[Diagnosis and treatment of oculomotor deficits in Möbius sequence]

This article reviews the spectrum of possible motility disorders and ocular misalignment in patients with Möbius sequence. The various options for strabismus surgery are discussed and a stepwise algorithm is presented.

A self-developed and constructed robot for minimally invasive cochlear implantation

Conclusion: A robot built specifically for stereotactic cochlear implantation provides equal or better accuracy levels together with a better integration into a clinical environment, when compared to existing approaches based on industrial robots. Objectives: To evaluate the technical accuracy of a robotic system developed specifically for lateral skull base surgery in an experimental setup reflecting the intended clinical application. The invasiveness of cochlear electrode implantation procedures may be reduced by replacing the traditional mastoidectomy with a small tunnel slightly larger in diameter than the electrode itself. Methods: The end-to-end accuracy of the robot system and associated image-guided procedure was evaluated on 15 temporal bones of whole head cadaver specimens. The main components of the procedure were as follows: reference screw placement, cone beam CT scan, computer-aided planning, pair-point matching of the surgical plan, robotic drilling of the direct access tunnel, and post-operative cone beam CT scan and accuracy assessment. Results: The mean accuracy at the target point (round window) was 0.56 ± 41 mm with an angular misalignment of 0.88 ± 0.41°. The procedural time of the registration process through the completion of the drilling procedure was 25 ± 11 min. The robot was fully operational in a clinical environment.

Pulse-front tilt for short-wavelength lasing by means of traveling-wave plasma-excitation

Generation of coherent short-wavelength radiation across a plasma column is dramatically improved under traveling-wave excitation (TWE). The latter is optimized when its propagation is close to the speed of light, which implies small-angle target-irradiation. Yet, short-wavelength lasing needs large irradiation angles in order to increase the optical penetration of the pump into the plasma core. Pulse-front back-tilt is considered to overcome such trade-off. In fact, the TWE speed depends on the pulse-front slope (envelope of amplitude), whereas the optical penetration depth depends on the wave-front slope (envelope of phase). Pulse-front tilt by means of compressor misalignment was found effective only if coupled with a high-magnification front-end imaging/focusing component. It is concluded that speed matching should be accomplished with minimal compressor misalignment and maximal imaging magnification.

Better conduct of clinical trials: the control group in critical care trials

OBJECTIVE: To review trial design issues related to control groups. DESIGN: Review of the literature with specific reference to critical care trials. MAIN RESULTS AND CONCLUSIONS: Performing randomized controlled trials in the critical care setting presents specific problems: studies include patients with rapidly lethal conditions, the majority of intensive care patients suffer from syndromes rather than from well-definable diseases, the severity of such syndromes cannot be precisely assessed, and the treatment consists of interacting therapies. Interactions between physiology, pathophysiology, and therapies are at best marginally understood and may have a major impact on study design and interpretation of results. Selection of the right control group is crucial for the interpretation and clinical implementation of results. Studies comparing new interventions with current ones or different levels of current treatments have the problem of the necessity of defining "usual care." Usual care controls without any constraints typically include substantial heterogeneity. Constraints in the usual therapy may help to reduce some variation. Inclusion of unrestricted usual care groups may help to enhance safety. Practice misalignment is a novel problem in which patients receive a treatment that is the direct opposite of usual care, and occurs when fixed-dose interventions are used in situations where care is normally titrated. Practice misalignment should be considered in the design and interpretation of studies on titrated therapies.

ATG5 is induced by DNA-damaging agents and promotes mitotic catastrophe independent of autophagy

Anticancer drug therapy activates both molecular cell death and autophagy pathways. Here we show that even sublethal concentrations of DNA-damaging drugs, such as etoposide and cisplatin, induce the expression of autophagy-related protein 5 (ATG5), which is both necessary and sufficient for the subsequent induction of mitotic catastrophe. We demonstrate that ATG5 translocates to the nucleus, where it physically interacts with survivin in response to DNA-damaging agents both in vitro and in carcinoma tissues obtained from patients who had undergone radiotherapy and/or chemotherapy. As a consequence, elements of the chromosomal passenger complex are displaced during mitosis, resulting in chromosome misalignment and segregation defects. Pharmacological inhibition of autophagy does not prevent ATG5-dependent mitotic catastrophe, but shifts the balance to an early caspase-dependent cell death. Our data suggest a dual role for ATG5 in response to drug-induced DNA damage, where it acts in two signalling pathways in two distinct cellular compartments, the cytosol and the nucleus.

A Process Model of Complementarity and Substitution of Contractual and Relational Governance in IS Outsourcing

This paper develops a process model of how and why complementarity and substitution form over time between contractual and relational governance in the context of information systems outsourcing. Our analysis identifies four distinct process patterns that explain this formation as the outcome of interaction processes between key elements of both contractual and relational governance. These patterns unveil the dynamic nature of complementarity and substitution. In particular, we show that the relationship between contractual and relational governance oscillates between complementarity and substitution. Those oscillations are triggered mainly by three types of contextual events (goal fuzziness, goal conflict, and goal misalignment). Surprisingly, substitution of informal control did not occur as an immediate reaction to external events but emerged as a consequence of preceding complementarity. Thus, our study challenges the prevailing view of an either/or dichotomy of complementarity and substitution by showing that they are causally connected over time.

Noninvasive referencing of intraocular tumors for external beam radiation therapy using optical coherence tomography: a proof of concept.

PURPOSE External beam radiation therapy is currently considered the most common treatment modality for intraocular tumors. Localization of the tumor and efficient compensation of tumor misalignment with respect to the radiation beam are crucial. According to the state of the art procedure, localization of the target volume is indirectly performed by the invasive surgical implantation of radiopaque clips or is limited to positioning the head using stereoscopic radiographies. This work represents a proof-of-concept for direct and noninvasive tumor referencing based on anterior eye topography acquired using optical coherence tomography (OCT). METHODS A prototype of a head-mounted device has been developed for automatic monitoring of tumor position and orientation in the isocentric reference frame for LINAC based treatment of intraocular tumors. Noninvasive tumor referencing is performed with six degrees of freedom based on anterior eye topography acquired using OCT and registration of a statistical eye model. The proposed prototype was tested based on enucleated pig eyes and registration accuracy was measured by comparison of the resulting transformation with tilt and torsion angles manually induced using a custom-made test bench. RESULTS Validation based on 12 enucleated pig eyes revealed an overall average registration error of 0.26 ± 0.08° in 87 ± 0.7 ms for tilting and 0.52 ± 0.03° in 94 ± 1.4 ms for torsion. Furthermore, dependency of sampling density on mean registration error was quantitatively assessed. CONCLUSIONS The tumor referencing method presented in combination with the statistical eye model introduced in the past has the potential to enable noninvasive treatment and may improve quality, efficacy, and flexibility of external beam radiotherapy of intraocular tumors.

Optical Tolerance Analysis of the Multi-Beam Limb Viewing Instrument STEAMR

In this paper, we report on an optical tolerance analysis of the submillimeter atmospheric multi-beam limb sounder, STEAMR. Physical optics and ray-tracing methods were used to quantify and separate errors in beam pointing and distortion due to reflector misalignment and primary reflector surface deformations. Simulations were performed concurrently with the manufacturing of a multi-beam demonstrator of the relay optical system which shapes and images the beams to their corresponding receiver feed horns. Results from Monte Carlo simulations show that the inserts used for reflector mounting should be positioned with an overall accuracy better than 100 μm (~ 1/10 wavelength). Analyses of primary reflector surface deformations show that a deviation of magnitude 100 μm can be tolerable before deployment, whereas the corresponding variations should be less than 30 μm during operation. The most sensitive optical elements in terms of misalignments are found near the focal plane. This localized sensitivity is attributed to the off-axis nature of the beams at this location. Post-assembly mechanical measurements of the reflectors in the demonstrator show that alignment better than 50 μm could be obtained.

Fourier optics study of traveling-wave excitation at short- wavelength plasma-lasing

Traveling-wave excitation close to the speed of light implies small-angle target-irradiation. Yet, short-wavelength lasing needs large irradiation angles. Pulse-front back-tilt is considered to overcome such trade-off. Pulse-front tilt by means of compressor misalignment was found effective only if coupled with a strong front-end imaging/focusing component.

A conceptual model of compensation/decompensation in lumbar segmental instability

Lumbar spinal instability (LSI) is a common spinal disorder and can be associated with substantial disability. The concept of defining clinically relevant classifications of disease or 'target condition' is used in diagnostic research. Applying this concept to LSI we hypothesize that a set of clinical and radiological criteria can be developed to identify patients with this target condition who are at high risk of 'irreversible' decompensated LSI for whom surgery becomes the treatment of choice. In LSI, structural deterioration of the lumbar disc initiates a degenerative cascade of segmental instability. Over time, radiographic signs become visible: traction spurs, facet joint degeneration, misalignment, stenosis, olisthesis and de novo scoliosis. Ligaments, joint capsules, local and distant musculature are the functional elements of the lumbar motion segment. Influenced by non-functional factors, these functional elements allow a compensation of degeneration of the motion segment. Compensation may happen on each step of the degenerative cascade but cannot reverse it. However, compensation of LSI may lead to an alleviation or resolution of clinical symptoms. In return, the target condition of decompensation of LSI may cause the new occurrence of symptoms and pain. Functional compensation and decompensation are subject to numerous factors that can change which makes estimation of an individual's long-term prognosis difficult. Compensation and decompensation may influence radiographic signs of degeneration, e.g. the degree of misalignment and segmental angulation caused by LSI is influenced by the tonus of the local musculature. This conceptual model of compensation/decompensation may help solve the debate on functional and psychosocial factors that influence low back pain and to establish a new definition of non-specific low back pain. Individual differences of identical structural disorders could be explained by compensated or decompensated LSI leading to changes in clinical symptoms and pain. Future spine surgery will have to carefully define and measure functional aspects of LSI, e.g. to identify a point of no return where multidisciplinary interventions do not allow a re-compensation and surgery becomes the treatment of choice.

Acute onset incomitant image disparity modifies saccadic and vergence eye movements.

New-onset impairment of ocular motility will cause incomitant strabismus, i.e., a gaze-dependent ocular misalignment. This ocular misalignment will cause retinal disparity, that is, a deviation of the spatial position of an image on the retina of both eyes, which is a trigger for a vergence eye movement that results in ocular realignment. If the vergence movement fails, the eyes remain misaligned, resulting in double vision. Adaptive processes to such incomitant vergence stimuli are poorly understood. In this study, we have investigated the physiological oculomotor response of saccadic and vergence eye movements in healthy individuals after shifting gaze from a viewing position without image disparity into a field of view with increased image disparity, thus in conditions mimicking incomitance. Repetitive saccadic eye movements into a visual field with increased stimulus disparity lead to a rapid modification of the oculomotor response: (a) Saccades showed immediate disconjugacy (p < 0.001) resulting in decreased retinal image disparity at the end of a saccade. (b) Vergence kinetics improved over time (p < 0.001). This modified oculomotor response enables a more prompt restoration of ocular alignment in new-onset incomitance.

An unusual stroke-like clinical presentation of Creutzfeldt-Jakob disease: acute vestibular syndrome

INTRODUCTION Vertigo and dizziness are common neurological symptoms in general practice. Most patients have benign peripheral vestibular disorders, but some have dangerous central causes. Recent research has shown that bedside oculomotor examinations accurately discriminate central from peripheral lesions in those with new, acute, continuous vertigo/dizziness with nausea/vomiting, gait unsteadiness, and nystagmus, known as the acute vestibular syndrome. CASE REPORT A 56-year-old man presented to the emergency department with acute vestibular syndrome for 1 week. The patient had no focal neurological symptoms or signs. The presence of direction-fixed, horizontal nystagmus suppressed by visual fixation without vertical ocular misalignment (skew deviation) was consistent with an acute peripheral vestibulopathy, but bilaterally normal vestibuloocular reflexes, confirmed by quantitative horizontal head impulse testing, strongly indicated a central localization. Because of a long delay in care, the patient left the emergency department without treatment. He returned 1 week later with progressive gait disturbance, limb ataxia, myoclonus, and new cognitive deficits. His subsequent course included a rapid neurological decline culminating in home hospice placement and death within 1 month. Magnetic resonance imaging revealed restricted diffusion involving the basal ganglia and cerebral cortex. Spinal fluid 14-3-3 protein was elevated. The rapidly progressive clinical course with dementia, ataxia, and myoclonus plus corroborative neuroimaging and spinal fluid findings confirmed a clinicoradiographic diagnosis of Creutzfeldt-Jacob disease. CONCLUSIONS To our knowledge, this is the first report of an initial presentation of Creutzfeldt-Jacob disease closely mimicking vestibular neuritis, expanding the known clinical spectrum of prion disease presentations. Despite the initial absence of neurological signs, the central lesion location was differentiated from a benign peripheral vestibulopathy at the first visit using simple bedside vestibular tests. Familiarity with these tests could help providers prevent initial misdiagnosis of important central disorders in patients presenting vertigo or dizziness.