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We developed an impedance bridge that operates at cryogenic temperatures (down to 60 mK) and in perpendicular magnetic fields up to at least 12 T. This is achieved by mounting a GaAs HEMT amplifier perpendicular to a printed circuit board containing the device under test and thereby parallel to the magnetic field. The measured amplitude and phase of the output signal allows for the separation of the total impedance into an absolute capacitance and a resistance. Through a detailed noise characterization, we find that the best resolution is obtained when operating the HEMT amplifier at the highest gain. We obtained a resolution in the absolute capacitance of 6.4 aF/Hz at 77 K on a comb-drive actuator while maintaining a small excitation amplitude of 15 kBT/e. We show the magnetic field functionality of our impedance bridge by measuring the quantum Hall plateaus of a top-gated hBN/graphene/hBN heterostructure at 60 mK with a probe signal of 12.8 kBT/e.
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We report on the fabrication and characterization of an optimized comb-drive actuator design for strain-dependent transport measurements on suspended graphene. We fabricate devices from highly p-doped silicon using deep reactive ion etching with a chromium mask. Crucially, we implement a gold layer to reduce the device resistance from ≈51.6 kΩ to ≈236 Ω at room temperature in order to allow for strain-dependent transport measurements. The graphene is integrated by mechanically transferring it directly onto the actuator using a polymethylmethacrylate membrane. Importantly, the integrated graphene can be nanostructured afterwards to optimize device functionality. The minimum feature size of the structured suspended graphene is 30 nm, which allows for interesting device concepts such as mechanically-tunable nanoconstrictions. Finally, we characterize the fabricated devices by measuring the Raman spectrum as well as the a mechanical resonance frequency of an integrated graphene sheet for different strain values.
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We present magneto-Raman spectroscopy measurements on suspended graphene to investigate the charge carrier density-dependent electron-electron interaction in the presence of Landau levels. Utilizing gate-tunable magnetophonon resonances, we extract the charge carrier density dependence of the Landau level transition energies and the associated effective Fermi velocity v_{F}. In contrast to the logarithmic divergence of v_{F} at zero magnetic field, we find a piecewise linear scaling of v_{F} as a function of the charge carrier density, due to a magnetic-field-induced suppression of the long-range Coulomb interaction. We quantitatively confirm our experimental findings by performing tight-binding calculations on the level of the Hartree-Fock approximation, which also allow us to estimate an excitonic binding energy of ≈6 meV contained in the experimentally extracted Landau level transitions energies.
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Ozone reacts with the musk fragrances tonalide and galaxolide with rate constants of 8 M(-1)s(-1) and 140 M(-1)s(-1), respectively. In wastewater, ozone eliminates only the more reactive compound, galaxolide, in competition with its reaction with the wastewater matrix. As both compounds are also stripped in a bubble column, tonalide is also eliminated to some extent.
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Benzopiranos/química , Ozônio/química , Perfumes/química , Tetra-Hidronaftalenos/química , Poluentes Químicos da Água/química , Purificação da Água/métodos , Animais , Benzopiranos/análise , Íons/química , Estrutura Molecular , Tetra-Hidronaftalenos/análise , ResíduosRESUMO
Recent aircraft and satellite laser altimeter surveys of the Amundsen Sea sector of West Antarctica show that local glaciers are discharging about 250 cubic kilometers of ice per year to the ocean, almost 60% more than is accumulated within their catchment basins. This discharge is sufficient to raise sea level by more than 0.2 millimeters per year. Glacier thinning rates near the coast during 2002-2003 are much larger than those observed during the 1990s. Most of these glaciers flow into floating ice shelves over bedrock up to hundreds of meters deeper than previous estimates, providing exit routes for ice from further inland if ice-sheet collapse is under way.
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Neonatal Escherichia coli meningitis is a serious disease with high mortality and poor outcome. Ventriculitis, brain abscess and subdural empyema are frequent, with no homogeneous recommendations available for these complications. The case of a newborn infant who developed sepsis and meningitis caused by E. coli is presented. During intravenous treatment with ampicillin, cefotaxime and gentamycin in recommended doses, the patient developed severe subdural abscesses detected on MRI. After consequent antibiotic therapy over 2 months with fosfomycin, amikacin and meropenem the patient improved clinically and the abscesses regressed and disappeared without neurosurgical intervention. At the age of 6.5 months the infant is healthy and well developed. The conservative treatment of subdural abscesses complicating neonatal Escherichia coli meningitis without neurosurgical intervention is possible. The treatment of the individual case should be discussed between pediatrician and neurosurgeon.
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Quimioterapia Combinada/uso terapêutico , Empiema Subdural/tratamento farmacológico , Infecções por Escherichia coli/tratamento farmacológico , Meningite devida a Escherichia coli/tratamento farmacológico , Amicacina/administração & dosagem , Encéfalo/patologia , Ecoencefalografia , Empiema Subdural/diagnóstico , Infecções por Escherichia coli/diagnóstico , Feminino , Fosfomicina/administração & dosagem , Humanos , Recém-Nascido , Terapia Intensiva Neonatal , Imageamento por Ressonância Magnética , Meningite devida a Escherichia coli/diagnóstico , Meropeném , Testes de Sensibilidade Microbiana , Equipe de Assistência ao Paciente , Tienamicinas/administração & dosagem , Resultado do TratamentoRESUMO
BACKGROUND: Capillary leak syndrome (CLS) is associated with increased morbidity and mortality in preterm newborns (PN) with sepsis or necrotizing enterocolitis. PATIENTS AND METHODS: In order to provide improved standards for measuring edema and for the definition of CLS, subcutaneous-thoracic ratios (S/T) were calculated from 821 anteroposterior supine chest radiographs of 119 PN with a birth weight below 1500 g. The S/T was computed by 100 % minus ratio of dividing the outer margins of the eighth rib by the total diameter of the thorax at the same position. Birth weight, gestational age, need for assisted ventilation and the position of the diaphragm did not significantly affect S/T. The S/T drifted downwards slightly with postnatal age. RESULTS: To provide normal standards of S/T in PN, the ratio was calculated in percentiles and the higher percentiles correlated with diseases. 771 S/T were lower than 10.1 % (95th percentile), 21 were 10.1 - 12.6 % (97.5th percentile) and 20 were even higher. 3 of the 100 PN (84 %) with an S/T < 10.1 % died because of extreme immaturity. Eight patients (6.7 %) had an S/T between the 95th and the 97.5th percentile in at least one of their radiographs. Four of them had a respiratory distress syndrome and one died. Eleven PN had an S/T > 12.6 %. All of them showed a multiple organ failure and four died. When the SIT was > 15 % the edema became visible. A CLS was diagnosed in two PN with an S/T > 20 %. CONCLUSIONS: The threshold for the capillary leak syndrome was found to be 12.6 % also in reference to the course of diseases. The S/T is a useful tool because it is simple to measure and calculate, and is available from a single frontal film. The ratio can measure objectively the edema and the CLS in PN.
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Síndrome de Vazamento Capilar/diagnóstico , Recém-Nascido de muito Baixo Peso , Radiografia Torácica , Dobras Cutâneas , Síndrome de Vazamento Capilar/mortalidade , Síndrome de Vazamento Capilar/fisiopatologia , Edema/diagnóstico , Edema/fisiopatologia , Enterocolite Necrosante/diagnóstico , Enterocolite Necrosante/mortalidade , Enterocolite Necrosante/fisiopatologia , Feminino , Mortalidade Hospitalar , Humanos , Recém-Nascido , Masculino , Insuficiência de Múltiplos Órgãos/diagnóstico , Insuficiência de Múltiplos Órgãos/mortalidade , Insuficiência de Múltiplos Órgãos/fisiopatologia , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Medição de Risco , Estatística como Assunto , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/mortalidade , Síndrome de Resposta Inflamatória Sistêmica/fisiopatologiaRESUMO
Hydroxyl radicals were generated in the Fenton reaction at pH 4 (Fe(2+) + H(2)O(2) --> Fe(3+) + .OH + OH-, k approximately equal to 60 L mol(-1) s(-1)) and by pulse radiolysis (for the determination of kinetic data). They react rapidly with 1,3-dimethyluracil, 1,3-DMU (k = 6 x 10(9) L mol(-1) s(-1)). With H(2)O(2) in excess and in the absence of O(2), 1,3-DMU consumption is 3.3 mol per mol Fe(2+). 1,3-DMUglycol is the major product (2.95 mol per mol Fe(2+)). Dimers, prominent products of .OH-induced reactions in the absence of Fe(2+)/Fe(3+) (Al-Sheikhly, M.; von Sonntag, C. Z. Naturforsch. 1983, 31b, 1622) are not formed. Addition of .OH to the C(5)-C(6) double bond of 1,3-DMU yields reducing C(6)-yl 1 and oxidizing C(5)-yl radicals 2 in a 4:1 ratio. The yield of reducing radicals was determined with tetranitromethane by following the buildup of nitroform anion. Reaction of 1 with Fe(3+) that builds up during the reaction or with H(2)O(2) gives rise to a short-chain reaction that is terminated by the reaction of Fe(2+) with 2, which re-forms 1,3-DMU. In the presence of O(2), 1.1 mol of 1,3-DMU and 0.6 mol of O(2) are consumed per mol Fe(2+) while 0.16 mol of 1,3-DMU-glycol and 0.17 mol of organic hydroperoxides (besides further unidentified products) are formed. In the presence of O(2), 1 and 2 are rapidly converted into the corresponding peroxyl radicals (k = 9.1 x 10(8) L mol(-1) s(-1)). Their bimolecular decay (2k = 1.1 x 10(9) L mol(-1) s(-1)) yields approximately 22% HO(2)./O(2).(-) in the course of fragmentation reactions involving the C(5)-C(6) bond. Reduction of Fe(3+) by O(2).(-) leads to an increase in .OH production that is partially offset by a consumption of Fe(2+) in its reaction with the peroxyl radicals (formation of organic hydroperoxides, k approximately 3 x 10(5) L mol(-1) s(-1); value derived by computer simulation).
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DNA/química , Uracila/análogos & derivados , Uracila/química , Simulação por Computador , Dano ao DNA , Compostos Férricos/química , Compostos Ferrosos/química , Peróxido de Hidrogênio/química , Radical Hidroxila/química , Cinética , Modelos Químicos , Oxirredução , Oxigênio/química , Radiólise de ImpulsoAssuntos
Sistema Digestório/embriologia , Proteínas de Homeodomínio/metabolismo , Fígado/embriologia , Peixe-Zebra/embriologia , Peixe-Zebra/genética , Animais , Sistema Digestório/crescimento & desenvolvimento , Sistema Digestório/metabolismo , Expressão Gênica , Proteínas de Homeodomínio/genética , Fígado/crescimento & desenvolvimento , Fígado/metabolismo , Morfolinas/metabolismo , Mutação/genética , Oligonucleotídeos Antissenso/genética , Oligonucleotídeos Antissenso/metabolismo , Pâncreas/embriologia , Pâncreas/crescimento & desenvolvimento , Pâncreas/metabolismo , Fenótipo , Proteínas Repressoras , Peixe-Zebra/crescimento & desenvolvimento , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismoRESUMO
INTRODUCTION: Complement activation occurs secondary to a variety of external stimuli. Lactic acidosis has been previously shown to activate the complement factors C3a and C5a. In the present investigation we examined the differential effect of lactic acidosis on anaphylatoxin levels in cord and adult blood. Furthermore we aimed to determine if the entire complement cascade could be activated by lactic acidosis. METHODS: Cord and adult blood samples (n = 20 each) were collected and incubated for one hour in either untreated condition or with the addition of lactate in two concentrations (5.5 mmol/l vs. 22 mmol/l). Following incubation, levels of C3a, C5a and sC5b-9, and blood gas parameters were determined. RESULTS: Anaphylatoxin (C3a and C5a) and sC5b-9 levels increased with the addition of lactate in a dose-dependent manner in cord and adult blood (C3a: 1 h, 5.5 mmo/l, 22 mmol/l: 418/498/622 microg/l in cord blood; 1010/1056/1381 microg/l in adult blood, p<0,05; similar results were found for C5a and sC5b-9). CONCLUSION: Lactic acidosis leads to an activation of the entire complement system in neonates and in adults. This activation is dose-dependent and more pronounced in adults as compared to neonates.
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Acidose Láctica/sangue , Anafilatoxinas/análise , Ativação do Complemento , Complexo de Ataque à Membrana do Sistema Complemento/análise , Adulto , Fatores Etários , Sangue Fetal , Humanos , Recém-NascidoRESUMO
OBJECTIVES: Capillary leak syndrome (CLS) is associated with significantly increased morbidity and occurs after cardiopulmonary bypass in children with congenital heart disease. We investigated the early clinical parameters that predict the development of CLS and examined the relationship between the presence of CLS and complement and contact activation and C1 esterase inhibitor (C1-INH) during and after bypass. DESIGN: In this prospective study we took serial serological measurements of the complement and contact system and C1-INH in a cohort of 27 infants before, during, and up to 96 h after open-heart surgery. RESULTS: Complement and contact activation and a decrease in C1-INH were measured in all infants during and after CPB. Ten infants developed CLS postoperatively. Younger age and longer bypass time were strongly correlated to the development of CLS. No relationship was found between the degree of hypothermia, weight, gender, or cross-clamp time. C1-INH concentration and activity were lower peri- and postoperatively in the CLS group. Infants with CLS had a more pronounced postoperative increase in the C5a and C3a levels, higher postoperative level of factor XIIa, and lower prekallikrein activity than those without CLS. CONCLUSION: Contact and complement activation occurs during cardiopulmonary bypass and contributes to CLS more frequently in infants of a younger age and with a prolonged bypass time. This activation and decrease in C1-INH was strongly expressed in the CLS group, and therefore early substitution of C1-INH may prevent CLS after open-heart surgery in high-risk infants.
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Síndrome de Vazamento Capilar/sangue , Ponte Cardiopulmonar , Ativação do Complemento , Proteínas Inativadoras do Complemento 1/metabolismo , Cardiopatias Congênitas/cirurgia , Complicações Pós-Operatórias , Síndrome de Vazamento Capilar/etiologia , Síndrome de Vazamento Capilar/fisiopatologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Prospectivos , Fatores de TempoRESUMO
The Cx43alpha1 gap junctions play an important role in cardiovascular development. Studies using transgenic mouse models have indicated that this involves an essential role for Cx43alpha1 in modulating neural crest cell motility. We previously showed that a 6.8 kb mouse genomic sequence containing the promoter and upstream regulatory sequences of the Cx43alpha1 gene can drive lacZ reporter gene expression in all neural crest cell lineages in the mouse embryo. To obtain further insights into the sequence motifs and regulatory pathways involved in targeting Cx43alpha1 gene expression in neural crest cells, we assayed the activity of the mouse Cx43alpha1 promoter in evolutionarily distantly related zebrafish embryos. For these studies, the 6.8kb Cx43alpha1 genomic sequence and various deletion derivatives were used to generate GFP or lacZ expression vectors. The transcriptional activities of these constructs were analyzed in vivo after microinjection into one- or two- cell stage zebrafish embryos. These studies indicated that the mouse Cx43alpha1 promoter can drive lacZ expression in neural crest cells in the zebrafish embryos. Analysis by whole mount in situ hybridization showed that the endogenous zebrafish Cx43alpha1 gene is expressed maternally and zygotically, and expression is observed in regions where neural crest cells are found. To further elucidate the developmental regulation of Cx43alpha1 gene expression, we screened a zebrafish BAC library and identified a clone containing the entire zebrafish Cx43alpha1 gene and flanking upstream and downstream sequences. The upstrean Cx43alpha1 promoter sequences from zebrafish, mouse, and human were analyzed for evolutionarily conserved DNA motifs. Overall these studies suggest that the sequence motifs and transcriptional regulation involved in the targeting Cx43alpha1 expression to neural crest cells are evolutionarily conserved in zebrafish and mouse embryos.
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Conexina 43/genética , Conexinas/genética , Junções Comunicantes/metabolismo , Regiões Promotoras Genéticas , Proteínas de Peixe-Zebra/genética , Peixe-Zebra/embriologia , Peixe-Zebra/genética , Animais , Conexina 43/metabolismo , Conexinas/metabolismo , Genes Reporter , Proteínas de Fluorescência Verde , Coração/embriologia , Coração/crescimento & desenvolvimento , Indicadores e Reagentes/metabolismo , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Camundongos , Camundongos Knockout , Crista Neural/citologia , Crista Neural/fisiologia , Análise de Sequência de DNA , Proteínas de Peixe-Zebra/metabolismoRESUMO
OBJECTIVE: To investigate the effect of an intratracheal surfactant fog on oxygenation, blood pressure, distribution, and recovery rate as a pilot study to intratracheal surfactant aerosol. DESIGN: Prospective, randomized study. SETTING: University laboratory. SUBJECTS: A total of 15 New Zealand White rabbits. INTERVENTIONS: The anesthetized ventilated rabbits were surfactant-deprived by repeated lung lavages and then received 200 mg/kg of a 99mTc-labeled porcine surfactant (Curosurf) either as bolus or as intratracheal surfactant fog. MEASUREMENTS AND MAIN RESULTS: Blood gases and pressure were measured and distribution as well as recovery rate of the surfactant determined by means of the radio label (gamma camera images and lung processing with subsequent gamma counter measurements). Respiratory function normalized immediately, no difference could be found between the two groups with regard to PaO2, PaCO2, and blood pressure. Even distribution of the radiolabel was found with both methods, the bolus group showing a higher percentage of lung pieces with label concentrations of double average or more. Recovery rates were 82.5%+/-13.1% (mean +/- SD) in the bolus group and 86.5%+/-7.7% in the fog group. CONCLUSION: Endotracheal surfactant fog application is as effective as bolus instillation and may have a role in the treatment of adult respiratory distress syndrome. It has to be considered as a first step in producing an effective aerosol.
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Produtos Biológicos , Fosfolipídeos , Surfactantes Pulmonares/administração & dosagem , Aerossóis , Análise de Variância , Animais , Pressão Sanguínea/efeitos dos fármacos , Instilação de Medicamentos , Intubação Intratraqueal , Nebulizadores e Vaporizadores , Tamanho da Partícula , Surfactantes Pulmonares/deficiência , Surfactantes Pulmonares/farmacocinética , Surfactantes Pulmonares/farmacologia , Coelhos , Tecnécio/farmacocinética , Distribuição TecidualRESUMO
Comparison of ice discharge from higher elevation areas of the entire Greenland Ice Sheet with total snow accumulation gives estimates of ice thickening rates over the past few decades. On average, the region has been in balance, but with thickening of 21 centimeters per year in the southwest and thinning of 30 centimeters per year in the southeast. The north of the ice sheet shows less variability, with average thickening of 2 centimeters per year in the northeast and thinning of about 5 centimeters per year in the northwest. These results agree well with those from repeated altimeter surveys, except in the extreme south, where we find substantially higher rates of both thickening and thinning.
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Aircraft laser-altimeter surveys over northern Greenland in 1994 and 1999 have been coupled with previously reported data from southern Greenland to analyze the recent mass-balance of the Greenland Ice Sheet. Above 2000 meters elevation, the ice sheet is in balance on average but has some regions of local thickening or thinning. Thinning predominates at lower elevations, with rates exceeding 1 meter per year close to the coast. Interpolation of our results between flight lines indicates a net loss of about 51 cubic kilometers of ice per year from the entire ice sheet, sufficient to raise sea level by 0.13 millimeter per year-approximately 7% of the observed rise.
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UNLABELLED: The aim of the study was to assess the effect of necrotizing enterocolitis (NEC) on neurodevelopmental outcome and growth. Neurodevelopmental outcome of 20 out of 22 suriviving very low birthweight infants (VLBW) diagnosed with NEC between 1992 and 1996 was compared with 40 control infants matched for gestational age and year of admission. Follow-up studies were performed at 12 and 20 mo of corrected age. The German revision of the Griffiths' scales was used for development assessment. Neurodevelopment was significantly delayed in infants with NEC at 12 mo (median general developmental quotient: 90.0 vs 97.8; p = 0.04) and 20 mo (86.4 vs 97.7; p = 0.004) of age. Somatic growth did not differ between infants with and without NEC. Fifty-five percent of infants suffering from NEC but only 22.5% of the infants without NEC were severely retarded (developmental quotient < -2 SD of a control group of healthy newborns) at 20 mo of corrected age. CONCLUSION: Preterm infants developing NEC are at risk for neurodevelopmental impairment and need close neurodevelopmental follow-up for the first years of life.
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Deficiências do Desenvolvimento/etiologia , Enterocolite Necrosante/complicações , Transtornos do Crescimento/etiologia , Recém-Nascido de muito Baixo Peso , Enterocolite Necrosante/fisiopatologia , Feminino , Seguimentos , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Masculino , Insuficiência de Múltiplos Órgãos/etiologia , Índice de Gravidade de DoençaRESUMO
OBJECTIVE: Extremely low birth weight (ELBW) infants frequently undergo transfusion because they are critically ill, often need artificial ventilation, and have the highest blood sampling loss in relation to their weight. During the last decade our transfusion guidelines were changed 3 times to become more restrictive. We hypothesized that these modifications substantially decreased the number of transfusions in our ELBW infants. METHODS: We performed a single-center analysis of 256 infants with birth weights from 500 to 999 g who were admitted from 1989 to 1997 and included 3 study periods, each starting with newly modified transfusion guidelines in April 1989, September 1991, and January 1995. We evaluated prospectively recorded clinical data and retrospective chart analysis for transfusion-related information. RESULTS: The median number of transfusions per infant decreased from 7 in the first period to 2 in the third period, whereas donor exposure decreased from 5 to 1 and blood volume transfused decreased from 131 to 37 mL/kg birth weight (P <.01). The median venous hematocrit measured before transfusion decreased from 43% to 35% in infants who underwent ventilation and from 41% to 31% in spontaneously breathing infants. The median birth weight decreased from 870 to 740 g and the median gestational age from 27 to 25 completed weeks (P <.01). The overall survival rate was 75% and did not change. The incidences of retinopathy, intraventricular hemorrhage, and patent ductus arteriosus remained unchanged. CONCLUSION: Over this 9-year period with increasingly restrictive transfusion guidelines, the transfusion number decreased by 71% and the donor exposure by 80% in ELBW infants without adverse clinical effects.
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Transfusão de Eritrócitos , Doenças do Prematuro/terapia , Recém-Nascido de muito Baixo Peso , Doadores de Sangue , Transfusão de Eritrócitos/estatística & dados numéricos , Eritropoetina/uso terapêutico , Feminino , Hematócrito , Humanos , Recém-Nascido , Masculino , Guias de Prática Clínica como Assunto , Estudos Prospectivos , Proteínas Recombinantes , Taxa de SobrevidaRESUMO
Our aim was to investigate the effect of C1-inhibitor (C1-INH) in a rat model of necrotizing enterocolitis (NEC). Twenty-four anesthetized and artificially ventilated rats received 0.1 mg/kg endotoxin. Fifteen minutes later, the animals in the study group (n = 12) were treated with 200 IU/kg C1-INH whereas the control animals (n = 12) received normal saline. In all animals, FiO(2) was reduced after 90 min from 0.21 to 0.05 and ventilation continued until 180 min or death. All animals developed shock symptoms. Drop in mean arterial blood pressure was more pronounced and survival time was shorter in the control group. Whereas the C1-INH activity increased in the study group, it decreased in the control group. The extent of macroscopic intestinal lesions did not differ between the groups. In conclusion, C1-INH did not prevent shock, but mitigated and delayed its course.
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Proteínas Inativadoras do Complemento 1/uso terapêutico , Enterocolite Necrosante/complicações , Choque/tratamento farmacológico , Animais , Pressão Sanguínea , Via Clássica do Complemento , Modelos Animais de Doenças , Enterocolite Necrosante/induzido quimicamente , Frequência Cardíaca , Lipopolissacarídeos , Masculino , Ratos , Ratos Sprague-Dawley , Choque/etiologia , Choque/fisiopatologiaRESUMO
Aircraft laser-altimeter surveys over southern Greenland in 1993 and 1998 show three areas of thickening by more than 10 centimeters per year in the southern part of the region and large areas of thinning, particularly in the east. Above 2000 meters elevation the ice sheet is in balance but thinning predominates at lower elevations, with rates exceeding 1 meter per year on east coast outlet glaciers. These high thinning rates occur at different latitudes and at elevations up to 1500 meters, which suggests that they are caused by increased rates of creep thinning rather than by excessive melting. Taken as a whole, the surveyed region is in negative balance.