61. Jouberts.html MAJOR MeSH HEADINGS *cerebellardiseases-congenital; *Cerebellum-abnormalities; MINOR MESH HEADINGS Apnea-pathology; cerebellar-diseases-pathology; http://www.indiana.edu/~pietsch/joubert.html

go to Shufflebrain main menu JOUBERT'S SYNDROME web contact: pietsch@indiana.edu Joubert's syndrome is a rare condition in which the middle part of the cerebellum (the vermis) doesn't properly form . The cerebellum helps regulate dynamic musclular activities such as dancing or playing musical instruments or complex movements of the tongue and vocal muscles. Below are the results of a recent survey of the scientific literature on subject to October 2000. For general information click here. A literature search at Indiana University, Bloomington, Indiana The following MEDLINE items were compiled by SilverPlatter and are presented with their generous co-operation and permission. ( See SilverPlatter's Worldwide Library for bibliographic search information Record 1 of 15 in MEDLINE EXPRESS (R) 1999/11-1999/12 TITLE: Joubert's syndrome and prenatal hydrocephalus. AUTHOR(S): Anderson-JS; Gorey-MT; Pasternak-JF; Trommer-BL ADDRESS OF AUTHOR: Northwestern University School of Medicine, and Division of Neuroradiology, Evanston Hospital, Illinois 60201, USA. SOURCE (BIBLIOGRAPHIC CITATION): Pediatr-Neurol. 1999 May; 20(5): 403-5

62. Cerebellum And Disease Models - Workshop Animal models for studying diseases of the cerebellar system Chair CI De Zeeuw,Department of Neuroscience, ERASMUS University Rotterdam, The Netherlands http://www.nesys.uio.no/Workshop2/

Cerebellum and Disease Models - Workshop The Norwegian Academy of Sciences, Oslo - May 27, 2004 The primary goal of this workshop is to initiate a discussion among investigators that are interested in cerebellar function and dysfunction from different perspectives, to explore long term possibilities for synergies at the European level. The workshop also includes speakers who are not primarily studying the cerebellum but who have access to methods and approaches that are highly needed also in future cerebellar research. The workshop is funded by the Centre for Molecular Biology and Neuroscience, University of Oslo, and the EU Neuroinformatics project CEREBELLUM. The meeting is organized by the Neural Systems and Graphics Computing Laboratory, University of Oslo. Speakers Discussants and Chairs Programme Participants ... Organization Speakers Egidio D'Angelo Department of Physiological and Pharmacological Sciences, University of Pavia Erik De Schutter Theoretical Neurobiology, University of Antwerp

63. Cerebellar Disease Dog cerebellar disease dog explanation cerebellar relating to or associatedwith the cerebellum; cerebellar dog disease cerebellar and more http://www.eprintcity.com/cerebellar_disease_dog.htm

Frontline Flea and Tick Heartgard + Advantage ... Medications cerebellar disease dog Search for the product: or Choose the product: Frontline Plus Heartgard Plus Advantage Frontline Topspot Rimadyl Sentinel Interceptor K9 Advantix Heartworm Athritis Dental Odor Control Wormers Vaccines Click here to get free shipping on orders over $39. Save on your pet's medications at 1-800-PetMeds. Parvo infected dog Q: Hello, i received a white german shepherd on a saturday delivered from california on a plane. on sunday she started vomiting. on monday she wouldn't hardly move and would not eat and drink. we took her to the vet and they put her on an iv to replenish her fluids. i read in one of your replies that some, (rarely) dogs could get parvo from the vaccine. the lady who sold us the dog said she does not have parvo at her kennel and the only place she could of contracted it was at the vet. the vet looked at her on the thursday before the saturday we received her. is it possible that maybe the stress of the flight could of let the vaccine turn into parvo? just trying to guess how she contracted the virus. thank you! A: It is possible that pet may have been incubating field strain parvo virus and was activated or prescipated by long flight and stress. or it is possible theoretically that pup had been vaccinated with modified live viral vaccine that had reverted to virulent form and caused disease due to stresses above

64. Pets Health Brain Abnormalities usually due to cerebellar disease. The cerebellum regulates Degenerative cerebellar disease may involve the following breeds. http://www.cah.com/dr_library/atax.html

SEARCH THIS SITE: a Home Online Resources The Library Imbalance (ataxia) In Pets TOPIC: Please select one... 9/11 Pets Loving Devotion A 9/11 Story Acupuncture and Tellington Ttouch Acupuncture in The Treatment For Animals Acupuncture-Uses and Benefits Addison's Disease (Hypoadrenocorticism) Addison's Disease-Newer Treatment Options Aging and Your Pet Age Analogy For Your Pet Aggression At The Vets Office Aggressive Behavior In Multi-Cat Households Aggression At The Vets Office ALLERGIES Anal Sac Disease ANEMIA- AUTOIMMUNE HEMOLYTIC Anesthesia and Your Pet Antifreeze Poisoning Arthritis Treatments For Cats and Dogs Asthma-Bronchitis in Cats Babesiosis in Dogs Babies and Pets-Introduction of Bacterial Skin Infections Behavior Guides for Cats Behavior Guides for Dogs Behavior Drug Therapy Birds Feeding Guide for Pet Birds Birds- Care of Bladder Stones (uroliths) Cardiac Diseases of Cats and Dogs Cat Breeds Cat Litter Cat Scratch Fever-Bartonellosis Cataracts and Your Pet Cerebellar Hypoplasia Cheytiella Dermatitis in Pets Chocolate Poisoning in Dogs Chronic Wasting Disease Clostridial Enteritis and Diarrhea in Your Pet Constipation and Your Cat Cruciate Ligament Damage and Repair Cushings Disease-Hyperadrenocorticism Cushings-Treatment of Dental Care and Your Cat Dental Tooth Abscess Diarrhea Dietary Management Demodex Mange in Dogs and Cats Dental Care Dental Care and Your Cat Dental Care Special Promotion for Your Pet Dermatomyositis Diabetes in Cats Diabetes in Dogs Digestive Disturbances in Cats Digestive Disturbances in Dogs Disasters and Emergencies-Be Prepared

65. Mapping Movement; Amy Bastian up about movement in cerebellar disease or PD, she says, and quantified it. she explained why patients with cerebellar disease overreach objects, http://www.neuro.jhmi.edu/BrainWaves/2004_Fall/Bastian.htm

Fall 2004 Volume 16, Number 4 Mapping Movement Recording what's normal when you walk or reach gives a telling contrast in disease. Many people with one-sided damage to cortical motor areas from trauma or a stroke, benign tumors or even the ultimate "damage" of a hemispherectomy can, fortunately, still walk. But they're troubled by an undeniable, unfixable limp. Now, after paving the way for several years, Amy Bastian, Ph.D. , is courting a remedy that's come from her study of the cerebellum, specifically, from a capability hard-wired in that organ. It's like finding $20 in the pocket of an old jacket. Bastian, whose doctoral degree is in movement science, has made it her work to deconstruct the action of trunk and limbs in both health and disease. At the Kennedy Krieger Motion Analysis Laboratory she directs-she's also with Hopkins' Neurology-Bastian first tracks normal movement with an infrared camera, then uses the computer to help save the data in a more useful form. Hollywood used similar kinematic analysis, as it's called, to create the motion of the creepy Gollum in Lord of the Rings. Bastian contrasts this normal movement with that typical of neurological problems like Parkinson's disease (PD), stroke and the spino-cerebellar ataxias-hereditary diseases marked by a reeling, uncoordinated gait. "We've captured what neurologists intuitively pick up about movement in cerebellar disease or PD," she says, "and quantified it."

66. Postural Instability, Balance, Parkinson Disease - Welcome To The National Parki The postural instability of cerebellar disease can usually be distinguished In cerebellar disease, muscle tone is decreased, the muscles are hypotonic. http://www.parkinson.org/site/pp.asp?c=9dJFJLPwB&b=100112

67. NEUROSCIENCE SAMPLE EXAM 1 Which of the following statements concerning cerebellar disease is INCORRECT? a.cerebellar disease may be accompanied by intention tremors http://www2.umdnj.edu/~paneuweb/exam1_95.htm

PA Neuroscience Home Page David P. Crockett, Ph.D. Department of Neuroscience and Cell Biology UMDNJ-Robert Wood Johnson Medical School Phone FAX E-mail crockett@umdnj.edu NEUROSCIENCE SAMPLE EXAM 1 PHYSICIAN ASSISTANT PROGRAM SPRING 1995 ROBERT WOOD JOHNSON MEDICAL SCHOOL Directions: Select the one best answer for each question. Note that some questions have 4 and others have 5 alternatives 1. Which of the following structures are NOT found in the diencephalon? a. habenula b. pineal gland c. dorsal thalamus d. epithalamus e. inferior colliculus 2. Which of the following associations is INCORRECT? a. lateral ventricle telencephalon b. cerebral aqueduct diencephalon c. central canal spinal cord d. fourth ventricle medulla 3. Which of the following statements concerning the neocortex is NOT true? a. It is developmentally derived from the telencephalon b. 90% of the cerebral cortex is said to be neocortex. c. At some point in its development, the neocortex has 6 layers. d. Most cortical afferents terminate in layer I, the molecular layer. 4. The cerebellar cortex is characterized by_layers.

68. Treatable Psychiatric Symptoms Common With Degenerative Brain Disease Sixtyeight per cent of those with cerebellar disease suffered from mood disorders Personality change was present in 26 per cent of cerebellar disease http://www.hopkinsmedicine.org/press/2002/August/020806.htm

August 6, 2002 MEDIA CONTACT: Trent Stockton PHONE: E-MAIL: tstockt1@jhmi.edu Treatable Psychiatric Symptoms Common With Degenerative Brain Disease Potentially treatable psychiatric problems are common in patients with degenerative brain diseases affecting movement and coordination, according to a study by Johns Hopkins scientists. Up to 80 per cent of those with either Huntington's disease or degenerative diseases affecting the cerebellum also suffer from depression, impaired thinking and changes in personality, the study found. "Traditionally, there has been this distinction between neurological and psychiatric disorders, but it is an artificial distinction," said lead author Russell L. Margolis, M.D., associate professor of psychiatry at Hopkins and director of the Laboratory of Genetic Neurobiology. "Indeed, the high rate of psychiatric disorders in these patients suggests that many, if not most, can benefit from treatment, even if the course of the brain disease itself cannot be reversed. Many symptoms can be eased, and the quality of life for these patients and their families can be greatly enhanced," says Margolis. "Our findings of high rates of psychiatric disorders in Huntington's disease confirm the results of previous studies, and we believe we've found the first well-established link between serious psychiatric disorders and the cerebellum, a region at the back of the brain densely packed with nerve cells," notes Margolis.

69. Non-motor Associative Learning In Patients With Isolated Degenerative Cerebellar Dissociation of HabitLearning in Parkinson s and cerebellar Disease J. Cogn.Neurosci., April 1, 2002; 14(3) 493 - 499. Abstract Full Text PDF http://brain.oxfordjournals.org/cgi/content/full/122/1/87

JOURNAL HOME HELP FEEDBACK SUBSCRIPTIONS ... TABLE OF CONTENTS QUICK SEARCH: [advanced] Author: Keyword(s): Year: Vol: Page: This Article Abstract FREE Full Text (PDF) Alert me when this article is cited ... Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed ... Cited by other online articles Search for citing articles in: ISI Web of Science (29) Request Permissions PubMed PubMed Citation Articles by Drepper, J. Articles by Diener, H. C. Brain, Vol. 122, No. 1, 87-97, January 1999 Oxford University Press Non-motor associative learning in patients with isolated degenerative cerebellar disease J. Drepper D. Timmann F. P. Kolb and H. C. Diener Department of Neurology, University of Essen, Essen and Institute of Physiology, University of Munich, Pettenkoferstrasse 12, Munich, Germany Correspondence to: J. Drepper, Department of Neurology, University of Essen, Hufelandstrasse 55, D-45122 Essen, Germany E-mail: Abstract Top Abstract Introduction Method Results Discussion References In recent decades it has become clear that the cerebellum is involved in associative motor learning, but its exact role in

70. Absence Of A Common Functional Denominator Of Visual Disturbances In Cerebellar of visual perception in patients suffering from cerebellar disease. from cerebellar disease with that of controls on a number of visual tasks, http://brain.oxfordjournals.org/cgi/content/full/122/11/2133

JOURNAL HOME HELP FEEDBACK SUBSCRIPTIONS ... TABLE OF CONTENTS QUICK SEARCH: [advanced] Author: Keyword(s): Year: Vol: Page: This Article Abstract FREE Full Text (PDF) Alert me when this article is cited ... Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed ... Cited by other online articles Search for citing articles in: ISI Web of Science (18) Request Permissions PubMed PubMed Citation Articles by Thier, P. Articles by Barash, S. Brain, Vol. 122, No. 11, 2133-2146, November 1999 Oxford University Press Invited review Absence of a common functional denominator of visual disturbances in cerebellar disease Peter Thier Thomas Haarmeier Stefan Treue and Shabtai Barash The Weizmann Institute, Rehovot, Israel Abstract Top Abstract Introduction Methods Results Discussion An anatomical denominator of... References Several studies have demonstrated disturbances of visual perception in patients suffering from cerebellar disease. In an attempt

71. Gordon Morgan Holmes (www.whonamedit.com) Inheritable disease picture with cerebellar ataxia due to a degeneration of Rebound phenomenon seen in cerebellar disease. StewartHolmes syndrome http://www.whonamedit.com/doctor.cfm/1189.html

Home List categories Eponyms A-Z Biographies by country ... Contact Whonamedit.com does not give medical advice. This survey of medical eponyms and the persons behind them is meant as a general interest site only. No information found here must under any circumstances be used for medical purposes, diagnostically, therapeutically or otherwise. If you, or anybody close to you, is affected, or believe to be affected, by any condition mentioned here: see a doctor. A recommendation: Hypography is an open community about science and all things related Gordon Morgan Holmes Irish neurologist, born February 22, 1876, Dublin; died December 29, 1965, Farnham, Surrey. Associated eponyms: Adie's syndrome A neurological phenomenon in which one or both pupils is dilated and responds slowly or not at all to light and a near stimulus, accompanied by slow constriction and relaxation in the change from near to distant vision, and impaired accommodation. Balint's syndrome A syndrome combining paralysis of visual fixation, optic ataxia, and impairment of visual fixation. Head-Holmes syndrome Sensory changes produced by lesions of the cerebral cortex and other parts of the brain.

72. STCA New Home Page The classic signs of cerebellar disease can therefore be summarized as wide basedstance, ataxia characterized by dysmetria, and intention tremor, http://www.amstaff.org/health.htm

Staffordshire Terrier Club of America Official Web Site Home (General Information) Officers (Contact a Board Member) Breed Information (Rescue, Breed Standard, Publications, New Year Book!) (PDF Format) STCA Legislative Committee (Links to help fight BSL) Events (National Show Information) Health Committee (New Fund Raiser, Health reports) Breeders (STCA Members) Membership Application (PDF Format) For technical support: STCA Web Support STCA Health Committee Contacts: Chairperson, Faith Beiser Members: Sharon Gregory Sandy Underwood and Heidi McClure Fund Raiser Wobbly Dogs Amstaff Ataxia FAQs ... OFA Health Committee AmStaff Print Fund Raiser! Limited Edition collectors item, numbered, only 100 available. Cost of print is $55, plus $6 shipping. For more information and to Order, click here! Contact Faith Beiser for information! Giclee archival print on Somerset velvet fine art paper, signed and numbered by the artist. Return to top of page.

73. Autosomal Dominant Cerebellar Ataxia - Patient UK Autosomal dominant cerebellar ataxia. MachadoJoseph disease. Most forms ofcerebellar ataxia are acquired disorders but hereditary forms can be autosomal http://www.patient.co.uk/showdoc/40000823/

PatientPlus articles are written for doctors and so the language can be technical. However, some people find that they add depth to the articles found in the other sections of this website which are written for non-medical people. Autosomal dominant cerebellar ataxia Machado-Joseph disease Most forms of cerebellar ataxia are acquired disorders but hereditary forms can be autosomal dominant , recessive or a few are X-linked. By and large the dominant forms are less severe than recessive ones. The classification includes the following diseases: Autosomal dominant cerebellar ataxia type I, II and III Cerebellar ataxia, dominant pure Cerebello-olivary atrophy Olivo-ponto-cerebellar atrophy Pierre Marie cerebellar ataxia Spinocerebellar ataxia, types 1-8,10-19,21-22 Autosomal dominant spinocerebellar ataxias (ADCA) are clinically and genetically varied disorders characterised by a slow progression of ataxia of gait, stance and limbs, dysarthria with or without oculomotor dysfunction due to cerebellar degeneration. The degenerative process can be limited to the cerebellum (ADCA type III) or may also involve the retina (ADCA type II), optic nerve, ponto-medullary systems, basal ganglia, cerebral cortex, spinal tracts or peripheral nerves (ADCA type I). In the genetic classification, ADCAs are called spinocerebellar ataxias (SCAs) and numbered in the order SCA1 to SCA22. They may show the phenomenon of anticipation with earlier onset and more severe disease in successive generations. Epidemiology Prevalence

74. Tremor - Patient UK Neurological disease eg severe cerebellar lesions, Wilson s disease, neurosyphilis, Associated with brain stem or cerebellar disease including MS, http://www.patient.co.uk/showdoc/40000127/

PatientPlus articles are written for doctors and so the language can be technical. However, some people find that they add depth to the articles found in the other sections of this website which are written for non-medical people. Tremor Three types of tremor: Static - occurs in a relaxed limb when fully supported at rest. Causes include Parkinson's disease , Parkinsonism, other extra pyramidal diseases, multiple sclerosis Postural - occurs when a part of the body is held in a fixed position (can also remain during movement). Types include physiological tremor, exaggerated physiological tremor e.g. in thyrotoxicosis , anxiety states, alcohol abuse , drugs (e.g. sympathomimetics, antidepressants, valproate, lithium), heavy metal poisoning ('hatter's shakes' from mercury). Neurological disease e.g. severe cerebellar lesions, Wilson's disease , neurosyphilis, peripheral neuropathies, Benign essential ( familial) tremor, task-specific tremors e.g. primary writing tremor. Kinetic or action tremor - occurs during voluntary active movement of upper body part. If action tremor worsens as goal-directed movement approaches its intended target, this is intention tremor. Associated with brain stem or cerebellar disease including MS, spinocerebellar degenerations, vascular disease, tumours. Also psychogenic tremors.

75. Neurosurgery - UserLogin Thus, it is suggested that cerebellar disease leads to less excitatory input from cerebellar tremors as a result of other disease processes have been http://www.neurosurgery-online.com/pt/re/neurosurg/fulltext.00006123-200504000-0

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76. Entrez PubMed Although ataxias of stance and gait are frequent manifestations of cerebellardisease, the number of human studies examining stance or gait in cerebellar http://www.jneuroengrehab.com/pubmed/11685415

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77. Spinocerebellar Ataxia In other words, stay tuned, but we aren t there yet. There are numerous nongeneticcauses of cerebellar disease. which are not covered here. http://www.dizziness-and-balance.com/disorders/central/cerebellar/sca.htm

Spinocerebellar Degenerations Timothy C. Hain, MD Please read our Return to Index Page last modified: August 6, 2005 Figure 1: Sagittal MRI of person with an inherited cerebellar degeneration (of unknown origin). This MRI shows prominent atrophy (shrinkage) of the midline (called the vermis). The main goal of this page is to serve as a repository for recent information about inherited cerebellar degenerations. It is not comprehensive, but we hope that it might be of some use to individuals searching for information about these rare conditions on the web. We highly recommend also using the OMIM database , which can be accessed on the web. A large number of the genetic ataxias can be tested for using contemporary methodology. An example of a lab that does this is Athena Most of the information here concerns inherited conditions, as there is considerable new data derived from researchers using a nearly complete map of the human genome (your tax dollar is doing some good !), and improvements in the technology of molecular biology. It seems quite feasible that within the next decade, we may be able to determine the gene that is damaged in most inherited cerebellar degenerations. As these data become known, it may also be possible to target specific therapies, probably over the next 2 decades. In other words, stay tuned, but we aren't there yet. There are numerous non-genetic causes of cerebellar disease.

78. Alphabetic List, Diseases And Disorders Acquired Facial Neuropathy (see Facial Nerve diseases) Arachnoidal CerebellarSarcoma, Circumscribed (see Medulloblastoma) Arachnoiditis http://www.mic.ki.se/Diseases/alphalist.html

search search staff sitemap ABOUT KAROLINSKA INSTITUTET ... print this page Alphabetic List of Specific Diseases/Disorders Start Page A B C ... Z A A-alphalipoprotein Neuropathy (see Tangier Disease) Abdominal Cramps (see Colic) Abdominal Delivery (see Cesarean Section) Abdominal Injuries Abnormalities Abortion, Induced Abortion, Spontaneous ... Abscess, Amebic (see Amebiasis) Abscess, Retropharyngeal (see Retropharyngeal Abscess) Acantholysis Bullosa (see Epidermolysis Bullosa) Acariasis (see Mite Infestations) Achalasia, Esophageal (see Esophageal Achalasia) Achondroplasia Achromatopsia (see Color Vision Defects) Acid-Base Imbalance Acidosis Acidosis, Diabetic (see Diabetic Ketoacidosis) Acne (see Acne Vulgaris) Acne Vulgaris Acoustic Neuroma (see Neuroma, Acoustic) Acquired Childhoood Aphasia with Convulsive Disorder (see Landau-Kleffner Syndrome) Acquired Facial Neuropathy (see Facial Nerve Diseases) Acquired Hyperostosis Syndrome Acquired Immunodeficiency Syndrome Acrocephalosyndactylia Acrocephaly (see Craniosynostoses) Acrodysplasia V (see Langer-Giedion Syndrome) Acromegaly Actinic Reticuloid Syndrome (see Photosensitivity Disorders) Actinomyces Infections (see Actinomycosis) Actinomycosis Action Tremor (see Tremor) Acupuncture Therapy Acute Autoimmune Neuropathy (see Guillain-Barre Syndrome) Acute Confusional Migraine (see Migraine) Acute Confusional Senile Dementia (see Alzheimer Disease) Acute Inflammatory Demyelinating Polyradiculoneuropathy (see Guillain-Barre Syndrome) Acute Inflammatory Polyneuropathy (see Guillain-Barre Syndrome)

79. IVertigo.net Vertigo , Central Neurologic Causes,   B.Todd Troost Demyelinating disease multiple sclerosis, postinfectious demyelination, posterior fossa such as hematoma, metastatic tumor, and cerebellar infarction) http://ivertigo.net/vertigo/vercentral.html

CENTRAL NEUROLOGIC CAUSES Central pathological causes of vertigo result from dysfunction of the vestibular portion of the VIII nerve, the vestibular nuclei within the brainstem and their central connections. (Table 4): TABLE 4. Central neurological causes of vertigo* 1. Brainstem ischemia and infarction 2. Demyelinating disease: multiple sclerosis, postinfectious demyelination, remote effect of carcinoma 3. Cerebellopontine angle tumor; acoustic neuroma, meningioma, cholesteatoma, metastatic tumor, etc. 4. Cranial neuropathy; focal involvement of VIII nerve or in association with systemic disorders 5. Intrinsic brainstem lesions (tumor, arteriovenous malformation, trauma-rare 6. Other posterior fossa lesions (primarily other intrinsic or extra-axial masses of the posterior fossa such as hematoma, metastatic tumor, and cerebellar infarction) 7. Seizure disorders-rare

80. Laboratory Medicine Neurology Widebased stance in animals with vestibular or cerebellar disease, or with alesion involving proprioceptive pathways between the spinal cord and the http://wsava2005.com/memorias/Diezmo1_2_3_4/03087LuisadeRisioNeurologicexaminati

Laboratory Medicine Neurology NEUROLOGIC EXAMINATION AND LESION LOCALIZATION Luisa De Risio, DMV, Dipl. ECVN, Animal Health Department, Faculty of Veterinary Medicine, University of Parma, Italy The neurological examination is the basic and most important tool of clinical neurology. The neurological examination allows: to determine if the nervous system is affected by a disease process to localize the lesion within the nervous system (neuroanatomic diagnosis) to assess the severity of dysfunction to construct a list of differential etiological diagnoses (along with the information provided by the signalment, the history and the general physical examination) These information are necessary to establish which diagnostic procedures are required (CBC, chemistry profile, serology, urinalysis, CSF analysis, survey radiographs, myelography, CT, MRI, electrodiagnostics, muscle/nerve biopsy, etc). I would like to emphasize that performing the neuroanatomic diagnosis should always precede consideration of the differential etiological diagnoses and therefore of the diagnostic work-up.

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