Holding the line: Confederate defense of the Staunton-Parkersburg Turnpike in the Fall of 1861

In June and Juy of 1861 the American Civil War\u27s first land campaign was conducted along the Staunton-Parkersburg turnpike in western Virginia. Although insignificant in the war\u27s eventual outcome, the early campaign in western Virginia seemed consequential at the time for several reasons. First, the Union offensive into the region was the initial military campaign of the war. As a result, news of the fighting in western Virginia was closely followed by citizens both North and South. Second, the region appeared to have strategic significance. If the Confederacy could hold all of Virginia, the northwestern portion of the state could be used as a staging ground for offensives into boarding Union states. Conversely, Union control would protect the B&O Railroad, a vital east-west corridor. Third, and perhaps most significantly, the 1861 Union offensive into western Virginia appeared to have importance due to the presence of the ambitious General George B. McClellan, whose actions were magnified by the Northern press

Purines and Neuronal Excitability: Links to the Ketogenic Diet [post-print]

ATP and adenosine are purines that play dual roles in cell metabolism and neuronal signaling. Acting at the A(1) receptor (A(1)R) subtype, adenosine acts directly on neurons to inhibit excitability and is a powerful endogenous neuroprotective and anticonvulsant molecule. Previous research showed an increase in ATP and other cell energy parameters when an animal is administered a ketogenic diet, an established metabolic therapy to reduce epileptic seizures, but the relationship among purines, neuronal excitability and the ketogenic diet was unclear. Recent work in vivo and in vitro tested the specific hypothesis that adenosine acting at A(1)Rs is a key mechanism underlying the success of ketogenic diet therapy and yielded direct evidence linking A(1)Rs to the antiepileptic effects of a ketogenic diet. Specifically, an in vitro mimic of a ketogenic diet revealed an A(1)R-dependent metabolic autocrine hyperpolarization of hippocampal neurons. In parallel, applying the ketogenic diet in vivo to transgenic mouse models with spontaneous electrographic seizures revealed that intact A(1)Rs are necessary for the seizure-suppressing effects of the diet. This is the first direct in vivo evidence linking A(1)Rs to the antiepileptic effects of a ketogenic diet. Other predictions of the relationship between purines and the ketogenic diet are discussed. Taken together, recent research on the role of purines may offer new opportunities for metabolic therapy and insight into its underlying mechanisms

Purines and the Anti-Epileptic Actions of Ketogenic Diets

Ketogenic diets are high in fat and low in carbohydrates and represent a well-established and effective treatmentalternative to anti-epileptic drugs. Ketogenic diets are used for the management of a variety of difficult-to-treat or intractableseizure disorders, especially pediatric refractory epilepsy. However, it has been shown that this dietary therapycan reduce seizures in people of all ages, and ketogenic diets are being applied to other prevalent medical conditions suchas diabetes. Although used effectively to treat epilepsy for nearly 90 years, the mechanism(s) by which ketogenic dietswork to reduce seizures remain ill-understood. One mechanism receiving increased attention is based on findings that ketogenicdiets increase the brain energy molecule ATP, and may also increase the levels and actions of the related endogenousinhibitory neuromodulator adenosine. ATP and adenosine have both been identified as important modulators of seizures;seizures increase the actions of these purines, these purines regulate epileptic activity in brain, adenosine receptorantagonists are pro-convulsant, and adenosinergic mechanisms have been implicated previously in the actions of approvedanti-epileptic therapeutics. Here we will review recent literature and describe findings that shed light on mechanistic relationshipsbetween ketogenic diets and the purines ATP and adenosine. These emerging mechanisms hold great promisefor the effective therapeutic management of epileptic seizures and other neurological conditions

Mortality of Patients with Hematological Malignancy after Admission to the Intensive Care Unit

Background: The admission of patients with malignancies to an intensive care unit (ICU) still remains a matter of substantial controversy. The identification of factors that potentially influence the patient outcome can help ICU professionals make appropriate decisions. Patients and Methods: 90 adult patients with hematological malignancy (leukemia 47.8%, high-grade lymphoma 50%) admitted to the ICU were analyzed retrospectively in this single-center study considering numerous variables with regard to their influence on ICU and day-100 mortality. Results: The median simplified acute physiology score (SAPS) II at ICU admission was 55 (ICU survivors 47 vs. 60.5 for non-survivors). The overall ICU mortality rate was 45.6%. With multivariate regression analysis, patients admitted with sepsis and acute respiratory failure had a significantly increased ICU mortality (sepsis odds ratio (OR) 9.12, 95% confidence interval (CI) 1.1-99.7, p = 0.04; respiratory failure OR 13.72, 95% CI 1.39-136.15, p = 0.025). Additional factors associated with an increased mortality were: high doses of catecholamines (ICU: OR 7.37, p = 0.005; day 100: hazard ratio (HR) 2.96, p < 0.0001), renal replacement therapy (day 100: HR 1.93, p = 0.026), and high SAPS II (ICU: HR 1.05, p = 0.038; day 100: HR 1.2, p = 0.027). Conclusion: The decision for or against ICU admission of patients with hematological diseases should become increasingly independent of the underlying malignant disease

Next-generation sequencing reveals substantial genetic contribution to dementia with Lewy bodies

Dementia with Lewy bodies (DLB) is the second most common neurodegenerative dementia after Alzheimer's disease. Although an increasing number of genetic factors have been connected to this debilitating condition, the proportion of cases that can be attributed to distinct genetic defects is unknown. To provide a comprehensive analysis of the frequency and spectrum of pathogenic missense mutations and coding risk variants in nine genes previously implicated in DLB, we performed exome sequencing in 111 pathologically confirmed DLB patients. All patients were Caucasian individuals from North America. Allele frequencies of identified missense mutations were compared to 222 control exomes. Remarkably, ~ 25% of cases were found to carry a pathogenic mutation or risk variant in APP, GBA or PSEN1, highlighting that genetic defects play a central role in the pathogenesis of this common neurodegenerative disorder. In total, 13% of our cohort carried a pathogenic mutation in GBA, 10% of cases carried a risk variant or mutation in PSEN1, and 2% were found to carry an APP mutation. The APOE ε4 risk allele was significantly overrepresented in DLB patients (p-value < 0.001). Our results conclusively show that mutations in GBA, PSEN1, and APP are common in DLB and consideration should be given to offer genetic testing to patients diagnosed with Lewy body dementia

Answer changing in multiple choice assessment change that answer when in doubt – and spread the word!

<p>Abstract</p> <p>Background</p> <p>Several studies during the last decades have shown that answer changing in multiple choice examinations is generally beneficial for examinees. In spite of this the common misbelief still prevails that answer changing in multiple choice examinations results in an increased number of wrong answers rather than an improved score. One suggested consequence of newer studies is that examinees should be informed about this misbelief in the hope that this prejudice might be eradicated. This study aims to confirm data from previous studies about the benefits of answer changing as well as pursue the question of whether students informed about the said advantageous effects of answer changing would indeed follow this advice and change significantly more answers. Furthermore a look is cast on how the overall examination performance and mean point increase of these students is affected.</p> <p>Methods</p> <p>The answer sheets to the end of term exams of 79 3^rdyear medical students at the University of Munich were analysed to confirm the benefits of answer changing. Students taking the test were randomized into two groups. Prior to taking the test 41 students were informed about the benefits of changing answers after careful reconsideration while 38 students did not receive such information. Both groups were instructed to mark all answer changes made during the test.</p> <p>Results</p> <p>Answer changes were predominantly from wrong to right in full accordance with existing literature resources. It was shown that students who had been informed about the benefits of answer changing when in doubt changed answers significantly more often than students who had not been informed. Though students instructed on the benefits of changing answers scored higher in their exams than those not instructed, the difference in point increase was not significant.</p> <p>Conclusion</p> <p>Students should be informed about the benefits of changing initial answers to multiple choice questions once when in reasonable doubt about these answers. Furthermore, reconsidering answers should be encouraged as students will heed the advice and change more answers than students not so instructed.</p

Results of endoscopic biliary drainage in patients with malignant hilar stricture

In Malignant Hilar Biliary Stricture (MHBS) palliative biliary drainage is a frequent strategy, improving the quality of life, reducing pruritus, loss of appetite and relieving cholangitis. The endoscopic approach is an effective, although challenging procedure. This study aimed to evaluate technical and clinical success rates of biliary drainage by ERCP. This is a retrospective study including all patients with MHBS referred to Instituto do Cancer do Hospital de São Paulo (ICESP) submitted to biliary drainage by ERCP, between January 2010 and December 2017. Multivariable logistic regression was performed to evaluate predictors of clinical failure, as total bilirubin levels, Bismuth classification, number of hepatic sectors drained and presence of cholangitis. In total, 82 patients presenting unresectable MHBS were included in this study. 58.5% female and 41.5% male, with a mean age of 60±13 years. Bismuth classification grades II, IIIA, IIIB and IV were noted in 23.2%, 15.9%, 14.6% and 46.3%, respectively. Technical and clinical success was achieved in 92.7% and 53.7% respectively. At multivariable logistic-regression analyses, Bismuth IV strictures were related to higher clinical failure rates when compared to other strictures levels, with an Odds Ratio of 5.8 (95% CI 1.28‒20.88). In conclusion, endoscopic biliary drainage for malignant hilar biliary stricture had a high technical success but suboptimal clinical success rate. Proximal strictures (Bismuth IV) were associated with poor drainage outcomes

URBAN WOOD/COAL CO-FIRING IN THE NIOSH BOILERPLANT

During the third quarter, the experimental portion of the project was carried out. Three one-day tests using wood/coal blends of 33% wood by volume (both construction wood and demolition wood) were conducted at the NIOSH Boiler Plant (NBP). Blends using hammer-milled wood were operationally successful and can form the basis of Phase II. Emissions of SO{sub 2} and NOx decreased and that of CO increased when compared with combusting coal alone. Mercury emissions were measured and the mathematical modeling of mercury speciation reactions continued, yielding many interesting results. Material and energy balances for the test periods at the NBP, as well as at the Bellefield Boiler Plant, were prepared. Steps were taken to remove severe constraints from the Pennsylvania Switchgrass Energy and Conservation Project and to organize the supplying of landfill gas to the Bruceton federal complex. Two presentations were made to meetings of the Electric Power Research Institute and the National Energy Technology Laboratory

History of Reading Struggles Linked to Enhanced Learning in Low Spatial Frequency Scenes

People with dyslexia, who face lifelong struggles with reading, exhibit numerous associated low-level sensory deficits including deficits in focal attention. Countering this, studies have shown that struggling readers outperform typical readers in some visual tasks that integrate distributed information across an expanse. Though such abilities would be expected to facilitate scene memory, prior investigations using the contextual cueing paradigm failed to find corresponding advantages in dyslexia. We suggest that these studies were confounded by task-dependent effects exaggerating known focal attention deficits in dyslexia, and that, if natural scenes were used as the context, advantages would emerge. Here, we investigate this hypothesis by comparing college students with histories of severe lifelong reading difficulties (SR) and typical readers (TR) in contexts that vary attention load. We find no differences in contextual-cueing when spatial contexts are letter-like objects, or when contexts are natural scenes. However, the SR group significantly outperforms the TR group when contexts are low-pass filtered natural scenes [F(3, 39) = 3.15, p<.05]. These findings suggest that perception or memory for low spatial frequency components in scenes is enhanced in dyslexia. These findings are important because they suggest strengths for spatial learning in a population otherwise impaired, carrying implications for the education and support of students who face challenges in school

Photoproduction off Nuclei and Point-like Photon Interactions Part I: Cross Sections and Nuclear Shadowing

High energy photoproduction off nuclear targets is studied within the Glauber-Gribov approximation. The photon is assumed to interact as a $q\bar{q}$-system according to the Generalized Vector Dominance Model and as a ``bare photon'' in direct scattering processes with target nucleons. We calculate total cross sections for interactions of photons with nuclei taking into account coherence length effects and point-like interactions of the photon. Results are compared to data on photon-nucleus cross sections, nuclear shadowing, and quasi- elastic $\rho$-production. Extrapolations of cross sections and of the shadowing behaviour to high energies are given.Comment: 15 pages, 12 figure