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PubMed2002

Association of a woman's own birth weight with subsequent risk for gestational diabetes.

CONTEXT: Several studies have reported links between reduced fetal growth and subsequent risk for type 2 diabetes among older adults, but the association between indices of fetal growth and gestational diabetes mellitus (GDM), a major complication of pregnancy and a strong predictor of type 2 diabetes, remains little explored. OBJECTIVE: To test the hypothesis that a woman's own fetal growth is inversely related to her later risk for GDM. DESIGN AND SETTING: Case-control study of linked hospital discharge and vital record data from the New York State Department of Health. POPULATION: Healthy women who completed their first pregnancies in New York State between 1994 and 1998 and who were also born in New York State. Records from each woman's first pregnancy were linked to those from her own birth (1970-1985). Cases were 440 women with a record of GDM. Controls were 22 955 remaining women with no indication of GDM. MAIN OUTCOME MEASURE: A woman's own birth weight, alone and adjusted for gestational age. RESULTS: Birth weight showed a U-shaped relationship to a woman's risk of GDM in her first pregnancy, with the highest risks associated with low and high birth weights. Odds ratios (ORs) adjusted for gestational age were 2.16 (95% confidence interval [CI], 1.04-4.50) for birth weight of less than 2000 g and 1.53 (95% CI, 1.03-2.27) for a birth weight of 4000 g or more. Adjustment for potential confounding factors, particularly prepregnancy body mass index and maternal diabetes, increased the OR for low birth weight to 4.23 (95% CI, 1.55-11.51), but reduced the OR for high birth weight to 0.92 (95% CI, 0.54-1.57), leaving a strong inverse dose-response relationship between birth weight and risk of GDM (adjusted P for trend <.001). CONCLUSIONS: In this large population-based study, a woman's own birth weight was strongly and inversely related to her risk of GDM, suggesting that early life factors may be important in the etiology of this disorder.

Adolescent↗

PubMed1998

Effectiveness of external ankle support. Bracing and taping in rugby union.

Ankle inversion sprain is common in rugby. This review outlines research evidence relating to the effects of external ankle support by means of bracing and taping, on the incidence of ankle injuries, how performance is affected by support, how support may act at the joint (with respect to end range of motion, strength, resistive torque, muscle activation patterns and proprioception) to prevent injury, and how exercise changes the effectiveness of support. In addition, the implications of the laws of rugby for the use of external support are discussed. Prospective epidemiological studies have shown a decrease in the incidence of ankle injury with external ankle support use. The effectiveness of external ankle support was dependent upon the material properties and application method of the tape or brace, and on the athlete's status of ankle stability or previous injury. Experimental studies have indicated that the degree of ankle inversion restriction provided, and the degree of loss of restriction after exercise, were dependent upon the external support tested. External ankle support has been reported to have no effect on performance, or to have an adverse effect on performance in a variety of movement tasks. No prophylactic external ankle support has been shown to improve performance. If an external support is to provide mechanical support to a ligament it should exceed the strength of the ligament, which for the anterior fibular ligament is a force limit of between 6 and 56 kg. Tape can provide only limited mechanical support of the ankle joint complex, but it may have proprioceptive effects. Taping may work as a psychological reminder, so that the athlete consciously moderates lower limb-loading behaviour. There is equivocal evidence of the effect of brace use on ground reaction force excursions, balance ability and ankle strength. It is concluded that while there have been many investigations of the effects of tape and some forms of brace on ankle range of motion with and without exercise, there is equivocal evidence regarding the mechanism by which an external support acts. It is recommended that future research address the effects of external ankle support during dynamic exercise and that brace manufacturers utilise the information in the development of future brace designs to help reduce the risk of ankle inversion sprain injury. As external support can decrease the incidence of ankle inversion sprain the International Rugby Board should consider the use of ankle braces in rugby, allowing for stiff lateral components of the brace.

Ankle↗

PubMed2003

On weighting the rates in non-response weights.

A basic estimation strategy in sample surveys is to weight units inversely proportional to the probability of selection and response. Response weights in this method are usually estimated by the inverse of the sample-weighted response rate in an adjustment cell, that is, the ratio of the sum of the sampling weights of respondents in a cell to the sum of the sampling weights for respondents and non-respondents in that cell. We show by simulations that weighting the response rates by the sampling weights to adjust for design variables is either incorrect or unnecessary. It is incorrect, in the sense of yielding biased estimates of population quantities, if the design variables are related to survey non-response; it is unnecessary if the design variables are unrelated to survey non-response. The correct approach is to model non-response as a function of the adjustment cell and design variables, and to estimate the response weight as the inverse of the estimated response probability from this model. This approach can be implemented by creating adjustment cells that include design variables in the cross-classification, if the number of cells created in this way is not too large. Otherwise, response propensity weighting can be applied.

Bias↗

PubMed1995

Protein structure-based design of potent orally bioavailable, nonpeptide inhibitors of human immunodeficiency virus protease.

A class of potent nonpeptidic inhibitors of human immunodeficiency virus protease has been designed by using the three-dimensional structure of the enzyme as a guide. By employing iterative protein cocrystal structure analysis, design, and synthesis the binding affinity of the lead compound was incrementally improved by over four orders of magnitude. An inversion in inhibitor binding mode was observed crystallographically, providing information critical for subsequent design and highlighting the utility of structural feedback in inhibitor optimization. These inhibitors are selective for the viral protease enzyme, possess good antiviral activity, and are orally available in three species.

Administration, Oral↗

PubMedDate not supplied

The effect of ankle braces on the prevention of dynamic forced ankle inversion.

BACKGROUND: Athletes often employ prophylactic braces to reduce the risk of ankle injuries. HYPOTHESIS: Ankle braces do not significantly decrease the risk of forced inversion on a standardized one-footed jump landing. STUDY DESIGN: Controlled laboratory study. METHODS: Fourteen healthy men with a mean age of 25.1 years were tested. Three braces, two semirigid (Aircast and Bledsoe) and one lace-up (Swede-O), were fitted to each subject. Forced dynamic ankle inversion of 24 degrees was to be resisted as the subjects landed on one foot with a force of two body weights on a stimulus presented randomly in 5 of 15 jump trial blocks onto a hard, level force plate. Subjects first completed 1 no-brace block of 5 trials to establish baseline performance, then 3 randomly ordered 15-trial blocks testing performance with each of the braces, and then finally a no-brace 5-trial block. RESULTS: The average no-brace success rate was 24%, which demonstrated the challenging nature of the task. All three braces increased the success rate (average, 44%); however, only the two semirigid braces proved to be significantly better than the unbraced state. CONCLUSION: This test holds promise for evaluating brace efficacy when landing with one foot unexpectedly on an object that acts to forcibly invert the ankle.

Adult↗

PubMed1988

Physiological sleep tendency on a simulated night shift: adaptation and effects of triazolam.

Daytime sleep and nocturnal sleepiness were examined in 18 normal sleepers (9 young adults, 9 middle-age adults) for 5.5 days following acute sleep/wake schedule inversion. Triazolam and placebo were compared in a counterbalanced, crossover design. Triazolam improved daytime sleep, but did not produce significant changes in sleep tendency at night. Physiological sleep tendency in the early morning hours (0200 to 0600) was profound, but decreased significantly within 3 to 4 days following sleep/wake inversion, irrespective of treatment condition. Nocturnal performance data generally were consistent with changes in physiological sleep tendency. We conclude that extending daytime sleep by an average of approximately 50 min per day via administration of a hypnotic does not appear to significantly reduce circadian sleep tendency in the early morning hours. Further, considerable adaptation, in terms of sleep tendency, occurred within a weak of simulated night shift despite a relatively constant daytime sleep pattern.

Adult↗

PubMed1979

Bioaccumulation of cadmium in marine organisms.

A general review of cadmium concentrations in marine organisms and studies of cadmium bioaccumulation is presented. Factors which influence cadmium concentrations, such as regional differences, seasonal fluctuations and salinity, are discussed and species which are likely to accumulate cadmium identified. Experimental studies designed to investigate the influence of some of these factors on cadmium bioaccumulation in a filter feeding bivalve mollusk, the American oyster (Crassostrea virginica), are presented. Field studies of seasonal dynamics of cadmium in oysters indicate patterns which may be correlated with seasonal physiological activity. The bioaccumulation of cadmium following input to estuarine systems by natural phenomena is observed. Cadmium concentrations in oysters collected from regions of different salinity suggest an inverse relationship between cadmium concentration and salinity. Laboratory experiments designed to investigate mechanisms of cadmium accumulation demonstrate that an inducible cadmium binding protein, similar to metallothiomein, is present in the American oyster.

Animals↗

PubMed1985

Rearrangements between the operators in the bacteriophage lambda.

The left operator mutant lambda v2s develops poorly during infection as a result of constitutive expression of the left operon. A revertant of lambda v2s, designated lambda iri, was found to contain an inversion of the cI region with the inversion endpoints to be within the lambda operators OL and OR. Formation of the inversion is facilitated by a translocation of right operator OcR mutant sequence to the left operator in lambda v2s. The inversion in lambda iri positions wild-type OR sequence at OL returning control of the left operon to repression by the lambda cro repressor.

Bacteriophage lambda↗

PubMed1989

Mean residence time for drugs subject to enterohepatic cycling.

A physiologically realistic model of enterohepatic cycling (EHC) which includes separate liver and gallbladder compartments, discontinuous gallbladder emptying and first-order absorption from both an oral formulation and secreted bile (kapo and kab, respectively) has been developed. The effect of EHC on area under the first-moment curve (AUMC) of drug concentration in plasma and on parameters derived from the AUMC was investigated. Unlike AUC, AUMC is dependent on the time and time-course of gallbladder emptying, increasing as the interval between gallbladder emptying increases. Consequently, mean residence time (MRT) is also a time-dependent parameter. Analytical solutions for MRTiv and MRTpo were derived. Mean absorption time (MAT = MRTpo - MRTiv) is also time-dependent, contrary to findings previously published for a model of EHC with a continuous time lag. MAT is also dependent on kapo, kba and the hepatic extraction ratio. The difference between MRTpos for two formulations with unequal kapo values may deviate from the difference in the inverse of their absorption rate constants. Implications for design and interpretation of pharmacokinetic studies include (i) MAT values may be dominated by the time-course of recycling rather than the time-course of the initial absorption, depending on the extent of EHC and (ii) the unpredictable nature of the time of gallbladder emptying will contribute to intrasubject variability in derived parameters during crossover studies. Knowledge of the extent of EHC is invaluable in deciding whether modification of the in vitro release characteristics of an oral formulation will have any effect on the overall time-course of absorption in vivo. Techniques to monitor or control gallbladder emptying may be helpful for reducing variability in pharmacokinetic studies for compounds which are extensively cycled in bile.

Absorption↗

PubMed2004

Identification of the piezoelectric material coefficients using the finite element method with an asymptotic waveform evaluation.

A rapid identification of the piezoelectric material constants for a piezoelectric transducer is proposed. The validity of a three-dimensional finite element routine was confirmed experimentally. The asymptotic waveform evaluation (AWE) was adopted for a fast frequency sweep of the finite element analysis. The three-dimensional finite element method with an AWE and a design sensitivity method was used for a material inversion scheme of piezoelectric transducers. In order to confirm the inversion routine of the material constants, the mechanical displacements, which mean the mode shape, were calculated along the vertical and lateral position of the sample transducer.

Journal Article↗

PubMed2001

The University of California, Irvine experience with tomotherapy using the Peacock system.

Our institutional experience using the Peacock system for intensity-modulated radiation therapy (IMRT) is summarized. Over 100 patients were treated using this system, which is fitted to a Clinac 600C linac. Both cranial and extracranial lesions have been treated using this modality. Immobilization is achieved either with the Talon system for cranial sites or an Aquaplast cast. Target volumes up to 500 cm3 have been treated. Multiple lesions (up to 3) were treated in one setup. The range of dose/fractionation schemes used was 15 Gy/1 fx (radiosurgical treatment) - 80 Gy/40 fx. Dose validation studies were carried out using film and ion chamber dosimetry in a specially designed phantom. Optimal dose distributions were attainable using inverse treatment planning for IMRT delivery. These were found to encompass the target volumes accurately using dose validation phantom studies. Immobilization methods used were accurate to within 1 mm, as evidenced by daily portal films. IMRT using the Peacock system offers the advantage of delivery of conformal therapy to high doses safely and accurately. This provides the opportunity for dose escalation studies, retreatment of previously treated tumors, as well as treating multiple targets in one setup. The system may be fitted to a conventional linac without major modifications.

Adenocarcinoma↗

PubMed2004

Mechanistic analysis of hydroarylation catalysts.

Recently, two organometallic systems ([Ir(micro-acac-O)(acac-O,O)(acac-C(3))](2) and (Tp)Ru(CO)(Ph)(NCCH(3))) have been discovered that catalyze hydroarylation of unactivated olefins. Herein, we use density functional theory (B3LYP) to study the factors underlying this class of catalysts. In addition, we calculate the key steps for Rh, Pd, Os, and Pt with similar ligand sets. We previously showed there to be two key steps in the process: (i) insertion of a phenyl into the pi bond of a coordinating olefin, and (ii) C-H activation/hydrogen transfer of an unactivated benzene. An important discovery in these studies is that the barriers for these two steps are inversely correlated, complicating optimization of the overall process. However, herein we elucidate the causes of this inverse correlation, laying the foundation for the rational design of improved catalysts. Both steps are directly influenced by the accessibility of the higher 2-electron oxidation state, M(n) --> M(n+2). Systems with an easily accessible M(n+2) state activate C-H bonds easily but suffer from high energy insertions due to significant back-bonding. Conversely, systems without an easily accessible M(n+2) state have no debilitating back-bonding which makes insertion steps facile, but cannot effectively activate the C-H bond (leading instead to polymerization). The relationship between accessibility of the M(n+2) state and the amount of back-bonding in the coordinating olefin can be visualized by inspecting the hybridization of the coordinating olefin. Furthermore, we find a linear relation between this hybridization and the barrier to insertion. On the basis of these concepts, we suggest some modifications of the sigma framework expected to improve the rates beyond this linear correlation.

Journal Article↗

PubMed2002

Mass rearing of temperature sensitive genetic sexing strains in the Mediterranean fruit fly (Ceratitis capitata).

Genetic sexing strains (GSS) based on the temperature sensitive lethal (tsl) mutation are being used to produce sterile male medflies for large scale sterile insect technique (SIT) programmes for this pest. The use of male-only strains increases the overall efficiency of the technique. Currently more than 1.4 billion sterile male-only pupae are produced per week in different facilities around the world. Due to the mutations used to construct these strains, that is, translocations and selectable markers, they require different and more careful mass rearing procedures than do bisexual strains (BSS). The basic rearing technology has been developed and can be used to produce only males on a predictable basis to a level of 99.9% accuracy. If specific rearing procedures are followed, then tsl-based GSS has a rearing efficiency that is equal to that of a BSS and it is already know that males produced by the tsl-based GSS are of equal quality to males produced by BSS. Based on current rearing technology the cost of production of male pupae is about the same for both types of strain. This is due to the large colony that is required for the tsl-based GSS. This paper discusses the considerations that need to be taken into account during mass rearing of GSS and identifies the most efficient production processes that are currently available.

Animal Feed↗

PubMed1992

Site-specific serine phosphorylation of spinach leaf sucrose-phosphate synthase.

We recently reported [Huber, Huber & Nielsen (1989) Arch. Biochem. Biophys. 270, 681-690] that spinach (Spinacia oleracea L.) sucrose-phosphate synthase (SPS; EC 2.4.1.14) was phosphorylated in vivo when leaves were fed [32P]Pi. In vitro the enzyme was phosphorylated and inactivated by using [gamma-32P]ATP. We now report that SPS is phosphorylated both in vivo and in vitro on serine residues. The protein is phosphorylated at multiple sites both in vivo and in vitro as indicated by two-dimensional peptide maps of the immunopurified SPS protein. After being fed with radiolabel, leaves were illuminated or given mannose (which activates the enzyme), in the presence or absence of okadaic acid. Feeding okadaic acid to leaves decreased the SPS activation state in the dark and light and in leaves fed mannose. Across all the treatments, the activation state of SPS in situ was inversely related to the labelling of two phosphopeptides (designated phosphopeptides 5 and 7). These two phosphopeptides are phosphorylated when SPS is inactivated in vitro with [gamma-32P]ATP, and thus are designated as regulatory (inhibitory) sites [Huber & Huber (1991) Biochim. Biophys. Acta 1091, 393-400]. Okadaic acid increased the total 32P-labelling of SPS and in particular increased labelling of the two regulatory sites, which explains the decline in activation state. In the presence of okadaic acid, two cryptic phosphorylation sites became labelled in vivo that were not apparent in the absence of the inhibitor. Overall, the results suggest that light/dark regulation of SPS activity occurs as a result of regulatory serine phosphorylation. Multiple sites are phosphorylated in vivo, but two sites in particular appear to regulate activity and dephosphorylation of these sites in vivo is sensitive to okadaic acid.

Amino Acids↗

PubMed1990

Association of magnesium deficiency with the blood pressure-lowering effects of calcium.

The role of dietary calcium and magnesium in the development of hypertension was studied in nine groups, each consisting of nine spontaneously hypertensive rats aged 8-31 weeks. The animals were fed AIN 76A semi-purified diets varying in calcium (0.075, 0.5 and 2.5%) and magnesium (0.01, 0.05 and 0.75%) concentrations according to a 3 x 3 factorial design. Dietary calcium and systolic blood pressure were inversely related, significantly (P less than 0.05) after 12 weeks. Total and ultrafilterable serum calcium concentrations were also significantly negatively correlated with blood pressure (r = -0.46; P = 0.001 and r = -0.57; P = 0.001, respectively). Repeated measures analysis of variance indicated that dietary magnesium had no effect on systolic blood pressure, and no calcium x magnesium interaction on blood pressure was observed. Signs of magnesium deficiency, calcium deposits in the kidneys, and histological lesions were observed in groups on a high-calcium diet receiving normal and low levels of magnesium. Thus a lowering of blood pressure by calcium supplementation, without concomitant magnesium supplementation, was accompanied by biochemical and histological abnormalities in this animal model.

Animals↗

PubMed2004

Alcohol consumption and arterial stiffness in men.

OBJECTIVE: Moderate alcohol consumption has been proposed to be anti-atherogenic and protect against coronary heart disease. Arterial stiffness provides a summary measure of atherosclerotic arterial damage and cardiovascular risk. A vascular protective effect of moderate alcohol consumption would be reflected in an inverse association between alcohol intake and aortic stiffness. DESIGN: A cross-sectional study. SETTING: The male population of Utrecht. PARTICIPANTS: Of 370 men, aged 40-80 years, alcohol intake was calculated from a standardized questionnaire and aortic stiffness was non-invasively assessed by pulse-wave velocity (PWV) measurement of the aorta. RESULTS: There were no non-drinkers; therefore the group consuming 0-3 glasses of alcoholic beverage per week was chosen as the reference group in the analyses. Those drinking 4-10, 11-21 and 22-58 glasses of alcoholic beverage per week had a -0.77 m/s (95% confidence interval, -1.26 to -0.28), -0.57 m/s (95% confidence interval, -1.07 to -0.08) and -0.14 m/s (95% confidence interval, -0.65 to 0.36) difference in mean PWV compared with those drinking 0-3 glasses per week. Adjustment for factors that correlated with PWV or alcohol consumption did not change the strength of the association. CONCLUSION: Among men aged 40-80 years there is a J-shaped association between alcohol consumption and PWV. This further supports a decreased risk of cardiovascular disease with moderate alcohol consumption.

Aged↗

PubMed2003

Local administration of nitric oxide donor significantly impacts microvascular thrombosis.

OBJECTIVES/HYPOTHESIS: Clinical pharmacotherapy has demonstrated a role in preventing microvascular thrombosis in both experimental and clinical settings. Previous studies in the rabbit model have noted an increased rate of thrombosis with intravenous infusion of nitric oxide antagonists. The study assessed the effects of local application of nitric oxide agonists and antagonists on microvascular anastomotic patency rates. STUDY DESIGN: A randomized, prospective analysis. METHODS: An arterial inversion graft microvascular thrombosis model was used in New Zealand white rabbits. The rabbits were randomly assigned to nitric oxide agonist, antagonist, and control groups. In each rabbit, the common femoral artery was surgically exposed and a 2-mm arterial inversion graft was harvested. The anastomosis of the graft to the common femoral artery was performed in solutions of either 100 micromol/L spermine NONOate (nitric oxide donor), 100 micromol/L nitro-L-arginine-methyl ester (L-NAME) (nitric oxide synthase inhibitor), or 0.9% sodium chloride (control) solution. The contralateral common femoral artery also underwent arterial inversion graft testing with the use of the same solution. Arterial patency was assessed 1 hour after anastomosis. RESULTS: Sixteen of 22 arterial inversion grafts performed in the spermine NONOate solution remained patent, and 6 of 22 clotted. Eleven of 21 arterial inversion grafts performed in the control solution remained patent, and 10 clotted. Seven of 21 arterial inversion grafts performed in the L-NAME solution remained patent, and 14 clotted. These results were found to be statistically significant using the chi test with a value of less than.05. CONCLUSIONS: In the rabbit model, local application of nitric oxide agonists and antagonists can significantly impact anastomotic patency rates. Further studies may demonstrate a role for the clinical use of nitric oxide in microvascular surgery.

Anastomosis, Surgical↗

PubMed2005

A risk score as part of an evidence-based approach to the selection of corneal replacement surgery.

PURPOSE: There is currently no standardized methodology that permits preoperative prediction of the surgical technique or drug regimen for corneal grafting most likely to succeed for an individual patient. A score factor related to the chance of successful penetrating keratoplasty (PK) may assist in standardization of graft outcome reporting and evidence-based management. METHODS: The Risk Score (RS) is based on factors shown to reduce the probability of 1-year survival of conventional PK in increments, using published Australian Corneal Graft Registry data. To asses its validity, Kaplan-Meier survival curves from 156 corneal replacement surgeries, stratified by preoperative RS, were used to derive the probability of survival at 1 year for donor PK, with or without systemic immunosuppression, and for synthetic PK with the AlphaCor artificial cornea. The probability of survival was then plotted against RS for each regimen, producing a family of curves. RESULTS: The mean RS for immunosuppressed cases was higher than for nonimmunosuppressed cases. The AlphaCor group had the highest scores. AlphaCor survival is little affected by the factors that affect the risk of graft survival, whereas the probability of donor graft survival, immunosuppressed or not, is inversely related to RS. CONCLUSIONS: This study was designed to test a method that allows objective comparison of outcomes of different methods of corneal replacement for different risk categories. Analysis of this small dataset supports the validity of the concept and suggests that the Risk Score is a useful descriptive statistic. With a sufficient sample size, statistically significant evidence of the optimum management method for an individual patient with a particular risk profile could be determined such that a prospective patient's preoperative RS could be used to assist management decisions. In particular, data allowing separation of different immunosuppression regimes would be useful. Functional outcomes such as visual acuity would be more significant clinically than the survival end point used in this study and the system also could be adapted to different follow-up periods.

Artificial Organs↗