Looking down: a model for visual route following in flying insects.

Insect visual navigation is often assumed to depend on panoramic views of the horizon, and how these change as the animal moves. However, it is known that honey bees can visually navigate in flat, open meadows where visual information at the horizon is minimal, or would remain relatively constant across a wide range of positions. In this paper we hypothesise that these animals can navigate using view memories of the ground. We find that in natural scenes, low resolution views from an aerial perspective of ostensibly self-similar terrain (e.g. within a field of grass) provide surprisingly robust descriptors of precise spatial locations. We propose a new visual route following approach that makes use of transverse oscillations to centre a flight path along a sequence of learned views of the ground. We deploy this model on an autonomous quadcopter and demonstrate that it provides robust performance in the real world on journeys of up to 30 m. The success of our method is contingent on a robust view matching process which can evaluate the familiarity of a view with a degree of translational invariance. We show that a previously developed wavelet based bandpass orientated filter approach fits these requirements well, exhibiting double the catchment area of standard approaches. Using a realistic simulation package, we evaluate the robustness of our approach to variations in heading direction and aircraft height between inbound and outbound journeys. We also demonstrate that our approach can operate using a vision system with a biologically relevant visual acuity and viewing direction.

Predictors of hematological abnormalities in multiple sclerosis patients treated with fingolimod and dimethyl fumarate and impact of treatment switch on lymphocyte and leukocyte count.

BACKGROUND: There is limited data regarding the predictors of hematological abnormalities in multiple sclerosis (MS) patients treated with dimethyl fumarate (DMF) or fingolimod (FNG), and the impact of treatment switch on lymphocyte and leukocyte count METHODS: We identified 405 patients on DMF and 300 patients on FNG (treatment duration: at least 12 month) within a large prospective study of MS patients conducted at the Partners MS Center, Brigham and Women's Hospital (CLIMB study) between Jan 2011 to Feb 2016. Patients had complete blood counts with differentials at baseline and every 6 months while on treatment. Most participants had a clinical visit with complete neurologic examinations every 6 months and brain MRI scan every 12 months. T cell subset profile was available for subgroup of patients (n = 116). RESULTS: In the FNG group, the risk of developing lymphopenia grade 4 (< 200) was higher in female patients (p = 0.0117) and those who were previously treated with natalizumab (p = 0.0116), while the risk of lymphopenia grade 3b+4 (< 350) was higher in female patients (p = 0.0009). DMF treated patients with lower baseline lymphocyte count had a higher chance of developing lymphopenia grade 2 (< 800) (p < 0.0001) or 2+3 (< 500) (p < 0.0001). We examined the effect of treatment switch between DMF and FNG. No significant recovery in lymphocyte and leukocyte count was observed after treatment switches. Reduced dosing of FNG in patients with lymphopenia led to increase in lymphocyte count but also increased disease activity in 25% of patients. CONCLUSION: Female sex and prior exposure to natalizumab increased the probability of lymphopenia on FNG, while low absolute lymphocyte count was associated with increased risk of lymphopenia on DMF. Parallel switch did not lead to recovery from hematological abnormalities. Long-term studies with larger number of patients are required to confirm our findings and to establish guidelines for prediction and management of hematological abnormalities.

Effects of A-site disorder in the properties of A2CoMnO6 (A = La, Tb).

We have studied the structural and physical properties of the La2-xTbxCoMnO6 series. The crystal and magnetic structures of these compounds were determined by x-ray and neutron diffraction techniques. All samples belong to the family of double perovskites with space group P21/n, but the Co/Mn ordering is not perfect, and antisite defects are formed. The concentration of these defects increases for intermediate compositions, indicating that La/Tb disorder influences the Co/Mn arrangement. A ferromagnetic ground state is established due to the strong Mn(4+)-O-Co(2+) superexchange interaction. For the intermediate compositions and at low temperature, the Co/Mn ordering is accompanied by the ordering of Tb(3+) moments in the ab-plane, indicating a mutual polarization between both sublattices. Macroscopic magnetic properties reveal that Curie temperature decreases as Tb content increases in correlation with the increase of the structural distortion. All samples show semiconducting behaviour, and overall the electrical resistivity increases with decreasing La-content. The dielectric constant (ε') has a value of around 12 at low temperatures for all samples, revealing the lack of permanent dipoles. The temperature dependence of ε' on warming exhibits a strong increase that depends heavily on the frequency of the electric field. This effect is ascribed to non-intrinsic effects such as contacts or internal barrier-layers.

Evolution of magnetoelectric properties of Sc-diluted TbMnO3.

The magnetoelectric properties of the TbMn(1-x)Sc(x)O3 series have been studied at low temperatures by means of heat capacity, magnetic measurements and impedance spectroscopy. TbMnO3 exhibits as expected three transitions upon lowering the temperature corresponding to the magnetic ordering of the two sublattices (Mn and Tb) and the ferroelectric transition. Ferroelectricity disappears with Sc dilution for x > 0.1 because the non-collinear magnetic arrangement is destroyed. The dilution of Mn with a non-magnetic ion is also detrimental to the magnetic ordering of both Mn and Tb sublattices. The system evolves to a magnetic glassy state for the intermediate compositions. Formal TbScO3 shows Sc-deficiency and long range magnetic ordering of Tb(3+) moments in the ab-plane brought by the direct interaction between Tb(3+) ions. This ordering is different from the one found in TbMnO3 due to the lack of magnetic coupling between Tb- and Mn-sublattices. A small substitution of Sc by Mn in TbScO3 destroys the Tb ordering giving rise to a magnetic glass behaviour. This effect is ascribed to the partial polarization of Tb sublattice by the paramagnetic Mn which competes with the direct Tb-Tb exchange.

Note: a sample holder design for sensitive magnetic measurements at high temperatures in a magnetic properties measurement system.

A sample holder design for high temperature measurements in a commercial MPMS SQUID magnetometer from Quantum Design is presented. It fulfills the requirements for the simultaneous use of the oven and reciprocating sample option (RSO) options, thus allowing sensitive magnetic measurements up to 800 K. Alternating current susceptibility can also be measured, since the holder does not induce any phase shift relative to the ac driven field. It is easily fabricated by twisting Constantan© wires into a braid nesting the sample inside. This design ensures that the sample be placed tightly into a tough holder with its orientation fixed, and prevents any sample displacement during the fast movements of the RSO transport, up to high temperatures.

A 3T MR imaging investigation of the topography of whole spinal cord atrophy in multiple sclerosis.

BACKGROUND AND PURPOSE: Spinal cord atrophy is a common feature of MS. However, it is unknown which cord levels are most susceptible to atrophy. We performed whole cord imaging to identify the levels most susceptible to atrophy in patients with MS versus controls and also tested for differences among MS clinical phenotypes. MATERIALS AND METHODS: Thirty-five patients with MS (2 with CIS, 27 with RRMS, 2 with SPMS, and 4 with PPMS phenotypes) and 27 healthy controls underwent whole cord 3T MR imaging. The spinal cord contour was segmented and assigned to bins representing each C1 to T12 vertebral level. Volumes were normalized, and group comparisons were age-adjusted. RESULTS: There was a trend toward decreased spinal cord volume at the upper cervical levels in PPMS/SPMS versus controls. A trend toward increased spinal cord volume throughout the cervical and thoracic cord in RRMS/CIS versus controls reached statistical significance at the T10 vertebral level. A statistically significant decrease was found in spinal cord volume at the upper cervical levels in PPMS/SPMS versus RRMS/CIS. CONCLUSIONS: Opposing pathologic factors impact spinal cord volume measures in MS. Patients with PPMS demonstrated a trend toward upper cervical cord atrophy. However patients with RRMS showed a trend toward increased volume at the cervical and thoracic levels, which most likely reflects inflammation or edema-related cord expansion. With the disease causing both expansion and contraction of the cord, the specificity of spinal cord volume measures for neuroprotective therapeutic effect may be limited.

Normal findings on brain fluid-attenuated inversion recovery MR images at 3T.

BACKGROUND AND PURPOSE: Fluid attenuated inversion recovery (FLAIR) MR imaging of the brain has become a routine tool for assessing lesions in patients with suspected neurologic disorders. There is growing interest in 3T brain FLAIR MR imaging but little normative data are available. The purpose of this study was to evaluate the frequency and topography of cerebral hyperintensities seen with FLAIR MR imaging of the brain at 3T in a normal population and compare those findings to 1.5T. MATERIALS AND METHODS: Whole-brain 2D FLAIR MR imaging was performed in 22 healthy controls (mean age, 44 +/- 8 years; range, 30-53 years) at 3T. Fifteen of these subjects also underwent 2D FLAIR at 1.5T, with similar optimized parameters and voxel size. Cerebral hyperintense areas, including discrete foci, anterior and posterior periventricular capping, diffuse parenchymal hyperintensity, septal hyperintensity, corticospinal tract hyperintensity, and CSF flow artifacts were assessed. The Spearman rank test assessed the correlation between discrete hyperintense foci and age. The Wilcoxon signed rank test compared foci detectability at 3T versus 1.5T. RESULTS: FLAIR at 3T commonly showed hyperintensities such as discrete foci (mean, 10.68 per subject; at least 1 present in 68% of subjects), anterior and posterior periventricular capping, diffuse posterior white matter hyperintensity, septal hyperintensity, corticospinal tract hyperintensity, and ventricular CSF flow artifacts. FLAIR at 3T showed a higher hyperintense foci volume (170 +/- 243 versus 93 +/- 152 mm3, P < .01) and number (9.4 +/- 13 versus 5.5 +/- 9.2, P < .01) than at 1.5T. No significant differences (P = .68) in the length/diameter of individual discrete hyperintense foci were seen between 3T and 1.5T. Discrete foci volume (r = 0.72 at 3T, r = 0.70 at 1.5T) and number (r = 0.74 at 3T; r = 0.69 at 1.5T) correlated with age to a similar degree on both platforms. All discrete foci were confined to the noncallosal supratentorial white matter. The other nonfocal hyperintensities (anterior and posterior periventricular capping, diffuse parenchymal hyperintensity, septal hyperintensity, corticospinal tract hyperintensity, and CSF flow artifacts) were generally more common and prominent at 3T than at 1.5T. CONCLUSIONS: Discrete and diffuse parenchymal brain white matter FLAIR hyperintensities are more common and prominent at 3T than at 1.5T in healthy volunteers.

Spinal cord lesions and clinical status in multiple sclerosis: A 1.5 T and 3 T MRI study.

OBJECTIVE: Assess the relationship between spinal cord T2 hyperintense lesions and clinical status in multiple sclerosis (MS) with 1.5 and 3 T MRI. METHODS: Whole cord T2-weighted fast spin-echo MRI was performed in 32 MS patients [Expanded Disability Status Scale (EDSS) score (mean+/-SD: 2+/-1.9), range 0-6.5]. Protocols at 1.5 T and 3 T were optimized and matched on voxel size. RESULTS: Moderate correlations were found between whole cord lesion volume and EDSS score at 1.5 T (r(s)=.36, p=0.04), but not at 3 T (r(s)=0.13, p=0.46). Pyramidal Functional System Score (FSS) correlated with thoracic T2 lesion number (r(s)=.46, p=0.01) and total spinal cord lesion number (r(s)=0.37, p=0.04) and volume (r(s)=0.37, p=0.04) at 1.5 T. Bowel/bladder FSS correlated with T2 lesion volume and number in the cervical, thoracic, and total spine at 1.5 T (r(s) 0.40-0.57, all p<0.05). These MRI-FSS correlations were non-significant at 3 T. However, these correlation coefficients did not differ significantly between platforms (Choi's test p>0.05). Correlations between whole cord lesion volume and timed 25-foot walk were non-significant at 1.5 T and 3 T (p>0.05). Lesion number and volume did not differ between MRI platforms in the MS group (p>0.05). CONCLUSIONS: Despite the use of higher field MRI strength, the link between spinal lesions and MS disability remains weak. The 1.5 T and 3 T protocols yielded similar results for many comparisons.

Can we talk about CD4+CD28- lymphocytes as a risk factor for ischemic stroke?

BACKGROUND: CD4+CD28- lymphocytes are implicated in the destabilization of atheromatous plaque, leading to acute coronary episodes. One may ask whether these cells play a similar role in ischemic stroke pathogenesis with an atherosclerotic background. METHODS: Flow cytometry was applied to determine the percentage of CD4+CD28- lymphocytes in the peripheral blood of patients during the acute phase of their first ischemic stroke (group I) and in patients without a history of stroke but with two of the most important risk factors (hypertension, diabetes) for atherosclerosis-related ischemic stroke (group II). The results were compared with healthy controls. RESULTS: The median percentages of CD4+CD28- lymphocytes in groups I and II did not differ significantly, but for each of these groups the percentage was higher than in the control group. The time of blood sampling from onset of stroke, presence of the ischemic focus in the CT brain scan and severity of neurological deficits did not correlate with the percentage of CD4+CD28- lymphocytes. CONCLUSIONS: We conclude that CD4+CD28- lymphocytes are implicated in mechanisms enhancing the risk of acute ischemic stroke and not a consequence of stroke.

Fatigue-crack growth properties of thin-walled superelastic austenitic Nitinol tube for endovascular stents.

Over the past 10 years, the supereleastic nickel-titanium alloy Nitinol has found widespread application in the manufacture of small-scale biomedical devices, such as self-expanding endovascular stents. Although conventional stress/strain-life (S/N) analyses are invariably used as the primary method for design against fatigue loading and for predicting safe lifetimes, fracture mechanics-based methodologies provide a vital means of assessing the quantitative effect of defects on such lifetimes. Unfortunately, fracture mechanics studies on fatigue in Nitinol are scarce, and most results do not pertain to the (thin-walled tube) product forms that are typically used in the manufacture of endovascular stents. In the current work, we document the basic fatigue-crack growth properties of flattened thin-walled ( approximately 400 microm thick) Nitinol tubing in a 37 degrees C air environment. Crack-growth behavior is characterized over a wide range of growth rates ( approximately 6 orders of magnitude) and load ratios, that is, as a function of the alternating and maximum stress intensities, at 50 Hz. Limited experiments at both 5 and 50 Hz were also performed in 37 degrees C air and simulated body fluid to determine whether the cyclic frequency affects the fatigue behavior. Fatigue-crack growth-rate properties in such thin-walled Nitinol tube are found to be quite distinct from limited published data on other (mainly bulk) product forms of Nitinol, for example, bar and strip, both in terms of the relative fatigue thresholds and the variation in steady-state growth rates.

Levetiracetam for seizures after liver transplantation.

Seizures may occur after orthotopic liver transplantation. Antiepileptic drugs (AEDs) are used to treat these seizures, but the immunosuppressant regimen also may be altered. Levetiracetam is an attractive treatment because of its efficacy, lack of hepatic enzyme induction, and its rapid attainment of serum levels. Treatment with levetiracetam is efficacious, and levetiracetam-treated patients require significantly lower doses of immunosuppressant medications to achieve an equivalent antirejection effect.

The effect of monoamine oxidase B (MAOB) and catechol-O-methyltransferase (COMT) polymorphisms on levodopa therapy in patients with sporadic Parkinson's disease.

OBJECTIVES: The etiology of sporadic idiopathic Parkinson's disease (PD) is considered multifactorial with both genetic and environmental factors modifying the disease expression. Recent studies suggest that polymorphism in monoamine oxidase B (MAOB) and catechol-O-methyltransferase (COMT) might influence the risk and treatment of PD. The aim of the study was to evaluate the effect of MAOB and COMT genetic polymorphism on effective daily dose of levodopa applied during the first 5 years of treatment, and to find out if a relationship exists between MAOB and COMT haplotypes and motor disturbances onset in PD patients treated with levodopa preparations. MATERIALS AND METHODS: A total of 95 patients (40 females and 55 males) of Polish origin diagnosed with sporadic PD were enrolled into the study, and were divided into two groups. Group 1 - patients treated with doses of levodopa below 500 mg/day during the first 5 years of treatment. Group 2 - patients requiring levodopa doses exceeding 500 mg/24 h during the first 5 years of treatment. Low activity alleles of MAOB and COMT, i.e. MAOB allele A and COMT(L) as well as high activity ones, i.e. MAOB allele G and COMT(H), were determined using PCR-RFLP method. RESULTS: No statistically significant differences were found in MAOB and COMT allele distribution in the two groups. However, the frequency of COMT(L/L) homozygotes was higher in the group treated with low doses of levodopa when compared with the second group. MAOB and COMT AG-HH haplotype predominated in the group of females treated with high daily doses of levodopa when compared with AG-LL haplotype in the group of females treated with low daily doses of levodopa (<500 mg/24 h). CONCLUSION: The results of the study suggest that patients with COMT(L/L) genotype and possibly MAOB genotype A may benefit from more efficient and safer levodopa therapy.

Protein farnesylation in mammalian cells: effects of farnesyltransferase inhibitors on cancer cells.

Protein farnesylation, catalyzed by protein farnesyltransferase, plays important roles in the membrane association and protein-protein interaction of a number of eukaryotic proteins. Recent development of farnesyltransferase inhibitors (FTIs) has led to further insight into the biological significance of farnesylation in cancer cells. A number of reports point to the dramatic effects FTIs exert on cancer cells. In addition to inhibiting anchorage-independent growth, FTIs cause changes in the cell cycle either at the G1/S or at the G2/M phase. Furthermore, induction of apoptosis by FTIs has been reported. FTIs also affects the actin cytoskeleton and cell morphology. This review summarizes these reports and discusses implications for farnesylated proteins responsible for these FTI effects.

Epidermal growth factor stimulation of the ACK1/Dbl pathway in a Cdc42 and Grb2-dependent manner.

The tyrosine kinase ACK1 phosphorylates and activates the guanine nucleotide exchange factor Dbl, which in turn directs the Rho family GTP-binding proteins. However, the regulatory mechanism of ACK1/Dbl signaling in response to extracellular stimuli remains poorly understood. Here we describe that epidermal growth factor stimulates the ACK1/Dbl pathway, leading to actin cytoskeletal rearrangements. The role of the two ACK1-binding proteins Cdc42 and Grb2 was assessed by overexpression of the Cdc42/Rac interactive binding domain and a dominant-negative Grb2 mutant, respectively. Specific inhibition of the interaction of ACK1 with Cdc42 or Grb2 by the use of these constructs diminished tyrosine phosphorylation of both ACK1 and Dbl in response to EGF. Therefore, the activation of ACK1 and subsequent downstream signaling require both Cdc42-dependent and Grb2-dependent processes within the cell. In addition, we show that EGF transiently induces formation of the focal complex and stress fibers when ACK1 was ectopically expressed. The induction of these structures was totally sensitive to the action of botulinum toxin C from Clostridium botulinum, suggesting a pivotal role of Rho. These results provide evidence that ACK1 acts as a mediator of EGF signals to Rho family GTP-binding proteins through phosphorylation and activation of GEFs such as Dbl.

Against all odds: an interesting foreign body problem and solution.

Difficult airway foreign bodies can create perplexing problems for the bronchoesophagologist. Sometimes, creative skills are necessary to allow removal of foreign bodies without the need for an external procedure. This article presents the first reported case of the removal of a severely impacted air valve cap in the left main bronchus and discusses the creative and innovative techniques and instrumentation that are required for successful removal when standard foreign body instrumentation is ineffective for the task. The case demonstrates that sometimes, against all odds, the most difficult airway problem can have a solution, avoiding increased patient morbidity.

Farnesylated proteins and cell cycle progression.

Post-translational modification of proteins by the addition of a farnesyl group is critical for the function of a number of proteins involved in signal transduction. Farnesylation facilitates their membrane association and also promotes protein-protein interaction. Recently, progress has been made in understanding the biological significance of farnesylation. First, effects of farnesyltransferase inhibitors (FTIs) on cancer cells have been examined using a variety of human cancer cells. This study showed that one of the major effects of FTIs is to alter cell cycle progression. Both G0/G1 enrichment and G2/M accumulation were observed depending on the cell line examined. Second, a number of novel farnesylated proteins have been characterized. Of these, Rheb and CENP-E,F are of particular interest. Rheb, a novel member of the Ras superfamily G-proteins, may play a role in the G1 phase of the cell cycle. CENP-E,F are centromere associated motors that play critical roles in mitosis. These results suggest important contributions of farnesylated proteins in the regulation of cell cycle progression.

Endoscopic versus traditional approaches to choanal atresia.

With the introduction of endoscopic techniques and powered instrumentation for pediatric sinusitis, one would expect that the definitive treatment of congenital choanal atresia has been established. An international survey of pediatric otolaryngologists and the plethora of surgical approaches in the literature, however, indicate that there is still much controversy in its management. This article addresses this controversy between endoscopic and traditional approaches to neonatal bilateral bony choanal atresia and proposes guidelines for optional treatment.

Frameless stereotactic localization in cranial base surgery.

Mastery of the three-dimensional anatomic relationships of the cranial base/paranasal sinuses is required to reduce the incidence of iatrogenic surgical complications, facilitate complete tumor extirpation, and enhance functional outcomes. Real-time intraoperative localization technology is one method available to assist the cranial base surgeon. We report our institutional experience with the StealthStationtrade mark treatment guidance platform. Eighty-eight consecutive patients with pathology of the cranial base/paranasal sinuses were operated on with the aid of real-time frameless stereotactic localization. Preoperative image data sets were acquired with either CT or MRI scans. Patient demographics, accuracy of the data sets, surgical approaches, pathology, complications, and further applications of this technology are presented. Procedures were performed on 47 women and 41 men ranging in age from 6 to 85 years. In these 88 procedures, 44 MRI and 44 CT scans with a mean accuracy of 1.57 and 1.23 mm, respectively, were used. Approaches to the cranial base included midface degloving (25), endoscopic (23), craniofacial (13), maxillectomy (12), rhinotomy without maxillectomy (5), transoral (5), pterional (2), transcondylar (1), and transcervical (2). Indications for surgery included severe inflammatory disease of the paranasal sinuses with epidural or subdoral abscess, or both (7), cerebrospinal fluid fistula or encephalocele, or both (11), and 40 benign and 30 malignant tumors. Complications occurred in 10 of 88 patients (11%). Real-time intraoperative localization can be applied to cranial base surgery in a variety of scenarios. The instantaneous transfer of imaging data to the surgical field is useful in localizing pathology, enhancing operative safety, and reducing morbidity, thereby improving outcomes. This technology will certainly play an integral role in minimizing complications and improving surgical outcomes as cranial base surgery moves into the next millennium.

Two faces of orbital hematoma in intranasal (endoscopic) sinus surgery.

Orbital hematoma and blindness can occur during or after sinus surgery. All orbital hematomas in 3500 endoscopic sinus ethmoidectomies were identified and evaluated for type, treatment, and sequelae. Fifteen orbital hematomas were identified, with 1 case of temporary blindness and no cases of permanent blindness. Two types of orbital hematoma were identified-slow (venous) and fast (arterial)-which differ in management. The venous type results from penetration of the lamina papyracea and disruption of veins. The arterial hematoma is caused by anterior or posterior ethmoid artery injury. The treatment approach to each is different, with blindness more likely occurring from a fast (arterial) hematoma. Of the 2 types of orbital hematoma that can occur during sinus surgery, surgical decompression and hemorrhage control are more likely with the fast arterial hematoma, which has not been the subject of any prior presentation. Cause and management of each will be discussed.