Dexterous helical magnetic robot for improved endovascular access.

Treating vascular diseases in the brain requires access to the affected region inside the body. This is usually accomplished through a minimally invasive technique that involves the use of long, thin devices, such as wires and tubes, that are manually maneuvered by a clinician within the bloodstream. By pushing, pulling, and twisting, these devices are navigated through the tortuous pathways of the blood vessels. The outcome of the procedure heavily relies on the clinician's skill and the device's ability to navigate to the affected target region in the bloodstream, which is often inhibited by tortuous blood vessels. Sharp turns require high flexibility, but this flexibility inhibits translation of proximal insertion to distal tip advancement. We present a highly dexterous, magnetically steered continuum robot that overcomes pushability limitations through rotation. A helical protrusion on the device's surface engages with the vessel wall and translates rotation to forward motion at every point of contact. An articulating magnetic tip allows for active steerability, enabling navigation from the aortic arch to millimeter-sized arteries of the brain. The effectiveness of the magnetic continuum robot has been demonstrated through successful navigation in models of the human vasculature and in blood vessels of a live pig.

Susceptibility and Tumor Size Changes During the Time Course of Standard Treatment in Recurrent Glioblastoma.

BACKGROUND AND PURPOSE: Susceptibility-weighted magnetic resonance imaging (SWI) yields information regarding tumor biology (e.g., hemorrhage) of growing gliomas. SWI changes can also be observed as a consequence of treatment, for example radiation therapy. The aim of our study was to investigate how susceptibility changes occur during the time course after completion of standard treatment in newly diagnosed glioblastoma (GBM). METHODS: Eighteen GBM patients were retrospectively analyzed. After completion of therapy, imaging was performed every 3 months. MRI was analyzed at the following time points: after the third and sixth cycle of adjuvant temozolomide chemotherapy, thereafter in 3 month intervals and at recurrence. The number of SWI positive tumor pixels was quantified and compared with progression as defined by the RANO criteria on T2- and contrast-enhanced T1-weighted MRI sequences (T1-CE). RESULTS: The MRI interval between completion of the sixth chemotherapy cycle and last MRI before progression was 390 ± 292 days. Between the last MRI before progression and at progression a significant increase in SWI positive tumor pixels was observed (P = .012), whereas tumor size remained unchanged (RANO T2: P = .385; RANO T1-CE: P = .165). The number of SWI positive pixels remained unchanged between last MRI before progression until progression (P = .149), whereas RANO T2 and T1-CE showed tumor progression (interval 128 ± 69 days). CONCLUSIONS: SWI positive pixel count increases significantly prior to changes in tumor size (RANO). Our findings may be explained by microbleeds compatible with stimulation of angiogenesis and possibly serve as an early biomarker of tumor progression.

Modulation of the Emotional Response to Viewing Strabismic Children in Mothers-Measured by fMRI.

PURPOSE: Strabismus influences not only the individual with nonparallel eyes but also the observer. It has previously been demonstrated by fMRI that adults viewing images of strabismic adults have a negative reaction to the images as demonstrated by limbic activation, especially activation of the left amygdala. The aim of this study was to see if mothers would have a similar reaction to viewing strabismic children and whether or not that reaction would be different in mothers of strabismic children. METHODS: Healthy mothers of children with strabismus (n = 10, Group I) and without strabismus (n = 15, Group II) voluntarily underwent fMRI at 3T. Blood oxygen level dependent signal responses to viewing images of strabismic and non-strabismic children were analyzed. RESULTS: Group II, while viewing images of strabismic children, showed significantly increased activation of the limbic network (p < 0.05) and bilateral amygdala activation. Group I showed considerably less limbic activation, compared to the group II, and had no amygdala activation. Both groups revealed statically significant activation in the FEF (frontal eye field) when they were viewing images of strabismic children as compared to when they were viewing children with parallel eyes. The activated FEF area for Group II was much larger than for group I. CONCLUSION: Mothers of non-strabismic children showed similar negative emotional fMRI patterns as adults did while viewing strabismic adults. Strabismus is an interpersonal organic issue for the observer, which also impacts the youngest members of our society.

Ischias. Von der Säftelehre zur Pathomorphologie.

Today, lumbar disc disease is a very common disease, which will be often seen in both the family practice as well as in the consultations of orthopedics, neurology, rheumatology or neurosurgery. Furthermore, lumbar disc surgery is one of the most common spinal surgical procedures worldwide. But, for many centuries, physician had no clear understanding of the anatomical condition and the pathomechanism of this disease. Therefore, no rational treatment was available. The Hippocratic physicians knew the signs and symptoms of lumbar disc disease, which they then called "sciatica". But, they subsumed different disorders, like hip diseases under this term. In the mid-18th century, it was the Italian physician Domenico Felice Antonio Cotugno (1736-1822), who first brought clarity in the concept of radicular syndromes; he recognized, that the so-called "sciatica" could be of neurogenic origin. In 1742, a contemporary of Cotugno, the German Josias Weitbrecht (1702-1747) has to be credited for the first precise description of the intervertebral disc. Nearby a hundred years later, the German Hubert von Luschka (1820-1875) described for the first time a herniated disc in a pathologic specimen. With the landmark report of the New England Journal of Medicine in 1934, the two American surgeons, William Jason Mixter (1880-1958) and Joseph Seaton Barr (1901-1963), finally cleared the pathomechanism of lumbar disc disease.

[Sciatica. From stretch rack to microdiscectomy]. / Ischias. Von der Streckbank zur Mikrodiskektomie.

In ancient times as well as in the Middle Ages treatment options for discogenic nerve compression syndrome were limited and usually not very specific because of low anatomical and pathophysiological knowledge. The stretch rack (scamnum Hippocratis) was particularly prominent but was widely used as a therapeutic device for very different spinal disorders. Since the beginning of the nineteenth century anatomical knowledge increased and the advances in the fields of asepsis, anesthesia and surgery resulted in an increase in surgical interventions on the spine. In 1908 the first successful lumbar discectomy was initiated and performed by the German neurologist Heinrich O. Oppenheim (1858-1919) and the surgeon Fedor Krause (1857-1937); however, neither recognized the true pathological condition of discogenic nerve compression syndrome. With the landmark report in the New England Journal of Medicine in 1934, the two American surgeons William Jason Mixter (1880-1958) and Joseph Seaton Barr (1901-1963) finally clarified the pathomechanism of lumbar disc herniation and furthermore, propagated discectomy as the standard therapy. Since then interventions on intervertebral discs rapidly increased and the treatment options for lumbar disc surgery quickly evolved. The surgical procedures changed over time and were continuously being refined. In the late 1960s the surgical microscope was introduced for spinal surgery by the work of the famous neurosurgeon Mahmut Gazi Yasargil and his colleague Wolfhard Caspar and so-called microdiscectomy was introduced. Besides open discectomy other interventional techniques were developed to overcome the side effects of surgical procedures. In 1964 the American orthopedic surgeon Lyman Smith (1912-1991) introduced chemonucleolysis, a minimally invasive technique consisting only of a cannula and the proteolytic enzyme chymopapain, which is injected into the disc compartment to dissolve the displaced disc material. In 1975 the Japanese orthopedic surgeon Sadahisa Hijikata described percutaneous discectomy for the first time, which was a further minimally invasive surgical technique. Further variants of minimally invasive surgical procedures, such as percutaneous laser discectomy in 1986 and percutaneous endoscopic microdiscectomy in 1997, were also introduced; however, open discectomy, especially microdiscectomy remains the therapeutic gold standard for lumbar disc herniation.

Outcomes and prognostic factors in patients with haematological malignancy admitted to a specialist cancer intensive care unit: a 5 yr study.

BACKGROUND: Long-held assumptions of poor prognoses for patients with haematological malignancies (HM) have meant that clinicians have been reluctant to admit them to the intensive care unit (ICU). We aimed to evaluate ICU, in-hospital, and 6 month mortality and to identify predictors for in-hospital mortality. METHODS: A cohort study in a specialist cancer ICU of adult HM patients admitted over 5 yr. Data acquired included: patient characteristics, haematological diagnosis, haematopoietic stem cell transplant (HSCT), reason for ICU admission, and APACHE II scores. Laboratory values, organ failures, and level of organ support were recorded on ICU admission. Predictors for in-hospital mortality were evaluated using uni- and multivariate analysis. RESULTS: Of 199 patients, median age was 58 yr [inter-quartile range (IQR) 46-66], 51.7% were emergency admissions, 42.2% post-HSCT, 51.9% required mechanical ventilation, median APACHE II was 21 (IQR 16-25), and median organ failure numbered 2 (IQR 1-4). ICU, in-hospital, and 6 month mortalities were 33.7%, 45.7%, and 59.3%, respectively. Univariate analysis revealed bilirubin >32 µmol litre(-1), mechanical ventilation, ≥2 organ failures, renal replacement therapy, vasopressor support (all P<0.001), graft-vs-host disease (P=0.007), APACHE II score (P=0.02), platelets ≤20×10(9) litre(-1) (P=0.03), and proven invasive fungal infection (P=0.04) were associated with in-hospital mortality. Multivariate analysis revealed that ≥2 organ failures [odds ratio (OR) 5.62; 95% confidence interval (95% CI), 2.30-13.70] and mechanical ventilation (OR 3.03; 95% CI, 1.33-6.90) were independently associated with in-hospital mortality. CONCLUSIONS: Mortality was lower than in previous studies. Mechanical ventilation and ≥2 organ failures were independently associated with in-hospital mortality. 'Traditional' variables such as neutropenia, transplantation status, and APACHE II score no longer appear to be predictive.

Perinatal and early surgical outcome for the fetus with hypoplastic left heart syndrome: a 5-year single institutional experience.

OBJECTIVES: To review our experience with the prenatal diagnosis of hypoplastic left heart syndrome (HLHS). Our goal was to establish the benchmark for perinatal and early surgical outcome in the current era, from a center with an aggressive surgical approach and a cohort with a high level of intention-to-treat. METHODS: Outcome was assessed in fetuses with HLHS following stratification into high-risk and standard-risk categories. High risk was defined as the presence of any of the following: extracardiac, genetic or chromosomal anomalies; prematurity of < 34 weeks' gestation; additional cardiac findings such as intact or highly restrictive atrial septum, severe degree of tricuspid regurgitation or severe ventricular dysfunction. Standard risk was defined as absence of these risk factors. RESULTS: Of 240 fetuses evaluated over 5 years, 162 (67.5%) were in the standard-risk group and 78 (32.5%) were in the high-risk group. Of the 240 sets of parents, 38 (15.8%) chose termination or non-intervention at birth at initial prenatal counseling and 185 of the neonates (77.1%) underwent first-stage Norwood surgery with 155 surviving and 30 deaths, giving an overall Norwood operative survival of 83.8%. Breakdown by risk class reveals a significant Norwood operative survival advantage for the standard-risk group (92.8%) over the high-risk group (56.5%) (P < 0.001). CONCLUSIONS: Following prenatal diagnosis of HLHS, families should be strongly encouraged to undertake comprehensive prenatal evaluation in order to obtain an accurate prognosis. One-third have additional risk factors that limit survival outcome, however two-thirds do not and have an excellent chance of early survival.

Correlation between critical temperature and strength of small-scale bcc pillars.

Microcompression tests were performed on focused-ion-beam-machined micropillars of several body-centered-cubic metals (W, Mo, Ta, and Nb) at room temperature. The relationship between yield strength and pillar diameter as well as the deformation morphologies were found to correlate with a parameter specific for bcc metals, i.e., the critical temperature T(c). This finding sheds new light on the phenomenon of small-scale plasticity in largely unexplored non-fcc metals.

Analyzing time-dependent microarray data using independent component analysis derived expression modes from human macrophages infected with F. tularensis holartica.

The analysis of large-scale gene expression profiles is still a demanding and extensive task. Modern machine learning and data mining techniques developed in linear algebra, like Independent Component Analysis (ICA), become increasingly popular as appropriate tools for analyzing microarray data. We applied ICA to analyze kinetic gene expression profiles of human monocyte derived macrophages (MDM) from three different donors infected with Francisella tularensis holartica and compared them to more classical methods like hierarchical clustering. Results were compared using a pathway analysis tool, based on the Gene Ontology and the MeSH database. We could show that both methods lead to time-dependent gene regulatory patterns which fit well to known TNFalpha induced immune responses. In comparison, the nonexclusive attribute of ICA results in a more detailed view and a higher resolution in time dependent behavior of the immune response genes. Additionally, we identified NFkappaB as one of the main regulatory genes during response to F. tularensis infection.

Impact of the Immediate Life Support course on the incidence and outcome of in-hospital cardiac arrest calls: an observational study over 6 years.

BACKGROUND: The Resuscitation Council (UK) Immediate Life Support (ILS) course provides training in the prevention and management of cardiac arrest. This course was introduced at our institution and we subsequently undertook an analysis to determine its impact on the incidence and outcome of in-hospital cardiac arrest. METHODS: A 6-year prospective audit of 3126 in-hospital emergency alert calls within a multi-site 1200 bedded London teaching hospital following the organisation-wide adoption of the ILS course. Key measures used to detect improvement were the incidence of emergency alert calls, in particular the proportion of calls which were pre-arrest versus cardiac arrest calls, episodes of resuscitations without return of spontaneous circulation, survival to hospital discharge; the proportion of clinical staff who were ILS trained was an important organisational measure. RESULTS: The total number of emergency alert calls showed no significant change. We observed a reduction in the proportion of calls for cardiac arrests (p<0.0001; from 85% in 2002 to 45% in 2007), a corresponding increase in the proportion of 'pre-arrest' calls (p<0.0001; from 15% in 2002 to 55% in 2007), a reduction in deaths at cardiac arrest (p=0.0002) and an increased survival to hospital discharge following an emergency call from 28% in 2004 to 39% in 2007. There was a temporal relationship between the proportion of staff who were ILS trained and outcome. CONCLUSION: The introduction of a simple and widespread educational programme was associated with a reduction in both the number of in-hospital cardiac arrests and unsuccessful cardiopulmonary resuscitation attempts.

Molecular and immunological characterization of novel weed pollen pan-allergens.

BACKGROUND: Pan-allergens like profilins, calcium-binding proteins (CBPs), and nonspecific lipid transfer proteins have been suggested as possible specific markers for multiple pollen sensitizations, and could be used to predict cross-sensitization/poly-sensitization to several pollen allergens. Therefore, the purification and characterization of cross-reacting allergens in pollen is an extremely important task towards correct allergy diagnosis. METHODS: New pan-allergens were identified by screening a ragweed pollen cDNA library with sera of patients allergic to mugwort pollen. Resulting proteins were cloned, expressed, purified and characterized. RESULTS: We report complete cDNA sequences of two profilin isoforms (Amb a 8.01 and Amb a 8.02), two isoforms of a 2EF-hand CBP (Amb a 9.01 and Amb a 9.02), a new 3EF-hand CBP (Amb a 10) from ragweed pollen and a 2EF-hand CBP from mugwort (Art v 5). All these proteins were expressed in Escherichia coli, purified to homogeneity and characterized by biochemical and immunological means. CONCLUSIONS: The identified proteins are novel pan-allergens and can be used as diagnostic markers for polysensitization and used in component-resolved diagnosis.

Prevalence of IgE-binding to Art v 1, Art v 4 and Amb a 1 in mugwort-allergic patients.

BACKGROUND: Mugwort (Artemisia vulgaris) represents an important source of weed pollen allergens. The objectives of the present study were (i) to analyze the IgE binding profiles in a group of mugwort-allergic patients, (ii) to identify individual marker allergens crucial for the diagnosis of mugwort allergy and (iii) to identify potential crossreactive allergens present in ragweed (Ambrosia artemisiifolia) pollen extract. METHODS: Sera from 100 pediatric mugwort-allergic patients were analyzed for their IgE binding pattern to natural mugwort and ragweed pollen proteins, purified natural and recombinant Art v 1, recombinant Art v 4 and recombinant Amb a 1 using immunoblots and ELISA. RESULTS: 91% of the patients' sera tested displayed IgE binding to one or more mugwort pollen allergens in ELISA and 88% were positive in immunoblot. Purified natural Art v 1 was recognized by 79%, the recombinant protein by 39% of the patients tested and purified recombinant Art v 4 by 34% of the patients' sera. 67% of the sera displayed crossreactive IgE to one or more ragweed pollen allergens. Recombinant Amb a 1 was noted in only 14% of the mugwort-allergic sera. CONCLUSIONS: Allergen-specific in vitro diagnosis was performed in 100 pediatric mugwort-allergic serum samples. Using two allergens (Art v 1 and Art v 4), 91% of the patients could be identified as mugwort pollen-sensitized patients by IgE in vitro tests. Crossreactivity to ragweed pollen allergens was demonstrated by in vitro experiments, suggesting a new important and potent allergen source expanding across Europe.

Spatiotemporal group ICA applied to fMRI datasets.

Exploratory data analysis techniques such as independent component analysis (ICA) do not depend on a priori hypotheses and are able to detect unknown, yet structured spatiotemporal processes in neuroimaging data. We present fMRI data of two different subject-groups (young and old), which performed a modified Wisconsin Card Sorting Test (WCST). Spatiotemporal ICA and SPM-generated brain maps of the subject data are compared. For the group analysis a singular value decomposition approach was used. Spatiotemporal ICA reveals a frontoparietal network being activated while subjects performed different variants of the WCST. Contrary to the SPM analysis, ICA analysis revealed significant differences between young and old subjects as well as significant within-group differences.While young subjects showed with increasing task demands (A>>B>>C) increasing activation of the right lateral prefrontal cortex and of the medial orbito-frontal cortex, old subjects showed no such gradient in activation pattern and appeared to be more distributed.

ICA analysis of retina images for glaucoma classification.

Glaucoma represent one of the most frequent causes of partial loss of the visual field. It comes along with an ongoing destruction of the optic nerve caused by an increased pressure of the eye liquid. The disease becomes obvious from investigations of the retina with scanning laser microscopes. In this report an image analysis and classification system based on independent component analysis and k-nearest-neighbor classification is proposed. The method is tested with 120 selected retina images collected with the Heidelberg Retina Tomograph and achieves a classification rate of 91%.

[Computer assisted orthopedics surgery]. / L'expérience de la navigation chirurgicale dans l'ouest.

Computer-assisted surgery has become commonplace in orthopedic surgery. The number of applications grows steadily as does the number of patients benefiting from these new techniques. The hearty debates heard when these techniques were first introduced have now given way to more evidence-based evaluation. Our objective here is to continue this approach by presenting our six-year experience with navigation. We will not discuss the theoretical background of these technologies nor attempt to present an exhaustive review of the literature but rather focus attention on surgical skills acquired by a group of surgeons working in a wide range of areas. The common point is that all have now integrated computer-assisted navigation into their routine surgical practices including: a) first-intention and revision knee arthroplasty; b) hip arthroplasty; c) anterior cruciate ligament surgery; d) proximal tibial osteotomy; e) shoulder arthroplasty. We will terminate this round table with a presentation of future technological advances and propose our advice for an increasingly widespread use of these new techniques.

Dimensional control of brittle nanoplatelets. A statistical analysis of a thin film cracking approach.

Nanoparticles are essential building blocks for nanotechnology. In this paper we demonstrate a novel method to create nanoplatelets by thin film cracking. The thickness of the resulting platelets is determined by the film thickness, and their aspect ratio is controlled by the total strain and the elastic mismatch between substrate and thin film. Platelets can be created from any brittle film independently of microstructure and materials class. The feasibility of this method is substantiated by a statistical analysis of the fracture process.

Automatic removal of high-amplitude artefacts from single-channel electroencephalograms.

In this work, we present a method to extract high-amplitude artefacts from single channel electroencephalogram (EEG) signals. The method is called local singular spectrum analysis (local SSA). It is based on a principal component analysis (PCA) applied to clusters of the multidimensional signals obtained after embedding the signals in their time-delayed coordinates. The decomposition of the multidimensional signals in each cluster is achieved by relating the largest eigenvalues with the large amplitude artefact component of the embedded signal. Then by reverting the clustering and embedding processes, the high-amplitude artefact can be extracted. Subtracting it from the original signal a corrected EEG signal results. The algorithm is applied to segments of real EEG recordings containing paroxysmal epileptiform activity contaminated by large EOG artefacts. We will show that the method can be applied also in parallel to correct all channels that present high-amplitude artefacts like ocular movement interferences or high-amplitude low frequency baseline drifts. The extracted artefacts as well as the corrected EEG will be presented.

Artemisia and Ambrosia hypersensitivity: co-sensitization or co-recognition?

BACKGROUND: Ragweed and mugwort have nearly identical flowering periods. Clinical and serological studies showed that ragweed and mugwort sensitization are often associated and this poses relevant clinical problems in patients for whom specific immunotherapy is warranted. OBJECTIVE: To establish whether the concurrent ragweed and mugwort pollen hypersensitivity is the result of co-sensitization or of co-recognition by using purified recombinant allergens. METHODS: Sensitization to ragweed and mugwort pollen was assessed by skin prick test (SPT) in all patients reporting allergic symptoms in August and September. IgE reactivity of sera from 42 patients (26 Amb+/Art+, 14 Amb+/Art-, and two Amb-/Art+) to ragweed and mugwort pollen extract as well as to several recombinant ragweed (rAmb a 1, rAmb a 5, rAmb a 6, rAmb a 8, rAmb a 9, and Amb a 10) and mugwort (rArt v 1, rArt v 4, rArt v 5, rArt v 6, and three EF-hand calcium-binding protein) allergens was detected by dot-blot and ELISA analyses. RESULTS: IgE reactivity of 372 weed pollen-allergic patients was studied. Mugwort reactivity was strongly associated with ragweed hypersensitivity: only 10/147 (7%) mugwort-hypersensitive patients were not sensitized to ragweed, whereas 225/362 (62%) ragweed-hypersensitive patients were not sensitized to mugwort. In vitro, 90% of ragweed-allergic patients reacted with rAmb a 1. Reactivity to other ragweed allergens ranged between 20% and 35%. Forty-six percent of the mugwort-sensitized patients recognized rArt v 1%, 25% reacted to Art v 4, Art v 5, and Art v 6, and 7% recognized the three-EF hand calcium-binding protein. Immunoblot inhibition experiments showed that pre-incubation with ragweed pollen extract only weakly decreased IgE reactivity to mugwort allergens. CONCLUSION: Patients showing both ragweed- and mugwort-positive SPT and/or RAST are co-sensitized. Future studies will establish whether IgE reactivity translates into clinical symptoms and, hence, if co-sensitized patients should undergo specific immunotherapy with extracts of both mugwort and ragweed pollen.