Evolution of coherence singularities in polarization singular beams.

The evolution of correlation singularities in partially coherent polarization singular beams (PC-PSBs) is investigated. Since PSBs are the superposition of two orthogonally polarized vortex beams, the occurrence of coherence singularities in PC-PSBs is strongly governed by the topological charge of the component vortex beams and the spatial coherence length. Coherence singularities appear in the form of ring dislocations in the modulus of the spectral degree of coherence (SDoC) profile, and the number of ring dislocations is equal to the higher value of the topological charge of the superposing vortex beam. Furthermore, the SDoC phase profile can be used to determine the polarity of a PC-PSB. The findings of the study could be valuable in various applications that rely on the spatial coherence of beams, such as free-space communication and imaging.

Investigation of partially coherent vector vortex beams with non-isotropic states of spatial correlation.

In this work, the far-field properties of non-isotropic partially coherent vector vortex beams (PCVVBs) are investigated both theoretically and experimentally. The term non-isotropic signifies that the spatial correlations between the parallel and orthogonal electric field components are distinguishable. It is found that self-orientation and shaping of intensity profile, correlation-induced polarization and depolarization are highly dependent on both the non-isotropic correlation parameters and Poincaré-Hopf index (PHI) of the beam. The simultaneous depolarization and polarization effects are due to the difference in the input correlation parameters that alter the state of polarization (SOP) and degree of polarization (DOP) distributions. The experimental results are in good agreement with the theoretical predictions. The distinguishability of correlation parameters at the source plane leads to significant changes on its intensity profile, DOP, and SOP distributions on far-field propagation, which may found potential applications in beam shaping, detecting and imaging atmospheric lidar, optical imaging and directional transportation where the self-rotation characteristic of beam plays an important role.

Coherence-induced depolarization effects in polarization singular beams.

We demonstrate theoretically and experimentally coherence-induced depolarization effects in generic and higher index polarization singular beams endowed with C-point (or V-point) polarization singularity. The irradiance profiles and degree of polarization (DoP) distributions are found to be governed by spatial coherence length, polarization singularity index, and orbital angular momentum (OAM) of the superposition states of the beams. On reducing the coherence length, the DoP distribution in the V-point deteriorates uniformly. In contrast, C-point beams resist depolarization exhibiting anti-depolarization around the central core of the beam due to the nonzero net OAM of the beam. Interestingly, the polarization vortex structure remains preserved on reducing the spatial coherence length.

Young's double-slit experiment with vector vortex beams.

In this Letter, Young's double-slit experiment with vector vortex beams is investigated. We present the results for various Poincaré-Hopf index beams of this class considering all four major types. Polarization associated morphological changes in the far-field interference pattern are studied both theoretically and experimentally. The Fraunhofer pattern consists of lattices of polarization singularities of the generic type, located on a line, in a direction perpendicular to the slit. The number of linear lattices varies as a function of Poincaré-Hopf index η of the beam that is diffracted, and the number of intensity nulls occurring along the vertical line is equal to |η|.

Single copy/knock-in models of ALS SOD1 in C. elegans suggest loss and gain of function have different contributions to cholinergic and glutamatergic neurodegeneration.

Mutations in Cu/Zn superoxide dismutase 1 (SOD1) lead to Amyotrophic Lateral Sclerosis (ALS), a neurodegenerative disease that disproportionately affects glutamatergic and cholinergic motor neurons. Previous work with SOD1 overexpression models supports a role for SOD1 toxic gain of function in ALS pathogenesis. However, the impact of SOD1 loss of function in ALS cannot be directly examined in overexpression models. In addition, overexpression may obscure the contribution of SOD1 loss of function in the degeneration of different neuronal populations. Here, we report the first single-copy, ALS knock-in models in C. elegans generated by transposon- or CRISPR/Cas9- mediated genome editing of the endogenous sod-1 gene. Introduction of ALS patient amino acid changes A4V, H71Y, L84V, G85R or G93A into the C. elegans sod-1 gene yielded single-copy/knock-in ALS SOD1 models. These differ from previously reported overexpression models in multiple assays. In single-copy/knock-in models, we observed differential impact of sod-1 ALS alleles on glutamatergic and cholinergic neurodegeneration. A4V, H71Y, G85R, and G93A animals showed increased SOD1 protein accumulation and oxidative stress induced degeneration, consistent with a toxic gain of function in cholinergic motor neurons. By contrast, H71Y, L84V, and G85R lead to glutamatergic neuron degeneration due to sod-1 loss of function after oxidative stress. However, dopaminergic and serotonergic neuronal populations were spared in single-copy ALS models, suggesting a neuronal-subtype specificity previously not reported in invertebrate ALS SOD1 models. Combined, these results suggest that knock-in models may reproduce the neurotransmitter-type specificity of ALS and that both SOD1 loss and gain of toxic function differentially contribute to ALS pathogenesis in different neuronal populations.

Coherence-induced polarization effects in vector vortex beams.

We demonstrate theoretically and experimentally coherence-induced polarization changes in higher-order vector vortex beams (VVBs) with polarization singularity. The prominent depolarization on decreasing the transverse correlation width in a focused partially coherent VVB provides a means to shape the intensity profile and degree of polarization (DOP) while preserving the polarization distribution. The intensity variation and DOP dip are found to be dependent on the polarization singularity index of the beam. Our results may provide an additional degree of freedom in myriad applications presently projected with VVBs.

Discriminating between sleep and exercise-induced fatigue using computer vision and behavioral genetics.

Following prolonged swimming, Caenorhabditis elegans cycle between active swimming bouts and inactive quiescent bouts. Swimming is exercise for C. elegans and here we suggest that inactive bouts are a recovery state akin to fatigue. It is known that cGMP-dependent kinase (PKG) activity plays a conserved role in sleep, rest, and arousal. Using C. elegans EGL-4 PKG, we first validate a novel learning-based computer vision approach to automatically analyze C. elegans locomotory behavior and an edge detection program that is able to distinguish between activity and inactivity during swimming for long periods of time. We find that C. elegans EGL-4 PKG function impacts timing of exercise-induced quiescent (EIQ) bout onset, fractional quiescence, bout number, and bout duration, suggesting that previously described pathways are engaged during EIQ bouts. However, EIQ bouts are likely not sleep as animals are feeding during the majority of EIQ bouts. We find that genetic perturbation of neurons required for other C. elegans sleep states also does not alter EIQ dynamics. Additionally, we find that EIQ onset is sensitive to age and DAF-16 FOXO function. In summary, we have validated behavioral analysis software that enables a quantitative and detailed assessment of swimming behavior, including EIQ. We found novel EIQ defects in aged animals and animals with mutations in a gene involved in stress tolerance. We anticipate that further use of this software will facilitate the analysis of genes and pathways critical for fatigue and other C. elegans behaviors.

Higher Neural Correlates in Patients with Multiple Sclerosis and Neurogenic Overactive Bladder Following Treatment with Intradetrusor Injection of OnabotulinumtoxinA.

PURPOSE: OnabotulinumtoxinA is a well described treatment of neurogenic overactive bladder. While motor effects on the detrusor muscle have been extensively studied, the sensory effects have not. The aim of this study was to evaluate the impact of intradetrusor onabotulinumtoxinA injection on brain activity in female patients with multiple sclerosis and neurogenic overactive bladder. MATERIALS AND METHODS: We prospectively studied 12 women with stable multiple sclerosis and neurogenic overactive bladder using concurrent functional magnetic resonance imaging and urodynamic studies prior to and 6 to 10 weeks following onabotulinumtoxinA injection. Individual functional magnetic resonance imaging activation maps at the time of strong urgency were averaged before and after onabotulinumtoxinA injection where areas of significant activation were identified. RESULTS: After onabotulinumtoxinA injection functional magnetic resonance imaging activation increased in the right cingulate body (p = 0.0012), the left posterior cingulate (p = 0.02), the left anterior cingulate (p = 0.0015), the right prefrontal cortex (p = 0.0015), the insula (p = 0.0138) and the pons micturition center (p = 0.05). Sparse areas showed decreased activity, including the left cerebellum (p = 0.001), the left fusiform gyrus (p = 0.065) and the bilateral lentiform nucleus (p = 0.026). CONCLUSIONS: Intradetrusor injection of onabotulinumtoxinA appeared to increase the activity of most brain regions known to be involved in the sensation and process of urinary urgency in female patients with multiple sclerosis and neurogenic overactive bladder. To our knowledge this is the first study of its kind to evaluate the possible effects of onabotulinumtoxinA at the human brain level where sensory awareness is located. This activation pattern may be used to further phenotype patients to optimize therapy or determine the sensory effects of onabotulinumtoxinA beyond the bladder.

Helicity conservation in V-point diffraction.

In singular beams, topological charge is conserved during diffraction. Like scalar field diffraction, in vector field diffraction also, there are conserved quantities. A diffracting V-point disintegrates into a number of C-points of the same polarity in which the polarization singularity index is conserved. In this Letter, we show for the first time, to the best of our knowledge, that apart from the index, the helicity (handedness) is also conserved in V-point diffraction. Since V-point is devoid of any handedness, the helicity conservation entails that there is an equal number of opposite handed C-points in the diffracted field, which are interestingly also found to be orthogonal pairs. Further, coexistence of C-points of opposite handedness in the diffraction demands the presence of L-line, which is also shown. We experimentally demonstrate these by studying the diffraction phenomenon through two different types of apertures.

Similarity of functional connectivity patterns in patients with multiple sclerosis who void spontaneously versus patients with voiding dysfunction.

AIM: To investigate if Multiple Sclerosis (MS) lesion characteristics affect functional brain connectivity (FC) during bladder voiding. METHODS: Twenty-seven ambulatory female patients with MS completed our functional magnetic resonance imaging (fMRI)/urodynamic testing (UDS) platform. Individual fMRI activation maps were generated at initiation of voiding. FC patterns of these regions were calculated and compared. Similarity of the FC pattern from one patient relative to all others was expressed by a parameter FC_sim. A statistical analysis was performed to reveal the relationship of the existence of an enhancing brain lesion, the size of the largest lesion and the ability to void spontaneously to this FC similarity measure. RESULTS: FC_sim values were significantly lower for patients with an enhancing MS lesion (11.7 ± 3.1 vs 5.3 ± 2.1 P < 0.001). Lesion size smaller than 20 mm inversely correlated significantly with FC_sim (R = -0.43, P = 0.05). Patients with the ability to void spontaneously had a higher FC_sim value (12.0 ± 2.8 vs 9.3 ± 4.4 s, P = 0.08). Patients that exhibited a decrease of compliance also showed a significantly lower FC_sim value (11.3 ± 3.5 vs 4.7 ± 0.7, P < 1e-5). CONCLUSION: FC connectivity analysis derived from an fMRI task-based study including repetitive voiding cycles is able to quantify the heterogeneity of connectivity patterns in the brain of MS patients. FC similarity decreased with maximum lesion size or the presence of enhancing lesions affecting the ability to void spontaneously.

Selective excitation of higher-order modes in etched gelatin-coated few-mode fiber and demonstration of high relative humidity measurement.

We report here our experimental studies on efficient excitation of higher-order modes in a few-mode fiber realized through selective chemical etching of single-mode fiber, depositing a dynamic refractive index profile coating (gelatin) and designing a well-performing high relative humidity (RH) (73%-99% RH) sensor with sensitivity as high as ∼1.2 dBm/% RH and fast response (∼125 ms). The design relies on fixing quasi-adiabatic transition of the single-mode-few-mode-single-mode configuration to launch light at angles corresponding to desired higher-order modes, pushing more power into the coating. Our systematic study using the devised hybrid theoretical ray- and wave-optic model uniquely interprets the variety of experimental results.

The Elution Kinetics of BMP-2, BMP-4, and BMP-7 From a Commercial Human Demineralized Bone Matrix Putty.

Bone morphogenetic proteins (BMPs) are associated with bone extracellular matrix and impart osteoinductive properties to demineralized bone matrix (DBM) grafts. The first step of the osteoinductive process is BMP release from DBM in situ; however, this has not been characterized for human DBM. The authors investigated the release of BMPs 2, 4, and 7 from a clinical human DBM putty (Bonus II DBM, Biomet Inc, Warsaw, IN). The DBM was placed in Sorensen buffer and the BMP concentrations in the Sorensen buffer and guanidine extracts of the DBM were measured concurrently by enzymelinked immunosorbant assay for up to 7 days. The baseline DBM concentrations were BMP-2: 28.1 ±â€Š1.3 ng/g DBM, BMP-4: 0.577 ±â€Š0.056 ng/g DBM, and BMP-7: 92.9 ±â€Š7.5 ng/g DBM. Relative to baseline, the proportions released by 7 days were 11.1%, 3.9%, and 29.3%, respectively. The early (0-8 hour) and late (8-168 hours) elution rates were BMP-2: 0.16 ±â€Š0.24 and 0.0089 ±â€Š0.012 ng/(g DBM hr), and BMP-7: 1.29 ±â€Š2.1 and 0.086 ±â€Š0.039 ng/(g DBM hr), respectively. Little BMP-4 elution occurred over the first 24 hours, with the rate for the remaining interval being 0.00014 ±â€Š0.00021 ng/(g DBM hr). The apparent DBM BMP profiles were counterintuitive in that the concentrations increased from baseline for some, or all, of the 7 days instead of monotonically decreasing. Similar behavior has previously been reported in bovine studies. This provides further evidence that BMPs are associated with at least 2 compartments in DBM differing by their affinity for BMPs and that guanidine extraction of BMPs is not 100% efficient.

Phase II trial of dasatinib for recurrent or metastatic c-KIT expressing adenoid cystic carcinoma and for nonadenoid cystic malignant salivary tumors.

BACKGROUND: Adenoid cystic carcinoma (ACC) is a subtype of malignant salivary gland tumors (MSGT), in which 90% of cases express cKIT. Dasatinib is a potent and selective inhibitor of five oncogenic protein tyrosine kinases (PTKs)/kinase families including cKIT. We conducted a phase II study to determine the antitumor activity of dasatinib in ACC and non-ACC MSGT. PATIENTS AND METHODS: In a two-stage design, patients with progressive, recurrent/metastatic ACC (+cKIT) and non-ACC MSGT (separate cohort) were treated with dasatinib 70 mg p.o. b.i.d. Response was assessed every 8 weeks using RECIST. RESULTS: Of 54 patients: 40 ACC, 14 non-ACC (1, ineligible excluded); M:F = 28 : 26, median age 56 years (range 20-82 years), ECOG performance status 0 : 1 : 2 = 24 : 28 : 2, prior radiation: 44, prior chemotherapy: 21. The most frequent adverse events (AEs) (as % of patients, worst grade 2 or higher) were: fatigue (28%), nausea (19%), headache (15%), lymphopenia (7%), dyspnea (11%), alanine aminotransferase increased (7%), anorexia (7%), vomiting (7%), alkaline phosphatase increased (6%), diarrhea (6%), neutropenia (6%), and noncardiac chest pain (6%). No grade 4 AE occurred, 15 patients experienced a grade 3 AE, primarily dyspnea (5) and fatigue (4), and cardiac toxicity (1 prolonged QTc). Among ACC patients, best response to dasatinib: 1 patient (2.5%) had partial response, 20 patients (50%) had stable disease (SD) (3-14 months), 12 patients (30%) had PD, 2 withdrew, 3 discontinued therapy due to AE, and 2 died before cycle 2. Median progression-free survival was 4.8 months. Median overall survival was 14.5 months. For 14 assessable non-ACC patients, none had objective response, triggering early stopping rule. Seven had SD (range 1-7 months), 4 PD, 2 discontinued therapy due to AE, and 1 died before cycle 2. CONCLUSION: Although there was only one objective response, dasatinib is well tolerated, with tumor stabilization achieved by 50% of ACC patients. Dasatinib demonstrated no activity in non-ACC MSGT.

Effect of parallel radiofrequency transmission on arterial input function selection in dynamic contrast-enhanced 3 Tesla pelvic MRI.

BACKGROUND: To evaluate whether parallel radiofrequency transmission (mTX) can improve the symmetry of the left and right femoral arteries in dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) of prostate and bladder cancer. METHODS: Eighteen prostate and 24 bladder cancer patients underwent 3.0 Tesla DCE-MRI scan with a single transmission channel coil. Subsequently, 21 prostate and 21 bladder cancer patients were scanned using the dual channel mTX upgrade. The precontrast signal ( S0) and the maximum enhancement ratio (MER) were measured in both the left and the right femoral arteries. Within the patient cohort, the ratio of S0 and MER in the left artery to that in the right artery ( S0_LR, MER_LR) was calculated with and without the use of mTX. Left to right asymmetry indices for S0 ( S0_LRasym) and MER ( MER_LRasym) were defined as the absolute values of the difference between S0_LR and 1, and the difference between MER_LR and 1, respectively. RESULTS: S0_LRasym, and MER_LRasym were 0.21 and 0.19 for prostate cancer patients with mTX, and 0.43 and 0.45 for the ones imaged without it (P < 0.001). Also, for the bladder cancer patients, S0_LRasym, and MER_LRasym were 0.11 and 0.9 with mTX, while imaging without it yielded 0.52 and 0.39 (P < 0.001). CONCLUSION: mTX can significantly improve left-to-right symmetry of femoral artery precontrast signal and contrast enhancement.

Single all-optical platform for measurement of twist and transverse stress using polarization modulation in distinct dual-mode fiber placed in a Sagnac loop.

We report here the experimental demonstration of measurement of both twist and transverse stress using polarization modulation in a single all-fiber circuit consisting of a single-mode fiber (SMF)/dual-mode fiber (DMF) in a Sagnac interferometer (SI) loop. The SMF-SI prototype setup is seen to be suitable for precise measurement of twist over a broad range of ±50° and transverse stress up to 5 N with a sensitivity as high as 2.85×10(6) pW/° and 2.08×10(7) pW/N, respectively. It is envisaged that nearly ideal operation for twist measurement can be achieved by appropriately selecting the operating domain (pretwisted Sagnac loop for practical realization of the device) and required magnitude of applied transverse stress (weight yielding maximum sensitivity). Unlike SMF-SI, a DMF assisted SI exhibits asymmetric transmittance yielding a peak shift (∼45°) in addition to falling/rising peak amplitude of effective power(∼20 µW). This key characteristic is further utilized for tunable measurement of torsion (unidirectional from -70° to 40°) while keeping the sensitivity fixed. This research problem is then analyzed on the avenue of theoretical consideration and using classical polarization optics; we have derived the Jones birefringence matrix that accurately describes the transmission behavior of the configured fiber circuit (SMF-SI and DMF-SI) for each of the three cases, namely, transverse stress, twist, and both twist and transverse stress. Series of experimental measurements for various conditions of induced birefringence (linear/circular) were performed at length, and the results were compared with those determined theoretically towards configuring a twist and stress measuring device. The study provides an understanding of the underlying physics of dual-mode interference in a Sagnac configuration experiencing linear and circular birefringence.

Polarization and propagation characteristics of switchable first-order azimuthally asymmetric beam generated in dual-mode fiber.

We report here the controlled generation of a linearly polarized first-order azimuthally asymmetric beam (F-AAB) in a dual-mode fiber (DMF) by appropriate superposition of selectively excited zeroth-order vector modes that are doughnut-shaped azimuthally symmetric beams (D-ASBs). We first demonstrate continually switching polarization mode structures having an identical two-lobe intensity profile (i.e., intra-F-AAB conversion). Then, under a distinct launching state, we generate mode structures progressively toggling between the doughnut-shaped profile and two-lobe pattern having dissimilar polarization orientations (i.e., F-AAB to D-ASB conversion). Interestingly, a decentralized elliptical Gaussian beam possessing homogenous spatial polarization is obtained by enhancing the contribution of the fundamental mode (HE11/LP01) in selectively excited F-AAB. A smoothly varying azimuth of the input beam in this situation resulted in redistribution of transverse energy procuring a unique and exciting unconventional two-grain T-polarized beam having mutually orthogonal state of polarization (SOP). All of the above three were achieved under a given set of launching conditions (tilt/offset) of a Gaussian mode (TEM00) devised with changing SOP of the input beam. A strong modulation in the output beam characteristics was also observed with the variation in propagation distance (for a fixed input SOP) owing to the large difference in propagation constants of the participating modes (LP01 and one of the F-AABs). Finally, this particular study led to a design for a low-cost highly sensitive strain measuring device based on tracking the centroid movement of the output intensity pattern. Each of our experimentally observed intensity/polarization distributions is theoretically mapped on a one-to-one basis considering a linear superposition of appropriately excited LP basis modes of the waveguide toward a complete understanding of the polarization and mode propagation in the dual-mode structure.

The extraction and measurement of bone morphogenetic protein 7 from bovine cortical bone as a function of particle size.

Bone morphogenetic proteins (BMPs), present in parts per billion in bone, endow demineralized bone matrix (DBM) with osteoinductive properties suitable for clinical use. Although BMPs are mainly associated with bone matrix, they also associate with other bone compartments as well, including the mineral phase. The purpose of this study was to gain a more complete understanding of the distribution of BMPs in undemineralized bone. Eleven discrete particle size ranges of bovine cortical bone were prepared, ranging between less than 25 µm and 600 to 710 µm for the smallest and largest sizes, respectively. The bone was extracted with 4-M guanidine-HCl/0.05-M Tris-HCl, and the amount of BMP-7 released was measured with enzyme-linked immunosorbant assay. In addition, 106- to 710-µm bone particles were demineralized and similarly extracted for comparison. The measured BMP-7 content of the DBM was 24.6 ± 1.56 ng/g. The values for bone increased nonlinearly with decreasing particle size, ranging from 1.13 ± 0.50 ng/g for the 600- to 710-µm particles to 4.18 ± 1.14 ng/g for the less than 25-µm particles (P < 0.001). However, modeling the bone particles as solid spheres to estimate total surface area showed that the extracted BMP-7 per unit area was greater for larger particle sizes. These seemingly opposing results suggest that BMPs may become proportionally damaged or altered in response to the increased forces required to generate smaller particles and, as such, may not be detectable with enzyme-linked immunosorbant assay. In addition, minimization of bone particle size is not an effective strategy to approach the BMP availability of DBM.

Posttraumatic stress symptoms and alcohol problems: self-medication or trait vulnerability?

BACKGROUND AND OBJECTIVES: Posttraumatic stress symptoms (PTSD) and problem alcohol use (ALC) commonly co-occur, but the nature of this co-occurrence is unclear. Self-medication explanations have been forwarded, yet traits such as tendency toward negative emotionality and behavioral disconstraint also have been implicated. In this study we test three competing models (Self-Medication, Trait Vulnerability, Combined Dual Pathway) of PTSD-ALC prospectively in a college sample. METHOD: Participants (N=659; 73% female, M age=18) provided data at college matriculation (Time 1) and 1 year later (Time 2). RESULTS: Structural equation models showed disconstraint to meditate the path from PTSD symptoms to alcohol problems, supporting a trait vulnerability conceptualization. Findings regarding negative emotionality and self-medication were more mixed. Negative emotionality played a stronger role in cross-sectional than in prospective analyses, suggesting the importance of temporal proximity. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Self-regulation skills may be an important focus for clinicians treating PTSD symptoms and alcohol misuse disorders concurrently.

Characteristics of transverse-stress-induced phase change through a distinct dual-mode fiber in a Sagnac loop.

We report here the experimental realization of a fiber-optic transverse-stress sensor devised by a dual-mode optical-fiber segment in a standard Sagnac interferometer loop. The intermodal interference of the LP01 and LP02 modes of the dual-mode fiber (DMF) configuration is analyzed theoretically in the platform of polarization transmittance of the Sagnac loop in implementing the theoretical model. Several experimental measurements for various conditions of applied birefringence are studied at length and the results are compared with those estimated theoretically toward configuring a stress-measuring device. The study provides an understanding of the underlying physics of the working of DMF interference in a Sagnac configuration.

Successful everolimus therapy for SEGA in pediatric patients with tuberous sclerosis complex.

PURPOSE: Tuberous sclerosis complex (TSC) is associated with hamartomatous growths including subependymal giant cell astrocytomas (SEGAs). Although, SEGAs are slow-growing glioneuronal tumors, they represent a significant cause of morbidity and mortality due to the risk of sudden death from acute hydrocephalus. Neurosurgical resection has been the mainstay of therapy, since radiotherapy and chemotherapy were proved inefficient in those tumors. Recent studies support the use of everolimus for subependymal giant cell astrocytomas associated with tuberous sclerosis and suggest it might represent a disease-modifying treatment for other aspects of tuberous sclerosis. METHODS: We describe the clinical and radiological progression of three pediatric patients with definitive diagnosis of TSC and SEGA, which have been treated with everolimus. RESULTS: Up to 34 % sustained SEGA decrease was observed in the three cases. All three patients have experienced seizure control and two of them have showed cognitive and behavioral improvement. Everolimus has been well tolerated by all. No severe adverse events have been observed to date. CONCLUSION: Everolimus offers significant promise in treating SEGAs. Studies are required to explore optimal therapy duration and management upon discontinuing therapy.