Stanford Surgical Epilepsy Program Select Publications

Select Publications

2017

Leonardo C. Faria, Feng Gua, Isabel Parada, Ben Barres, Z. David Luoc, David A. Prince. Epileptiform activity and behavioral arrests in mice overexpressing the calcium channel subunit α2δ-1. Neurobiology of Disease, 2017 102: 70–80

Bui, A., Alexander, A. and Soltesz, I. Seizing control: From current treatments to optogenetic interventions in epilepsy. The Neuroscientist, 2017 23: 68-81.

Buckmaster PS (in press) Comparative biology and species effects on expression of epilepsy. In: Models of Seizure and Epilepsy, Second Edition, Pitkänen A, Buckmaster PS, Galanopoulo AS, Moshe SM, eds. Elsevier, New York.

Buckmaster PS (in press) Naturally occurring epilepsy and status epilepticus in sea lions. In: Models of Seizure and Epilepsy, Second Edition, Pitkänen A, Buckmaster PS, Galanopoulo AS, Moshe SM, eds. Elsevier, New York.

Sorokin J, Davidson T, Frechette E, Abramian A, Deisseroth D, Huguenard JR, Paz J (2016) Bi-directional control of generalized epileptic networks via rapid real-time switching of firing mode. Neuron, 2017 93:194-210.  

Makinson CD, Tanaka BS, Sorokin J, Wong JC, Christian CA, Goldin AL, Escayg A*, Huguenard JR* (2017) Regulation of thalamic and cortical network synchrony by Scn8a. Neuron, 2017 Mar 8;93(5):1165-1179

2016

D. Koji Takahashi, Feng Gu, Isabel Parada, Shri Vyas, David A. Prince. Aberrant excitatory rewiring of layer V pyramidal neurons early after neocortical trauma. Neurobiology of Disease 91 (2016) 166–181.

Martha J. Morrell, Casey Halpern. Responsive Direct Brain Stimulation for Epilepsy. Neurosurg Clin N Am, 27 (2016) 111–121 

Allen L. Ho, Eric S. Sussman, Arjun V. Pendharkar, Alessandra Mantovani, Alaine C. Keebaugh, Gerald A. Grant, Casey Halpern. Improved operative efficiency using a real-time MRI-guided stereotactic platform for laser amygdalohippocampotomy. Neurosurgical Focus

Ha H, Huguenard JR (2016) Criminal Minds: Cav3.2 Channels Are the Culprits, but NMDAR Are the Co-Conspirators. Epilepsy Currents, 2016 Jan-Feb;16(1):36-8.

Brill J, Mattis J, Deisseroth K, Huguenard JR (2016) LSPS/optogenetics to improve synaptic connectivity mapping: unmasking the role of basket cell mediated feed-forward inhibition. eNeuro, 2016 Aug 8;3(4).

Fogerson PM, Huguenard JR (2016) Tapping the brakes: cellular and synaptic mechanisms that regulate thalamic oscillations, Neuron, 92:687-704

Hiu T, Farzampour Z, Paz JT, Wang EH, Badgely C, Olson A, Micheva KD, Wang G, Lemmens R, Tran KV, Nishiyama Y, Liang X, Hamilton SA, O'Rourke N, Smith SJ, Huguenard JR, Bliss TM, Steinberg GK. Enhanced phasic GABA inhibition during the repair phase of stroke: a novel therapeutic target. Brain, 2016 Feb;139(Pt 2):468-80.

Velez, M., Fisher, R. S., Bartlett, V., Le, S. Tracking generalized tonic-clonic seizures with a wrist accelerometer linked to an online database. Seizure-European Journal of Epilepsy, 2016; 39: 13-18.

Aghaei-Lasboo, A., Fisher, R. S. Methods for Measuring Seizure Frequency and Severity. Neurol Clin, 2016; 34 (2): 383-94.

Fisher, R. S., Afra, P., Macken, M., Minecan, D. N., Bagic, A., Benbadis, S. R., Helmers, S. L., Sinha, S. R., Slater, J., Treiman, D., Begnaud, J., Raman, P., Najimipour, B. Automatic Vagus Nerve Stimulation Triggered by Ictal Tachycardia: Clinical Outcomes and Device Performance--The US E-37 Trial Neuromodulation, 2016; 19 (2): 188-195.

Meador, K. J., Loring, D. W., Boyd, A., Echauz, J., LaRoche, S., Velez-Ruiz, N., Korb, P., Byrnes, W., Dilley, D., Borghs, S., De Backer, M., Story, T., Dedeken, P., Webster, E. Randomized double-blind comparison of cognitive and EEG effects of lacosamide and carbamazepine. Epilepsy Behav, 2016; 62: 267-275.

Lagae, L., Villanueva, V., Meador, K. J., Bagul, M., Laurenza, A., Kumar, D., Yang, H. Adjunctive perampanel in adolescents with inadequately controlled partial-onset seizures: A randomized study evaluating behavior, efficacy, and safety. Epilepsia, 2016; 57 (7): 1120-1129.

Meador, K. J., Yang, H., Pina-Garza, J. E., Laurenza, A., Kumar, D., Wesnes, K. A. Cognitive effects of adjunctive perampanel for partial-onset seizures: A randomized trial. Epilepsia, 2016; 57 (2): 243-251.

Chak, K., Roy-Chaudhuri, B., Kim, H. K., Kemp, K. C., Porter, B. E., Kay, M. A. Increased precursor microRNA-21 following status epilepticus can compete with mature microRNA-21 to alter translation. Experimental neurology, 2016; 286: 137-146.

Kim, S. Y., Porter, B. E., Friedman, A., Kaufer, D. A Potential Role for Glia-Derived Extracellular Matrix Remodeling in Postinjury Epilepsy. J Neurosci Res, 2016; 94 (9): 794-803.

Donti, T. R., Cappuccio, G., Hubert, L., Neira, J., Atwal, P. S., Miller, M. J., Cardon, A. L., Sutton, V. R., Porter, B. E., Baumer, F. M., Wangler, M. F., Sun, Q., Emrick, L. T., Elsea, S. H. Diagnosis of adenylosuccinate lyase deficiency by metabolomic profiling in plasma reveals a phenotypic spectrum. Molecular genetics and metabolism reports, 2016; 8: 61-66.

Spelbrink, E. M., Mabud, T. S., Reimer, R., Porter, B. E. Plasma taurine levels are not affected by vigabatrin in pediatric patients. Epilepsia, 2016; 57 (8): e168-72.

Klotz, J., Porter, B. E., Colas, C., Schlessinger, A., Pajor, A. M. Mutations in the Na(+)/citrate cotransporter NaCT (SLC13A5) in pediatric patients with epilepsy and developmental delay. Molecular medicine, 2016 May 26;22.

2015

Ho Allen L., Miller Kai J., Cartmell Sam, Inoyama Katherine, Fisher Robert S., Halpern Casey H., Stereotactic laser ablation of the splenium for intractable epilepsy: A case report, Epilepsy & Behavior Case Reports, 2016 Jan 13;5:23-6.

Kai J. Miller *, Terry C. Burns, Gerald A. Grant, Casey H. Halpern. Responsive stimulation of motor cortex for medically and surgically refractive epilepsy. Seizure, 2015 33: 38–40.

Krook-Magnuson, E. and Soltesz, I. Beyond the hammer and the scalpel: selective circuit control for the epilepsies. Nature Neuroscience, 2015 18(3): 331-8.

Soltesz, I., Alger, B.E., Kano, M., Lee, S.H., Lovinger, D.M., Ohno-Shosaku, T., Watanabe, M.  Weeding out bad waves: Towards selective cannabinoid circuit control in epilepsy.  Nature Reviews Neuroscience, 2015 16: 264-277.

Leone DP, Heavner WE, Ferenczi EA, Dobreva G, Huguenard JR, Grosschedl R, McConnell SK. Satb2 Regulates the Differentiation of Both Callosal and Subcerebral Projection Neurons in the Developing Cerebral Cortex. Cereb Cortex, 2015 Oct;25(10):3406-19.

Farzampour Z, Reimer RJ, Huguenard J. Endozepines. Adv Pharmacol, 2015; 72:147-64.

Farzampour Z, Huguenard J. Seizing upon Mechanisms for Impaired Consciousness. Neuron, 2015 Feb 4;85(3):453-5.

Paz JT, Huguenard JR. Optogenetics and epilepsy: past, present and future. Epilepsy Curr, 2015 Jan-Feb;15(1):34-8.

Paz JT, Huguenard JR. Microcircuits and their interactions in epilepsy: is the focus out of focus? Nat Neurosci, 2015 Mar;18(3):351-9.

Weissberg I, Wood L, Kamintsky L, Vazquez O, Milikovsky DZ, Alexander A, Oppenheim H, Ardizzone C, Becker A, Frigerio F, Vezzani A, Buckwalter MS, Huguenard J, Friedman A, Kaufer D. Albumin induces excitatory synaptogenesis through astrocytic TGF-β/ALK5 signaling in a model of acquired epilepsy following blood-brain barrier dysfunction. Neurobiol Dis, 2015 Jun;78:115-25.

Paşca AM, Sloan SA, Clarke LE, Tian Y, Makinson CD, Huber N, Kim CH, Park JY, O'Rourke NA, Nguyen KD, Smith SJ, Huguenard JR, Geschwind DH, Barres BA, Paşca SP. Functional cortical neurons and astrocytes from human pluripotent stem cells in 3D culture. Nat Methods, 2015 Jul;12(7):671-8.

Fisher, R.S. Stimulation of the medial septum should benefit patients with temporal lobe epilepsy.  Med Hypotheses, 2015; 84 (6): 543-550.

Fisher, R. S., Bartfeld, E., Cramer, J. A. Use of an online epilepsy diary to characterize repetitive seizures. Epilepsy Behav,  2015; 47: 66-71.

Fisher, R. S. Redefining epilepsy. Curr Opin Neurol, 2015; 28 (2): 130-135.

Salanova, V., Witt, T., Worth, R., Henry, T. R., Gross, R. E., Nazzaro, J. M., Labar, D., Sperling, M. R., Sharan, A., Sandok, E., Handforth, A., Stern, J. M., Chung, S., Henderson, J. M., French, J., Baltuch, G., Rosenfeld, W. E., Garcia, P., Barbaro, N. M., Fountain, N. B., Elias, W. J., Goodman, R. R., Pollard, J. R., Troester, A. I., Irwin, C. P., Lambrecht, K., Graves, N., Fisher, R. Long-term efficacy and safety of thalamic stimulation for drug-resistant partial epilepsy. Neurology, 2015; 84 (10): 1017-1025.

Frechette, E. S., Bell-Stephens, T. E., Steinberg, G. K., Fisher, R. S. Electroencephalographic features of moyamoya in adults. Clinical Neurophysiology, 2015; 126 (3): 481-485.

Weitz, A. J., Fang, Z., Lee, H. J., Fisher, R. S., Smith, W. C., Choy, M., Liu, J., Lin, P., Rosenberg, M., Lee, J. H. Optogenetic fMRI reveals distinct, frequency-dependent networks recruited by dorsal and intermediate hippocampus stimulations. Neuroimage,  2015; 107: 229-241.

Fisher, R. S., Nune, G., Roberts, S. E., Cramer, J. A. The Personal Impact of Epilepsy Scale (PIES), Epilepsy Behav,  2015; 42: 140-146.

Fisher, R. S., Eggleston, K. S., Wright, C. W. Vagus nerve stimulation magnet activation for seizures: a critical review. Acta Neurologica Scand, 2015; 131 (1): 1-8.

Loring, D. W., Kapur, R., Meador, K. J., Morrell, M. J. Differential neuropsychological outcomes following targeted responsive neurostimulation for partial-onset epilepsy. Epilepsia, 2015; 56 (11): 1836-1844.

Daffner, K. R., Gale, S. A., Barrett, A. M., Boeve, B. F., Chatterjee, A., Coslett, H. B., D'Esposito, M., Finney, G. R., Gitelman, D. R., Hart, J. J., Lerner, A. J., Meador, K. J., Pietras, A. C., Voeller, K. S., Kaufer, D. I. Improving clinical cognitive testing Report of the AAN Behavioral Neurology Section Workgroup. Neurology, 2015; 85 (10): 910-918.

Inoyama, K., Meador, K. J. Cognitive outcomes of prenatal antiepileptic drug exposure. Epilepsy Research, 2015; 114: 89-97.

Meador, K. J., Kapur, R., Loring, D. W., Kanner, A. M., Morrell, M. J. Quality of life and mood in patients with medically intractable epilepsy treated with targeted responsive neurostimulation. Epilepsy Behav,  2015; 45: 242-247.

Wen, X., Meador, K. J., Hartzema, A. Antiepileptic drug use by pregnant women enrolled in Florida Medicaid. Neurology, 2015; 84 (9): 944-950.

Velez-Ruiz, N. J., Meador, K. J. Neurodevelopmental Effects of Fetal Antiepileptic Drug Exposure. Drug Safety, 2015; 38 (3): 271-278.

Baker, G. A., Bromley, R. L., Briggs, M., Cheyne, C. P., Cohen, M. J., Garcia-Finana, M., Gummery, A., Kneen, R., Loring, D. W., Mawer, G., Meador, K. J., Shallcross, R., Clayton-Smith, J. IQ at 6 years after in utero exposure to antiepileptic drugs: A controlled cohort study. Neurology, 2015; 84 (4): 382-390.

Drane, D. L., Loring, D. W., Voets, N. L., Price, M., Ojemann, J. G., Willie, J. T., Saindane, A. M., Phatak, V., Ivanisevic, M., Millis, S., Helmers, S. L., Miller, J. W., Meador, K. J., Gross, R. E. Better object recognition and naming outcome with MRI-guided stereotactic laser amygdalohippocampotomy for temporal lobe epilepsy. Epilepsia, 2015; 56 (1): 101-113.

Herzog, A. G., Fowler, K. M., Sperling, M. R., Massaro, J. M., Progesterone Trial Study Group, Distribution of seizures across the menstrual cycle in women with epilepsy. Epilepsia,  2015; 56: e58-62.

Foster, B. L., Rangarajan, V., Shirer, W. R., Parvizi, J. Intrinsic and Task-Dependent Coupling of Neuronal Population Activity in Human Parietal Cortex. Neuron, 2015; 86 (2): 578-590.

Rankin-Gee, E. K., McRae, P. A., Baranov, E., Rogers, S., Wandrey, L., Porter, B. E. Perineuronal net degradation in epilepsy. Epilepsia, 2015; 56 (7): 1124-1133.

2014

Xiaoming Jin, Kewen Jiang, and David A. Prince. Excitatory and inhibitory synaptic connectivity to layer V fast-spiking interneurons in the freeze lesion model of cortical microgyria. J Neurophysiol, 2014; 112: 1703–1713.

Buckmaster P.S. Does mossy fiber sprouting give rise to the epileptic state? Adv in Exp Med Biol 2014; 813:161-168.

Kyuyoung CL, Huguenard JR.  Modulation of short-term plasticity in the corticothalamic circuit by group III metabotropic glutamate receptors. J Neurosci, 2014 Jan 8;34(2):675-87.

Tani H, Dulla CG, Farzampour Z, Taylor-Weiner A, Huguenard JR, Reimer RJ.  A local glutamate-glutamine cycle sustains synaptic excitatory transmitter release. Neuron, 2014 Feb 19;81(4):888-900.

Eggleston, K. S., Olin, B. D., Fisher, R. S. Ictal tachycardia: The head-heart connection. Seizure, 2014; 23 (7): 496-505.

Fisher, R. S., Velasco, A. L. Electrical brain stimulation for epilepsy. Nat Rev Neurol, 2014; 10 (5): 261-27.

Fisher, R. S., Acevedo, C., Arzimanoglou, A., Bogacz, A., Cross, J. H., Elger, C. E., Engel, J., Forsgren, L., French, J. A., Glynn, M., Hesdorffer, D. C., Lee, B. I., Mathern, G. W., Moshe, S. L., Perucca, E., Scheffer, I. E., Tomson, T., Watanabe, M., Wiebe, S. ILAE Official Report: A practical clinical definition of epilepsy. Epilepsia, 2014; 55 (4): 475-48.

Kalanithi, P. S., Arrigo, R. T., Tran, P., Gephart, M. H., Shuer, L., Fisher, R., Boakye, M. Rehospitalization and Emergency Department Use Rates Before and After Vagus Nerve Stimulation for Epilepsy: Use of State Databases to Provide Longitudinal Data Across Multiple Clinical Settings. Neuromodulation, 2014; 17 (1): 60-6.

Fisher, R. S., Scharfman, H. E., deCurtis, M. How Can We Identify Ictal and Interictal Abnormal Activity? Adv Exp Med Biol, 2014; 813: 3-23.

Teagarden, D. L., Meador, K. J., Loring, D. W. Low vitamin D levels are common in patients with epilepsy Epilepsy Res, 2014; 108 (8): 1352-1356.

Meador, K. J., Baker, G. A., Browning, N., Cohen, M. J., Bromley, R. L., Clayton-Smith, J., Kalayjian, L. A., Kanner, A., Liporace, J. D., Pennell, P. B., Privitera, M., Loring, D. W. Breastfeeding in children of women taking antiepileptic drugs: cognitive outcomes at age 6 years. JAMA pediatr, 2014; 168 (8): 729-736.

Meador, K. J. Breastfeeding and Antiepileptic Drugs. JAMA, 2014; 311 (17): 1797-1798.

Loring, D. W., Gaillard, W. D., Bookheimer, S. Y., Meador, K. J., Ojemann, J. G. Cortical cartography reveals political and physical maps. Epilepsia, 2014; 55 (5): 633-637.

Karakis, I., Montouris, G. D., Piperidou, C., San Luciano, M., Meador, K. J., Cole, A. J. Patient and caregiver quality of life in psychogenic non-epileptic seizures compared to epileptic seizures. Seizure, 2014; 23 (1): 47-54.

Meador, K. J. Seizure Reduction with Fluoxetine in Dravet Syndrome. Epilepsy behav case rep, 2014; 2: 54-56.

Karakis, I., Cole, A. J., Montouris, G. D., San Luciano, M., Meador, K. J., Piperidou, C. Caregiver burden in epilepsy: determinants and impact. Epilepsy res treat, 2014; 2014: 808421.

Maclean, J., Porter, B. 50 years ago in the journal of pediatrics: convulsive equivalent syndrome of childhood.  J pediatrics, 2014; 164 (5): 1050.

2013

Krook-Magnuson, E., Armstrong, C., and Soltesz, I. On-demand optogenetic control of spontaneous seizures in temporal lobe epilepsy. Nature Communications. 2013; 4:1376.

Armstrong, C., Krook-Magnuson, E., Oijala, M. & Soltesz, I. Closed-loop optogenetic intervention in mice. Nature Protocols 2013; 8: 1475-1493.

Christian CA, Herbert AG, Holt RL, Peng K, Sherwood KD, Pangratz-Fuehrer S, Rudolph U, Huguenard JR. Endogenous Positive Allosteric Modulation of GABAA Receptors by Diazepam binding inhibitor. Neuron, 2013 Jun 19;78(6):1063-74.

Christian CA, Huguenard JR. Astrocytes potentiate GABAergic transmission in the thalamic reticular nucleus via endozepine signaling.  Proc Natl Acad Sci U S A, 2013 Dec 10;110(50):20278-83.

Fisher, R. S. Deep brain stimulation for epilepsy. Handbook of clinical neurology  2013; 116: 217-234.

Harden, C. L., Meador, K. J. Do antiepileptic drugs cause suicidal behavior? Neurology, 2013; 81 (22): 1889-1890.

Cohen, M. J., Meador, K. J., Browning, N., May, R., Baker, G. A., Clayton-Smith, J., Kalayjian, L. A., Kanner, A., Liporace, J. D., Pennell, P. B., Privitera, M., Loring, D. W. Fetal antiepileptic drug exposure: Adaptive and emotional/behavioral functioning at age 6 years. Epilepsy Behav, 2013; 29 (2): 308-315.

Karakis, I., Montouris, G. D., Piperidou, C., San Luciano, M., Meador, K. J., Cole, A. J. The effect of epilepsy surgery on caregiver quality of life. Epilepsy Res, 2013; 107 (1-2): 181-189.

Reisinger, T. L., Newman, M., Loring, D. W., Pennell, P. B., Meador, K. J. Antiepileptic drug clearance and seizure frequency during pregnancy in women with epilepsy. Epilepsy Behav, 2013; 29 (1): 13-18.

Meador, K. J. Comment: valproate dose effects differ across congenital malformations. Neurology, 2013; 81 (11): 1002-?

Burneo, J. G., Sirven, J. I., Kiesel, L. W., Vecht, C. J., Jehi, L., Chung, S. S., Uhm, J., Politsky, J. M., Chang, E. F., Husain, A. M., Tatum, W. O., Meador, K. J., Noe, K., Hesdorffer, D. C., Herman, S. T., Wiebe, S., Engel, J., Schrader, S., Parko, K. L., Dichter, M. A., Kwan, P., Kossoff, E., Sperling, M. R. Managing common complex symptomatic epilepsies: tumors and trauma: american epilepsy society - 2012 annual course summary. Epilepsy currents, 2013; 13 (5): 232-235.

Meador, K. J., Loring, D. W. Prenatal valproate exposure is associated with autism spectrum disorder and childhood autism. J Pediatr, 2013; 163 (3): 924-924.

Drane, D. L., Ojemann, J. G., Phatak, V., Loring, D. W., Gross, R. E., Hebb, A. O., Silbergeld, D. L., Miller, J. W., Voets, N. L., Saindane, A. M., Barsalou, L., Meador, K. J., Ojemann, G. A., Tranel, D. Famous face identification in temporal lobe epilepsy: Support for a multimodal integration model of semantic memory. Cortex, 2013; 49 (6): 1648-1667.

Rudzinski, L. A., Meador, K. J. Epilepsy and neuropsychological comorbidities. Continuum (Minneapolis, Minn.)  2013; 19 (3 Epilepsy): 682-696.

Meador, K. J., Loring, D. W. Risks of In Utero Exposure to Valproate. JAMA, 2013; 309 (16): 1730-1731.

Meador, K. J., Baker, G. A., Browning, N., Cohen, M. J., Bromley, R. L., Clayton-Smith, J., Kalayjian, L. A., Kanner, A., Liporace, J. D., Pennell, P. B., Privitera, M., Loring, D. W. Fetal antiepileptic drug exposure and cognitive outcomes at age 6 years (NEAD study): a prospective observational study. Lancet Neurol, 2013; 12 (3): 244-252.

Parvizi, J., Rangarajan, V., Shirer, W. R., Desai, N., Greicius, M. D. The Will to Persevere Induced by Electrical Stimulation of the Human Cingulate Gyrus. Neuron, 2013; 80 (6): 1359-1367

Dastjerdi, M., Ozker, M., Foster, B. L., Rangarajan, V., Parvizi, J. Numerical processing in the human parietal cortex during experimental and natural conditions. Nature Comm, 2013; 4

Shum, J., Hermes, D., Foster, B. L., Dastjerdi, M., Rangarajan, V., Winawer, J., Miller, K. J., Parvizi, J. A Brain Area for Visual Numerals. J Neuroscie, 2013; 33 (16): 6709-6715

Porter, B. E., Jacobson, C. Report of a parent survey of cannabidiol-enriched cannabis use in pediatric treatment-resistant epilepsy. Epilepsy Behav, 2013; 29 (3): 574-577

Paciorkowski, A. R., Traylor, R. N., Rosenfeld, J. A., Hoover, J. M., Harris, C. J., Winter, S., Lacassie, Y., Bialer, M., Lamb, A. N., Schultz, R. A., Berry-Kravis, E., Porter, B. E., Falk, M., Venkat, A., Vanzo, R. J., Cohen, J. S., Fatemi, A., Dobyns, W. B., Shaffer, L. G., Ballif, B. C., Marsh, E. D. MEF2C Haploinsufficiency features consistent hyperkinesis, variable epilepsy, and has a role in dorsal and ventral neuronal developmental pathways. Neurogenetics, 2013; 14 (2): 99-111

Ortiz-Gonzalez, X. R., Poduri, A., Roberts, C. M., Sullivan, J. E., Marsh, E. D., Porter, B. E. Focal cortical dysplasia is more common in boys than in girls. Epilepsy Behav, 2013; 27 (1): 121-123

Risbud, R. M., Porter, B. E. Changes in MicroRNA Expression in the Whole Hippocampus and Hippocampal Synaptoneurosome Fraction following Pilocarpine Induced Status Epilepticus. PLoS ONE, 2013; 8 (1)

Research

Our researchers are currently engaged in groundbreaking studies on the causes of epilepsy, the effect of seizures and medications on human cognition and emotion, and developing new wireless devices and electrodes for epilepsy treatment.

Featured Publication

Laser Interstitial Thermal Therapy (LITT): Seizure Outcomes for Intractable Mesial Temporal Lobe Epilepsy