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We examined the ability of 40 young children (aged five to eight) to understand speech (monosyllables, spondees, trochees, and trisyllables) when listening in a background of real-life classroom noise. All children had some difficulty understanding speech when the noise was at levels found in many classrooms (i.e., 65 dBA). However, at an intermediate (-6 dB SNR) level, kindergarten and grade 1 children had much more difficulty than did older children. All children performed well in quiet, with results being comparable to or slightly better than those reported in previous studies, suggesting that the task was age appropriate and well understood. These results suggest that the youngest children in the school system, whose classrooms also tend to be among the noisiest, are the most susceptible to the effects of noise. [ABSTRACT FROM AUTHOR]

This article highlights information from the 2000 National Conference for Nurse Practitioners symposium held in Washington, D.C., on November 9, 2000. It was sponsored by The Nursing Institute of Springhouse Corporation and funded by an unrestricted educational grant from Merck & Co., Inc. The firsttopic, 'Overview of Migraine: Compelling Effects on Patients and Society,' was presented for Dedie Downey Russell, CNP, ANP/GNP, MS. The second topic, 'Understanding Pathophysiology: Evolving from Traditional to Current Therapeutic Options,' was presented by Dara G. Jamieson, MD. Maureen Moriarty-Sheehan, MS, CRNP, who also served as chairperson, presented the third topic, 'Developing a Management Plan for Optimal Patient Benefit.' [ABSTRACT FROM AUTHOR]

Perturbation analysis of sustained vowel waveforms is used routinely in the clinical evaluation of pathological voices and in monitoring patient progress during treatment. Accurate estimation of voice fundamental frequency (F0) is essential for accurate perturbation analysis. Several algorithms have been proposed for fundamental frequency extraction. To be appropriate for clinical use, a key consideration is that an F0 extraction algorithm be robust to such extraneous factors as the presence of noise and modulations in voice frequency and amplitude that are commonly associated with the voice pathologies under study. This work examines the performance of seven F0 algorithms, based on the average magnitude difference function (AMDF), the input autocorrelation function (AC), the autocorrelation function of the center-clipped signal (ACC), the autocorrelation function of the inverse filtered signal (IFAC), the signal cepstrum (CEP), the Harmonic Product Spectrum (HPS) of the signal, and the waveform matching function (WM) respectively. These algorithms were evaluated using sustained vowel samples collected from normal and pathological subjects. The effect of background noise and of frequency and amplitude modulations on these algorithms was also investigated, using synthetic vowel waveforms. [ABSTRACT FROM AUTHOR]

New onset or exacerbation of preexisting neurologic symptoms during pregnancy often necessitates brain or spinal cord imaging. Magnetic resonance techniques are preferred imaging modalities during pregnancy and the postpartum period. Ionizing radiation with computed tomography and intravenous contrast material with magnetic resonance or computed tomography should be avoided during pregnancy. New onset of headaches in the last trimester or in the postpartum period may indicate cerebrovascular disease or a mass lesion, for which brain imaging is necessary. The continuum of cerebrovascular complications of pregnancy and enlarging lesions may produce neurologic symptoms later in pregnancy and after delivery, necessitating imaging., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Pregnant women may have exacerbation of preexisting neurologic disorders or new-onset neurologic symptoms for which brain or spinal cord imaging is appropriate. Primary headaches in early pregnancy can be diagnosed and treated without imaging. Headaches later in pregnancy or in the peripartum period may need to be evaluated by brain and/or vascular imaging. Cerebrovascular complications have distinctive imaging but overlapping presentations. Mass lesions can enlarge, producing neurologic symptoms, late in pregnancy. Imaging may be necessary to diagnose neurologic disorders in pregnancy and the peripartum period. MRI is preferred during pregnancy; imaging involving ionizing radiation and/or contrast should be avoided., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Acute disseminated encephalomyelitis (ADEM) is a rare demyelinating disease of the central nervous system (CNS) that classically occurs in children and adolescents. It characteristically presents with acute inflammation, resulting in demyelination, often following an infectious disease. ADEM has been described in adult patients, but the incidence in the adult and especially elderly population is low., Cases: We describe five older adults (age 57 to 85) who presented with acute neurological symptoms. Three patients presented with an infectious illness preceding the event, 4 patients were encephalopathic, and oligoclonal bands (OCBs) were negative in all tested cases. The clinical scenario and imaging studies suggested alternative diagnoses, such as metastasis, primary CNS tumor, or stroke. Two patients had contrast enhancing lesions, two other patients had lesions with restricted diffusion on diffusion-weighted imaging. Neuropathologic diagnostic from biopsy or autopsy was eventually conclusive, showing perivascular zones of myelin loss with relative axonal sparing in all five cases., Conclusion: Each of these patients was found to have pathological findings of acute demyelination on tissue diagnosis, suggesting ADEM or ADEM-like disease. The initial presentation and imaging was pointing toward other diagnoses. Broad differential diagnosis is important, especially for older patients, and pathological proof might be warranted for a conclusive diagnosis., (Copyright © 2016 by the American Society of Neuroimaging.)

Pre-eclampsia (PE) is a clinical syndrome characterized by new-onset hypertension and proteinuria at ≥20 weeks of gestation, and is a leading cause of maternal and perinatal morbidity and mortality. Previous studies have gathered abundant data about PE such as risk factors and pathological findings. However, most of these data are not semantically structured. Clinical data on PE patients are often generated with semantic heterogeneity such as using disparate terminology to describe the same phenomena. In clinical studies, interoperability of heterogenic clinical data is required in various situations. In such a situation, it is necessary to develop an interoperable and standardized semantic framework to research the pathology of PE more comprehensively and to achieve interoperability of heterogenic clinical data of PE patients. In this study, we developed an ontology representing clinical features, treatments, genetic factors, environmental factors, and other aspects of the current knowledge in the domain of PE. We call this pre-eclampsia ontology "PEO". To achieve interoperability with other ontologies, the core structure of PEO was compliant with the hierarchy of the Basic Formal Ontology (BFO). The PEO incorporates a wide range of key concepts and terms of PE from clinical and biomedical research in structuring the knowledge base that is specific to PE; therefore, PEO is expected to enhance PE-specific information retrieval and knowledge discovery in both clinical and biomedical research fields., Competing Interests: DGJ is employed by Biorelate Inc. This commercial Cover Letter affiliation does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

Background: Prostate cancer (PCa) is the most common male cancer in the United Kingdom and we aimed to identify clinically relevant biomarkers corresponding to stage progression of the disease., Methods: We used enhanced proteomic profiling of PCa progression using iTRAQ 3D LC mass spectrometry on high-quality serum samples to identify biomarkers of PCa., Results: We identified >1000 proteins. Following specific inclusion/exclusion criteria we targeted seven proteins of which two were validated by ELISA and six potentially interacted forming an 'interactome' with only a single protein linking each marker. This network also includes accepted cancer markers, such as TNF, STAT3, NF-κB and IL6., Conclusions: Our linked and interrelated biomarker network highlights the potential utility of six of our seven markers as a panel for diagnosing PCa and, critically, in determining the stage of the disease. Our validation analysis of the MS-identified proteins found that SAA alongside KLK3 may improve categorisation of PCa than by KLK3 alone, and that TSR1, although not significant in this model, might also be a clinically relevant biomarker.

Pregnant women are most likely to have primary headaches, such as migraine and tension-type headaches, which can be diagnosed and treated without brain imaging. Primary headaches may even start de novo during pregnancy, especially in the first few months. However, when the headache occurs late in pregnancy or in the peripartum period, secondary causes of headaches need to be considered and evaluated by brain and/or vascular imaging, generally using magnetic resonance techniques. There is considerable overlap between the cerebrovascular complications of pregnancy, including preeclampsia/eclampsia, posterior reversible encephalopathy syndrome (PRES), reversible cerebral vasoconstriction syndrome (RCVS), and both hemorrhagic and ischemic strokes; although, their imaging may be distinctive. Imaging is necessary to distinguish between arterial and venous pathology causing headache in the peripartum patient, as there can be similar presenting symptoms. Mass lesions, both neoplastic and inflammatory, can enlarge and produce headaches and neurological symptoms late in pregnancy.

Dabigatran is effective in decreasing the risk of ischaemic stroke in patients with atrial fibrillation. However, like all anticoagulants, it is associated with a risk of bleeding. In cases of trauma or emergency surgery, emergency reversal of dabigatran-induced anticoagulation may be required. A specific reversal agent for dabigatran, idarucizumab, has been approved by the US Food and Drug Administration. Alternative reversal agents are available, such as prothrombin complex concentrates (PCCs) and activated PCCs (aPCCs). In this review we evaluate the role of PCCs and aPCCs in the reversal of dabigatran anticoagulation and consider which tests are appropriate for monitoring coagulation in this setting. Pre-clinical studies, small clinical studies and case reports indicate that PCCs and aPCCs may be able to reverse dabigatran-induced anticoagulation in a dose-dependent manner. However, dosing based on coagulation parameters can be difficult because available assays may not provide adequate sensitivity and specificity for measuring anticoagulation induced by dabigatran or the countering effects of PCCs/aPCCs. In addition, PCCs or aPCCs can potentially provoke thromboembolic complications. Despite these limitations and the fact that PCCs and aPCCs are not yet licensed for dabigatran reversal, their use appears to be warranted in patients with life-threatening haemorrhage if idarucizumab is not available.

Understanding the molecular mechanisms associated with disease is a central goal of modern medical research. As such, many thousands of experiments have been published that detail individual molecular events that contribute to a disease. Here we use a semi-automated text mining approach to accurately and exhaustively curate the primary literature for chronic pain states. In so doing, we create a comprehensive network of 1,002 contextualized protein-protein interactions (PPIs) specifically associated with pain. The PPIs form a highly interconnected and coherent structure, and the resulting network provides an alternative to those derived from connecting genes associated with pain using interactions that have not been shown to occur in a painful state. We exploit the contextual data associated with our interactions to analyse subnetworks specific to inflammatory and neuropathic pain, and to various anatomical regions. Here, we identify potential targets for further study and several drug-repurposing opportunities. Finally, the network provides a framework for the interpretation of new data within the field of pain., (Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.)

Disorders associated with prominent headaches, such as migraine with aura and cerebral arterial and venous diseases, increase the risk of ischemic and hemorrhagic stroke. Central nervous system vasculitis, posterior reversible encephalopathy syndrome, reversible cerebral vasoconstriction syndrome, and cerebral venous thrombosis are all disorders associated with severe or persistent headache in which the risk for ischemic and hemorrhagic stroke is increased. Hemorrhagic strokes, more frequently than ischemic strokes, present with distinct headaches, usually accompanied by focal neurological symptoms. Pregnancy, and especially the postpartum period, is a time of overlap between new-onset headache and stroke risk.

Nonneurologists who treat patients with headaches should be able recognize common headache types and to initiate therapy for tension-type headaches and migraines. Patients with complicated headache scenarios should be referred to a neurologist for consultation., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Treatment 2.0 is an initiative launched by UNAIDS and WHO in 2011 to catalyze the next phase of treatment scale-up for HIV. The initiative defines strategic activities in 5 key areas, drugs, diagnostics, commodity costs, service delivery and community engagement in an effort to simplify treatment, expand access and maximize program efficiency. For adults, many of these activities have already been turned into treatment policies. The recent WHO recommendation to use a universal first line regimen regardless of gender, pregnancy and TB status is a treatment simplification very much in line with Treatment 2.0. But despite that fact that Treatment 2.0 encompasses all people living with HIV, we have not seen the same evolution in policy development for children. In this paper we discuss how Treatment 2.0 principles can be adapted for the pediatric population. There are several intrinsic challenges. The need for distinct treatment regimens in children of different ages makes it hard to define a one size fits all approach. In addition, the fact that many providers are reluctant to treat children without the advice of specialists can hamper decentralization of service delivery. But at the same time, there are opportunities that can be availed now and in the future to scale up pediatric treatment along the lines of Treatment 2.0. We examine each of the five pillars of Treatment 2.0 from a pediatric perspective and present eight specific action points that would result in simplification of pediatric treatment and scale up of HIV services for children.

The vast collection of biomedical literature and its continued expansion has presented a number of challenges to researchers who require structured findings to stay abreast of and analyze molecular mechanisms relevant to their domain of interest. By structuring literature content into topic-specific machine-readable databases, the aggregate data from multiple articles can be used to infer trends that can be compared and contrasted with similar findings from topic-independent resources. Our study presents a generalized procedure for semi-automatically creating a custom topic-specific molecular interaction database through the use of text mining to assist manual curation. We apply the procedure to capture molecular events that underlie 'pain', a complex phenomenon with a large societal burden and unmet medical need. We describe how existing text mining solutions are used to build a pain-specific corpus, extract molecular events from it, add context to the extracted events and assess their relevance. The pain-specific corpus contains 765 692 documents from Medline and PubMed Central, from which we extracted 356 499 unique normalized molecular events, with 261 438 single protein events and 93 271 molecular interactions supplied by BioContext. Event chains are annotated with negation, speculation, anatomy, Gene Ontology terms, mutations, pain and disease relevance, which collectively provide detailed insight into how that event chain is associated with pain. The extracted relations are visualized in a wiki platform (wiki-pain.org) that enables efficient manual curation and exploration of the molecular mechanisms that underlie pain. Curation of 1500 grouped event chains ranked by pain relevance revealed 613 accurately extracted unique molecular interactions that in the future can be used to study the underlying mechanisms involved in pain. Our approach demonstrates that combining existing text mining tools with domain-specific terms and wiki-based visualization can facilitate rapid curation of molecular interactions to create a custom database. Database URL: •••

Manual curation has long been used for extracting key information found within the primary literature for input into biological databases. The human immunodeficiency virus type 1 (HIV-1), human protein interaction database (HHPID), for example, contains 2589 manually extracted interactions, linked to 14,312 mentions in 3090 articles. The advancement of text-mining (TM) techniques has offered a possibility to rapidly retrieve such data from large volumes of text to a high degree of accuracy. Here, we present a recreation of the HHPID using the current state of the art in TM. To retrieve interactions, we performed gene/protein named entity recognition (NER) and applied two molecular event extraction tools on all abstracts and titles cited in the HHPID. Our best NER scores for precision, recall and F-score were 87.5%, 90.0% and 88.6%, respectively, while event extraction achieved 76.4%, 84.2% and 80.1%, respectively. We demonstrate that over 50% of the HHPID interactions can be recreated from abstracts and titles. Furthermore, from 49 available open-access full-text articles, we extracted a total of 237 unique HIV-1-human interactions, as opposed to 187 interactions recorded in the HHPID from the same articles. On average, we extracted 23 times more mentions of interactions and events from a full-text article than from an abstract and title, with a 6-fold increase in the number of unique interactions. We further demonstrated that more frequently occurring interactions extracted by TM are more likely to be true positives. Overall, the results demonstrate that TM was able to recover a large proportion of interactions, many of which were found within the HHPID, making TM a useful assistant in the manual curation process. Finally, we also retrieved other types of interactions in the context of HIV-1 that are not currently present in the HHPID, thus, expanding the scope of this data set. All data is available at http://gnode1.mib.man.ac.uk/HIV1-text-mining.

Stroke, a major cause of morbidity and mortality in the general population, varies in incidence in men and women of different age groups: more boys than girls have strokes; the incidence of stroke is greater in men in their 60s and 70s; and stroke is more common in women after age 80 years. These differences are attributed to hormonal (sex-related) changes and variable risk factors in women, as well as lifestyle and environmental (gender-related) co-morbid conditions. A woman, who is more likely to have a stroke in her lifetime than a myocardial infarction, has a different response to primary and secondary prevention as compared with a man. Although response to thrombolysis is similar, older age and more severe strokes in women lead to poorer outcomes in female stroke survivors.

Background: Stroke is a major cause of morbidity and mortality in the general population and especially in older women., Review Summary: The incidence of stroke differs between men and women of a range of ages, with a higher lifetime risk for women than men. Pregnancy and the postpartum period are times of increased risk of stroke. Use of exogenous estrogen, especially in vulnerable populations, increases stroke risk. Women and men have different responses to primary and secondary stroke prevention. Women may not be offered acute ischemic stroke treatment as frequently as men; and female stroke survivors have worse outcomes., Conclusions: Gender-related differences in stroke are attributed to the hormonal changes that women experience through their lifetime, diverse risk factors for stroke in men and women, and specific lifestyles, and comorbid conditions. Neurologists need to be aware of aspects of stroke that are particularly relevant to women.

Early stroke management, and early initiation of secondary stroke prevention, may improve outcomes in patients with acute ischemic stroke. However, <10% of patients with acute ischemic stroke arrive at the receiving hospital within 3 hours of symptom onset. Factors such as poor public awareness of symptoms, lack of rapid detection by emergency medical services (EMS), poor coordination between EMS and the hospital emergency department, or delay of diagnosis on arrival at the emergency department are all contributing factors in the failure to provide prompt diagnosis and treatment of acute ischemic stroke. This article focuses on the critical steps in diagnosing ischemic stroke, starting at the initial patient evaluation by emergency personnel. Stroke mimics and different imaging techniques that may be used in the differential diagnosis and evaluation of acute ischemic stroke are also discussed.

Despite recent advances in the acute treatment of stroke, prevention and risk factor modification remain the mainstays of management for patients with ischemic stroke and transient ischemic attack. The majority of noncardioembolic ischemic strokes are atherothrombotic, presumed to be associated with the activation and aggregation of platelets. Antiplatelet medications have been shown to be effective in the secondary prevention of stroke of presumed arterial origin, both as monotherapy and in combination. Among combination of antiplatelet agents, aspirin plus extended-release dipyridamole has demonstrated statistically significant additive benefit over monotherapy with each agent. Clopidogrel plus aspirin does not prevent recurrent ischemic stroke over each component individually, and the combination increases the risk of hemorrhagic side effects. This article reviews the most recent studies on antiplatelet medications, including the combination of aspirin and clopidogrel or extended-release dipyridamole, and discusses some of the controversies that still exist with the use of antiplatelet agents.

Survivors of ischemic stroke are at significant risk for recurrent stroke. Appropriate therapy for stroke prevention is needed given the significant morbidity and mortality associated with stroke, the high financial costs, and the neurologic disability associated with treatment failure. A treatment strategy based on assessed risk represents an appropriate use of medical resources and results in improved outcomes. This approach requires evaluation of major risk factors, the most serious of which is a history of ischemic stroke or transient ischemic attack. The annual risk for recurrent stroke is 6% during the first 5 years after an initial stroke. Non-modifiable risk factors include age, race, ethnicity, gender, family history, and geography. The most important modifiable risk factor is hypertension. Diabetes mellitus, hyperlipidemia, left ventricular hypertrophy, atrial fibrillation, and lifestyle factors such as smoking, alcohol abuse, and obesity contribute to stroke risk. Antihypertensive, lipid-lowering, and antiplatelet therapies have been successful in reducing the incidence of secondary stroke. Clinical trials validate the benefits of statin therapy in reducing the risk for secondary stroke. Studies of antiplatelet agents, including aspirin, clopidogrel, and aspirin combined with extended-release dipyridamole, have evaluated the risk reduction in recurrent stroke and have been concerned particularly with the risk for hemorrhage. Therapy for stroke prevention based on risk stratification can identify patients who are appropriate targets for aggressive intervention.

Patients experiencing stroke or transient ischemic attack (TIA) are at high risk for recurrent (secondary) strokes, which comprise 29% of all strokes in the United States. Current recommendations for prevention of secondary stroke from the American College of Chest Physicians (ACCP) call for the broad use of platelet antiaggregation (antiplatelet) agents for patients with a history of noncardioembolic stroke or TIA. Five agents--aspirin, ticlopidine, clopidogrel, extended-release dipyridamole (ER-DP), and triflusal--have demonstrated efficacy in large-scale clinical studies in the prevention of recurrent vascular events and/or stroke in patients with a history of stroke. The results of the following studies are reviewed and compared: the Swedish Aspirin Low-Dose Trial (SALT), the United Kingdom Transient Ischaemic Attack (UK-TIA) Aspirin Trial, Dutch Transient Ischemic Attack (Dutch TIA) study (aspirin), the Canadian American Ticlopidine Study (CATS), the Ticlopidine Aspirin Stroke Study (TASS), the African American Antiplatelet Stroke Prevention Study (AAASPS) (ticlopidine), the Clopidogrel versus Aspirin in Patients at Risk of Recurrent Ischemic Events (CAPRIE) trial, the Management of Atherothrombosis With Clopidogrel in High-Risk Patients study (MATCH) (clopidogrel), the second European Stroke Prevention Study (ESPS2) (aspirin plus ER-DP), and the Triflusal versus Aspirin in Cerebral Infarction Prevention (TACIP) study. In comparative monotherapy studies of patients with previous stroke, ticlopidine demonstrates statistically significant improved efficacy over aspirin, and clopidogrel demonstrates nonsignificant slight improvement over aspirin for the prevention of ischemic cardiac and cerebrovascular events; however, the adverse event profile of ticlopidine (including rash, diarrhea, and neutropenia) will probably limit its long-term use. Among combination approaches, only aspirin plus ER-DP has demonstrated statistically significant, clinically meaningful additive benefit over monotherapy with each agent. Clopidogrel plus aspirin did not significantly improve preventive efficacy and increased the risk of serious side effects, including life-threatening bleeding episodes. The 15,500-patient PRoFESS (the Prevention Regimen for Effectively Avoiding Second Strokes) study, with results expected in 2008, will directly compare aspirin plus ER-DP with clopidogrel monotherapy for the prevention of recurrent stroke and should provide statistically robust estimates of comparative efficacy for the development of improved recommendations.

Acoustical measures of vocal function are routinely used in the assessments of disordered voice, and for monitoring the patient's progress over the course of voice therapy. Typically, acoustic measures are extracted from sustained vowel stimuli where short-term and long-term perturbations in fundamental frequency and intensity, and the level of "glottal noise" are used to characterize the vocal function. However, acoustic measures extracted from continuous speech samples may well be required for accurate prediction of abnormal voice quality that is relevant to the client's "real world" experience. In contrast with sustained vowel research, there is relatively sparse literature on the effectiveness of acoustic measures extracted from continuous speech samples. This is partially due to the challenge of segmenting the speech signal into voiced, unvoiced, and silence periods before features can be extracted for vocal function characterization. In this paper we propose a joint time-frequency approach for classifying pathological voices using continuous speech signals that obviates the need for such segmentation. The speech signals were decomposed using an adaptive time-frequency transform algorithm, and several features such as the octave max, octave mean, energy ratio, length ratio, and frequency ratio were extracted from the decomposition parameters and analyzed using statistical pattern classification techniques. Experiments with a database consisting of continuous speech samples from 51 normal and 161 pathological talkers yielded a classification accuracy of 93.4%.

We investigated how standard speech coders, currently used in modern communication systems, affect the quality of the speech of persons who have common speech and voice disorders. Three standardized speech coders (GSM 6.10 RPE-LTP, FS1016 CELP, and FS1015 LPC) and two speech coders based on subband processing were evaluated for their performance. Coder effects were assessed by measuring the quality of speech samples both before and after processing by the speech coders. Speech quality was rated by 10 listeners with normal hearing on 28 different scales representing pitch and loudness changes, speech rate, laryngeal and resonatory dysfunction, and coder-induced distortions. Results showed that (a) nine scale items were consistently and reliably rated by the listeners; (b) all coders degraded speech quality on these nine scales, with the GSM and CELP coders providing the better quality speech; and (c) interactions between coders and individual voices did occur on several voice quality scales.

We investigated how standard speech coders, currently used in modern communication systems, affect the intelligibility of the speech of persons who have common speech and voice disorders. Three standardized speech coders (viz., GSM 6.10 [RPE-LTP], FS1016 [CELP], FS1015 [LPC]) and two speech coders based on subband processing were evaluated for their performance. Coder effects were assessed by measuring the intelligibility of vowels and consonants both before and after processing by the speech coders. Native English talkers who had normal hearing identified these speech sounds. Results confirmed that (a) all coders reduce the intelligibility of spoken language; (b) these effects occur in a consistent manner, with the GSM and CELP coders providing the least degradation relative to the original unprocessed speech; and (c) coders interact with individual voices so that speech is degraded differentially for different talkers.

We evaluated acoustic voice characteristics of 18 male patients undergoing radiotherapy. The subjects were seen for voice assessment preradiotherapy and at 1 month, 3 months, 6 months, and 1 year following radiotherapy. A multidimensional voice analysis computer program (IVANS, Avaaz Innovations, 1998) was employed to evaluate measures of traditional frequency and amplitude perturbation as well as time-based and linear prediction (LP) modeled "noise" parameters of the acoustic output in conjunction with perceptual judgments of overall vocal quality. The results indicate vocal deterioration of vocal function immediately following radiotherapy with gradual and significant improvement in acoustic and perceptual features over 9 to 12 months following the radiation treatment. Measures of glottal noise demonstrated higher sensitivity than frequency-based measures of voice perturbation, and with more consistent, less variable changes in acoustical voice output from the preradiation to the 12 month postradiation periods. Future research evaluating vowel type and acoustic perturbation measures with a larger sample of subjects over a longer time period seems warranted.

The introduction of the triptans (5-hydroxytryptophan [5-HT] (1B/1D) agonists) in the past decade has brought migraine-specific pain relief to those suffering from migraine. These drugs activate the serotonin receptors 5-HT(1B) and 5-HT(1D) on cerebral vessels. Concerns about their safety, particularly in patients with vascular risk factors, have been raised because triptans also activate the 5-HT(1B) receptors on coronary arteries. Although triptans are contraindicated in patients with cardiac or cerebrovascular disease, they are safer than many other medications used to treat patients with migraine, including the nonspecific serotonin-agonist ergot preparations.

Headaches are a universal experience and one of the most common causes for physician consultation. The physician must determine whether a neuroimaging study is warranted to aid in the diagnosis of primary or secondary headaches. Guidelines on neuroimaging of headache patients have been developed based on review of the literature; however, their applicability must be adapted to specific clinical situations. In general, neuroimaging is most likely to be useful if the history is not typical of a primary headache type (e.g., tension type, migraine, cluster headaches) or the neurological examination is abnormal. Neuroimaging has been crucial in the investigation of the pathogenesis of migraine and cluster headaches. Secondary headaches, which may be diagnosed by neuroimaging studies, include subarachnoid hemorrhage, cerebral venous thrombosis, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, aqueductal stenosis, and arterial dissection.

Atherosclerosis is associated with arterial deposition of low density lipoprotein (LDL) and lipoprotein(a), Lp(a). Both lipoproteins have been detected in atherosclerotic vessels; however, while LDL has been shown to be only blood-derived, it is not clear whether Lp(a) is also produced within the vessel wall. In the present investigation we studied gene expression of apo(a) and apoB in human blood vessels. Aorta, carotid arteries and liver specimens from 29 adult and pediatric autopsy cases were studied by RT-PCR and Southern blot analysis with primers and probes specific for apo(a), apoB and GAPDH (a control housekeeping gene). The mRNA of apo(a), but not apoB, was found within the vessel wall in both adult atherosclerotic arterial vessels and in pediatric non atherosclerotic vessels. Neither apo(a) nor apoB mRNA was detected in femoral veins. To verify the nature of the detected transcripts, we cloned the 162 base pair (bp) RT-PCR product derived from the arterial wall total RNA. Nucleotide sequencing revealed 100% homology with the apo(a) gene. Thus, while LDL in atherosclerotic arteries is exclusively blood-derived, the accumulation of Lp(a) within the artery may be due in part to in situ production of apo(a) within the vessel wall.

Serum levels of lipoprotein(a), Lp(a), have been shown to be associated with increased risk of atherosclerosis (AS) and AS-related diseases such as myocardial and ischemic cerebral infarcts (ICI). Lp(a) has been detected in the vascular wall of the aorta and coronary vessels, and we documented the presence of apo(a) in cerebral vessels of the Circle of Willis, associated with AS changes. In this study we further investigated and characterized the biochemical nature of Lp(a) detected in both large and small cerebral parenchymal vessels. Autopsy specimens of cerebral vessels of 51 patients were examined by immunohistochemistry with monoclonal antibodies against apo(a), apoB, and plasminogen. Lp(a) was detected in cerebral capillaries and arterioles. All of the 8 patients with ICI expressed Lp(a) in parenchymal vessels, generally (6/8) in both capillaries and arterioles. Of 43 patients without ICI only 25 had Lp(a) detected. Among the patients without ICI, there was a slightly increased incidence of parenchymal Lp(a) in those patients who had severe hypoxic brain damage (12/20) compared to those patients without severe hypoxic damage (9/23). Thus, the presence of Lp(a) in small cerebral parenchymal vessels may reflect the role of Lp(a) in ICI., (Copyright 2001 Academic Press.)

Acoustic measures provide an objective means to describe pathological voices and are a routine component of the clinical voice examination. Because the voice sample is obtained using a microphone, microphone characteristics have the potential to influence the values of parameters obtained from a voice sample. This project examined how the choice of microphone affects key voice parameters and investigated how one might compensate for such microphone effects through filtering or by including additional parameters in the decision process. A database of 53 normal voice samples and 100 pathological voice samples was used in four experiments conducted in an anechoic chamber using four different microphones. One omnidirectional microphone and three cardioid microphones were used in these experiments. The original voice samples were presented to each microphone through a speaker located in an anechoic chamber, and the output of each microphone sampled to computer disk. Each microphone modified the frequency spectrum of the voice signal; this, in turn, affected the values of the voice parameters obtained. These microphone effects reduced the accuracy with which acoustic measures of voice could be used to discriminate pathological from normal voices. Discrimination performance improved when the microphone output was filtered to compensate for microphone frequency response. Performance also improved when spectral moment coefficient parameters were added to the vocal function parameters already in use.

We investigated the ability of acoustic measures to discriminate between normal and pathological talkers. Two groups of measures were compared: (a) those extracted from sustained vowels and (b) those based on continuous speech samples. Nine acoustic measures, which include fundamental frequency and amplitude perturbation measures, long term average spectral measures, and glottal noise measures were extracted from both sustained vowel and continuous speech samples. Our experiments were performed on a published database of 53 normal talkers and 175 talkers with a pathological voice. The classification performance of the nine acoustic measures was quantified using linear discriminant analysis and receiver operating characteristic (ROC) curve analysis. When individual measures were considered in isolation, classification was more accurate for measures extracted from sustained vowels than for those based on continuous speech samples. Classification accuracy improved when combinations of acoustic parameters were considered. For such combinations of measures, classification results were comparable for measures extracted from continuous speech samples and for those based on sustained vowels.