Statistical Evaluation of Evidence for Clonal Allelic Alterations in array-CGH Experiments

In recent years numerous investigators have conducted genetic studies of pairs of tumor specimens from the same patient to determine whether the tumors share a clonal origin. These studies have the potential to be of considerable clinical significance, especially in clinical settings where the distinction of a new primary cancer and metastatic spread of a previous cancer would lead to radically different indications for treatment. Studies of clonality have typically involved comparison of the patterns of somatic mutations in the tumors at candidate genetic loci to see if the patterns are sufficiently similar to indicate a clonal origin. More recently, some investigators have explored the use of array CGH for this purpose. Standard clustering approaches have been used to analyze the data, but these existing statistical methods are not suited to this problem due to the paired nature of the data, and the fact that there exists no “gold standard” diagnosis to provide a definitive determination of which pairs are clonal and which pairs are of independent origin. In this article we propose a new statistical method that focuses on the individual allelic gains or losses that have been identified in both tumors, and a statistical test is developed that assesses the degree of matching of the locations of the markers that indicate the endpoints of the allelic change. The validity and statistical power of the test is evaluated, and it is shown to be a promising approach for establishing clonality in tumor samples

Effects of a Parallel Magnetic Field on the Metal-Insulator Transition in a Dilute Two-Dimensional Electron System

The temperature dependence of conductivity $\sigma (T)$ of a two-dimensional electron system in silicon has been studied in parallel magnetic fields B. At B=0, the system displays a metal-insulator transition at a critical electron density $n_c(0)$, and $d\sigma/dT >0$ in the metallic phase. At low fields ($B\lesssim 2$ T), $n_c$ increases as $n_c(B) - n_c(0) \propto B^{\beta}$ ($\beta\sim 1$), and the zero-temperature conductivity scales as $\sigma (n_s,B,T=0)/\sigma (n_s,0,0)=f(B^{\beta}/\delta_n)$ (where $\delta_n=(n_s-n_c(0))/n_c(0)$, and $n_s$ is electron density) as expected for a quantum phase transition. The metallic phase persists in fields of up to 18 T, consistent with the saturation of $n_c$ at high fields

Extremely efficient clocked electron transfer on superfluid helium

Unprecedented transport efficiency is demonstrated for electrons on the surface of micron-scale superfluid helium filled channels by co-opting silicon processing technology to construct the equivalent of a charge-coupled device (CCD). Strong fringing fields lead to undetectably rare transfer failures after over a billion cycles in two dimensions. This extremely efficient transport is measured in 120 channels simultaneously with packets of up to 20 electrons, and down to singly occupied pixels. These results point the way towards the large scale transport of either computational qubits or electron spin qubits used for communications in a hybrid qubit system

Non-invasive ventilation in patients with an altered level of consciousness : a clinical review and practical insights

Non-invasive ventilation has gained an increasingly pivotal role in the treatment of acute hypoxemic and/or hypercapnic respiratory failure and offers multiple advantages over invasive mechanical ventilation. Some of these advantages include the preservation of airway defense mechanisms, a reduced need for sedation, and an avoidance of complications related to endotracheal intubation. Despite its advantages, non-invasive ventilation has some contraindications that include, among them, severe encephalopathy. In this review article, the rationale, evidence, and drawbacks of the use of noninvasive ventilation in the context of hypercapnic and non-hypercapnic patients with an altered level of consciousness are analyzed

ETISEQ – an algorithm for automated elution time ion sequencing of concurrently fragmented peptides for mass spectrometry-based proteomics

<p>Abstract</p> <p>Background</p> <p>Concurrent peptide fragmentation (i.e. shotgun CID, parallel CID or MS^E) has emerged as an alternative to data-dependent acquisition in generating peptide fragmentation data in LC-MS/MS proteomics experiments. Concurrent peptide fragmentation data acquisition has been shown to be advantageous over data-dependent acquisition by providing greater detection dynamic range and providing more accurate quantitative information. Nevertheless, concurrent peptide fragmentation data acquisition remains to be widely adopted due to the lack of published algorithms designed specifically to process or interpret such data acquired on any mass spectrometer.</p> <p>Results</p> <p>An algorithm called Elution Time Ion Sequencing (ETISEQ), has been developed to enable automated conversion of concurrent peptide fragmentation data acquisition data to LC-MS/MS data. ETISEQ generates MS/MS-like spectra based on the correlation of precursor and product ion elution profiles. The performance of ETISEQ is demonstrated using concurrent peptide fragmentation data from tryptic digests of standard proteins and whole influenza virus. It is shown that the number of unique peptides identified from the digests is broadly comparable between ETISEQ processed concurrent peptide fragmentation data and the data-dependent acquired LC-MS/MS data.</p> <p>Conclusion</p> <p>The ETISEQ algorithm has been designed for easy integration with existing MS/MS analysis platforms. It is anticipated that it will popularize concurrent peptide fragmentation data acquisition in proteomics laboratories.</p

COMT Val 158 Met polymorphism is associated with nonverbal cognition following mild traumatic brain injury

Mild traumatic brain injury (mTBI) results in variable clinical outcomes, which may be influenced by genetic variation. A single-nucleotide polymorphism in catechol-o-methyltransferase (COMT), an enzyme which degrades catecholamine neurotransmitters, may influence cognitive deficits following moderate and/or severe head trauma. However, this has been disputed, and its role in mTBI has not been studied. Here, we utilize the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot) study to investigate whether the COMT Val (158) Met polymorphism influences outcome on a cognitive battery 6 months following mTBI--Wechsler Adult Intelligence Test Processing Speed Index Composite Score (WAIS-PSI), Trail Making Test (TMT) Trail B minus Trail A time, and California Verbal Learning Test, Second Edition Trial 1-5 Standard Score (CVLT-II). All patients had an emergency department Glasgow Coma Scale (GCS) of 13-15, no acute intracranial pathology on head CT, and no polytrauma as defined by an Abbreviated Injury Scale (AIS) score of ≥3 in any extracranial region. Results in 100 subjects aged 40.9 (SD 15.2) years (COMT Met (158) /Met (158) 29 %, Met (158) /Val (158) 47 %, Val (158) /Val (158) 24 %) show that the COMT Met (158) allele (mean 101.6 ± SE 2.1) associates with higher nonverbal processing speed on the WAIS-PSI when compared to Val (158) /Val (158) homozygotes (93.8 ± SE 3.0) after controlling for demographics and injury severity (mean increase 7.9 points, 95 % CI [1.4 to 14.3], p = 0.017). The COMT Val (158) Met polymorphism did not associate with mental flexibility on the TMT or with verbal learning on the CVLT-II. Hence, COMT Val (158) Met may preferentially modulate nonverbal cognition following uncomplicated mTBI.Registry: ClinicalTrials.gov Identifier NCT01565551

Non-invasive ventilation in patients with an altered level of consciousness. A clinical review and practical insights

Non-invasive ventilation has gained an increasingly pivotal role in the treatment of acute hypoxemic and/or hypercapnic respira-tory failure and offers multiple advantages over invasive mechanical ventilation. Some of these advantages include the preserva-tion of airway defense mechanisms, a reduced need for sedation, and an avoidance of complications related to endotracheal intubation.Despite its advantages, non-invasive ventilation has some contraindications that include, among them, severe encephalopathy. In this review article, the rationale, evidence, and drawbacks of the use of noninvasive ventilation in the context of hypercapnic and non-hypercapnic patients with an altered level of consciousness are analyzed

Status and prospects for renewable energy using wood pellets from the southeastern United States

The ongoing debate about costs and benefits of wood-pellet based bioenergy production in the southeastern United States (SE USA) requires an understanding of the science and context influencing market decisions associated with its sustainability. Production of pellets has garnered much attention as US exports have grown from negligible amounts in the early 2000s to 4.6 million metric tonnes in 2015. Currently, 98% of these pellet exports are shipped to Europe to displace coal in power plants. We ask, ‘How is the production of wood pellets in the SE USA affecting forest systems and the ecosystem services they provide?’ To address this question, we review current forest conditions and the status of the wood products industry, how pellet production affects ecosystem services and biodiversity, and what methods are in place to monitor changes and protect vulnerable systems. Scientific studies provide evidence that wood pellets in the SE USA are a fraction of total forestry operations and can be produced while maintaining or improving forest ecosystem services. Ecosystem services are protected by the requirement to utilize loggers trained to apply scientifically based best management practices in planning and implementing harvest for the export market. Bioenergy markets supplement incomes to private rural landholders and provide an incentive for forest management practices that simultaneously benefit water quality and wildlife and reduce risk of fire and insect outbreaks. Bioenergy also increases the value of forest land to landowners, thereby decreasing likelihood of conversion to nonforest uses. Monitoring and evaluation are essential to verify that regulations and good practices are achieving goals and to enable timely responses if problems arise. Conducting rigorous research to understand how conditions change in response to management choices requires baseline data, monitoring, and appropriate reference scenarios. Long-term monitoring data on forest conditions should be publicly accessible and utilized to inform adaptive management