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PubMed1996

Skeletal muscle metabolism during exercise in patients with chronic heart failure.

OBJECTIVE: To investigate the metabolic response of skeletal muscle to exercise in patients with chronic heart failure and determine its relation to central haemodynamic variables. SETTING: University hospital in Sweden. PARTICIPANTS: 16 patients in New York Heart Association class II-III and 10 healthy controls. MAIN OUTCOME MEASURES: Skeletal muscle biopsies were obtained from the quadriceps muscle at rest and at submaximal and maximal exercise. Right sided heart catheterisation was performed in eight patients. RESULTS: The patients had lower maximal oxygen consumption than the control group (13.2 (2.9) v 26.8 (4.4) ml/kg/min, P < 0.001). They had reduced activities of citrate synthetase (P < 0.05) and 3-hydroxyacyl-CoA dehydrogenase (P < 0.05) compared with the controls. At maximal exercise adenosine triphosphate (P < 0.05), creatine phosphate (P < 0.01), and glycogen (P < 0.01) were higher whereas glucose (P < 0.001) and lactate (P < 0.06) were lower in the patients than in the controls. Citrate synthetase correlated inversely with skeletal muscle lactate at submaximal exercise (r = -0.90, P < 0.003). No correlations between haemodynamic variables and skeletal muscle glycogen, glycolytic intermediates, and adenosine nucleotides during exercise were found. CONCLUSION: Neither skeletal muscle energy compounds nor lactate accumulation were limiting factors for exercise capacity in patients with chronic heart failure. The decreased activity of oxidative enzymes may have contributed to the earlier onset of anaerobic metabolism, but haemodynamic variables seemed to be of lesser importance for skeletal muscle metabolism during exercise.

Adenosine Triphosphate↗
PubMed2002

The effect of cephalosporin resistance on mortality in adult patients with nonmeningeal systemic pneumococcal infections.

PURPOSE: To evaluate the clinical relevance of cephalosporin (ceftriaxone/cefotaxime) resistance among patients with nonmeningeal systemic pneumococcal infection. SUBJECTS AND METHODS: From January 1994 to October 2000, we prospectively studied 522 episodes of nonmeningeal systemic pneumococcal infections (448 pneumonias) in 499 adults who were treated according to hospital guidelines. In vitro antibiotic susceptibility, as the minimum inhibitory concentration (MIC), was determined by microdilution method. The MIC methods and breakpoints (cutoffs) were established by the National Committee for Clinical Laboratory Standards. RESULTS: Of the 522 pneumococcal strains, 413 strains (79%) were susceptible to ceftriaxone/cefotaxime, MIC < or =0.5 microg/mL; 79 (15%) were intermediate, MIC = 1 microg/mL; and 30 (6%) were resistant, MIC = 2 microg/mL. After adjusting for several variables, including pneumococcal serogroups/serotypes, infections due to nonsusceptible (intermediate and resistant) pneumococcal strains were independently associated with prior antibiotic therapy, with an odds ratio of 5.9 (95% confidence interval: 2.6 to 13.6). Thirty-day mortality among the 185 patients who were treated with ceftriaxone (1 g/d) or cefotaxime (1.5 g every 8 hours) did not differ by cephalosporin susceptibility: 18% (26/148) among those with susceptible organisms, 13% (3/24) with intermediate organisms, and 15% (2/13) in resistant cases (P = 0.81). CONCLUSION: Ceftriaxone or cefotaxime were effective in treating patients with nonmeningeal systemic pneumococcal infections caused by strains with MIC < or =2 microg/mL. These results support the newly established ceftriaxone/cefotaxime MIC breakpoints (cutoffs) for nonmeningeal pneumococcal infections.

Adult↗
PubMed1984

Genetic control of collagen-induced arthritis in rats: the immune response to type II collagen among susceptible and resistant strains and evidence for multiple gene control.

We evaluated the cellular and humoral immune response to type II collagen and the relative susceptibility to type II collagen-induced arthritis (CIA) in 14 inbred rat strains representing six RT1 specificities and including four congenic strain pairs differing only at RT1, by using a standard protocol with native calf type II collagen as the immunogen: WF(RT1u) was a high responder and susceptible; RT1c , RT1a , and RT1l strains were intermediate responders and, on a strain basis, were variably susceptible or resistant; RT1b and RT1n strains were low responders and resistant to CIA. An intermediate to high immune response to type II collagen, although associated with CIA, was not sufficient for the induction of clinical arthritis. A high degree of cross-reactivity between calf and rat type II collagen was found. No selective, antigen-specific decrease in immune response to rat type II collagen as compared to calf type II collagen was found in the resistant strains. In six strains, resistance correlated with the expression of public Ia antigens cross-reactive with the public Ia antigens of BN. The non-MHC-linked BN genome also exerted a suppressive effect on the incidence and severity of CIA in strains carrying collagen-responder and CIA-susceptible RT1 alleles. Together, the data show that CIA in rats is under the control of multiple genes, both RT1-linked and nonlinked .

Animals↗
PubMed2002

Biotransformation of L-cysteine S-conjugates and N-acetyl-L-cysteine S-conjugates of the sevoflurane degradation product fluoromethyl-2,2-difluoro-1-(trifluoromethyl)vinyl ether (compound A) in human kidney in vitro: interindividual variability in N-acetylation, N-deacetylation, and beta-lyase-catalyzed metabolism.

Fluoromethyl-2,2-difluoro-1-(trifluoromethyl)vinyl ether (FDVE; 1) is a fluoroalkene formed by the base-catalyzed degradation of the anesthetic sevoflurane. FDVE is nephrotoxic in rats. In both rats and humans, FDVE undergoes glutathione-dependent conjugation, cleavage to cysteine S-conjugates, and renal beta-lyase-catalyzed metabolism to reactive intermediates, which may cause nephrotoxicity. Interindividual variability in renal metabolism of FDVE is unknown. Therefore, this investigation quantified beta-lyase-catalyzed bioactivation and N-acetyltransferase-catalyzed inactivation of FDVE cysteine S-conjugates and reactivation of mercapturates by N-deacetylase in cytosol and microsomes from 20 human kidneys. In cytosol, N-acetylation ranged from 0.008 to 0.045 (0.024 +/- 0.01) nmol of mercapturate/mg/min and 0.001 to 0.07 (0.024 +/- 0.02) nmol of mercapturate/mg/min for alkane and alkene cysteine S-conjugates, respectively. Similar results for microsomal N-acetylation were obtained; N-acetylation ranged from 0.005 to 0.055 (0.025 +/- 0.02) nmol of mercapturate/mg/min and 0.001 to 0.06 (0.030 +/- 0.02) nmol of mercapturate/mg/min for alkane and alkene cysteine S-conjugates, respectively. Beta-lyase-catalyzed metabolism to pyruvate varied from 0.004 to 0.14 (0.051 +/- 0.04) nmol/mg/min and from 0.10 to 0.40 (0.26 +/- 0.08) nmol/mg/min for alkane and alkene cysteine-S-conjugates, respectively. N-deacetylation of mercapturates ranged from 0.8 to 2.5 (1.25 +/- 0.57) nmol of cysteine S-conjugate formed/mg/min and 0.05 to 0.37 (0.17 +/- 0.10) nmol of cysteine S-conjugate formed/mg/min for alkane and alkene FDVE mercapturates. Cytosolic cysteine S-conjugates metabolism by renal beta-lyase predominated over N-acetylation (ratio of activities was 0.2-6 and 3-146 for the alkane and alkene cysteine S-conjugates). N-deacetylation predominated over N-acetylation (ratio of activities was 20-205 and 2-54 for alkane and alkene S-conjugates). There was considerable (up to 50-fold) interindividual variability in rates of FDVE toxication (beta-lyase metabolism and N-deacetylation) and detoxication. This interindividual variability may effect individual susceptibility to the nephrotoxicity of FDVE and other haloalkenes.

Acetylation↗
PubMed2000

Treatment with 2% clindamycin vaginal cream prior to first trimester surgical abortion to reduce signs of postoperative infection: a prospective, double-blinded, placebo-controlled, multicenter study.

BACKGROUND: Bacterial vaginosis (BV) and intermediate flora is known risk-factor for postoperative infection after surgical termination of pregnancy. Vaginal application of 2% clindamycin cream is an efficacious treatment for BV, but it is not known whether preoperative administration of clindamycin cream might reduce the signs of post-abortion infection after surgical termination of pregnancy. AIM: To evaluate whether preoperative treatment with clindamycin cream might reduce the signs of post-abortion infection after legal abortion. DESIGN: Prospective, double-blinded, placebo-controlled, multicenter study. MATERIAL AND METHODS: Consecutive women attending for surgical termination prior to 11+4 gestational weeks were approached. We randomized participants to preoperative vaginal treatment with 2% clindamycin cream or placebo cream in a double-blinded fashion. At all visits vaginal smears were air dried on microscopy slides to be stored. The rate of postoperative pelvic infection according to our definition was the main outcome variable, the cure rates of BV and of intermediate flora were secondary outcome variables. RESULTS: Of 1655 enrolled women, 1102 were evaluable for analyses. Fifty-eight women developed signs of post-abortion infection. Preoperative treatment with clindamycin cream significantly (RR: 4.2, 95% C.I. 1.2-15.9) reduced the risk of post-abortion infection among women with abnormal vaginal flora (BV and intermediate flora). Treatment with clindamycin cream in women with normal lactobacilli flora did not demonstrate any difference compared to the non-treatment group. CONCLUSION: Preoperative treatment for at least three days with clindamycin cream significantly reduced the risk for developing signs of post-abortion infection only among women with preoperative abnormal vaginal flora (BV and intermediate flora).

Abortion, Induced↗
PubMed2006

Prognostic variability among nonsmall cell lung cancer patients with pathologic N1 lymph node involvement. Epidemiological figures with strong clinical implications.

BACKGROUND: Patients who have nonsmall cell lung cancer with N1 lymph node status are an intermediate group of patients who have a variable prognosis. Differences in lymph node level (hilar or pulmonary lymph nodes) may influence patient survival. The authors retrospectively analyzed the factors that influenced prognosis, including the level of N1 lymph node involvement. METHODS: The authors used the Tuscan Cancer Registry archives to retrieve records on 2523 patients who had lung tumors diagnosed during the period from 1996 and 1998 in the provinces of Florence and Prato, central Italy. To analyze the survival of patients according to the level of lymph node involvement, the prognoses of patients with nonsmall cell lung cancer who had N1 lymph node status were compared in a population-based case series. Among 112 patients with pathologic N1 status, the following variables were analyzed for their influence on postoperative survival: gender, age, cell type, pathologic tumor status, the number of metastatic lymph nodes, the level of metastatic lymph nodes (hilar or pulmonary), and the type of surgical resection. RESULTS: The 5-year survival rates for patients who had involvement of pulmonary and hilar lymph nodes were 41.2% and 21.8%, respectively (P =.005). A Cox proportional hazards model analysis indicated that the presence of hilar lymph node involvement was an independent prognostic factor. CONCLUSIONS: N1 pathologic lymph node status was identified in a combination of subgroups with different prognoses, and the presence of hilar lymph node disease had prognostic significance. This difference in survival may lead to the use of different therapies for these subgroups of patients with pathologic N1 non-small cell lung cancer.

Adult↗
PubMed1990

Perinatal risk for infants of unmarried mothers over a period of 20 years.

The perinatal events of the infants of 444 unmarried mothers, 3.7% of the total Northern Finland birth cohort from 1966, were compared with those of infants of 11,525 married mothers (95.5%), and a similar comparison was made between 395 (4.2%) unmarried mothers and 7516 (80.3%) married mothers in a second Northern Finland birth cohort in 1985-86. 1336 mothers, 14.3% of the mothers in this later cohort, were cohabiting. Divorced and widowed mothers were excluded from both cohorts. The infants of the unmarried mothers had a significantly lower mean birth weight, were more likely to be small for their gestational age (SGA), of low birth weight (LBW) (below 2500 g) and had a higher incidence of pre-term births than those of the married mothers in both cohorts. Perinatal mortality was significantly higher among the unmarried mothers only in the former cohort. These differences in perinatal events diminished markedly after adjustment for maternal age, parity, height, years of schooling and smoking habits, but did not totally disappear. The difference in the incidence of pre-term births diminished, but remained significant in both cohorts. The difference in mean birth weight, in the incidence of LBW infants and in perinatal mortality remained significantly less favourable to the unmarried mothers only in the 1966 cohort. It seems that the gap between the married and unmarried mothers had diminished. The incidence of SGA infants did not differ significantly between the married and unmarried mothers in either cohort after adjustment for the background variables. The cohabiting mothers formed an intermediate group between the married and single unmarried mothers in respect of perinatal events, but were close to the married mothers. In raw figures, the mean birth weight in this group was significantly lower and the incidence of SGA infants higher than among the married mothers, but these differences also disappeared after adjustment of the background variables.

Body Height↗
PubMed2005

Predicting the overall management outcome in patients with a subarachnoid hemorrhage accompanied by a massive intracerebral or full-packed intraventricular hemorrhage: a 15-year retrospective study.

BACKGROUND: Patients with a subarachnoid hemorrhage (SAH) accompanied by a massive intracerebral hemorrhage (ICH) or a full-packed intraventricular hemorrhage (IVH) have poor outcomes. We evaluated the clinical factors to predict the overall outcome in such patients. METHODS: Data on nontraumatic SAH patients were collected and classified into 3 groups: the pure SAH group (SAH accompanied with neither ICH nor IVH), the ICH group (SAH accompanied with a massive ICH; hematoma 30 mL), and the IVH group (SAH and all ventricles were full-packed with hematoma). One hundred seventy-nine patients were in the ICH group and 109 in the IVH group. We evaluated clinical factors, such as the Hunt & Hess (H&H) score on admission, age, sex, history, rebleeding ratio, and the computerized tomography findings (SAH score). RESULTS: The result of multivariate logistic regression analysis of clinical variables in the ICH group, good and intermediate H&H grades, younger age (<70), no rebleeding, and lower SAH score were associated with a favorable outcome. In the result of the multivariate logistic regression analysis of clinical variables in the IVH group, only a higher SAH score was associated with an unfavorable outcome. CONCLUSIONS: In the ICH group, factors that could be used to predict a favorable outcome included good and intermediate H&H scores (1, 2, and 3) on admission, younger age (<70), and a lower SAH score. In the IVH group, the main factor that could be used to predict a favorable outcome was a lower SAH score.

Adult↗
PubMed1995

Intermediate results from the period of the Congenital Heart Surgeons Transposition Study: 1985 to 1989. Congenital Heart Surgeons Society Database.

BACKGROUND: The period of the Congenital Heart Surgeons Society (CHSS) study (1985 to 1989) provided a transition in the treatment of d-transposition of the great arteries. During this unusual time frame neonatal arterial switch (AS) and neonatal or late atrial baffle repair (Senning) were used in near equal proportion at one reporting institution. All the procedures were performed at this single institution, avoiding the variability intrinsic to a multicenter study. Intermediate follow-up of the results is presented. METHODS: During the period of the CHSS study, January 1985 to March 1989, 46 patients were enrolled in the CHSS study at one institution. Forty-four underwent either neonatal arterial (n = 14, 32%) or neonatal atrial (n = 19, 43%) or late atrial (n = 11, 25%) repair of d-transposition of the great arteries. Ages ranged from 4 to 80 days. Overall survival for the entire series was 91% (40/44). The survival of the AS group operate on in the neonatal period was 93% (13/14). The survival of the Senning group was 90% (27/30); late Sennings, 91% (10/11); and neonatal Sennings, 92% (12/13). Six neonatal Sennings were crossovers from the AS group with an 83% survival (5/6). RESULTS: Intermediate follow-up of 5.2 to 9.2 years revealed no late deaths. In the AS group there was no ventricular failure, no arrhythmias, and one reoperation for supravalvar pulmonic stenosis. In the Senning group, there was no ventricular failure, but significant complications developed in 10 patients: cardiac arrhythmias in 7, tachyarrhythmias requiring pharmacologic therapy in 4, and bradyarrhythmias in 3, 2 requiring permanent pacemaker insertion. Left ventricular outflow tract (subpulmonic) stenosis developed in 3 patients, 1 requiring a left ventricular to pulmonary artery conduit and permanent pacemaker. Systemic atrioventricular valve insufficiency has developed in 3 patients. CONCLUSIONS: Results at one reporting institution from the CHSS study during this period of transition from late atrial repair (Senning) to neonatal atrial or arterial repair show comparable early mortality in all groups. However, the intermediate results at a mean of 6.7 years reveal fewer arrhythmic and functional complications in the AS group. The possibility of neonatal repair combined with low early and intermediate morbidity and mortality confirm AS as the treatment of choice for d-transposition of the great arteries.

Arrhythmias, Cardiac↗
PubMed1981

Kindling in developing rats: variability of afterdischarge thresholds with age.

In the kindling model, the occurrence of afterdischarges is necessary for the development of seizures. In this study, the afterdischarge thresholds of the amygdala were determined in rats of 4 different age groups, beginning with 15-day-old suckling rats. Afterdischarges were triggered in 75% of the suckling rats and in all of the rats in the older age groups. The afterdischarge thresholds varied with age, being highest in the suckling group, lowest in the 35-day-old group and intermediate in the older groups. This variability of the thresholds did not correlate with the alterations in the catecholamine levels in the amygdala that occur during maturation. The failure of 25% of suckling rats to develop afterdischarges may explain why some suckling rats do not kindle.

Aging↗
PubMed1988

Premature termination of variable gene rearrangement in B lymphocytes from X-linked agammaglobulinemia.

X-linked agammaglobulinemia (XLA) results from failure of B lymphocyte development. Immature B cells from a patient with XLA were found to produce truncated mu and delta immunoglobulin H chains encoded by D-JH-C (mu delta). The 5' terminal sequence of cDNA encoding the H chains is composed of D-JH with the characteristic GGTTTGAAG/CACTGTG consensus sequence utilized for VH gene rearrangement upstream, and a leader sequence that serves for translation of this intermediate stage of rearrangement. Failure of variable region gene rearrangement may underlie the failure of B lymphoid development in XLA.

Agammaglobulinemia↗
PubMed1990

RECPAM analysis of prognostic factors in patients with stage III breast cancer.

A retrospective chart review was conducted of women with stage III breast cancer seen at the Princess Margaret Hospital between January 1977 and December 1980. Three hundred and sixty-nine patients were available for analysis. These cases were evaluated to determine the prognostic factors of patients presenting with this stage of the disease using a recursive partitioning technique, RECPAM, and a Cox regression model. A non-mathematical description of RECPAM is presented and the advantages of RECPAM over Cox analysis are discussed. The results identify primary tumour size, axillary node involvement, internal mammary node involvement, and estrogen receptor status as the most important prognostic variables. RECPAM identified 3 prognostic groups and simultaneously provided rules based on the prognostic variables to assign patients to poor, intermediate, or good prognosis categories. Patients with estrogen receptor negative tumours, or those with axillary node involvement, primary tumours greater than 5 cm, and serum alkaline phosphatase greater than 60 IU/L, or those with internal mammary node involvement, no skin changes, and serum alkaline phosphatase greater than 60 IU/L, define a group with a poor prognosis. Patients with estrogen receptor positive tumours, no axillary node involvements, and primary tumours greater than 5 cm, or estrogen receptor positive tumours, axillary node involvement, primary tumours greater than 5 cm, but serum alkaline phosphatase less than or equal to 60 U/L, have an intermediate prognosis. The good prognosis group consists of those patients with estrogen receptor positive tumours who have either skin changes or primary tumours less than or equal to 5 cm. The effect of loco-regional and systemic therapy was assessed and there was no association between treatment assignment and prognostic group. On the basis of this RECPAM analysis, we have defined important prognostic variables to be used in the design of clinical trials, and three major patient subgroups which can be used in routine oncologic practice as a guide to patient management.

Biomarkers, Tumor↗
PubMed2006

Analysis of nucleotide diversity of NAT2 coding region reveals homogeneity across Native American populations and high intra-population diversity.

N-acetyltransferase 2 (NAT2), an important enzyme in clinical pharmacology, metabolizes antibiotics such as isoniazid and sulfamethoxazole, and catalyzes the transformation of aromatic and heterocyclic amines from the environment and diet into carcinogenic intermediates. Polymorphisms in NAT2 account for variability in the acetylator phenotype and the pharmacokinetics of metabolized drugs. Native Americans, settled in rural areas and large cities of Latin America, are under-represented in pharmacogenetics studies; therefore, we sequenced the coding region of NAT2 in 456 chromosomes from 13 populations from the Americas, and two from Siberia, detecting nine substitutions and 11 haplotypes. Variants *4 (37%), *5B (23%) and *7B (24%) showed high frequencies. Average frequencies of fast, intermediate and slow acetylators across Native Americans were 18, 56 and 25%, respectively. NAT2 intra-population genetic diversity for Native Americans is higher than East Asians and similar to the rest of the world, and NAT2 variants are homogeneously distributed across native populations of the continent.

Acetylation↗
PubMed1993

Proposed standards for judging the success of the treatment of obesity.

The purpose of this report is to propose standards for the successful treatment of obesity. This process is somewhat arbitrary because obesity is a multifactorial disease and because standards need revision as diagnostic and treatment techniques improve. Weight loss, the classic standard of success, does not account for individual variability. Reduction in other measures of body size, such as body mass index, percentage of excess weight, and body fat, may be preferable. Improvement in known complications of obesity (diabetes mellitus, hypertension, hyperlipoproteinemia, sleep apnea, and psychosocial problems) are equally valid measures of success. Because obesity is a chronic disease, maintenance of weight loss is included as a standard of success. Response to obesity treatment varies, and thus criteria to define minimal, intermediate, and full success for each variable are necessary.

Adipose Tissue↗
PubMed1997

Information in the neuronal representation of individual stimuli in the primate temporal visual cortex.

To analyze the information provided about individual visual stimuli in the responses of single neurons in the primate temporal lobe visual cortex, neuronal responses to a set of 65 visual stimuli were recorded in macaques performing a visual fixation task and analyzed using information theoretical measures. The population of neurons analyzed responded primarily to faces. The stimuli included 23 faces and 42 nonface images of real-world scenes, so that the function of this brain region could be analyzed when it was processing relatively natural scenes. It was found that for the majority of the neurons significant amounts of information were reflected about which of several of the 23 faces had been seen. Thus the representation was not local, for in a local representation almost all the information available can be obtained when the single stimulus to which the neuron responds best is shown. It is shown that the information available about any one stimulus depended on how different (for example, how many standard deviations) the response to that stimulus was from the average response to all stimuli. This was the case for responses below the average response as well as above. It is shown that the fraction of information carried by the low firing rates of a cell was large--much larger than that carried by the high firing rates. Part of the reason for this is that the probability distribution of different firing rates is biased toward low values (though with fewer very low values than would be predicted by an exponential distribution). Another factor is that the variability of the response is large at intermediate and high firing rates. Another finding is that at short sampling intervals (such as 20 ms) the neurons code information efficiently, by effectively acting as binary variables and behaving less noisily than would be expected of a Poisson process.

Action Potentials↗
PubMed2002

Genetic drift and gene flow in a prehistoric population of the Azapa valley and coast, Chile.

The present paper studies the evolutionary process operating on prehistoric groups from the Azapa valley and coast (northern Chile). The sample consists of 237 crania from the Archaic Late, Early Intermediate, Middle, Late Intermediate, and Late periods. Six metric variables were used, which were transformed to eliminate the special environmental component and to increase the proportion of genetic variance. Population structure was assessed using a method based on quantitative genetic theory, which predicts a lineal relationship between average within-group phenotypic variance and group distance to the population centroid. Results indicate that 17.5% of the total variance accounts for special environmental variance. An excess in extraregional genetic flow is observed in the population corresponding to the Early Intermediate period in the valley. A reduced differentiation is observed between Archaic and Early Intermediate coastal groups, as well as between the latter and the inhabitants of the valley in the same period. Genetic differences between both areas increased substantially since the Middle period. Evidence indicates that long-range gene flow was lower on the coast than in the valley, the lowest estimated Fst being 0.0199 for the total population (coast and valley), 0.0111 for the coastal population, and 0.0057 for the valley. Results are discussed in terms of regional archeological and ethnohistorical evidence, and a microevolutionary model is presented to account for the biological history of the population.

Anthropology↗
PubMed2001

Process performance models in the optimization of multiproduct protein production plants.

In this work we propose a model that simultaneously optimizes the process variables and the structure of a multiproduct batch plant for the production of recombinant proteins. The complete model includes process performance models for the unit stages and a posynomial representation for the multiproduct batch plant. Although the constant time and size factor models are the most commonly used to model multiproduct batch processes, process performance models describe these time and size factors as functions of the process variables selected for optimization. These process performance models are expressed as algebraic equations obtained from the analytical integration of simplified mass balances and kinetic expressions that describe each unit operation. They are kept as simple as possible while retaining the influence of the process variables selected to optimize the plant. The resulting mixed-integer nonlinear program simultaneously calculates the plant structure (parallel units in or out of phase, and allocation of intermediate storage tanks), the batch plant decision variables (equipment sizes, batch sizes, and operating times of semicontinuous items), and the process decision variables (e.g., final concentration at selected stages, volumetric ratio of phases in the liquid-liquid extraction). A noteworthy feature of the proposed approach is that the mathematical model for the plant is the same as that used in the constant factor model. The process performance models are handled as extra constraints. A plant consisting of eight stages operating in the single product campaign mode (one fermentation, two microfiltrations, two ultrafiltrations, one homogenization, one liquid-liquid extraction, and one chromatography) for producing four different recombinant proteins by the genetically engineered yeast Saccharomyces cerevisiae was modeled and optimized. Using this example, it is shown that the presence of additional degrees of freedom introduced by the process performance models, with respect to a fixed size and time factor model, represents an important development in improving plant design.

Automation↗
PubMed1989

Maternal employment and infant mortality: an examination of the role of breastfeeding as an intermediate factor.

In a survey of 2111 mothers in Ile-Ife, Nigeria, the relationship between infant mortality and maternal employment was examined. By the use of logit regression taking socioeconomic variables and breastfeeding into account, it was shown that children of working class mothers are likely to experience higher rates of infant death than those of non-working mothers, and these rates are higher in mothers working in the informal than in the formal sector. No effect of duration of breastfeeding was detectable, probably due to the universal practice of long lactation among the Yoruba. Intensity of breastfeeding is a key variable, for when this is taken into account, the effect of maternal occupation on infant death disappears. Other variables associated with infant mortality are mother's education, father's income, mother's age, and age of infant.

Africa↗