Orientador: Danilo Domingues Millen / Resumo: O objetivo deste estudo foi avaliar os efeitos da duração do período de adaptação à dieta de alto teor de concentrado sobre o desempenho, comportamento ingestivo, características de carcaça, saúde do rúmen e digestibilidade do amido, FDN e MS em bovinos Nelore e ½ Angus/Nelore terminados em confinamento. Setenta e dois bovinos machos (com 313,5 kg ± 24,5 em média), não castrados, 36 da raça Nelore e 36 ½ Angus/Nelore, provenientes de sistema de recria em pasto, foram aleatorizados e mantidos em 24 baias (3 animais por baia) de chão batido (24 m² e 2,0 m de cocho por animal), de acordo com os tratamentos: bovinos Nelore adaptados por 9 dias, bovinos Nelore adaptados por 14 dias, bovinos ½ Angus/Nelore adaptados por 9 dias, e bovinos ½ Angus/Nelore adaptados por 14 dias, constituindo-se assim delineamento experimental em blocos casualizados em arranjo fatorial 2 × 2 (2 grupos genéticos e 2 durações do período de adaptação) com medidas repetidas no tempo, as quais foram tomadas de acordo com a variável analisada. Cada tratamento foi composto por 6 baias, as quais foram consideradas as unidades experimentais neste estudo. Após 9 ou 14 dias de adaptação, os animais receberam a ração final com 86% de concentrado. No início do período experimental e a cada 28 dias todos os animais foram pesados. A IMS foi medida todos os dias, para então calcular-se ganho de peso diário e conversão alimentar. Da mesma forma, os animais foram submetidos a avaliações de ultrassonografia no início e no... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The objective of this study was to evaluate the length of adaptation period to high concentrate diets on performance, feeding behavior, carcass traits, rumen health and starch, NDF and DM digestibility of Nellore and ½ Angus/Nellore cattle finished in feedlot. Seventy-two yearling bulls (313.5 kg ± 24.5 on the average), 36 Nellore and 36 ½ Angus/Nellore, backgrounded on pasture were randomly allocated and kept in 24 pens (3 animals/pen) with concrete floor (24 m² and 2,0 m bunk per animal) according to the treatments: Nellore adapted for 9 days, Nellore adapted for 14 days, ½ Angus/Nellore adapted for 9 days, and ½ Angus/Nellore adapted for 14 days, characterizing a randomized block design with a 2 x 2 factorial arrangement of treatments (2 genotypes and 2 lengths of adaptation period) with repeated measures over time according to the dependent variable measured. Each treatment was composed by 6 pens which was considered the experimental unit to this study. After 9 or 14 days of adaptation, yearling bulls received the finishing diet containing 86% concentrate. At the beginning of experimental period and every 28 days, yearling bulls were weighted. Dry matter intake was measure every day, and average daily gain and feed efficiency were calculate. Likewise, the deposition of muscle and fat were evaluate by ultrasound at the beginning and at the end of the study where the yearling bulls were slaughter in a commercial abattoir after 89 days of feed reaching average live body weig... (Complete abstract click electronic access below) / Mestre

Orientador: Valéria Nobre Leal de Souza Oliva / Banca: Paulo Sérgio Patto dos Santos. / Banca: Rodrigo Cardoso Rabelo. / Resumo: A avaliação da perfusão tecidual com macroparâmetros não permite a detecção precoce de alteração na microvasculatura. A anestesia da gestante requer avaliação da perfusão e a eficácia do lactato na identificação de complicações em crianças após o parto já foi descrita. O presente estudo objetivou validar o lactato sanguíneo e correlacioná-lo a métodos, na avaliação de neonatos de parto normal ou cesariana eletiva sob anestesia geral inalatória. Foram utilizadas oito cadelas para realização de parto normal ou cesariana eletiva, com o protocolo composto de morfina, propofol e sevofluorano. Foram avaliados 24 neonatos de parto normal (GN) e 30 de cesariana (GC), com exames de sangue umbilical no nascimento para dosagem de lactato, hemogasometria, hematócrito, glicose e eletrólitos. No nascimento e aos 10 minutos de vida foram realizadas avaliações Apgar e neurológica. O lactato foi avaliado aos 10 minutos, 4 e 30 dias de vida. Os filhotes apresentaram acidose respiratória, acidemia e hipoxemia ao nascimento, mais elevada no GC. Os animais do GC apresentaram notas de Apgar e resposta neurológica menores ao nascimento, com melhora aos 10 minutos. O lactato sanguíneo foi maior nos animais do GN no nascimento, e foi maior nos animais que morreram. A correlação entre o lactato e as variáveis ocorreu em GN. O lactato sanguíneo associado aos demais parâmetros foi útil na avaliação dos neonatos do GN, porém nos animais do GC não houve correlação com a condição clínica dos animais no momento do nascimento. O procedimento anestésico influencia nos valores de lactato, e a determinação do melhor intervalo para sua avaliação nesses pacientes é necessária. / Abstract: The assessment of tissue perfusion using macro parameters does not allow early detection of changes in the microvasculature. Anesthesia for pregnant patient requires evaluation of perfusion, and the lactate effectiveness in identifying complications in children after birth has been described. This study aimed to validate the blood lactate and its correlation with other methods, in the evaluation of neonates born from vaginal delivery or elective cesarean section under inhalator anesthesia. Eight dogs were used to perform normal delivery or cesarean section, with the protocol consisting of morphine, propofol and sevoflurane. At birth were evaluated 24 neonates born from vaginal delivery (NG) and 30 born from cesarean section (CG) using umbilical blood to test lactate, blood gas, hematocrit, glucose and electrolytes. Apgar score and neurologic tests were performed at birth and at 10 minutes of life. Lactate levels were evaluated at 10 minutes, 4 and 30 days of life. The puppies showed respiratory acidosis, hypoxemia and acidemia at birth, higher in the CG. The animals of CG presented lower Apgar scores and neurological response at birth, which improved in 10 minutes. Blood lactate was higher in NG animals at birth, and was higher in those who died. The correlation between lactate and the variables occurred on NG. Association of blood lactate with other parameters was useful in the evaluation of neonates on NG, but in the animals of CG there was no correlation with the clinical condition of animals at birth. Anesthesia influences the lactate values, and it is necessary to determine the best interval for evaluation in these patients. / Mestre

Orientador: Jose Antonio Rocha Gontijo / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-06T03:50:35Z (GMT). No. of bitstreams: 1 Bento_LedaMarciaAraujo_D.pdf: 18154421 bytes, checksum: cb3c676e5986d07c3462c4afdbcc4d15 (MD5) Previous issue date: 2006 / Resumo: Estudos em animais demonstram que a acidose metabólica promove muitas mudanças morfológicas e bioquímicas nos rins, que estão intimamente associadas com a hipertrofia do órgão Confirmamos que a acidose metabólica crónica causada pela ingestão de cloreto de amónia (NH4Cl), promove a hipertrofia do órgão e também uma diminuição da reabsorção de água e sais pelos rins. Aventamos a hipótese que esses são processos que competem pela energia disponível pelas células tubulares Como a mitocòndria tem sido implicada em uma variedade de processos metabólicos, nós estudamos o comportamento das mitocôndrias isoladas de rins de ratos tratados com NH4Cl As mitocôndrias de rim de ratos (MRR) acidóticos apresentaram uma diminuição de aproximadamente 25% da eficiência da respiração, através do controle respiratório Usando o mesmo substrato (succinato), nós achamos a relação ADP/O significativamente menor nos animais acidóticos quando comparados aos controles Em concordância com esses resultados, o potencial transmembrana mitocondrial, apresentou o tempo de fosforilação aumentado nesses animais, determinado pelo método da safranina. Nenhuma diferença significativa foi observada no potencial em ambas as mitocôndrias. Interessantemente, na determinação do transporte de cálcio, verificamos uma captação inicial mais rápida e maior nas MRR acidóticos, quando comparadas aos controles, mantida equilibrada por mais tempo com a adição do inibidor do poro de transição de permeabilidade mitocondrial, a ciclosporina A (CsA). Não foi observada nenhuma diferença significativa na liberação do cálcio após adição de vermelho de Rutênio (RR) e cloreto de sódio (NaCl). Nós também analisamos todos esses parâmetros em mitocôndrias de fígado de rato, para saber se esse efeito da acidose é particular do rim, ou outros órgãos também apresentam. Não verificamos alterações nas funções mitocondriais, induzidas pela acidose. durante dois dias de tratamento com NH4Cl, nessas mitocôndrias Para sabermos se essas alterações nas mitocôndrias renais estariam relacionadas à proteína desacopladora (UCP), utilizamos em nossos experimentos de controle respiratório inibidores da atividade dessas proteínas CAT, GDP e BSA Observamos indiretamente que a UCP esta ativada nas MRR acidóticos, respondendo o desacoplamento observado na situação de acidose nessas mitocôndrias / Abstract: Studies in animals have shown that metabolic acidosis causes several morphologic and biochemical changes in kidney, which are ultimately associated with organ hypertrophy We have previously shown that chronic metabolic acidosis caused by feeding NH4Cl lead to nephron hypertrophy and to a decreased water-salt reabsortion by the kidneys Since mitochondria have been implicated in a variety of metabolic disorders, we examined energy linked functions in isolated mitochondria from rat kidneys with chronic metabolic acidosis induced by NH4Cl Mitochondria from acidotic rats presented resting respiration supported by succinate oxidation 25% slower when compared to control mitochondria Using the same substrate we found an ADP/O ratio of 1,4 in control and 1,1 in isolated mitochondria from acidotic rats. Accordingly, the transient decrease in ?? that occurs during ADP phosphorylation was much larger in mitochondria from acidotic rat kidneys as evidenced by the safranine method No significant difference in ?? could be detected in both types of mitochondria using this method. Interestingly, determination of Ca2+ transport showed a faster rate of initial Ca2+ up take by mitochondria from acidotics and a lower concentration of extramitochondrial Ca2+ under steady state conditions (Ca2+ set point) by these mitochondria compared to control mitochondria In contrast, no significant differences could be detected in rates of Na+ or ruthenium red induced Ca2+ efflux. The data provided evidence that: succinate oxidation is inhibited in mitochondria isolated from acidotic rats while the Ca2+ influx pathway is activated in these mitochondria / Doutorado / Doutor em Farmacologia

O presente trabalho avaliou a possibilidade de duas diferentes quantidades de melão, com alto teor de açúcares, em causar acidose ruminal em ovinos não adaptados. Foram utilizados 12 ovinos mestiços Santa Inês, machos, providos de cânula ruminal, com 25 kg de P.V. e 8 m de idade, que nunca receberam rações concentradas, frutas ou raízes, anteriormente. Os animais foram mantidos em baias coletivas com dieta basal composta de volumoso (feno de capim Cynodon dactylon - Coast cross) na base de 2,3% de seus pesos vivos, providos de água e sal mineralizado à vontade. Após 30 dias de adaptação, os ovinos foram distribuídos aleatoriamente em dois grupos iguais, assim constituídos: G1: 25% da M.S. de melão e G2: 75% de melão. O melão inteiro, sem as sementes, com 12º Bx de grau Brix (120 g sacarose/kg polpa e 7,8 % M.S.) foi triturado administrando-se pela cânula ruminal 130 g e 389,4 g de sacarose no G1 e G2, respectivamente, após os animais permanecerem em jejum por 12 horas. Foram realizados exames físicos, coletadas amostras de fluido ruminal e sangue nos seguintes tempos após a administração do substrato: zero, 3, 6, 12, 18 e 24 h. Os animais do G1 apresentaram durante a 3ª a 6ª h quadro de acidose ruminal por AGVs (subaguda) caracterizado por pH ruminal ligeiramente inferior a 5,6; discreto aumento no teor de ácido láctico-L, no potencial de oxirredução (POR) e no tempo de redução do azul de metileno (RAM) ruminais, sem que os animais manifestassem quaisquer sintomatologia clínica. Os animais do G2 desenvolveram quadro de acidose láctica ruminal, evidenciado pelo baixo pH (< 5,0), altos teores de lactato-L, valores de POR e da RAM, aumento temporário de osmolaridade ruminal, porém os animais não se tornaram desidratados, e apresentaram uma intensa diurese enquanto perdurou marcada hiperglicemia. Os animais evoluíram para uma moderada acidose metabólica sistêmica. A taquicardia e a taquipnéia foram provocadas pelo aumento da circunferência abdominal, devido ao grande volume de conteúdo administrado pela cânula, não sendo no caso da taquicardia gerada pelo aumento do volume globular, oriunda da desidratação e encontrada classicamente nesse tipo de acidose. A diminuição dos movimentos do rúmen foi correspondente a queda no pH ruminal e elevação dos teores de lactato-L no rúmen. O baixo pH e os altos valores de POR interferiram no aumento do tempo da RAM. Não se recomenda o oferecimento de altas quantidades de melão (75% da M.S.), porém acredita-se que os ovinos não terão problema de ingerir a quantia de 25% da M.S., desde que se tomem cuidados para a adaptação gradual dos animais ao substrato. / The present study evaluated the possibility of ruminal acidosis being caused by two distinct amounts of melon with high sugar content on non-adapted sheep. Twelve crossbreed Santa- Inês sheep with rumen cannula were used. Animals were male, 8 months old, 25 kg B. W., and had never eaten concentrated feed, fruits or roots of any kind before. They were kept in collective pens and their basal diet was composed on 2.3% of their B. W. of Coast cross (Cynodon dactylon) hay, water, and mineral salt Ad libitum. After 30 days of adaption, animals were divided in two groups: G1: 25% of D. M. of melon; and G2: 75% of D. M. of melon. The animals fasted for 12 hours. Then the whole melon, without seeds, 12º Bx (120 g sucrose/kg pulp and 7.8% D. M.) was crushed and administered through the rumen cannula, it represented 130 g and 389.4 g of sucrose on G1 and G2, respectively. Physical examinations along with the collection of ruminal fluid and blood were done after the administration of the substrate at: 0, 3, 6, 12, 18, and 24 h. G1 sheep presented VFAs ruminal acidosis (sub-acute) between the 3ª and 6ª h, characterized by rumen pH slightly inferior to 5.6, discrete lactic-L acid content increase, increased redox potential (RP) and methylene blue redox (MBR) time of the ruminal fluid, and lack of clinical signs. G2 presented lactic ruminal acidosis, ruminal fluid pH < 5.0, high lactate-L content, increased RP and MBR time, increased ruminal fluid osmolarity, no dehydration, and increased diuresis during hypoglycemic period. Animals had moderate systemic acidosis. Tachycardia and tachypnea were caused by an increase on abdominal circumference, resultant of the large amount of melon administrated through the cannula. Therefore these conditions were not caused by the increased globular volume and dehydration typically found on this type of acidosis. Reduced ruminal movements frequency corresponded to decreased ruminal pH and increased Lactate-L ruminal content. Reduced rumen pH and increased RP caused the increase on MBR time. Therefore, it is not recommended offering of large amounts of melon (75% da D.M.) on the diet, though it is believed that sheep will have no problems ingesting 25% of D.M. of melon, whenever the proper gradual adaptation is performed previously.

Diabetes Mellitus (DM) is on the increase globally, with further increases expected in developing countries, such as South Africa. World Health Organization (Medical Chronicle, 2006:14) estimations indicate that the number of DM sufferers will double over the next 30 years. This increasing number of diabetics is expected to have enormous economical implications. One of the consequences of the increase in DM sufferers is the increase in deaths due to diabetes related complications. In 2000, 3.2 million people died of DM and diabetes related complications compared with 3 million who died from HIV/AIDS related illnesses (William & Pickup, 2004:64). Health services are financially burdened by DM complications that result in heavy demands in both direct costs of hospitalization and medication as well as indirect costs such as manpower of staff involved in the care of the patient (Leuner, 2000:410). Diabetic ketoacidosis (DKA) is a prominent life-threatening complication of type 1 diabetes mellitus and, if not treated medically, it can lead to coma and death. DKA accounts for 14 per cent of all diabetic related hospital admissions and has a mortality rate of 5 to 10 per cent (Pickup & Williams, 2003:1). Rapid identification of DKA is necessary to improve patient care. George- Gray and Chernecky (2002:96) suggest patient outcomes are affected by the nurse’s ability to recognize the clinical features of DKA. It is important, therefore, for the nurses to understand the signs and symptoms and treatment of this diabetes related complication. National health policies and treatment guidelines should be aimed at addressing DKA treatment through setting guidelines for diabetic care (Peters, 2004:22). The main goal of this study was to determine registered nurses’ knowledge of DKA and to develop guidelines to assist registered nurses in providing adequate and effective health care to prevent DKA reoccurrence. The research study is based pm Bergam’s model on quality of care and accountability. Bergman claims that several preconditions must be filled in order to be accountable, including: • Accountability • Responsibility • Authority • Ability (Bergman (1982:8) emphasizes that ability reflects the registered nurses’ accountability, which is composed of values, knowledge and skills.) The study was divided into two phases. Phase one determined registered nurses’ knowledge related to the management of DKA. Phase two of the study included the developing guidelines to assist registered nurses in providing adequate and effective health care to patients with DKA. The design of the study is quantitative, explorative, descriptive and contextual; a survey was performed using a questionnaire based on a literature study. Ethical principals were maintained throughout the study. Permission to the study was sought from the Local Health Authorities and the heads of department where the research was undertaken. Findings of the research were analysed and discussed in the research. The knowledge of the majority of the respondents was found to be average. Out of the thirty- two respondents 52.8 percent possessed adequate knowledge the management of DKA and 63.4 percent possessed adequate knowledge on the management of DM. Two recommendations to assist registered nurses in the implementation of guidelines of the recommendations were also provided.

Orientadores: Caroline Dário Capitani, Marcelo Saldanha Aoki / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Aplicadas / Made available in DSpace on 2018-08-27T04:18:29Z (GMT). No. of bitstreams: 1 Cunha_VivianCostaResende_M.pdf: 1876869 bytes, checksum: ae33265fb59060e2348349bf854e1379 (MD5) Previous issue date: 2014 / Resumo: O presente estudo teve os seguintes objetivos: caracterizar as demandas fisiológicas de diferentes rotinas de treinamento e, avaliar o efeito da suplementação de citrato de sódio sobre o desempenho de habilidades específicas do Tênis após uma simulação de partida. Dez jogadores de Tênis juvenis, do sexo masculino (17,0 ± 1,2 anos; estatura: 176,7 ± 5,2 cm; peso: 68,4 ± 7,9 kg; gordura corporal: 11,7 ± 1,4%) participaram dos estudos. No primeiro estudo foram realizadas quatro rotinas de treinamento, cada qual com seis pontos. As rotinas se diferiram entre si pelo número de rebatidas por ponto (duas, quatro, sete e dez rebatidas por ponto). Foram avaliados frequência cardíaca (FC), percepção subjetiva de esforço (PSE) e concentração de lactato ([La]) após o primeiro, terceiro e sexto ponto de cada rotina. O segundo estudo consistiu na suplementação de citrato de sódio (0,5 g.kg-1 de peso) ou placebo - NaCl (0,1 g.kg-1 de peso). Após 120 minutos da ingestão do suplemento, foram realizados testes de habilidades específicas no Tênis (Loughborough Tennis Skill Test ¿ LTST e Repeated Sprint Ability Shuttle Test ¿ RSA) antes e após a simulação de uma partida de 60 minutos. Observou-se que todos os parâmetros avaliados no primeiro estudo (FC, PSE e [La]) aumentaram progressivamente durante as rotinas de treinamento, à medida que se aumentava o número de rebatidas por ponto, indicando que rotinas de treinamento com sete e dez rebatidas por ponto induziram respostas maiores associadas ao nível de estresse do que observado nas rotinas mais curtas. No segundo estudo observou-se aumento significante (p<0,05) da [HCO3-] e do excesso de base no grupo suplementado com citrato de sódio comparado ao placebo. Após a simulação de partida houve aumento da [La] e de pH no grupo suplementado com citrato de sódio ([La]: 5,46 mmol.L-1; pH: 7,48) comparado ao grupo placebo ([La]: 2,28 mmol.L-1; pH: 7,34). A capacidade de sprints repetidos avaliada pelo RSA não apresentou diferença (p>0,05) entre os testes pré e pós simulação de partida. Apesar do total de golpes desenvolvidos pelos jogadores não apresentarem diferença significante (p>0,05) antes e após a simulação de partida, observou-se declínio (p<0,05) na consistência dos golpes para o grupo placebo (pré: 53,5%; pós: 40,4%) quando comparado ao grupo suplementado com citrato de sódio (pré: 50,2%; pós: 58,5%). Portanto, sugere-se que a suplementação de citrato de sódio pode prevenir o declínio do desempenho das habilidades específicas do Tênis, após uma simulação de partida / Abstract: This study had the following objectives: To characterize the physiological demands of different training routines and evaluate the effect of sodium citrate supplementation on the performance of specific tennis skills after a simulated match. Ten young male tennis players (17,0 ± 1,2 years old; height: 176,7 ± 5,2 cm; weight: 68,4 ± 7,9 kg; body fat: 11,7 ± 1,4%) participated in the studies. In the first study, four training routines were performed, each with six points. The routines differed according to the number of hits per point (two, four, seven and ten hits per point). Heart rate (HR), rating of perceived exertion (RPE) and blood lactate concentration ([La]) were assessed after the first, third and sixth points of each routine. The second study consisted of supplementing with sodium citrate (0,5 g.kg-1 body weight) or placebo - NaCl (0,1 g.kg-1 wt). One-hundred and twenty minutes after taking the supplement, tests were performed for specific tennis skills (Loughborough Tennis Skill Test - LTST and Repeated Sprint Ability Test Shuttle - RSA) before and after simulating a match of 60 minutes. All parameters evaluated in the first study (HR, RPE and [La]) were found to increase progressively during training routines, as the number of hits per point increased, indicating that training routines with seven and ten hits per point were associated with higher levels of stress than for the shorter routines. The second study demonstrated a significant increase (p <0,05) in [HCO3-] and base excess in the group supplemented with sodium citrate, compared with placebo. After the match simulation, increases were observed in [La] and pH in the group supplemented with sodium citrate ([La]: 5,46 mmol.L-1; pH: 7,4), compared to the placebo group ([La]: 2,28 mmol.L-1; pH: 7,34). The ability to repeat sprints, as evaluated by RSA, did not differ (p > 0,05) between the pre and post match simulation. Although the total number of hits performed by the players was not significantly different (p>0,05) before and after starting the simulation, we observed a decrease (p<0,05) in the consistency of the hits in the placebo group (pre: 53,5%; post: 40,4%), when compared to the group supplemented with sodium citrate (pre: 50,2%; post: 58,5%). Therefore, we suggest that supplementation of sodium citrate may prevent the decline in performance of specific tennis skills after a simulated match / Mestrado / Nutrição / Mestra em Ciências da Nutrição e do Esporte e Metabolismo

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A fairly large portion of patients receiving surgical or intensive care will need mechanical ventilation at some point. The potential ventilator-induced lung injury (VILI) is thus of interest. One of the main causal factors in VILI is the cyclic energy shifts, i.e. tidal volumes, in the lung during mechanical ventilation. The problem can be approached in two ways. Firstly, one can utilize apneic oxygenation and thus not cause any tidal injuries at all. Secondly, and more traditionally, one can simply lower the tidal volumes and respiratory rates used. The following describes a series of animal experiments exploring these options. In the first two papers, I explored and improved upon the methodology of apneic oxygenation. There is a generally held belief that it is only possible to perform apneic oxygenation by prior denitrogenation and by using 100% oxygen during the apnea. As 100% oxygen is toxic, this has prevented apneic oxygenation from more widespread use. The first paper proves that it is indeed possible to perform apneic oxygenation with less than 100% oxygen. I also calculated the alveolar nitrogen concentration which would conversely give the alveolar oxygen concentration. The second paper addresses the second large limitation of apneic oxygenation, i.e. hypercapnia. Using a high dose infusion of tris(hydroxymethyl)aminomethane (THAM) buffer, a pH &gt; 7.2 could be maintained during apneic oxygenation for more than 4.5 hours. In the last two papers, THAM’s properties as a proton acceptor are explored during respiratory acidosis caused by very low volume ventilation. In paper III, I found that THAM does not, in the long term, affect pH in respiratory acidosis after stopping the THAM infusion. It does, however, lower PVR, even though the PaCO2 of THAM-treated animals had rebounded to levels higher than that of the controls. In the last experiment, I used volumetric capnography to confirm our hypothesis that carbon dioxide elimination through the lungs was lower during the THAM infusion. Again, the PaCO2 rebounded after the THAM infusion had stopped and I concluded that renal elimination of protonated THAM was not sufficient.