Narkolepsiaan sairastuneiden lasten ja nuorten perheiden arki ja sopeutumisvalmennuskurssilta saatu tuki

Suomessa varauduttiin maailmanlaajuisesti levinneeseen sikainfluenssaan aloittamalla lokakuussa 2009 Pandemrix-rokotukset väestön suojaamiseksi. Helmikuussa 2010 diagnosoitiin ensimmäinen päiväaikaista nukahtelua aiheuttava narkolepsia lapsella, joka oli saanut Pandemrix-rokotuksen. Sosiaali- ja terveysministeriö antoi Kelalle tehtäväksi järjestää narkolepsiaan sairastuneille lapsille ja nuorille sopeutumisvalmennuskursseja. Kelan tutkimusosasto, Lapin yliopisto ja Suomen Mielenterveysseura toteuttivat tutkimuksen, jonka päätavoite oli selvittää, mitkä olivat sairastuneiden ja heidän perheidensä tarpeet ja odotukset sekä miten hyvin kurssit pystyivät vastaamaan niihin. Aineiston keruu toteutui kevään 2012 ja syksyn 2013 välisenä aikana. Narkolepsiaan liittyviä päiväaikaista nukahtelua, käyttäytymisen muutoksia ja keskittymisen vaikeuksia esiintyi lähes kaikilla tutkimukseen osallistuneilla lapsilla ja nuorilla. Muistin ja oppimisen vaikeuksia sekä katapleksiaa oli yli puolella ja harha-aistimuksia noin kolmanneksella. Käyttäytymisen ja mielialan muutokset vaikuttivat koko perheen arkeen. Vanhemmat olivat huolissaan nuoren tulevaisuudesta, omien auttamiskeinojensa riittävyydestä, sisarusten voinnista ja omasta jaksamisestaan. Perheillä oli runsaasti psykososiaalisen tuen tarpeita. Perheiden odotukset painottuivat vertaistuen saamiseen, ja kurssit vastasivat näihin odotuksiin. Enemmistö koki saaneensa jonkin verran etäisyyttä arkisiin huoliin, tukea tunteiden käsittelyyn ja sairastuneen vahvuuksien tunnistamiseen. Asiantuntijatiedon ja ammatillisen psykososiaalisen tuen tarpeeseen kurssit eivät vastanneet. Sopeutumisvalmennuskurssien toimeenpanossa ilmeni useita kehittämisen kohteita. Kurssien tavoitteiden tarkentaminen, asiantuntijatiedon vahvistaminen, yksilöllisten työmenetelmien valinnan mahdollisuus, ennakkoinformaation lisääminen sekä Kelan ja palveluntuottajan välisen yhteistyön vahvistaminen mahdollistavat kuntoutujalähtöisiin tarpeisiin vastaamisen

Healthy people in healthy premises: the Finnish Indoor Air and Health Programme 2018-2028

Clean and fresh indoor air supports health and well-being. However, indoor air can contain pollutants that can cause a variety of symptoms and reduce well-being. Individual exposure agents can also increase the risk of certain diseases. Finns have taken major steps to improve the quality of indoor air for several decades. The primary focus of these activities has been the prevention and reduction of exposure to poor indoor air quality through guidance and regulation directing remediation of damaged buildings. Nevertheless, reported symptoms related to poor indoor air quality are common in Finland. In addition to exposure to indoor air pollutants, this may be partly due to the lively public discussion on the health risks caused by poor indoor air quality, conflicting views between experts, and mistrust towards public authorities, building owners and builders. Because of the scale of the indoor air problems in Finland, people's needs for reliable information and support, and the major costs involved, there is a call for new evidence-based methods, perspectives and solutions. Therefore, the Finnish Institute for Health and Welfare initiated the Finnish Indoor Air and Health Programme 2018-2028 together with a number of collaborators and stakeholders. The primary, long-term objective of the programme is to reduce hazards to health and well-being linked to indoor environments in Finland. To fulfill this objective, the programme will focus on the promotion of human health and well-being, the prevention of hazards, improved communication and engage the whole health-care sector to manage better patients ' symptoms and complaints. The 10-year Finnish Indoor Air and Health Programme consists of four areas that aim (1) to increase understanding of the effects of indoor environments on health and well-being; (2) to develop the management of problems linked to indoor environments; (3) to improve the treatment and working and functional capacity of people with symptoms and illnesses; and (4) to strengthen the competence in matters related to indoor environments. The progress of the programme and reaching the predefined, quantitative goals will be monitored throughout the programme

The Bits of Silence : Redundant Traffic in VoIP

Human conversation is characterized by brief pauses and so-called turn-taking behavior between the speakers. In the context of VoIP, this means that there are frequent periods where the microphone captures only background noise – or even silence whenever the microphone is muted. The bits transmitted from such silence periods introduce overhead in terms of data usage, energy consumption, and network infrastructure costs. In this paper, we contribute by shedding light on these costs for VoIP applications. We systematically measure the performance of six popular mobile VoIP applications with controlled human conversation and acoustic setup. Our analysis demonstrates that significant savings can indeed be achievable - with the best performing silence suppression technique being effective on 75% of silent pauses in the conversation in a quiet place. This results in 2-5 times data savings, and 50-90% lower energy consumption compared to the next better alternative. Even then, the effectiveness of silence suppression can be sensitive to the amount of background noise, underlying speech codec, and the device being used. The codec characteristics and performance do not depend on the network type. However, silence suppression makes VoIP traffic network friendly as much as VoLTE traffic. Our results provide new insights into VoIP performance and offer a motivation for further enhancements, such as performance-aware codec selection, that can significantly benefit a wide variety of voice assisted applications, as such intelligent home assistants and other speech codec enabled IoT devices.Peer reviewe

An Extended Gene Protein/Products Boolean Network Model Including Post-Transcriptional Regulation

Background: Networks Biology allows the study of complex interactions between biological systems using formal, well structured, and computationally friendly models. Several different network models can be created, depending on the type of interactions that need to be investigated. Gene Regulatory Networks (GRN) are an effective model commonly used to study the complex regulatory mechanisms of a cell. Unfortunately, given their intrinsic complexity and non discrete nature, the computational study of realistic-sized complex GRNs requires some abstractions. Boolean Networks (BNs), for example, are a reliable model that can be used to represent networks where the possible state of a node is a boolean value (0 or 1). Despite this strong simplification, BNs have been used to study both structural and dynamic properties of real as well as randomly generated GRNs. Results: In this paper we show how it is possible to include the post-transcriptional regulation mechanism (a key process mediated by small non-coding RNA molecules like the miRNAs) into the BN model of a GRN. The enhanced BN model is implemented in a software toolkit (EBNT) that allows to analyze boolean GRNs from both a structural and a dynamic point of view. The open-source toolkit is compatible with available visualization tools like Cytoscape and allows to run detailed analysis of the network topology as well as of its attractors, trajectories, and state-space. In the paper, a small GRN built around the mTOR gene is used to demonstrate the main capabilities of the toolkit. Conclusions: The extended model proposed in this paper opens new opportunities in the study of gene regulation. Several of the successful researches done with the support of BN to understand high-level characteristics of regulatory networks, can now be improved to better understand the role of post-transcriptional regulation for example as a network-wide noise-reduction or stabilization mechanism

Minimising impairment: Protocol for a multicentre randomised controlled trial of upper limb orthoses for children with cerebral palsy.

BACKGROUND: Upper limb orthoses are frequently prescribed for children with cerebral palsy (CP) who have muscle overactivity predominantly due to spasticity, with little evidence of long-term effectiveness. Clinical consensus is that orthoses help to preserve range of movement: nevertheless, they can be complex to construct, expensive, uncomfortable and require commitment from parents and children to wear. This protocol paper describes a randomised controlled trial to evaluate whether long-term use of rigid wrist/hand orthoses (WHO) in children with CP, combined with usual multidisciplinary care, can prevent or reduce musculoskeletal impairments, including muscle stiffness/tone and loss of movement range, compared to usual multidisciplinary care alone. METHODS/DESIGN: This pragmatic, multicentre, assessor-blinded randomised controlled trial with economic analysis will recruit 194 children with CP, aged 5-15 years, who present with flexor muscle stiffness of the wrist and/or fingers/thumb (Modified Ashworth Scale score =1). Children, recruited from treatment centres in Victoria, New South Wales and Western Australia, will be randomised to groups (1:1 allocation) using concealed procedures. All children will receive care typically provided by their treating organisation. The treatment group will receive a custom-made serially adjustable rigid WHO, prescribed for 6 h nightly (or daily) to wear for 3 years. An application developed for mobile devices will monitor WHO wearing time and adverse events. The control group will not receive a WHO, and will cease wearing one if previously prescribed. Outcomes will be measured 6 monthly over a period of 3 years. The primary outcome is passive range of wrist extension, measured with fingers extended using a goniometer at 3 years. Secondary outcomes include muscle stiffness, spasticity, pain, grip strength and hand deformity. Activity, participation, quality of life, cost and cost-effectiveness will also be assessed. DISCUSSION: This study will provide evidence to inform clinicians, services, funding agencies and parents/carers of children with CP whether the provision of a rigid WHO to reduce upper limb impairment, in combination with usual multidisciplinary care, is worth the effort and costs. TRIAL REGISTRATION: ANZ Clinical Trials Registry: U1111-1164-0572

Salivary gland branching morphogenesis: a quantitative systems analysis of the Eda/Edar/NFκB paradigm

<p>Abstract</p> <p>Background</p> <p>Ectodysplasin-A appears to be a critical component of branching morphogenesis. Mutations in mouse <it>Eda </it>or human <it>EDA </it>are associated with absent or hypoplastic sweat glands, sebaceous glands, lacrimal glands, salivary glands (SMGs), mammary glands and/or nipples, and mucous glands of the bronchial, esophageal and colonic mucosa. In this study, we utilized <it>Eda</it>^{<it>Ta </it>}(Tabby) mutant mice to investigate how a marked reduction in functional Eda propagates with time through a defined genetic subcircuit and to test the proposition that canonical NFκB signaling is sufficient to account for the differential expression of developmentally regulated genes in the context of <it>Eda </it>polymorphism.</p> <p>Results</p> <p>The quantitative systems analyses do not support the stated hypothesis. For most NFκB-regulated genes, the observed time course of gene expression is nearly unchanged in Tabby (<it>Eda</it>^<it>Ta</it>) as compared to wildtype mice, as is NFκB itself. Importantly, a subset of genes is dramatically differentially expressed in Tabby (<it>Edar</it>, <it>Fgf8</it>, <it>Shh</it>, <it>Egf</it>, <it>Tgfa</it>, <it>Egfr</it>), strongly suggesting the existence of an alternative Eda-mediated transcriptional pathway pivotal for SMG ontogeny. Experimental and <it>in silico </it>investigations have identified C/EBPα as a promising candidate.</p> <p>Conclusion</p> <p>In Tabby SMGs, upregulation of the Egf/Tgfα/Egfr pathway appears to mitigate the potentially severe abnormal phenotype predicted by the downregulation of Fgf8 and Shh. Others have suggested that the buffering of the phenotypic outcome that is coincident with variant Eda signaling could be a common mechanism that permits viable and diverse phenotypes, normal and abnormal. Our results support this proposition. Further, if branching epithelia use variations of a canonical developmental program, our results are likely applicable to understanding the phenotypes of other branching organs affected by <it>Eda </it>(<it>EDA</it>) mutation.</p

Genome-wide association meta-analysis identifies 48 risk variants and highlights the role of the stria vascularis in hearing loss

Hearing loss is one of the top contributors to years lived with disability and is a risk factor for dementia. Molecular evidence on the cellular origins of hearing loss in humans is growing. Here, we performed a genome-wide association meta-analysis of clinically diagnosed and self-reported hearing impairment on 723,266 individuals and identified 48 significant loci, 10 of which are novel. A large proportion of associations comprised missense variants, half of which lie within known familial hearing loss loci. We used single-cell RNA-sequencing data from mouse cochlea and brain and mapped common-variant genomic results to spindle, root, and basal cells from the stria vascularis, a structure in the cochlea necessary for normal hearing. Our findings indicate the importance of the stria vascularis in the mechanism of hearing impairment, providing future paths for developing targets for therapeutic intervention in hearing loss

Data-analysis strategies for image-based cell profiling

Image-based cell profiling is a high-throughput strategy for the quantification of phenotypic differences among a variety of cell populations. It paves the way to studying biological systems on a large scale by using chemical and genetic perturbations. The general workflow for this technology involves image acquisition with high-throughput microscopy systems and subsequent image processing and analysis. Here, we introduce the steps required to create high-quality image-based (i.e., morphological) profiles from a collection of microscopy images. We recommend techniques that have proven useful in each stage of the data analysis process, on the basis of the experience of 20 laboratories worldwide that are refining their image-based cell-profiling methodologies in pursuit of biological discovery. The recommended techniques cover alternatives that may suit various biological goals, experimental designs, and laboratories' preferences.Peer reviewe