study size was 65 cases and 35 controls, and the bulk of studies (71%) included less than 100 patients. Studies either estimated cfDNA levels non-specifically or tested for cancer-specific mutations or methylation changes (the majority using PCR-based methods). Conclusion: We have systematically reviewed ctDNA blood biomarkers for the early detection of cancer. Pre-analytical, analytical, and post-analytical considerations were identified which need to be addressed before such biomarkers enter clinical practice. The value of small studies with no comparison between methods, or even the inclusion of controls is highly questionable, and larger validation studies will be required before such methods can be considered for early cancer detection

Brain energy rescue:an emerging therapeutic concept for neurodegenerative disorders of ageing

The brain requires a continuous supply of energy in the form of ATP, most of which is produced from glucose by oxidative phosphorylation in mitochondria, complemented by aerobic glycolysis in the cytoplasm. When glucose levels are limited, ketone bodies generated in the liver and lactate derived from exercising skeletal muscle can also become important energy substrates for the brain. In neurodegenerative disorders of ageing, brain glucose metabolism deteriorates in a progressive, region-specific and disease-specific manner — a problem that is best characterized in Alzheimer disease, where it begins presymptomatically. This Review discusses the status and prospects of therapeutic strategies for countering neurodegenerative disorders of ageing by improving, preserving or rescuing brain energetics. The approaches described include restoring oxidative phosphorylation and glycolysis, increasing insulin sensitivity, correcting mitochondrial dysfunction, ketone-based interventions, acting via hormones that modulate cerebral energetics, RNA therapeutics and complementary multimodal lifestyle changes

Discovery of cahuitamycins as biofilm inhibitors derived from a convergent biosynthetic pathway

Pathogenic microorganisms often have the ability to attach to a surface, building a complex matrix where they colonize to form a biofilm. This cellular superstructure can display increased resistance to antibiotics and cause serious, persistent health problems in humans. Here we describe a high-throughput in vitro screen to identify inhibitors of Acinetobacter baumannii biofilms using a library of natural product extracts derived from marine microbes. Analysis of extracts derived from Streptomyces gandocaensis results in the discovery of three peptidic metabolites (cahuitamycins A–C), with cahuitamycin C being the most effective inhibitor (IC50=14.5 μM). Biosynthesis of cahuitamycin C proceeds via a convergent biosynthetic pathway, with one of the steps apparently being catalysed by an unlinked gene encoding a 6-methylsalicylate synthase. Efforts to assess starter unit diversification through selective mutasynthesis lead to production of unnatural analogues cahuitamycins D and E of increased potency (IC50=8.4 and 10.5 μM).Great Lakes Regional Center of Excellence for Biodefense and Emerging Infectious Diseases/[U54 AI57153]/GLRCE/Estados UnidosArmy Research Office/[W911NF-12-1-0059]/ARO/Estados UnidosNational Institutes of Health/[1R01GM098350]/NIH/Estados UnidosInternational Cooperative Biodiversity Groups-Fogarty International Center/[U01 TW007404]/ICBG/Estados UnidosUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Básicas::Centro de Investigaciones en Productos Naturales (CIPRONA