2,951 research outputs found

    Primed to Sleep: The Dynamics of Synaptic Plasticity Across Brain States

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    It is commonly accepted that brain plasticity occurs in wakefulness and sleep. However, how these different brain states work in concert to create long-lasting changes in brain circuitry is unclear. Considering that wakefulness and sleep are profoundly different brain states on multiple levels (e.g., cellular, molecular and network activation), it is unlikely that they operate exactly the same way. Rather it is probable that they engage different, but coordinated, mechanisms. In this article we discuss how plasticity may be divided across the sleepā€“wake cycle, and how synaptic changes in each brain state are linked. Our working model proposes that waking experience triggers short-lived synaptic events that are necessary for transient plastic changes and mark (i.e., ā€˜primeā€™) circuits and synapses for further processing in sleep. During sleep, synaptic protein synthesis at primed synapses leads to structural changes necessary for long-term information storage

    Estimating the opportunity costs of bed-days.

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    Opportunity costs of bed-days are fundamental to understanding the value of healthcare systems. They greatly influence burden of disease estimations and economic evaluations involving stays in healthcare facilities. However, different estimation techniques employ assumptions that differ crucially in whether to consider the value of the second-best alternative use forgone, of any available alternative use, or the value of the actually chosen alternative. Informed by economic theory, this paper provides a taxonomic framework of methodologies for estimating the opportunity costs of resources. This taxonomy is then applied to bed-days by classifying existing approaches accordingly. We highlight differences in valuation between approaches and the perspective adopted, and we use our framework to appraise the assumptions and biases underlying the standard approaches that have been widely adopted mostly unquestioned in the past, such as the conventional use of reference costs and administrative accounting data. Drawing on these findings, we present a novel approach for estimating the opportunity costs of bed-days in terms of health forgone for the second-best patient, but expressed monetarily. This alternative approach effectively re-connects to the concept of choice and explicitly considers net benefits. It is broadly applicable across settings and for other resources besides bed-days

    Genome of Drosophila suzukii, the spotted wing drosophila.

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    Drosophila suzukii Matsumura (spotted wing drosophila) has recently become a serious pest of a wide variety of fruit crops in the United States as well as in Europe, leading to substantial yearly crop losses. To enable basic and applied research of this important pest, we sequenced the D. suzukii genome to obtain a high-quality reference sequence. Here, we discuss the basic properties of the genome and transcriptome and describe patterns of genome evolution in D. suzukii and its close relatives. Our analyses and genome annotations are presented in a web portal, SpottedWingFlyBase, to facilitate public access

    721-6 Pulmonary Balloon Valvuloplasty: Effective Palliation for Infants with Tetralogy of Fallot and Small Pulmonary Arteries

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    Infants with tetralogy of Fallot (TOF) and small pulmonary arteries (PAs) may need palliation to improve pulmonary blood flow and allow growth of the PAs prior to complete repair. Shunts may become occluded, distort the PAs or cause pulmonary overcirculation. As an alternative palliation, we performed pulmonary balloon valvuloplasty (PBV) on infants with TOF and small PAs.20 infants, ages 1.8Ā±1.5 mo and weights 4.1Ā±1.6kg, undervvent PBV as initial palliation for persistent cyanosis or ā€œspellsā€. 4/20 pts were intubated prior to or for PBV All pts had pre and post-PBV angiograms. In all pts, single balloon valvuloplasty was performed. The ratio of balloon: pulmonary valve annulus (PVA) diameter was 1.51Ā±0.32. Post-PBV, there was no change in the PYA diameter (5.2Ā±1.1mm vs 5.6 + 1.1mm; p=0.1) or PA branch diameter(4.1Ā±1.6mm vs 4.5Ā±1.7mm, p>0.05). The systemic 02 saturation increased from 81Ā±8% to 93Ā±6%. (p<0.001)7/20 pts undervvent follow-up (F/U) cath 8.2Ā±2.4 mo post-PBV Compared to pre-PBV measurements, the PYA diameter increased from 5.2 Ā± 1.1mm to 7.1Ā±1.4mm (p<0.03) and the McGoon ratio increased from 1.4Ā±0.4 to 2.1Ā±0.3 (p<0.02).Of the 20 pts, 11 pts undervvent corrective surgery 8.0Ā±3.1 mo post-PBV with no surgical deaths; 5 pts remain in stable condition awaiting surgery; 3 pts required shunt placement 9-66 days post-PBV; 1 pt died due to other congenital anomalies.ConclusionsPulmonary balloon valvuloplasty promotes growth of the PAs and PYA in infants with TOF and small PAs, offering a safe and effective alternative palliation for infants who are not yet candidates for complete repair

    Estimating the Hospital Burden of Norovirus-Associated Gastroenteritis in England and Its Opportunity Costs for Nonadmitted Patients.

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    Background: Norovirus places a substantial burden on healthcare systems, arising from infected patients, disease outbreaks, beds kept unoccupied for infection control, and staff absences due to infection. In settings with high rates of bed occupancy, opportunity costs arise from patients who cannot be admitted due to beds being unavailable. With several treatments and vaccines against norovirus in development, quantifying the expected economic burden is timely. Methods: The number of inpatients with norovirus-associated gastroenteritis in England was modeled using infectious and noninfectious gastrointestinal Hospital Episode Statistics codes and laboratory reports of gastrointestinal pathogens collected at Public Health England. The excess length of stay from norovirus was estimated with a multistate model and local outbreak data. Unoccupied bed-days and staff absences were estimated from national outbreak surveillance. The burden was valued conventionally using accounting expenditures and wages, which we contrasted to the opportunity costs from forgone patients using a novel methodology. Results: Between July 2013 and June 2016, 17.7% (95% confidence interval [CI], 15.6%ā€’21.6%) of primary and 23.8% (95% CI, 20.6%ā€’29.9%) of secondary gastrointestinal diagnoses were norovirus attributable. Annually, the estimated median 290000 (interquartile range, 282000ā€’297000) occupied and unoccupied bed-days used for norovirus displaced 57800 patients. Conventional costs for the National Health Service reached Ā£107.6 million; the economic burden approximated to Ā£297.7 million and a loss of 6300 quality-adjusted life-years annually. Conclusions: In England, norovirus is now the second-largest contributor of the gastrointestinal hospital burden. With the projected impact being greater than previously estimated, improved capture of relevant opportunity costs seems imperative for diseases such as norovirus

    False positive acetaminophen concentrations in patients with liver injury

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    AbstractBackgroundAcetaminophen toxicity is the most common form of acute liver failure in the U.S. After acetaminophen overdoses, quantitation of plasma acetaminophen can aid in predicting severity of injury. However, recent case reports have suggested that acetaminophen concentrations may be falsely increased in the presence of hyperbilirubinemia.MethodsWe tested sera obtained from 43 patients with acute liver failure, mostly unrelated to acetaminophen, utilizing 6 different acetaminophen quantitation systems to determine the significance of this effect. In 36 of the 43 samples with bilirubin concentrations ranging from 1.0ā€“61.5Ā mg/dl no acetaminophen was detectable by gas chromatography-mass spectroscopy. These 36 samples were then utilized to test the performance characteristics of 2 immunoassay and 4 enzymaticā€“colorimetric methods.ResultsThree of four colorimetric methods demonstrated ā€˜detectableā€™ values for acetaminophen in from 4 to 27 of the 36 negative samples, low concentration positive values being observed when serum bilirubin concentrations exceeded 10Ā mg/dl. By contrast, the 2 immunoassay methods (EMIT, FPIA) were virtually unaffected. The false positive values obtained were, in general, proportional to the quantity of bilirubin in the sample. However, prepared samples of normal human serum with added bilirubin showed a doseā€“response curve for only one of the 4 colorimetric assays.ConclusionsFalse positive acetaminophen tests may result when enzymaticā€“colorimetric assays are used, most commonly with bilirubin concentrations >10Ā mg/dl, leading to potential clinical errors in this setting. Bilirubin (or possibly other substances in acute liver failure sera) appears to affect the reliable measurement of acetaminophen, particularly with enzymaticā€“colorimetric assays

    Correlations of gene expression with ratings of inattention and hyperactivity/impulsivity in tourette syndrome:a pilot study

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    BACKGROUND: Inattentiveness, impulsivity and hyperactivity are the primary behaviors associated with attention-deficit hyperactivity disorder (ADHD). Previous studies showed that peripheral blood gene expression signatures can mirror central nervous system disease. Tourette syndrome (TS) is associated with inattention (IA) and hyperactivity/impulsivity (HI) symptoms over 50% of the time. This study determined if gene expression in blood correlated significantly with IA and/or HI rating scale scores in participants with TS. METHODS: RNA was isolated from the blood of 21 participants with TS, and gene expression measured on Affymetrix human U133 Plus 2.0 arrays. To identify the genes that correlated with Connersā€™ Parents Ratings of IA and HI ratings of symptoms, an analysis of covariance (ANCOVA) was performed, controlling for age, gender and batch. RESULTS: There were 1201 gene probesets that correlated with IA scales, 1625 that correlated with HI scales, and 262 that correlated with both IA and HI scale scores (P<0.05, |Partial correlation (r(p))|>0.4). Immune, catecholamine and other neurotransmitter pathways were associated with IA and HI behaviors. A number of the identified genes (n=27) have previously been reported in ADHD genetic studies. Many more genes correlated with either IA or HI scales alone compared to those that correlated with both IA and HI scales. CONCLUSIONS: These findings support the concept that the pathophysiology of ADHD and/or its subtypes in TS may involve the interaction of multiple genes. These preliminary data also suggest gene expression may be useful for studying IA and HI symptoms that relate to ADHD in TS and perhaps non-TS participants. These results will need to be confirmed in future studies
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