Frequency and Severity of Neutropenia Associated with Food and Drug Administration Approved and Compounded Formulations of Lomustine in Dogs with Cancer.

BackgroundCompounded lomustine is used commonly in veterinary patients. However, the potential variability in these formulations is unknown and concern exists that compounded formulations of drugs may differ in potency from Food and Drug Administration (FDA)-approved products.Hypothesis/objectivesThe initial objective of this study was to evaluate the frequency and severity of neutropenia in dogs treated with compounded or FDA-approved formulations of lomustine. Subsequent analyses aimed to determine the potency of lomustine obtained from several compounding pharmacies.AnimalsThirty-seven dogs treated with FDA-approved or compounded lomustine.MethodsDogs that received compounded or FDA-approved lomustine and had pretreatment and nadir CBCs performed were eligible for inclusion. Variables assessed included lomustine dose, neutrophil counts, and severity of neutropenia. Lomustine 5 mg capsules from 5 compounding sources were tested for potency using high-pressure liquid chromatography (HPLC) with ultraviolet (UV) detection.ResultsTwenty-one dogs received FDA-approved lomustine and 16 dogs were treated with lomustine prescribed from a single compounding pharmacy. All dogs treated with FDA-approved lomustine were neutropenic after treatment; 15 dogs (71%) developed grade 3 or higher neutropenia. Four dogs (25%) given compounded lomustine became neutropenic, with 2 dogs (12.5%) developing grade 3 neutropenia. The potency of lomustine from 5 compounding pharmacies ranged from 50 to 115% of the labeled concentration, with 1 sample within ±10% of the labeled concentration.Conclusions and clinical importanceThese data support broader investigation into the potency and consistency of compounded chemotherapy drugs and highlight the potential need for greater oversight of these products

Diagnostic yield of cytologic analysis of pericardial effusion in dogs.

BackgroundPericardial effusion cytology is believed by many to be of limited value, yet few studies have evaluated its diagnostic utility.ObjectivesTo determine the diagnostic utility of cytologic analysis of pericardial effusion in dogs and to determine if consideration of additional data could improve the diagnostic yield.AnimalsTwo hundred and fifty-nine dogs with cytologic analysis of pericardial effusion performed between April 1990 and June 2012.MethodsElectronic medical records from a university teaching hospital were retrospectively reviewed; signalment, complete blood count, serum biochemistry, cytologic analysis of pericardial effusion, and echocardiographic data were recorded. Cytology was classified as diagnostic (infectious or neoplastic) or nondiagnostic (hemorrhagic or other) and groups were compared with multiple Student's t-tests.ResultsCytology was grouped as nondiagnostic (92.3%) or diagnostic (7.7%) and characterized as hemorrhagic (90%), neoplastic (4.6%), infectious (3.1%), or other (2.3%). Overall cytologic analysis of pericardial effusion diagnostic utility was 7.7% and increased to 20.3% if the effusion hematocrit (HCT) <10%; echocardiographic evidence of a mass did not result in a significant increase in the diagnostic utility.Conclusions and clinical importanceThe diagnostic utility of cytologic analysis of canine pericardial effusion is variable depending on the underlying etiology. In this group of dogs, the diagnostic yield of cytologic analysis was greater for pericardial effusion samples in which the HCT was less than 10%

Potential uses of Numerical Simulation for the Modelling of Civil Conflict

This paper explores ways in which civil conflict can be simulated using numerical methods. A general two-party model of conflict is developed by extending an approach proposed by [Christia, F., (2012), Alliance Formation in Civil Wars, Cambridge University Press, New York], which is based on a metric of the 'relative power' that exists between the state and a rebel group. Various definitions of relative power are considered and one of these is chosen to illustrate different types of two-sided armed conflict, namely direct-fire, guerrilla and asymmetric warfare. The additional suggestion of Christia that random or stochastic events can lead to unexpected conflict outcomes is also further extended in this paper. The inclusion in the model of terms describing concurrent rebel recruitment of civilians and state deployment of troops are then described. Examples are presented for various hypothetical cases. It is demonstrated that numerical simulation techniques have great potential for modelling civil war. The Christia approach is shown to provide an excellent basis from which numerical models of civil conflict can be built and from which the progress of a conflict can usefully be visualised graphically

The Use of a Numerical Weather Prediction Model to Simulate Near-Field Volcanic Plumes

In this paper, a state-of the art numerical weather prediction (NWP) model is used to simulate the near-field plume of a Plinian-type volcanic eruption. The NWP model is run at very high resolution (of the order of 100 m) and includes a representation of physical processes, including turbulence and buoyancy, that are essential components of eruption column dynamics. Results are shown that illustrate buoyant gas plume dynamics in an atmosphere at rest and in an atmosphere with background wind, and we show that these results agree well with those from theoretical models in the quiescent atmosphere. For wind-blown plumes, we show that features observed in experimental and natural settings are reproduced in our model. However, when comparing with predictions from an integral model using existing entrainment closures there are marked differences. We speculate that these are signatures of a difference in turbulent mixing for uniform and shear flow profiles in a stratified atmosphere. A more complex implementation is given to show that the model may also be used to examine the dispersion of heavy volcanic gases such as sulphur dioxide. Starting from the standard version of the weather research and forecasting (WRF) model, we show that minimal modifications are needed in order to model volcanic plumes. This suggests that the modified NWP model can be used in the forecasting of plume evolution during future volcanic events, in addition to providing a virtual laboratory for the testing of hypotheses regarding plume behaviour

The Dynamics of Observed Lee Waves over the Snæfellsnes Peninsula in Iceland

On 20 October 2016, aircraft observations documented a significant train of lee waves above and downstream of the Snæfellsnes Peninsula on the west coast of Iceland. Simulations of this event with the Weather Research and Forecasting (WRF) Model provide an excellent representation of the observed structure of these mountain waves. The orographic features producing these waves are characterized by the isolated Snæfellsjökull volcano near the tip of the peninsula and a fairly uniform ridge along its spine. Sensitivity simulations with the WRF Model document that the observed wave train consists of a superposition of the waves produced individually by these two dominant orographic features. This behavior is consistent with idealized simulations of a flow over an isolated 3D mountain and over a 2D ridge, which reproduce the essential behavior of the observed waves and those captured in the WRF simulations. Linear analytic analysis confirms the importance of a strong inversion at the top on the boundary layer in promoting significant wave activity extending far downstream of the terrain. However, analysis of the forced and resonant modes for a two-layer atmosphere with a capping inversion suggest that this wave train may not be produced by resonant modes whose energy is trapped beneath the inversion. Rather, these appear to be vertically propagating modes with very small vertical group velocity that can persist far downstream of the mountain. These vertically propagating waves potentially provide a mechanism for producing near-resonant waves farther aloft due to interactions with a stable layer in the midtroposphere

Establishing a Statistical Link between Network Oscillations and Neural Synchrony

Pairs of active neurons frequently fire action potentials or “spikes” nearly synchronously (i.e., within 5 ms of each other). This spike synchrony may occur by chance, based solely on the neurons’ fluctuating firing patterns, or it may occur too frequently to be explicable by chance alone. When spike synchrony above chances levels is present, it may subserve computation for a specific cognitive process, or it could be an irrelevant byproduct of such computation. Either way, spike synchrony is a feature of neural data that should be explained. A point process regression framework has been developed previously for this purpose, using generalized linear models (GLMs). In this framework, the observed number of synchronous spikes is compared to the number predicted by chance under varying assumptions about the factors that affect each of the individual neuron’s firing-rate functions. An important possible source of spike synchrony is network-wide oscillations, which may provide an essential mechanism of network information flow. To establish the statistical link between spike synchrony and network-wide oscillations, we have integrated oscillatory field potentials into our point process regression framework. We first extended a previously-published model of spike-field association and showed that we could recover phase relationships between oscillatory field potentials and firing rates. We then used this new framework to demonstrate the statistical relationship between oscillatory field potentials and spike synchrony in: 1) simulated neurons, 2) in vitro recordings of hippocampal CA1 pyramidal cells, and 3) in vivo recordings of neocortical V4 neurons. Our results provide a rigorous method for establishing a statistical link between network oscillations and neural synchrony

First trimester myomectomy as an alternative to termination of pregnancy in a woman with a symptomatic uterine leiomyoma: a case report

<p>Abstract</p> <p>Introduction</p> <p>Performing a myomectomy during pregnancy is extremely rare due to the risk of pregnancy loss, hemorrhage and hysterectomy. Favorable outcomes have been demonstrated with select second trimester gravid myomectomies. Literature documenting first trimester surgical management of myomas during pregnancy is scant. Patients with symptomatic myomas failing conservative management in the first trimester may be counseled to abort the pregnancy and then undergo myomectomy. Reports focusing on myomectomy in the first trimester are needed to permit more thorough options counseling for patients failing conservative management in the first trimester.</p> <p>Case presentation</p> <p>A 30-year-old Caucasian primagravid (G1P0) was referred for termination of her pregnancy at 10 weeks due to a 14 cm myoma causing severe pain, constipation and urine retention. Her referring physician planned an interval myomectomy following the abortion. Instead, our patient underwent myomectomy at 11 weeks. Two leiomyomas were successfully removed; she delivered a healthy infant at term.</p> <p>Conclusion</p> <p>Patients in the first trimester should not be counseled that termination followed by myomectomy is the best option for symptomatic myomas, failing conservative treatment. Management should be individualized after taking into account the patient's symptoms, gestational age and the location of the myomas in relation to the placenta. Any field providing women's health services will be impacted by the ability to offer more thorough options counseling for women with refractory myomas in the first trimester.</p

Treatment outcomes of new tuberculosis patients hospitalized in Kampala, Uganda: a prospective cohort study.

BACKGROUND: In most resource limited settings, new tuberculosis (TB) patients are usually treated as outpatients. We sought to investigate the reasons for hospitalisation and the predictors of poor treatment outcomes and mortality in a cohort of hospitalized new TB patients in Kampala, Uganda. METHODS AND FINDINGS: Ninety-six new TB patients hospitalised between 2003 and 2006 were enrolled and followed for two years. Thirty two were HIV-uninfected and 64 were HIV-infected. Among the HIV-uninfected, the commonest reasons for hospitalization were low Karnofsky score (47%) and need for diagnostic evaluation (25%). HIV-infected patients were commonly hospitalized due to low Karnofsky score (72%), concurrent illness (16%) and diagnostic evaluation (14%). Eleven HIV uninfected patients died (mortality rate 19.7 per 100 person-years) while 41 deaths occurred among the HIV-infected patients (mortality rate 46.9 per 100 person years). In all patients an unsuccessful treatment outcome (treatment failure, death during the treatment period or an unknown outcome) was associated with duration of TB symptoms, with the odds of an unsuccessful outcome decreasing with increasing duration. Among HIV-infected patients, an unsuccessful treatment outcome was also associated with male sex (P = 0.004) and age (P = 0.034). Low Karnofsky score (aHR = 8.93, 95% CI 1.88 - 42.40, P = 0.001) was the only factor significantly associated with mortality among the HIV-uninfected. Mortality among the HIV-infected was associated with the composite variable of CD4 and ART use, with patients with baseline CD4 below 200 cells/µL who were not on ART at a greater risk of death than those who were on ART, and low Karnofsky score (aHR = 2.02, 95% CI 1.02 - 4.01, P = 0.045). CONCLUSION: Poor health status is a common cause of hospitalisation for new TB patients. Mortality in this study was very high and associated with advanced HIV Disease and no use of ART

Pre-cooling for endurance exercise performance in the heat: a systematic review.

PMCID: PMC3568721The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1741-7015/10/166. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Endurance exercise capacity diminishes under hot environmental conditions. Time to exhaustion can be increased by lowering body temperature prior to exercise (pre-cooling). This systematic literature review synthesizes the current findings of the effects of pre-cooling on endurance exercise performance, providing guidance for clinical practice and further research

Cross-Sample Validation Provides Enhanced Proteome Coverage in Rat Vocal Fold Mucosa

The vocal fold mucosa is a biomechanically unique tissue comprised of a densely cellular epithelium, superficial to an extracellular matrix (ECM)-rich lamina propria. Such ECM-rich tissues are challenging to analyze using proteomic assays, primarily due to extensive crosslinking and glycosylation of the majority of high Mr ECM proteins. In this study, we implemented an LC-MS/MS-based strategy to characterize the rat vocal fold mucosa proteome. Our sample preparation protocol successfully solubilized both proteins and certain high Mr glycoconjugates and resulted in the identification of hundreds of mucosal proteins. A straightforward approach to the treatment of protein identifications attributed to single peptide hits allowed the retention of potentially important low abundance identifications (validated by a cross-sample match and de novo interpretation of relevant spectra) while still eliminating potentially spurious identifications (global single peptide hits with no cross-sample match). The resulting vocal fold mucosa proteome was characterized by a wide range of cellular and extracellular proteins spanning 12 functional categories