Tentacle probes: eliminating false positives without sacrificing sensitivity

The majority of efforts to increase specificity or sensitivity in biosensors result in trade-offs with little to no gain in overall accuracy. This is because a biosensor cannot be more accurate than the affinity interaction it is based on. Accordingly, we have developed a new class of reagents based on mathematical principles of cooperativity to enhance the accuracy of the affinity interaction. Tentacle probes (TPs) have a hairpin structure similar to molecular beacons (MBs) for enhanced specificity, but are modified by the addition of a capture probe for increased kinetics and affinity. They produce kinetic rate constants up to 200-fold faster than MB with corresponding stem strengths. Concentration-independent specificity was observed with no false positives at up to 1 mM concentrations of variant analyte. In contrast, MBs were concentration dependent and experienced false positives above 3.88 μM of variant analyte. The fast kinetics of this label-free reagent may prove important for extraction efficiency, hence sensitivity and detection time, in microfluidic assays. The concentration-independent specificity of TPs may prove extremely useful in assays where starting concentrations and purities are unknown as would be the case in bioterror or clinical point of care diagnostics

Herpes zoster risk factors in a national cohort of veterans with rheumatoid arthritis

BACKGROUND: Herpes zoster occurs more commonly in patients taking immunosuppressive medications, though the risk associated with different medications is poorly understood. METHODS: Retrospective cohort study including 20,357 patients who were followed in the Veterans Affairs healthcare system and treated for rheumatoid arthritis from October 1998 through June 2005. Cox proportional hazards regression was used to determine risk factors for herpes zoster, and herpes zoster-free survival. Chart review was performed to validate the diagnosis of herpes zoster. RESULTS: The incidence of herpes zoster was 9.96 per 1000 patient-years. In time-to-event analysis, patients receiving medications used to treat mild rheumatoid arthritis were less likely to have an episode of herpes zoster than patients receiving medications used to treat moderate and severe rheumatoid arthritis (p<0.001). Independent risk factors for herpes zoster included older age, prednisone use, medications used to treat moderate and severe rheumatoid arthritis, malignancy, chronic lung disease, renal failure, and liver disease. Among patients receiving tumor necrosis factor-alpha antagonists, etanercept (HR 0.62) and adalimumab (HR 0.53) were associated with lower risk of herpes zoster. There was excellent agreement between ICD-9-CM diagnosis of herpes zoster and diagnosis by chart review (kappa = 0.92). CONCLUSIONS: Risk factors for herpes zoster included older age, prednisone use, medications used to treat moderate and severe rheumatoid arthritis, and several comorbid medical conditions. These results demonstrate that the Department of Veterans Affairs’ national administrative databases can be used to study rare adverse drug events

Morning Increase in Onset of Ischemic Stroke

The Time of Onset of Ischemic Stroke Was Determined for 1,167 of 1,273 Patients during the Collection of Data by Four Academic Hospital Centers between June 30, 1983, and June 30, 1986. More Strokes Occurred in Awake Patients from 10:00 Am to Noon Than during Any Other 2-Hour Interval. the Incidence of Stroke Onset Declined Steadily during the Remainder of the Day and Early Evening. the Onset of Stroke is Least Likely to Occur in the Late Evening, Before Midnight. © 1989 American Heart Association, Inc

Interobserver Agreement in the Diagnosis of Stroke Type

Interobserver Agreement is Essential to the Reliability of Clinical Data from Cooperative Studies and Provides the Foundation for Applying Research Results to Clinical Practice. in the Stroke Data Bank, a Large Cooperative Study of Stroke, We Sought to Establish the Reliability of a Key Aspect of Stroke Diagnosis: The Mechanism of Stroke. Seventeen Patients Were Evaluated by Six Neurologists. Interobserver Agreement Was Measured When Diagnosis Was based on Patient History and Neurologic Examination Only, as Well as When It Was based on Results of a Completed Workup, Including a Computed Tomographic Scan. Initial Clinical Impressions, based Solely on History and One Neurologic Examination, Were Fairly Reliable in Establishing the Mechanism of Stroke (Ie, Distinguishing among Infarcts, Subarachnoid Hemorrhages, and Parenchymatous Hemorrhages). Classification into One of Nine Stroke Subtypes Was Substantially Reliable When Diagnoses Were based on a Completed Workup. Compared with Previous Findings for the Same Physicians and Patients, the Diagnosis of Stroke Type Was Generally More Reliable Than Individual Signs and Symptoms. These Results Suggest that Multicentered Studies Can Rely on the Independent Diagnostic Choices of Several Physicians When Common Definitions Are Employed and Data from a Completed Workup Are Available. Furthermore, Reliability May Be Less for Individual Measurements Such as Signs or Symptoms Than for More-Complex Judgments Such as Diagnoses. © 1986, American Medical Association. All Rights Reserved

Interobserver Reliability in the Interpretation of Computed Tomographic Scans of Stroke Patients

Interobserver Reliability in Interpretation of Computed Tomographic Images Was Studied by Six Senior Neurologists Who Independently Evaluated on a Standardized Stroke Data Bank Form the Brain Lesions of 17 Patients. the Results Analyzed with K Statistics Yielded Moderate to Substantial Agreement on Most Items of Interest Including the Stroke Pathology and Anatomy. in General, the Levels of Agreement Were as High as Previously Reported for the Diagnosis of the Mechanism of the Stroke, and Much Higher Than on Many Stroke History Items and Items of Neurologic Examination. Excellent Agreement Was Obtained for the Detection of Infarcts and Intracerebral Hemorrhage, and Substantial Agreement Was Obtained on Whether the Computed Tomographic Images Were Normal or Indicative of Small Deep Infarcts, Superficial and Deep Infarcts, and Aneurysms. the Level of Agreement on Anatomy of the Lesions Was Best for the Frontal, Parietal, and Temporal Lobes, Putamen, Cerebellum, and Subarachnoid Space. Implications for Clinical Research and Diagnosis Are Discussed. © 1987 American Medical Association All Rights Reserved

Interobserver Variability in the Assessment of Neurologic History and Examination in the Stroke Data Bank

Interobserver Reliability in Obtaining Neurologic Histories and Examinations Was Investigated among Neurologists Collaborating in the Stroke Data Bank (SDB). Seventeen In-Hospital Stroke Patients Were Examined by Six Neurologists Experienced in Stroke over the Course of Three Days. Patients Were Examined Twice a Day for Two Successive Days, with Each Patient Seen by Four Different Neurologists. Data Were Recorded on SDB Forms, According to Definitions and Procedures Established for the SDB. Percent Agreement and Κ Coefficients Were Calculated to Assess the Levels of Agreement for Each Item. Important Differences in Levels of Agreement Were Found among Items on Both Neurologic History and Examination. Agreement among Neurologists Was Higher for Neurologic Examination Than for History. Patterns of Agreement for Items with Low Prevalence or with Numerous Unknown Ratings Are Discussed. Improvement in Interobserver Agreement Due to Data Editing for Intra-Observer Consistency Was Shown. © 1985, American Medical Association. All Rights Reserved

Association of Endodontic Involvement with Tooth Loss in the Veterans Affairs Dental Longitudinal Study

The effect of endodontic involvement on tooth loss has not been quantified, so the present study aimed to assess this relationship after controlling for other relevant risk factors for tooth loss

Predicting the corona for the 21 August 2017 total solar eclipse

D.H.M. thanks both the UK STFC and the Leverhulme Trust for their financial support.The total solar eclipse that occurred on 21 August 2017 across the United States provided an opportunity to test a magnetohydrodynamic model of the solar corona driven by measured magnetic fields. We used a new heating model based on the dissipation of Alfvén waves, and a new energization mechanism to twist the magnetic field in filament channels. We predicted what the corona would look like one week before the eclipse. Here, we describe how this prediction was accomplished, and show that it compared favourably with observations of the eclipse in white light and extreme ultraviolet. The model allows us to understand the relationship of observed features, including streamers, coronal holes, prominences, polar plumes and thin rays, to the magnetic field. We show that the discrepancies between the model and observations arise from limitations in our ability to observe the Sun’s magnetic field. Predictions of this kind provide opportunities to improve the models, forging the path to improved space weather prediction.PostprintPeer reviewe

Common psychiatric comorbidities in epilepsy: How big of a problem is it?

Psychiatric illness and epilepsy commonly co-occur in adults and in children and adolescents. Theories of comorbidity are complex, but recurring associations between the conditions suggest overlap that is more than simple co-occurrence. Common underlying pathophysiology may imply that epilepsy itself may constituently include psychiatric symptoms. Conditions such as depression or cognitive difficulties commonly occur and in some cases, are considered to be associated with specific epilepsy characteristics such as localization or seizure type. Regardless of etiologic attributions to psychiatric comorbidity, it is clear today that treatment for epilepsy needs to target psychiatric illness. In many cases, quality-of-life improvements depend more upon addressing psychiatric symptoms than seizures themselves