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Combined Lagrange multiplier test for ARCH in vector autoregressive models
No full textAbstractA combined Lagrange multiplier (LM) test for autoregressive conditional heteroskedastic (ARCH) errors in vector autoregressive (VAR) models is proposed by replacing an exact Monte Carlo (MC) test by a bootstrap MC test when the model includes lags. The test circumvents the problem of high dimensionality in multivariate tests for ARCH in VAR models. It only requires computing univariate statistics. A computational advantage is therefore that the number of parameters to be estimated is independent of the dimension of the VAR process. The bootstrap MC test is shown to be asymptotically valid. Monte Carlo simulations show that the test has good finite-sample properties. The test is robust against a non-normal error distribution. Two financial applications of multivariate LM tests for ARCH to credit default swap (CDS) prices and Euribor interest rates are presented. The results indicate that the errors are skewed and heavy-tailed, and that there are significant ARCH effects
Atrial electromechanical delay, and left ventricular strain in pre-diabetic patients
No full textAbstractObjectivesThe aim of this study was to investigate the subclinical myocardial affection in prediabetics with the evaluation of left ventricular (LV) systolic strain and strain rate by speckle tracking echocardiography (STE), and atrial electromechanical delay.Study designGlobal Longitudinal strain (GLS) and strain rate (GLSR) were assessed by STE, and Intra- and interatrial electromechanical delay (EMD) were measured utilizing tissue Doppler imaging (TDI) in 108 pre-diabetic patients and 72 age and gender matched healthy volunteers.ResultsThe GLS (−19.4±2.8 vs. 23.8±2.1%; p<0.001) and GLSR () were significantly lower in prediabetics when compared with the healthy control. Pre-diabetic patients had significantly prolonged PA lateral, PA septum and PA tricuspid. The intra- (PA septum-PA tricuspid) and interatrial (PA lateral-PA tricuspid) electromechanical delays were prolonged compared to controls (p<0.0001, p<0.05, p<0.001, and p<0.002, respectively). The GLS%, GLSR and atrial electromechanical delay were highly significantly correlated with fasting blood glucose, and modestly correlated to systolic blood pressure, total cholesterol, triglycerides, and left ventricular mass index.ConclusionGLS%; GLSR assessed by STE was decreased; intra- and interatrial electromechanical delays were prolonged, in pre-diabetic subjects. These non-invasive indices broaden the spectrum of subclinical myocardial dysfunction in pre-diabetic patients
Clinical implications of Paracoccus yeeii bacteremia in a patient with decompensated cirrhosis
No full textAbstractInfections in patients with cirrhosis are common among those who develop variceal hemorrhage. Prophylactic antimicrobial treatment with third generation cephalosporins is recommended in patients with advanced cirrhosis and gastrointestinal hemorrhage. However no infectious source is identified in up to 50% of patients with cirrhosis and clinical sepsis. We report the first case of Paracoccus yeeii bacteremia in a patient with decompensated cirrhosis who presented with variceal hemorrhage. This rare gram negative organism that occurs naturally in the soil has been difficult to isolate until recent technological advances and may not be susceptible to third generation cephalosporins. Our case reinforces the challenges in isolating rare infections in patients with cirrhosis, the need to consider uncommon organisms in infected but culture negative patients with cirrhosis, and the importance of optimizing antimicrobials to reduce the incidence of drug resistant organisms
NGP 555, a γ-secretase modulator, lowers the amyloid biomarker, Aβ42, in cerebrospinal fluid while preventing Alzheimer's disease cognitive decline in rodents
No full textAbstractIntroductionAlzheimer's disease (AD) is defined by the progressive accumulation of amyloid plaques and neurofibrillary tangles in the brain which precedes cognitive decline by years.MethodsUsing amyloid biomarkers, chemical modeling, mouse behavioral models, and drug development techniques, we investigate the properties of NGP 555, a clinical-stage γ-secretase modulator.ResultsNGP 555 shifts amyloid peptide production to the smaller, nonaggregating forms of amyloid. Our preclinical studies show beneficial effects on amyloid biomarkers, pathology, and cognition. NGP 555 has successfully completed chemistry, pharmacology, toxicity, metabolism, and safety studies.DiscussionAbundant data support Aβ42 as a target for prophylactic or early-stage intervention therapies in AD. The γ-secretase modulator, NGP 555 is being actively developed in human clinical trials for the prevention of Alzheimer's disease with the overall aim to achieve an appropriate balance of potency/efficacy on reducing the toxic forms of amyloid versus safety
Design, synthesis and molecular docking study of thienopyrimidin-4(3H)-thiones as antifungal agents
No full textAbstractIn an attempt to find a new class of antimicrobial agents, a series of thienopyrimidin-4(3H)-thiones 4(H1–H36) were synthesized and evaluated for in vitro antifungal activity against Candida albicans (NCIM 3471), Aspergillus niger (NCIM 545), and Penicillium chrysogenum (NCIM 709). The title compounds were synthesized by thionation of thienopyrimidin-4(3H)-ones 3(H1–H36) using Lawesson’s reagent. All the compounds were characterized using elemental analytical (C, H, and N) and spectral (FT-IR, 1H NMR, 13C NMR and MS) data. Among the tested compounds, 5-(4-chlorophenyl)-2-(pyridin-3-yl)thieno[2,3-d]pyrimidine-4(3H)-thione 4(H11), 2-sulfanyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidine-4(3H)-thione 4(H18), and 2-(butylsulfanyl)-5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidine-4(3H)-thione 4(H32) were identified as potentially excellent antifungal agents. They exhibited potent antifungal activity against C. albicans (MIC; 4μg/mL), A. niger (MIC; 2μg/mL), and P. chrysogenum (MIC; 2μg/mL) comparable with that of ketoconazole. The binding mode of compounds by SP docking studies shows that it fits well into the active site cavity of DHFR. Lipinski’s rule and in silico ADME pharmacokinetic parameters are within the acceptable range defined for human use thereby indicating their potential as drug-like molecules
Anemia and hematinic deficiencies in anti-gastric parietal cell antibody-positive or all autoantibodies-negative recurrent aphthous stomatitis patients
No full textBackground/purposeApproximately 13% of recurrent aphthous stomatitis (RAS) patients have serum anti-gastric parietal cell antibody (GPCA) positivity. This study assessed whether serum GPCA or RAS itself was a significant factor causing hematinic deficiencies and anemia statuses in GPCA-positive RAS (GPCA+/RAS) and all autoantibodies-negative RAS (Abs−/RAS) patients.MethodsThe mean corpuscular volume (MCV) and mean blood hemoglobin (Hb), iron, vitamin B12, and folic acid levels were measured and compared between any two of three groups of 31 GPCA+/RAS patients, 240 Abs−/RAS patients, and 342 healthy control subjects.ResultsGPCA+/RAS patients had significantly lower mean Hb and serum iron level (for women only) as well as significantly greater frequencies of Hb, iron, and vitamin B12 deficiencies than healthy control subjects. Moreover, GPCA+/RAS patients had a significantly higher MCV and a significantly greater frequency of vitamin B12 deficiency than Abs−/RAS patients. Furthermore, Abs−/RAS patients did have significantly lower mean Hb, MCV, iron, and folic acid levels and significantly greater frequencies of Hb, iron, vitamin B12, and folic acid deficiencies than healthy control subjects. Of 31 GPCA+/RAS patients, 3 (9.7%) had PA, 6 (19.4%) had vitamin B12 deficiency, and 3 (9.7%) had macrocytosis. Moreover, normocytic anemia (54.0%) and iron deficiency anemia (26.4%) are the two more common types of anemia in our RAS patients.ConclusionsWe conclude that serum GPCA plays a significant role in causing vitamin B12 deficiency and high MCV in GPCA+/RAS patients. RAS itself does play a significant role in causing anemia and hematinic deficiencies in both GPCA+/RAS and Abs−/RAS patients
Characterization of cochlear implant artifacts in electrically evoked auditory steady-state responses
No full textAbstractObjectiveElectrically evoked auditory steady-state responses (EASSRs) are neural potentials measured in the electroencephalogram (EEG) in response to periodic pulse trains presented, for example, through a cochlear implant (CI). EASSRs could potentially be used for objective CI fitting. However, EEG signals are contaminated with electrical CI artifacts. In this paper, we characterized the CI artifacts for monopolar mode stimulation and evaluated at which pulse rate, linear interpolation over the signal part contaminated with CI artifact is successful.MethodsCI artifacts were characterized by means of their amplitude growth functions and duration.ResultsCI artifact durations were between 0.7 and 1.7ms, at contralateral recording electrodes. At ipsilateral recording electrodes, CI artifact durations are range from 0.7 to larger than 2ms.ConclusionAt contralateral recording electrodes, the artifact was shorter than the interpulse interval across subjects for 500pps, which was not always the case for 900pps.SignificanceCI artifact-free EASSRs are crucial for reliable CI fitting and neuroscience research. The CI artifact has been characterized and linear interpolation allows to remove it at contralateral recording electrodes for stimulation at 500pps
Late recurrent adrenocortical carcinoma presenting radiologically as a gastrointestinal stromal tumour: A case report
No full textAbstractIntroductionAdrenocortical carcinoma (ACC) is a rare malignancy with an estimated incidence of 1–2 per million people. It may recur, after complete surgical removal by local or distant metastasis.ObservationWe report a case of late metastatic ACC presented as a mesenteric mass, 10 years post left adrenalectomy. Our case was initially misdiagnosed radiologically as gastrointestinal stromal tumour (GIST), and then the decision for exploration was made. The mass could be safely excised and confirmed pathologically to be an adrenocortical tumour
Factors associated with re-entry to out-of-home care among children in England
No full textAbstractExiting and re-entering out-of-home care (OHC) is considered a disruption to permanence which may have long-lasting, negative consequences for children due to a lack of stability and continuity. Each year approximately one-third of children in OHC in England exit, but information is lacking on rates of re-entries and associated factors. Using national administrative data, we calculated rates of re-entry among children exiting OHC from 2007 to 2012, identified key child and care factors associated with re-entry using Cox proportional hazards modelling, and developed a simple probability calculator to estimate which groups of children are most likely to re-enter OHC within three months. Between 2007 and 2012 re-entries to OHC in England decreased (from 23.3% to 14.4% within one year of exit, p<0.001), possibly due to concurrent changes in the way children exited OHC. Overall, more than one-third of children exiting OHC in 2008 re-entered within five years (35.3%, N=4076), but rates of re-entry varied by child and care characteristics including age, ethnicity, mode of exit, and placement stability. Based on these associated factors, we developed a calculator that can estimate the likelihood of rapid re-entry to OHC for a group of children and could be used by social care practitioners or service planners. Our findings provide insight into which groups of children are most likely to re-enter OHC, who may benefit from additional support or ongoing monitoring
Hailey–Hailey disease: A review of clinical features in 26 cases with special reference to the secondary infections and their control
No full textAbstractBackground/ObjectiveHailey–Hailey disease (HHD) is a rare autosomal dominant hereditary disorder that manifests with skin blisters. Controlling secondary infections is indispensable for this condition in conjunction with treatment using anti-inflammatory drugs such as topical steroids. This study aimed to investigate the clinical features and secondary infections associated with HHD.MethodsWe retrospectively reviewed the records of 26 patients affected by HHD who visited our hospital over a 10-year period. We explored the patients' age at onset, time from onset to diagnosis, affected sites, symptoms, secondary infections and their control, other treatment responses, and family history for HHD.ResultsThe mean age at disease onset was 35 years. The average time from onset to diagnosis was 7 years. The lesions were located at the neck, inframammary folds, axillae, groin, and perineum. Secondary infection accompanied HHD in 22 patients (85%); the most common infectious agents were Staphylococcus aureus and Candida albicans. Our cases demonstrated that first-line treatment for HHD was successful in most patients, which included topical corticosteroids in combination with topical or oral antibiotics and/or antifungal agents.ConclusionControlling the secondary infection is indispensable for treatment of skin lesions in HHD; however, none of the treatment modalities prevented relapse after discontinuation of treatment