Stress and visual function in infantile nystagmus syndrome.

PURPOSE: Infantile nystagmus syndrome (INS) is an involuntary oscillation of the eyes that has been reported to impair vision and worsen under stress. This investigation aimed to measure visual function in terms of visual acuity (VA) and response time (RT), when INS subjects are placed under stress. METHODS: A total of 23 subjects with INS and 20 control subjects performed a 2-alternative forced choice (2AFC) staircase procedure identifying the gap in a Landolt C, under 4 experimental conditions: initial acclimatization (A); task demand (TD), during which subjects received a small electrical shock for every incorrect answer; anticipatory anxiety (AA), during which subjects received a small shock at random intervals; and relaxed (R). Arousal was monitored with galvanic skin conductance (SkC). In addition to VA and eye movements, RTs were recorded. RESULTS: The SkC was higher in the TD and AA periods and lower during A and R. Shock significantly increased nystagmus amplitude (P < 0.01) and intensity (P < 0.007), and reduced foveation periods (FPs, P < 0.022). In both groups, VA was not reduced, but showed a slight improvement. However, shock increased RT (P < 0.009), and INS subjects were slower than controls (P < 0.0005). CONCLUSIONS: Increased arousal ("stress") provoked more intense nystagmus eye movements. As seen in other studies, stress did not reduce VA despite the shorter FPs. Although VA and FP can correlate across subjects, there would appear to be little correlation, if any, within a subject. However, RTs did increase with stress and shorter FPs, which may have an adverse impact on the visual performance of those with INS

An automated segmentation approach to calibrating infantile nystagmus waveforms

Infantile nystagmus (IN) describes a regular, repetitive movement of the eyes. A characteristic feature of each cycle of the IN eye movement waveform is a period in which the eyes are moving at minimal velocity. This so-called “foveation” period has long been considered the basis for the best vision in individuals with IN. In recent years, the technology for measuring eye movements has improved considerably, but there remains the challenge of calibrating the direction of gaze in tracking systems when the eyes are continuously moving. Identifying portions of the nystagmus waveform suitable for calibration typically involves time-consuming manual selection of the foveation periods from the eye trace. Without an accurate calibration, the exact parameters of the waveform cannot be determined. In this study, we present an automated method for segmenting IN waveforms with the purpose of determining the foveation positions to be used for calibration of an eye tracker. On average, the “point of regard” was found to be within 0.21° of that determined by hand-marking by an expert observer. This method enables rapid clinical quantification of waveforms and the possibility of gaze-contingent research paradigms being performed with this patient group

Patterns of Suicidal Ideation and Behavior in Northern Ireland and Associations with Conflict Related Trauma

In this study, data from the World Mental Health Survey's Northern Ireland (NI) Study of Health and Stress (NISHS) was used to assess the associations between conflict- and non-conflict-related traumatic events and suicidal behaviour, controlling for age and gender and the effects of mental disorders in NI. DSM mental disorders and suicidal ideation, plans and attempts were assessed using the Composite International Diagnostic Interview (CIDI) in a multi-stage, clustered area probability household sample (N = 4,340, response rate 68.4%). The traumatic event categories were based on event types listed in the PTSD section of the CIDI. Suicidal ideation and attempts were more common in women than men, however, rates of suicide plans were similar for both genders. People with mood, anxiety and substance disorders were significantly more likely than those without to endorse suicidal ideation, plan or attempt. The highest odds ratios for all suicidal behaviors were for people with any mental disorder. However, the odds of seriously considering suicide were significantly higher for people with conflict and non-conflict-related traumatic events compared with people who had not experienced a traumatic event. The odds of having a suicide plan remain significantly higher for people with conflict-related traumatic events compared to those with only non-conflict-related events and no traumatic events. Finally, the odds of suicide attempt were significantly higher for people who have only non-conflict-related traumatic events compared with the other two categories. The results suggest that traumatic events associated with the NI conflict may be associated with suicidal ideation and plans, and this effect appears to be in addition to that explained by the presence of mental disorders. The reduced rates of suicide attempts among people who have had a conflict-related traumatic event may reflect a higher rate of single, fatal suicide attempts in this population

Selecting a BRCA risk assessment model for use in a familial cancer clinic

<p>Abstract</p> <p>Background</p> <p>Risk models are used to calculate the likelihood of carrying a <it>BRCA1 </it>or <it>BRCA2 </it>mutation. We evaluated the performances of currently-used risk models among patients from a large familial program using the criteria of high sensitivity, simple data collection and entry and <it>BRCA </it>score reporting.</p> <p>Methods</p> <p>Risk calculations were performed by applying the BRCAPRO, Manchester, Penn II, Myriad II, FHAT, IBIS and BOADICEA models to 200 non-<it>BRCA </it>carriers and 100 <it>BRCA </it>carriers, consecutively tested between August 1995 and March 2006. Areas under the receiver operating characteristic curves (AUCs) were determined and sensitivity and specificity were calculated at the conventional testing thresholds. In addition, subset analyses were performed for low and high risk probands.</p> <p>Results</p> <p>The BRCAPRO, Penn II, Myriad II, FHAT and BOADICEA models all have similar AUCs of approximately 0.75 for <it>BRCA </it>status. The Manchester and IBIS models have lower AUCs (0. and 0.47 respectively). At the conventional testing thresholds, the sensitivities and specificities for a <it>BRCA </it>mutation were, respectively, as follows: BRCAPRO (0.75, 0.62), Manchester (0.58,0.71), Penn II (0.93,0.31), Myriad II (0.71,0.63), FHAT (0.70,0.63), IBIS (0.20,0.74), BOADICEA (0.70, 0.65).</p> <p>Conclusion</p> <p>The Penn II model most closely met the criteria we established and this supports the use of this model for identifying individuals appropriate for genetic testing at our facility. These data are applicable to other familial clinics provided that variations in sample populations are taken into consideration.</p

Use of Recombinant Adenovirus Vectored Consensus IFN-α to Avert Severe Arenavirus Infection

Several arenaviruses can cause viral hemorrhagic fever, a severe disease with case-fatality rates in hospitalized individuals ranging from 15-30%. Because of limited prophylaxis and treatment options, new medical countermeasures are needed for these viruses classified by the National Institutes of Allergy and Infectious Diseases (NIAID) as top priority biodefense Category A pathogens. Recombinant consensus interferon alpha (cIFN-α) is a licensed protein with broad clinical appeal. However, while cIFN-α has great therapeutic value, its utility for biodefense applications is hindered by its short in vivo half-life, mode and frequency of administration, and costly production. To address these limitations, we describe the use of DEF201, a replication-deficient adenovirus vector that drives the expression of cIFN-α, for pre- and post-exposure prophylaxis of acute arenaviral infection modeled in hamsters. Intranasal administration of DEF201 24 h prior to challenge with Pichindé virus (PICV) was highly effective at protecting animals from mortality and preventing viral replication and liver-associated disease. A significant protective effect was still observed with a single dosing of DEF201 given two weeks prior to PICV challenge. DEF201 was also efficacious when administered as a treatment 24 to 48 h post-virus exposure. The protective effect of DEF201 was largely attributed to the expression of cIFN-α, as dosing with a control empty vector adenovirus did not protect hamsters from lethal PICV challenge. Effective countermeasures that are highly stable, easily administered, and elicit long lasting protective immunity are much needed for arena and other viral infections. The DEF201 technology has the potential to address all of these issues and may serve as a broad-spectrum antiviral to enhance host defense against a number of viral pathogens

Myocardial tagging by Cardiovascular Magnetic Resonance: evolution of techniques--pulse sequences, analysis algorithms, and applications

Cardiovascular magnetic resonance (CMR) tagging has been established as an essential technique for measuring regional myocardial function. It allows quantification of local intramyocardial motion measures, e.g. strain and strain rate. The invention of CMR tagging came in the late eighties, where the technique allowed for the first time for visualizing transmural myocardial movement without having to implant physical markers. This new idea opened the door for a series of developments and improvements that continue up to the present time. Different tagging techniques are currently available that are more extensive, improved, and sophisticated than they were twenty years ago. Each of these techniques has different versions for improved resolution, signal-to-noise ratio (SNR), scan time, anatomical coverage, three-dimensional capability, and image quality. The tagging techniques covered in this article can be broadly divided into two main categories: 1) Basic techniques, which include magnetization saturation, spatial modulation of magnetization (SPAMM), delay alternating with nutations for tailored excitation (DANTE), and complementary SPAMM (CSPAMM); and 2) Advanced techniques, which include harmonic phase (HARP), displacement encoding with stimulated echoes (DENSE), and strain encoding (SENC). Although most of these techniques were developed by separate groups and evolved from different backgrounds, they are in fact closely related to each other, and they can be interpreted from more than one perspective. Some of these techniques even followed parallel paths of developments, as illustrated in the article. As each technique has its own advantages, some efforts have been made to combine different techniques together for improved image quality or composite information acquisition. In this review, different developments in pulse sequences and related image processing techniques are described along with the necessities that led to their invention, which makes this article easy to read and the covered techniques easy to follow. Major studies that applied CMR tagging for studying myocardial mechanics are also summarized. Finally, the current article includes a plethora of ideas and techniques with over 300 references that motivate the reader to think about the future of CMR tagging

Multiplicity of cerebrospinal fluid functions: New challenges in health and disease

This review integrates eight aspects of cerebrospinal fluid (CSF) circulatory dynamics: formation rate, pressure, flow, volume, turnover rate, composition, recycling and reabsorption. Novel ways to modulate CSF formation emanate from recent analyses of choroid plexus transcription factors (E2F5), ion transporters (NaHCO3 cotransport), transport enzymes (isoforms of carbonic anhydrase), aquaporin 1 regulation, and plasticity of receptors for fluid-regulating neuropeptides. A greater appreciation of CSF pressure (CSFP) is being generated by fresh insights on peptidergic regulatory servomechanisms, the role of dysfunctional ependyma and circumventricular organs in causing congenital hydrocephalus, and the clinical use of algorithms to delineate CSFP waveforms for diagnostic and prognostic utility. Increasing attention focuses on CSF flow: how it impacts cerebral metabolism and hemodynamics, neural stem cell progression in the subventricular zone, and catabolite/peptide clearance from the CNS. The pathophysiological significance of changes in CSF volume is assessed from the respective viewpoints of hemodynamics (choroid plexus blood flow and pulsatility), hydrodynamics (choroidal hypo- and hypersecretion) and neuroendocrine factors (i.e., coordinated regulation by atrial natriuretic peptide, arginine vasopressin and basic fibroblast growth factor). In aging, normal pressure hydrocephalus and Alzheimer's disease, the expanding CSF space reduces the CSF turnover rate, thus compromising the CSF sink action to clear harmful metabolites (e.g., amyloid) from the CNS. Dwindling CSF dynamics greatly harms the interstitial environment of neurons. Accordingly the altered CSF composition in neurodegenerative diseases and senescence, because of adverse effects on neural processes and cognition, needs more effective clinical management. CSF recycling between subarachnoid space, brain and ventricles promotes interstitial fluid (ISF) convection with both trophic and excretory benefits. Finally, CSF reabsorption via multiple pathways (olfactory and spinal arachnoidal bulk flow) is likely complemented by fluid clearance across capillary walls (aquaporin 4) and arachnoid villi when CSFP and fluid retention are markedly elevated. A model is presented that links CSF and ISF homeostasis to coordinated fluxes of water and solutes at both the blood-CSF and blood-brain transport interfaces

Search for High-Mass Resonances Decaying to τν in pp Collisions at √s=13 TeV with the ATLAS Detector

A search for high-mass resonances decaying to τν using proton-proton collisions at √s=13 TeV produced by the Large Hadron Collider is presented. Only τ-lepton decays with hadrons in the final state are considered. The data were recorded with the ATLAS detector and correspond to an integrated luminosity of 36.1 fb−1. No statistically significant excess above the standard model expectation is observed; model-independent upper limits are set on the visible τν production cross section. Heavy W′ bosons with masses less than 3.7 TeV in the sequential standard model and masses less than 2.2–3.8 TeV depending on the coupling in the nonuniversal G(221) model are excluded at the 95% credibility level

Search for the direct production of charginos and neutralinos in final states with tau leptons in √s=13 TeV collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with at least two hadronically decaying tau leptons is presented. The analysis uses a dataset of pp collisions corresponding to an integrated luminosity of 36.1 fb−1, recorded with the ATLAS detector at the Large Hadron Collider at a centre-of-mass energy of 13TeV.Nosignificant deviation from the expected Standard Model background is observed. Limits are derived in scenarios of ˜χ+1 ˜χ−1 pair production and of ˜χ±1 ˜χ02 and ˜χ+1 ˜χ−1 production in simplified models where the neutralinos and charginos decay solely via intermediate left-handed staus and tau sneutrinos, and the mass of the ˜ τL state is set to be halfway between the masses of the ˜χ±1 and the ˜χ01. Chargino masses up to 630 GeV are excluded at 95% confidence level in the scenario of direct production of ˜χ+1 ˜χ−1 for a massless ˜χ01. Common ˜χ±1 and ˜χ02 masses up to 760 GeV are excluded in the case of production of ˜χ±1 ˜χ02 and ˜χ+1 ˜χ−1 assuming a massless ˜χ01. Exclusion limits for additional benchmark scenarios with large and small mass-splitting between the ˜χ±1 and the ˜χ01 are also studied by varying the ˜ τL mass between the masses of the ˜χ±1 and the ˜χ01