Personalized drug administrations using Support Vector Machine

The decision-making process regarding drug dose, regularly used in everyday medical practice, is critical to patients' health and recovery. It is a challenging process, especially for a drug with narrow therapeutic ranges, in which a medical doctor decides the quantity (dose amount) and frequency (dose interval) on the basis of a set of available patient features and doctor's clinical experience (a priori adaptation). Computer support in drug dose administration makes the prescription procedure faster, more accurate, objective, and less expensive, with a tendency to reduce the number of invasive procedures. This paper presents an advanced integrated Drug Administration Decision Support System (DADSS) to help clinicians/patients with the dose computing. Based on a support vector machine (SVM) algorithm, enhanced with the random sample consensus technique, this system is able to predict the drug concentration values and computes the ideal dose amount and dose interval for a new patient. With an extension to combine the SVM method and the explicit analytical model, the advanced integrated DADSS system is able to compute drug concentration-to-time curves for a patient under different conditions. A feedback loop is enabled to update the curve with a new measured concentration value to make it more personalized (a posteriori adaptation).

Patient-ventilator asynchrony during noninvasive pressure support ventilation and neurally adjusted ventilatory assist in infants and children.

OBJECTIVES: To document the prevalence of asynchrony events during noninvasive ventilation in pressure support in infants and in children and to compare the results with neurally adjusted ventilatory assist. DESIGN: Prospective randomized cross-over study in children undergoing noninvasive ventilation. SETTING: The study was performed in a PICU. PATIENTS: From 4 weeks to 5 years. INTERVENTIONS: Two consecutive ventilation periods (pressure support and neurally adjusted ventilatory assist) were applied in random order. During pressure support (PS), three levels of expiratory trigger (ETS) setting were compared: initial ETS (PSinit), and ETS value decreased and increased by 15%. Of the three sessions, the period allowing for the lowest number of asynchrony events was defined as PSbest. Neurally adjusted ventilator assist level was adjusted to match the maximum airway pressure during PSinit. Positive end-expiratory pressure was the same during pressure support and neurally adjusted ventilator assist. Asynchrony events, trigger delay, and cycling-off delay were quantified for each period. RESULTS: Six infants and children were studied. Trigger delay was lower with neurally adjusted ventilator assist versus PSinit and PSbest (61 ms [56-79] vs 149 ms [134-180] and 146 ms [101-162]; p = 0.001 and 0.02, respectively). Inspiratory time in excess showed a trend to be shorter during pressure support versus neurally adjusted ventilator assist. Main asynchrony events during PSinit were autotriggering (4.8/min [1.7-12]), ineffective efforts (9.9/min [1.7-18]), and premature cycling (6.3/min [3.2-18.7]). Premature cycling (3.4/min [1.1-7.7]) was less frequent during PSbest versus PSinit (p = 0.059). The asynchrony index was significantly lower during PSbest versus PSinit (40% [28-65] vs 65.5% [42-76], p < 0.001). With neurally adjusted ventilator assist, all types of asynchronies except double triggering were reduced. The asynchrony index was lower with neurally adjusted ventilator assist (2.3% [0.7-5] vs PSinit and PSbest, p < 0.05 for both comparisons). CONCLUSION: Asynchrony events are frequent during noninvasive ventilation with pressure support in infants and in children despite adjusting the cycling-off criterion. Compared with pressure support, neurally adjusted ventilator assist allows improving patient-ventilator synchrony by reducing trigger delay and the number of asynchrony events. Further studies should determine the clinical impact of these findings.

Cross-Border Innovation Support Platform for the SMEs: The Case of St. Petersburg Corridor Region

Työssä tutkitaan eri mekanismeja rajojen ylittävään innovaatioiden edistämiseen pienten ja keskisuurten yritysten näkökulmasta. Case ympäristönä on Kaakkois-Suomen ja Luoteis-Venäjän alueeli Pietarin Corridor. Tavoitteena on löytää tarkemmat määritykset ja rajauksetnäille mekanismeille. Teoriassa muodostettiin viitekehys rajojen ylittävälle innovaatioiden edistämismallille. Mallin pohjalta toteutettiinhaastattelututkimus, joka suoritettiin case-ympäristössä. Haastattelujoukko koostui yritysten edustajista, tutkimus-henkilöstöstä sekä julkisista toimijoista. Innovaatiojärjestelmä oli avoin uusille toimintamenetelmille.Menetelmien toteuttamistapa kuitenkin jakoi mielipiteitä. Toimijoiden välille tarvitaan parempaa yhteistyötä ja tämän kautta selkeämpää kommunikointia yritysten suuntaan. Innovaatioiden edistämiseen ehdotetaan Innovation Relay Centre tyyppisen toiminnan laajentamista Corridorin alueelle sekä sen käyttämän teknologioiden välittämismallin sekä kansainvälisen verkoston hyödyntämistä. Edistämisen tukena tulisi käyttää innovaatiotietokanta-työkalua.

Altered processing of contextual information during fear extinction in PTSD: an fMRI study.

Medial prefrontal cortical areas have been hypothesized to underlie altered contextual processing in posttraumatic stress disorder (PTSD). We investigated brain signaling of contextual information in this disorder. Eighteen PTSD subjects and 16 healthy trauma-exposed subjects underwent a two-day fear conditioning and extinction paradigm. On day 1, within visual context A, a conditioned stimulus (CS) was followed 60% of the time by an electric shock (conditioning). The conditioned response was then extinguished (extinction learning) in context B. On day 2, recall of the extinction memory was tested in context B. Skin conductance response (SCR) and functional magnetic resonance imaging (fMRI) data were collected during context presentations. There were no SCR group differences in any context presentation. Concerning fMRI data, during late conditioning, when context A signaled danger, PTSD subjects showed dorsal anterior cingulate cortical (dACC) hyperactivation. During early extinction, when context B had not yet fully acquired signal value for safety, PTSD subjects still showed dACC hyperactivation. During late extinction, when context B had come to signal safety, they showed ventromedial prefrontal cortex (vmPFC) hypoactivation. During early extinction recall, when context B signaled safety, they showed both vmPFC hypoactivation and dACC hyperactivation. These findings suggest that PTSD subjects show alterations in the processing of contextual information related to danger and safety. This impairment is manifest even prior to a physiologically-measured, cue-elicited fear response, and characterized by hypoactivation in vmPFC and hyperactivation in dACC.

Abnormal social behaviors and altered gene expression rates in a mouse model for Potocki-Lupski syndrome.

The Potocki-Lupski syndrome (PTLS) is associated with a microduplication of 17p11.2. Clinical features include multiple congenital and neurobehavioral abnormalities and autistic features. We have generated a PTLS mouse model, Dp(11)17/+, that recapitulates some of the physical and neurobehavioral phenotypes present in patients. Here, we investigated the social behavior and gene expression pattern of this mouse model in a pure C57BL/6-Tyr(c-Brd) genetic background. Dp(11)17/+ male mice displayed normal home-cage behavior but increased anxiety and increased dominant behavior in specific tests. A subtle impairment in the preference for a social target versus an inanimate target and abnormal preference for social novelty (the preference to explore an unfamiliar mouse versus a familiar one) was also observed. Our results indicate that these animals could provide a valuable model to identify the specific gene(s) that confer abnormal social behaviors and that map within this delimited genomic deletion interval. In a first attempt to identify candidate genes and for elucidating the mechanisms of regulation of these important phenotypes, we directly assessed the relative transcription of genes within and around this genomic interval. In this mouse model, we found that candidates genes include not only most of the duplicated genes, but also normal-copy genes that flank the engineered interval; both categories of genes showed altered expression levels in the hippocampus of Dp(11)17/+ mice.

Nestmate recognition and levels of aggression are not altered by changes in genetic diversity in a socially polymorphic ant

The ability to distinguish nestmates from foreign individuals is central to the functioning of insect societies. In ants, workers from multiple-queen colonies are often less aggressive than workers from single-queen ones. In line with this observation, it has been hypothesized that workers from multiple-queen colonies have less precise recognition abilities than workers from single-queen ones because their colonies contain genetically more diverse individuals, which results in a broader template of recognition cues. Here, we assessed the impact of social structure ( queen number) variation on nestmate recognition and aggression in a large population of the socially polymorphic ant Formica selysi. We staged unilateral aggression tests on the nest surface. Workers from single-and multiple-queen colonies had good nestmate recognition ability and did not differ significantly in their level of aggression towards foreign, immobilized workers ( cue-bearers). In particular, workers from multiple-queen colonies efficiently recognized non-nestmates despite the higher genetic diversity in their colony. Cue-bearers from single- and multiple-queen colonies elicited similar reactions. However, the level of aggression was higher between than within social forms, suggesting that workers detect a signal that is specific to the colony social structure. Finally, the level of aggression was not correlated with the genetic distance between colonies. Overall, we found no evidence for the hypothesis that the presence of multiple breeders in the same colony decreases recognition abilities and found no simple relationship between genetic diversity and aggression level. (c) 2007 The Association for the Study of Animal Behaviou

Special commentary : a call for intensive metabolic support.

PURPOSE OF REVIEW: This special commentary addresses recent clinical reviews regarding appropriate nutrition and metabolic support in the critical care setting. RECENT FINDINGS: There are divergent approaches between North America and Europe for the use of early nutrition support and combined enteral nutrition and parenteral nutrition support possibly due to the commercial availability of specific parenteral nutrients. The advent of intensive insulin therapy has changed the landscape of metabolic support in the intensive care unit, and previous notions about infective risk of parenteral nutrition will need to be re-addressed. Patients with brain failure may benefit from an intensive insulin therapy with a blood glucose target that is higher than that used in patients without brain failure. Patients with heart failure may benefit from the addition of nutritional pharmacology that targets proximate oxidative pathophysiological pathways. Intradialytic parenteral nutrition may be viewed as another form of supplemental parenteral nutrition when enteral nutrition is insufficient in patients on hemodialysis in the intensive care unit. SUMMARY: It is proposed that intensive metabolic support be routinely implemented in the intensive care unit based on the following steps: intensive insulin therapy with an appropriate blood glucose target, nutrition risk assessment, early and if needed combined enteral nutrition and parenteral nutrition to target 20-25 kcal/kg/day and 1.2-1.5 g protein/kg/day, and nutritional and metabolic monitoring.

Task Support in Scenario Process: Case LUT 2016

This thesis attempts to find whether scenario planning supports the organizational strategy as a method for addressing uncertainty. The main issues are why, what and how scenario planning fits in organizational strategy and how the process could be supported to make it more effective. The study follows the constructive approach. It starts with examination of competitive advantage and the way that an organization develops strategy and how it addresses the uncertainty in its operational environment. Based on the conducted literature review, scenario methods would seem to provide versatile platform for addressing future uncertainties. The construction is formed by examining the scenario methods and presenting suitable support methods, which results in forming of the theoretical proposition for supporter scenario process. The theoretical framework is tested in laboratory conditions, and the results from the test sessions are used a basis for scenario stories. The process of forming the scenarios and the results are illustrated and presented for scrutiny

Troubleshooting in extracorporeal life support.

Since the first clinical use of extracorporeal circulation in the last century [1] by John Gibbon and the first successful mechanical support of the left ventricular function by Forest Dodrill [2], the progress of techniques and technologies has helped to develop minimised systems for extracorporeal circulatory and respiratory support. However, the fact is that, despite the advanced technologies used for extracorporeal support, successful application in order to be benefit a critically ill population requires highly trained and skilled teams. Application of these highly sophisticated techniques in life-saving situations inside and/or outside the operating room is a procedure with certain pitfalls and dangers. The aim of this review is to provide a short overview of the technical aspects of extracorporeal circulation, with a look at the recent literature and clinical experiences focusing on technical as well surgical considerations regarding the urgent and/or emergent usage of a central as well as peripheral extracorporeal system.

The power of support: an exploration of the mentoring relationship

Tutkimuksen pääasiallisena tavoitteena on selvittää ne moninaiset näkökulmat, joita mentori sekä mentoroitava läpikäyvät osallistuessaan mentorointiohjelmaan. Tutkimuksen avulla pyritään myös selvittämään vastaavanlaisen tuen saannin tehokkuutta sekä mentoroinnin sisältäminen elementtien hyödyllisyyttä. Pyrkimyksenä on myös selvittää sekä ymmärtää ne dynaamiset mentorointiprosessin ominaisuudet molempien prosessiin osallistuvien tahojen näkökulmasta. Tutkimuksen teoriaosuudessa käsitellään mentorointia, mentorointiin liittyviä vuorovaikutussuhteita sekä näihin liittyviä eri näkökulmia. Teoria koostuu monipuolisesta, kansainvälisestä sekä kotimaisesta kirjallisuudesta. Tutkimuksen aineiston keruu suoritetaan puolistrukturoiduilla avoimilla haastatteluilla, jotka suoritetaan järjestämällä kahdenkeskisiä teemahaastatteluita. Mentorointisuhteella on todettu olevan voimakas vaikutus siihen osallistuvien henkilöiden elämään. Mentorointisuhteen tarkoituksellisuus on tullut todettua myös kun itse vuorovaikutussuhde on osoittautunut hyödylliseksi osallistujille. Mentoroitavilla on odotuksia, että mentorit täyttävät seuraavanlaisia rooleja: neuvonantaja, roolimalli sekä mahdollisesti tukea antava ystävä. Kaikissa läpikäydyissä tapauksissa mentori pystyi tarjoamaan jonkun näistärooleista mentoroitavalle. Mentoroitava, puolestaan, otti tämän tuen vastaan jahyötyi siitä.

Arabidopsis Basic Helix-Loop-Helix Transcription Factors MYC2, MYC3, and MYC4 Regulate Glucosinolate Biosynthesis, Insect Performance, and Feeding Behavior.

Arabidopsis thaliana plants fend off insect attack by constitutive and inducible production of toxic metabolites, such as glucosinolates (GSs). A triple mutant lacking MYC2, MYC3, and MYC4, three basic helix-loop-helix transcription factors that are known to additively control jasmonate-related defense responses, was shown to have a highly reduced expression of GS biosynthesis genes. The myc2 myc3 myc4 (myc234) triple mutant was almost completely devoid of GS and was extremely susceptible to the generalist herbivore Spodoptera littoralis. On the contrary, the specialist Pieris brassicae was unaffected by the presence of GS and preferred to feed on wild-type plants. In addition, lack of GS in myc234 drastically modified S. littoralis feeding behavior. Surprisingly, the expression of MYB factors known to regulate GS biosynthesis genes was not altered in myc234, suggesting that MYC2/MYC3/MYC4 are necessary for direct transcriptional activation of GS biosynthesis genes. To support this, chromatin immunoprecipitation analysis showed that MYC2 binds directly to the promoter of several GS biosynthesis genes in vivo. Furthermore, yeast two-hybrid and pull-down experiments indicated that MYC2/MYC3/MYC4 interact directly with GS-related MYBs. This specific MYC-MYB interaction plays a crucial role in the regulation of defense secondary metabolite production and underlines the importance of GS in shaping plant interactions with adapted and nonadapted herbivores.

Altered high-energy phosphate metabolism predicts contractile dysfunction and subsequent ventricular remodeling in pressure-overload hypertrophy mice.

To study the role of early energetic abnormalities in the subsequent development of heart failure, we performed serial in vivo combined magnetic resonance imaging (MRI) and (31)P magnetic resonance spectroscopy (MRS) studies in mice that underwent pressure-overload following transverse aorta constriction (TAC). After 3 wk of TAC, a significant increase in left ventricular (LV) mass (74 +/- 4 vs. 140 +/- 26 mg, control vs. TAC, respectively; P < 0.000005), size [end-diastolic volume (EDV): 48 +/- 3 vs. 61 +/- 8 microl; P < 0.005], and contractile dysfunction [ejection fraction (EF): 62 +/- 4 vs. 38 +/- 10%; P < 0.000005] was observed, as well as depressed cardiac energetics (PCr/ATP: 2.0 +/- 0.1 vs. 1.3 +/- 0.4, P < 0.0005) measured by combined MRI/MRS. After an additional 3 wk, LV mass (140 +/- 26 vs. 167 +/- 36 mg; P < 0.01) and cavity size (EDV: 61 +/- 8 vs. 76 +/- 8 microl; P < 0.001) increased further, but there was no additional decline in PCr/ATP or EF. Cardiac PCr/ATP correlated inversely with end-systolic volume and directly with EF at 6 wk but not at 3 wk, suggesting a role of sustained energetic abnormalities in evolving chamber dysfunction and remodeling. Indeed, reduced cardiac PCr/ATP observed at 3 wk strongly correlated with changes in EDV that developed over the ensuing 3 wk. These data suggest that abnormal energetics due to pressure overload predict subsequent LV remodeling and dysfunction.