'Comfort Me With Apples': Ambivalent Allusion in Paradise Lost

Paradise Lost can be read on various levels, some of which challenge or even contradict others. The main, explicit narrative from Genesis chapters 2 and 3 is shadowed by many other related stories. Some of these buried tales question or subvert the values made explicit in the dominant narrative. An attentive reader needs to be alert to the ways in which such references introduce teasing complexities. The approach of Satan to Eve in the ninth book of Paradise Lost is loaded in just that way with allusion to the literature of Greece and Rome. The poem recovers for this long and intricately constructed passage the weight of classical reference, especially in similes, that it had during the first Satanic books. Gardens, both classical and biblical, disguised or transformed serpents, and the weight of allusions that Eve is required to bear, all threaten to undermine the meanings of the overt narrative. The narrator has difficulty rescuing Eve from the allusions she attracts, or the many stories told about her.

Determination of Rumble Strip Effectiveness, HR-184, 1979

Rumble strips are patches of specially treated pavement surfaces which are designed to produce aural and tactile stimuli inside vehicles. The intent is to alert drivers and when desirable, cause them to slow down or come to a stop. Installations were made in a three-county area in Iowa to study rumble strip effectiveness as an accident reducing measure. The investigation of accidents at the various test sites showed that rumble strips were effective in reducing certain types of intersection accidents. Although no statistically significant effect of the saturation use was found on total accidents, there are indications that accidents may be reduced when used in low density i.e., rural type areas.

Auditory spatio-temporal brain dynamics and their consequences for multisensory interactions in humans.

Recent multisensory research has emphasized the occurrence of early, low-level interactions in humans. As such, it is proving increasingly necessary to also consider the kinds of information likely extracted from the unisensory signals that are available at the time and location of these interaction effects. This review addresses current evidence regarding how the spatio-temporal brain dynamics of auditory information processing likely curtails the information content of multisensory interactions observable in humans at a given latency and within a given brain region. First, we consider the time course of signal propagation as a limitation on when auditory information (of any kind) can impact the responsiveness of a given brain region. Next, we overview the dual pathway model for the treatment of auditory spatial and object information ranging from rudimentary to complex environmental stimuli. These dual pathways are considered an intrinsic feature of auditory information processing, which are not only partially distinct in their associated brain networks, but also (and perhaps more importantly) manifest only after several tens of milliseconds of cortical signal processing. This architecture of auditory functioning would thus pose a constraint on when and in which brain regions specific spatial and object information are available for multisensory interactions. We then separately consider evidence regarding mechanisms and dynamics of spatial and object processing with a particular emphasis on when discriminations along either dimension are likely performed by specific brain regions. We conclude by discussing open issues and directions for future research.

Long term retention of retigabine in a cohort of people with drug resistant epilepsy.

PURPOSE: To assess the utility of retigabine (RTG) for epilepsy in clinical practice at a single UK tertiary centre. METHODS: We identified all individuals who were offered RTG from April 2011 to May 2013. We collected demographics, seizure types, previous and current antiepileptic drugs (AEDs), starting and maximum attained daily dose of RTG, clinical benefits, side effects, and reason to discontinue RTG from in- and outpatient encounters until February 28, 2014. RESULTS: 145 people who had failed a median of 11 AEDs took at least one dose of RTG. One year retention was 32% and decreased following the safety alert by the US Federal Drug Administration (FDA) in April 2013. None became seizure free. 34 people (24%) reported a benefit that was ongoing at last assessment in five (3%). The most relevant benefit was the significant reduction or cessation of drop attacks or seizure-related falls in four women, this persisted at last assessment in two. The presence of simple partial seizures was associated with longer retention, as was a higher attained dose of RTG. Adverse effects were seen in 74% and largely CNS-related or nonspecific and affected the genitourinary system in 13%. CONCLUSION: Retention of RTG was less favourable compared to data from open label extension studies of the regulatory trials. In comparison with historical data on similar retention audits retention of RTG at one year appears to be less than lamotrigine, topiramate, levetiracetam, pregabalin, zonisamide, and lacosamide, and slightly higher than gabapentin.

AGNP consensus guidelines for therapeutic drug monitoring in psychiatry: update 2011.

Therapeutic drug monitoring (TDM), i. e., the quantification of serum or plasma concentrations of medications for dose optimization, has proven a valuable tool for the patient-matched psychopharmacotherapy. Uncertain drug adherence, suboptimal tolerability, non-response at therapeutic doses, or pharmacokinetic drug-drug interactions are typical situations when measurement of medication concentrations is helpful. Patient populations that may predominantly benefit from TDM in psychiatry are children, pregnant women, elderly patients, individuals with intelligence disabilities, forensic patients, patients with known or suspected genetically determined pharmacokinetic abnormalities or individuals with pharmacokinetically relevant comorbidities. However, the potential benefits of TDM for optimization of pharmacotherapy can only be obtained if the method is adequately integrated into the clinical treatment process. To promote an appropriate use of TDM, the TDM expert group of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) issued guidelines for TDM in psychiatry in 2004. Since then, knowledge has advanced significantly, and new psychopharmacologic agents have been introduced that are also candidates for TDM. Therefore the TDM consensus guidelines were updated and extended to 128 neuropsychiatric drugs. 4 levels of recommendation for using TDM were defined ranging from "strongly recommended" to "potentially useful". Evidence-based "therapeutic reference ranges" and "dose related reference ranges" were elaborated after an extensive literature search and a structured internal review process. A "laboratory alert level" was introduced, i. e., a plasma level at or above which the laboratory should immediately inform the treating physician. Supportive information such as cytochrome P450 substrate and inhibitor properties of medications, normal ranges of ratios of concentrations of drug metabolite to parent drug and recommendations for the interpretative services are given. Recommendations when to combine TDM with pharmacogenetic tests are also provided. Following the guidelines will help to improve the outcomes of psychopharmacotherapy of many patients especially in case of pharmacokinetic problems. Thereby, one should never forget that TDM is an interdisciplinary task that sometimes requires the respectful discussion of apparently discrepant data so that, ultimately, the patient can profit from such a joint eff ort.

AGNP Consensus Guidelines for Therapeutic Drug Monitoring in Psychiatry: Update 2011.

Therapeutic drug monitoring (TDM), i. e., the quantification of serum or plasma concentrations of medications for dose optimization, has proven a valuable tool for the patient-matched psychopharmacotherapy. Uncertain drug adherence, suboptimal tolerability, non-response at therapeutic doses, or pharmacokinetic drug-drug interactions are typical situations when measurement of medication concentrations is helpful. Patient populations that may predominantly benefit from TDM in psychiatry are children, pregnant women, elderly patients, individuals with intelligence disabilities, forensic patients, patients with known or suspected genetically determined pharmacokinetic abnormalities or individuals with pharmacokinetically relevant comorbidities. However, the potential benefits of TDM for optimization of pharmacotherapy can only be obtained if the method is adequately integrated into the clinical treatment process. To promote an appropriate use of TDM, the TDM expert group of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) issued guidelines for TDM in psychiatry in 2004. Since then, knowledge has advanced significantly, and new psychopharmacologic agents have been introduced that are also candidates for TDM. Therefore the TDM consensus guidelines were updated and extended to 128 neuropsychiatric drugs. 4 levels of recommendation for using TDM were defined ranging from "strongly recommended" to "potentially useful". Evidence-based "therapeutic reference ranges" and "dose related reference ranges" were elaborated after an extensive literature search and a structured internal review process. A "laboratory alert level" was introduced, i. e., a plasma level at or above which the laboratory should immediately inform the treating physician. Supportive information such as cytochrome P450 substrate- and inhibitor properties of medications, normal ranges of ratios of concentrations of drug metabolite to parent drug and recommendations for the interpretative services are given. Recommendations when to combine TDM with pharmacogenetic tests are also provided. Following the guidelines will help to improve the outcomes of psychopharmacotherapy of many patients especially in case of pharmacokinetic problems. Thereby, one should never forget that TDM is an interdisciplinary task that sometimes requires the respectful discussion of apparently discrepant data so that, ultimately, the patient can profit from such a joint effort.

The reappearance of a forgotten disease in the oral cavity: syphilis

Syphilis is a sexually transmitted disease (STD) produced by Treponema pallidum, which mainly affects humans and is able to invade practically any organ in the body. Its infection facilitates the transmission of other STDs. Since the end of the last decade, successive outbreaks of syphilis have been reported in most western European countries. Like other STDs, syphilis is a notifiable disease in the European Union. In Spain, epidemiological information is obtained nationwide via the country"s system for recording notifiable diseases (Spanish acronym EDO) and the national microbiological information system (Spanish acronym SIM), which compiles information from a network of 46 sentinel laboratories in twelve Spanish regions. The STDs that are epidemiologically controlled are gonococcal infection, syphilis, and congenital syphilis. The incidence of each of these diseases is recorded weekly. The information compiled indicates an increase in the cases of syphilis and gonococcal infection in Spain in recent years. According to the EDO, in 1999, the number of cases of syphilis per 100,000 inhabitants was recorded to be 1.69, which has risen to 4.38 in 2007. In this article, we review the reappearance and the evolution of this infectious disease in eight European countries, and alert dentists to the importance of a) diagnosing sexuallytransmitted diseases and b) notifying the centres that control them

Proaktiivinen verkonvalvonta ja reaaliaikainen dokumentaatio

Nykyaikaisen teollisuusympäristön toiminta nojaa pitkälti tietotekniikkaan,erityisesti tietoliikenneverkolla on merkittävä rooli. Jos verkkokatkon vuoksi informaatio ei kulje tehtaan eri yksiköiden välillä, saattaa koko tehdas pysähtyä. Tästä puolestaan voi seurata merkittäviä tuotannollisia menetyksiä. Tietoliikenneverkon häiriöttömän toiminnan varmistamisessa valvonta onkeskeisessä asemassa. Valvontatyökaluilla nähdään muun muassa verkon eri osa-alueiden kuormitus ja saadaan hälytys, jos jokin raja-arvo ylitetään tai jokin komponentti lakkaa toimimasta. Toinen tärkeä seikka on tietoliikenneverkon dokumentaatio, josta nähdään verkon rakenne, komponenttien fyysinen sijainti ja miten neon kytketty toisiinsa. Yhdistämällä valvonnan, dokumentaation ja osaavan henkilökunnan, päästään proaktiiviiseen verkonvalvontaan, jossa vikoja voidaan välttääja ehkäistä ennakkoon tehdyillä toimenpiteillä. Tärkeydestään huolimatta tietoliikenneverkon dokumentaatio on usein jätetty kokonaan tekemättä tai ainakaan se ei ole ajan tasalla. Tähän on monia syitä, joista eräs on kunnollisen dokumentaatio-ohjelmiston puuttuminen. Siksi tässä työssä kehitetään reaaliaikainen dokumentaatiojärjestelmä, jonka avulla tietoliikenneverkon dokumentointi voidaan tehdä, ja jonka ansiosta se myös pysyy ajan tasalla tietojen automaattisen päivityksen ansiosta.

BAPNE method and N eurorehabilitation in patients with severe acquired brain injury

The use of body percussion through BAPNE method in neurorehabilitation offers the possibility of studying the development of motor skills, attention, coordination, memory and social interaction of patients with neurological diseases. The experimental protocol was carried out on 52 patients with severe acquired brain injury. Patients were selected for the cut - off scores in the standard neuropsychologic al tests of sustained attention , divided and alert ; at least one emisoma intact, cut -off scores in the standard for procedural and semantic memory ; eye sight , hearing and speech intact. The first group of patients has supported the protocol BAPNE tougher with the traditional rehabilitation activities . The control group continued to perform exclusively the cognitive and neuromotor rehabilitation according to traditional protocols. At 6 months after administration of the protocol is expected to re-test to assess if present , the maintenance of the effects of rehabilitation obtained. Experimentation is carried out for 10 weeks following the protocol of BAPNE method in the Roboris Foundation of Rome.

Prediction of Post-Weaning Fibrinogen Status during Cardiopulmonary Bypass: An Observational Study in 110 Patients.

BACKGROUND: After cardiac surgery with cardiopulmonary bypass (CPB), acquired coagulopathy often leads to post-CPB bleeding. Though multifactorial in origin, this coagulopathy is often aggravated by deficient fibrinogen levels. OBJECTIVE: To assess whether laboratory and thrombelastometric testing on CPB can predict plasma fibrinogen immediately after CPB weaning. PATIENTS / METHODS: This prospective study in 110 patients undergoing major cardiovascular surgery at risk of post-CPB bleeding compares fibrinogen level (Clauss method) and function (fibrin-specific thrombelastometry) in order to study the predictability of their course early after termination of CPB. Linear regression analysis and receiver operating characteristics were used to determine correlations and predictive accuracy. RESULTS: Quantitative estimation of post-CPB Clauss fibrinogen from on-CPB fibrinogen was feasible with small bias (+0.19 g/l), but with poor precision and a percentage of error >30%. A clinically useful alternative approach was developed by using on-CPB A10 to predict a Clauss fibrinogen range of interest instead of a discrete level. An on-CPB A10 ≤10 mm identified patients with a post-CPB Clauss fibrinogen of ≤1.5 g/l with a sensitivity of 0.99 and a positive predictive value of 0.60; it also identified those without a post-CPB Clauss fibrinogen <2.0 g/l with a specificity of 0.83. CONCLUSIONS: When measured on CPB prior to weaning, a FIBTEM A10 ≤10 mm is an early alert for post-CPB fibrinogen levels below or within the substitution range (1.5-2.0 g/l) recommended in case of post-CPB coagulopathic bleeding. This helps to minimize the delay to data-based hemostatic management after weaning from CPB.

Transcriptional regulator PRDM12 is essential for human pain perception.

Pain perception has evolved as a warning mechanism to alert organisms to tissue damage and dangerous environments. In humans, however, undesirable, excessive or chronic pain is a common and major societal burden for which available medical treatments are currently suboptimal. New therapeutic options have recently been derived from studies of individuals with congenital insensitivity to pain (CIP). Here we identified 10 different homozygous mutations in PRDM12 (encoding PRDI-BF1 and RIZ homology domain-containing protein 12) in subjects with CIP from 11 families. Prdm proteins are a family of epigenetic regulators that control neural specification and neurogenesis. We determined that Prdm12 is expressed in nociceptors and their progenitors and participates in the development of sensory neurons in Xenopus embryos. Moreover, CIP-associated mutants abrogate the histone-modifying potential associated with wild-type Prdm12. Prdm12 emerges as a key factor in the orchestration of sensory neurogenesis and may hold promise as a target for new pain therapeutics.

Les maladies rénales chroniques ne sont pas toutes silencieuses [Chronic kidney diseases do not always pass unnoticed].

Kidney diseases are frequent, but most of the time, they develop unnoticed. This paucity of symptoms may lead to delayed diagnosis with important consequences on their outcome. Nevertheless, specific systemic signs such as skin lesions, joint pain or electrolytes disturbances may sometimes alert the clinician and direct the diagnosis to an underlying nephropathy. A high awareness of clinicians is warranted to recognize these red flags and diagnose these diseases early, as illustrated by two clinical cases discussed in this article.

Caracterização hidrogeoquímica de água subterrânea em área de influência de futuras instalações de usinas hidrelétricas: bacia hidrográfica do rio Taquari-Antas/RS, Brasil

The identification and characterization of the hydrochemistry of the groundwaters has been done for seven wells. The sampling occurred during three bimonthly campaigns. The results classified the waters as of the calcium bicarbonated type for the majority of the samples, except for one well, whose composition is of the sodium bicarbonated type. The major ions found and how they determine the quality parameters are consistent with the reactions of mineral dissolution of the majority of volcanic rocks and the reactions with intrusion of alkaline rock in only one well. Anomalous values of nitrate in some wells alert to the impact of especially polluting sources at the time the reservoirs of the hydroeletric plant were formed.

Incorporació d'estratègies innovadores de la FEMA en la protecció civil de Catalunya

FEMA’s Integrated Public Alert and Warning System (IPAWS): El sistema integrat públic d’alertes i avisos de FEMA és una eina basada en internet que les autoritats Federals, Estatals, territorials, tribals i locals poden fer servir per enviar avisos i alertes públiques crítiques. IPAWS és accessible a través d’un software i uns requeriments de sistemes sense cost en l’enviament de missatge (tot i que sí pot tenir cost l’adaptació dels sistemes per la compatibilitat amb el software). No és obligatori i no substitueix els mecanismes existents d’alerta sinó que complementa els sistemes existents i ofereix noves capacitats.

¿Qué entienden los jóvenes universitarios por monogamia y sexo sin penetración, como estrategias preventivas de la transmisión sexual del virus del SIDA? = What university students understand by monogamy and sex without penetration as preventive strategies of sexual transmission of AIDS virus?

Monogamy and sex without penetration are behaviors recommended by the WHO to avoid AIDS virus sexual transmission. Seven hundred and fifty university students from 18 to 25 years (67.7% women) were surveyed and they were asked to give a maximum of three free definitions of the words monogamy and sex without penetration to prevent AIDS virus sexual transmission. Their participation was voluntary and anonymous. Although the majority of the answers was correct, there was a considerable percentage of wrong answers, either for monogamy (3.7% masturbation; 2.1% to have many partners; 0.9% homosexual relations), or for sex without penetration (20.5% oral sex; 1.1% anal coitus; 0.8% coitus without orgasm; 0.4% coitus interruptus). Some definitions or examples differ by gender. The amount of wrongs or incomplete answers put researchers on the alert about insufficient preventive knowledge in a population with a high educational level