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Physical frailty and cognitive frailty share biological mechanisms, but sex-specific biomarkers associated with transitions in gait speed and cognition during ageing are poorly understood.Gait speed, cognition (3MSE), body composition (DXA) and serological biomarkers were assessed annually over 9 years in 216 males (72.7 + 8.07 years) and 384 females (71.1 +8.44 years). In females, maintaining normal gait speed was associated with lower percent body fat (IRR 0.793, p= 0.001, 95%CI 0.691–0.910) and lower lactate dehydrogenase (LDH) (IRR 0.623, p = 0.00, 95%CI 0.514–0.752), and in males, the association was with higher cholesterol (IRR 1.394, p= 0.001, 95%CI 1.154–1.684). Abnormal to normal gait speed transitions were associated with higher insulin in females (IRR 1.325, p= 0.022, 95%CI 1.041–1.685) and lower creatinine in males (IRR 0.520, p= 0.01, 95%CI 0.310–0.870). Normal to slow gait speed transitions in males were associated with IGF-1 (IRR 1.74, p= 0.022, 95%CI 1.08–2.79) and leptin in females (IRR 1.39, p= 0.043, 95%CI 1.01–1.91.) Maintaining normal cognition was associated with lower LDH in females (IRR 0.276, p= 0.013, 95%CI 0.099–0.765) and higher appendicular skeletal muscle mass in males (IRR 1.52, p= 0.02, 95%CI 1.076–2.135). Improved cognition was associated with higher leptin (IRR 7.5, p= 0.03, 95%CI 1.282–44.34) and lower triglyceride (IRR 0.299, p= 0.017, 95%CI 0.110–0.809) in males. Education was protective against cognitive decline in females (IRR 0.84, p= 0.037, 0.732–0.982). Sex-specific biomarkers of muscle (LDH, Creatinine, IGF-1, APSM) and metabolism (%fat, insulin,cholesterol, leptin, tryglycerides) were associated with gait speed and cognitive transitions. These data suggest that modifiable biomarkers of muscle and metabolism could be targeted for interventions.

The possibility of the future deployment of tethered satellites has created a need for a preliminary orbit determination method capable of determining whether or not a satellite is tethered to another satellite. Classical preliminary orbit determination methods, which are used for untethered satellites, typically require two or more position vectors along with their respective observation times in order to determine a preliminary orbital element set. However, these conventional methods can’t distinguish between an untethered satellite and a tethered one, whose motion is modified due to the presence of a tether force. The use of conventional methods on a satellite which is part of a tethered satellite system will result in the calculation of inaccurate orbital elements. Modifications have been made to the p-iteration preliminary orbit determination method in order to allow for the identification of these tethered satellites. The modifications allow for the calculation of a modified gravitational parameter, which can be used to distinguish between a tethered satellite and an untethered one. This paper applies this modified p-iteration method to the problem of the quick identification of a tethered satellite. The performance of this method is evaluated through scenarios of differing tether lengths, levels of observation error, and orbital eccentricities. Due to the need for the preliminary orbit determination to be achieved quickly, only short time intervals between observations were considered. The manner in which this preliminary orbit information can be used to obtain tether parameters for the subsequent differential correction process is also described.

We analyzed the changes in serum potassium concentration ([K]) and acid-base parameters in 43 episodes of dialysis-associated hyperglycemia (serum glucose level > 33.3 mmol/L), 22 of which were characterized as diabetic ketoacidosis (DKA) and the remaining 21 as nonketotic hyperglycemia (NKH). All episodes were treated with insulin therapy only. Age, gender, initial and final serum values of glucose, sodium, chloride, tonicity and osmolality did not differ between DKA and NKH. At presentation, serum values of [K] (DKA 6.2 ± 1.3 mmol/L; NKH 5.2 ± 1.5 mmol/L) and anion gap [AG] (DKA 27.2 ± 6.4 mEq/L; NKH 15.4 ± 3.5 mEq/L) were higher in DKA, whereas serum total carbon dioxide content [TCO2] (DKA 12.0 ± 4.6 mmol/L; NKH 22.5 ± 3.1 mmol/L), arterial blood pH (DKA 7.15 ± 0.09; NKH 7.43 ± 0.07) and arterial blood PaCO2(DKA 26.2 ± 12.3 mm Hg; NKH 34.5 ± 6.7 mm Hg) were higher in NKH. At the end of insulin treatment, serum values of [K] (DKA 4.0 ± 0.7 mmol/L, NKH 4.0 ± 0.5 mmol/L), [AG] (DKA 16.3 ± 5.4 mEq/L, NKH 14.9 ± 3.0 mEq/L), [TCO2] (DKA 23.5 ± 5.0 mmol/L, NKH 24.1 ± 4.2 mmol/L), arterial blood pH (DKA 7.42 ± 0.09, NKH 7.51 ± 0.14) and arterial blood PaCO2(DKA 31.8 ± 6.7 mm Hg, NKH 34.2 ± 8.3 mm Hg) did not differ between the two groups. Linear regression of the decrease in serum [K] value during treatment, (?[K]), on the presenting serum [K] concentration,([K]2), was: DKA, ?[K] = 2.78 – 0.81 × [K]2, r = -0.85, p < 0.001; NKH, ?[K] = 2.44 – 0.71 × [K]2, r = -0.90, p < 0.001. The slopes of the regressions were not significantly different. Stepwise logistic regression including both DKA and NKH cases identified the presenting serum [K] level and the change in serum [TCO2] value during treatment as the predictors of ?[K] (R2= 0.81). Hyperkalemia is a feature of severe hyperglycemia (DKA or NKH) occurring in patients on dialysis. Insulin administration brings about correction of DKA and return of serum [K] concentration to the normal range in the majority of the hyperglycemic episodes without the need for other measures. The initial serum [K] value and the change in serum [TCO2] level during treatment influence the decrease in serum [K] value during treatment of dialysis-associated hyperglycemia with insulin.

A renewed interest in the deployment of tethered satellites has motivated recent studies addressing the problem of the accurate identification, orbit determination, and motion prediction of a tethered satellite system (TSS). If the motion of a TSS is not analyzed accurately, a tethered satellite could be incorrectly identified as an object on a re-entry trajectory. Classical orbit determination methods do not possess the capabilities to determine whether or not a tracked satellite is part of a TSS. The problem of identification is compounded by the fact that this process must be performed quickly using a short arc of observational data. Once this “quick-look” identification is achieved, it is also important to have the capabilities to precisely determine the orbit of the TSS for future tracking and orbit prediction purposes. This paper presents a three-stage methodology which has been developed to address the accurate identification, orbit determination, and long-term orbit prediction of a TSS. The first stage uses recently developed preliminary orbit determination (POD) methods which have the capability to determine whether an observed satellite is part of a TSS or not using only a few observations. The second stage utilizes ridge-type estimation methods, which have been shown to be capable of obtaining a more accurate state of the observed satellite using a short arc of observational data. The third-stage analysis utilizes an enhanced tether satellite dynamical model suited for the long-term orbit determination and motion prediction. The effectiveness of this proposed three-stage method is demonstrated using both simulated tether satellite data and actual data obtained from the Tether Physics Survivability (TiPS) Experiment.

OBJECTIVE: To investigate the effects of cigarette smoking and alcohol consumption on the development of systemic lupus erythematosus (SLE). METHODS: We interviewed 125 patients with SLE and 125 controls in a case-control study. Demographically similar controls randomly selected from outpatient clinics were matched to SLE cases for sex and age. Clinical data, including cigarette smoking, drinking habits, and other demographic variables, were collected by an interview-administered questionnaire. RESULTS: To minimize bias associated with reactive habits induced by disease, cigarette smoking before the diagnosis of SLE was the primary variable for subsequent analysis. Analysis of the data by multivariate conditional logistic regression revealed that both cigarette smoking before SLE diagnosis and ex-smoking before SLE diagnosis significantly increased the risk of development of SLE (OR 6.69, 95% CI 2.59, 17.28, p < 0.001; and OR 3.62, 95% CI 1.22, 10.70, p = 0.02, respectively). This association remained even when statistically controlling for the effects of family history and education, indicating an independent effect. Alcohol did not place an individual at increased risk nor did it have a protective role. CONCLUSION: The results of this study provide further evidence that cigarette smoking may be an associated risk factor for the development of SLE.

The sexual function of women with and without urinary incontinence and/or pelvic organ prolapse (UI/POP) was compared using a condition-specific validated questionnaire, the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ). Eighty-three women with UI/POP and 56 without agreed to participate. PISQ scores were significantly lower among women with UI/POP than in those without (P= 0.003). No differences in the stages of sexual excitement were noted between groups. The frequency of intercourse was less with UI/POP than without (P= 0.04). Women with UI/POP restricted sexual activity for fear of losing urine more frequently than did those without (P= 0.005). No differences were reported in patients’ or partners’ sexual satisfaction. This study found that women with UI/POP have poorer sexual functioning than those without, as measured by the PISQ, and report less frequent sexual activity. In addition, women with UI/POP are more likely to restrict sexual activity for fear of incontinence, although they report similar levels of satisfaction with their sexual relationships as do women without UI/POP.

Objective : To determine whether high-dose (100 μg) misoprostol was able to increase the rate of successful labor induction and lower the incidence of Cesarean section without adverse fetal effects. Methods : A total of 360 women were randomized to receive either oxytocin ( n = 192) by intravenous infusion, or misoprostol ( n = 168) 100 μg intravaginally every 4 h. The Cesarean section rate was the primary end-point. Incidences of uterine and fetal heart rate abnormalities during labor and adverse neonatal outcomes were assessed as secondary end-points. Results : Compared with those women receiving oxytocin, patients given misoprostol had a significantly shortened labor (10.7 ±6.0 vs. 15.4 ±10.4 h, p ≤0.001). The Cesarean section rate did not differ between patients receiving misoprostol or oxytocin (36 (21.4%) vs. 38 (19.8%), p = 0.79) despite a sample size adequate to detect a 13 percentage point difference in this outcome. Patients receiving misoprostol had a higher incidence of the hyperstimulation syndrome (27 (16.1%) vs. 9 (4.7%), p < 0.001), and of fetal intolerance of labor as an indication for Cesarean delivery (23 (63.9%) vs. 15 (39.5%), p = 0.06), and had a greater number of umbilical artery cord blood pH findings of < 7.20 (20 (43.5%) vs. 6 (17.1%), p = 0.02). These worrisome trends on interim analysis resulted in our prematurely terminating the study. Conclusion : High-dose intravaginal misoprostol did not reduce the Cesarean section rate and was associated with a greater hazard of fetal intolerance of labor.

1,3,5-Trinitrobenzene (TNB) is a soil and water contaminant at certain military installations. Encephalopathy in rats given 10 daily oral doses of TNB has been reported. The lesion was bilaterally symmetric vacuolation and microcavitation in the cerebellar roof nuclei, vestibular nuclei, olivary nuclei, and inferior colliculi. The contribution of the blood-brain barrier (BBB) in the genesis of these lesions remains uncertain. One of the main goals of the present work was to evaluate the functional state of the BBB. Male Fischer 344 rats (five rats/group) were euthanatized after four, five, six, seven, eight, or 10 daily doses of TNB (71 mg/kg). A different set of rats (five rats/group) was allowed to recover for 10 or 30 days after receiving 10 doses of TNB. Integrity of the BBB was assessed by immunohistochemical staining for extrav-asated plasma albumin on paraffin-embedded sections. Rats euthanatized after four to eight doses had no lesions, and albumin extravasation in the susceptible regions of the brain was minimal. Rats receiving 10 daily doses of TNB had bilaterally symmetric vacuolation and microcavitation in the cerebellar nuclei, vestibular nuclei, and inferior colliculi in association with multifocal, often confluent foci of extravasated albumin in susceptible nuclei. Albumin was present in vascular walls, extracellular space, and neurons. Immunoreactivity in neurons was of two types: cytoplasmic staining representing pinocytic uptake and homogenous staining of the entire neuron (nucleus and cytoplasm) due to uncontrolled albumin leakage through the damaged cell membrane. In rats allowed to recover for 10 days, the microcavitated foci were infiltrated by glial and gitter cells. Albumin immunoreactivity was present as extracellular granular debris, and neuronal staining (for albumin) was mild. In rats allowed to recover for 30 days, immunoreactivity to albumin was not seen. This study demonstrates that TNB-mediated tissue damage is accompanied by breakdown of the BBB. The presence of vacuolation and associated extravasated serum proteins in TNB-treated rats is an indication of vasogenic brain edema, which appears to be a critical event in TNB toxicity. Additional studies are needed to determine the reason for selective regional vulnerability and brain microvasculature susceptibility to TNB.

Many factors, both environmental and biotic, have been suggested to facilitate or hinder the evolution of viviparity (live‐bearing) in reptiles. Viviparity has evolved recently withinthe Australian scincid lizard Lerista bougainvilliiand the species includes oviparous, viviparous, and reproductively intermediate (with prolonged egg retention) populations; thus, it offers an exceptional opportunity to evaluate the validity of these hypotheses. We carried out such tests by (i) comparing environmental conditions over the geographic ranges occupied by oviparous, viviparous, and intermediate populations (to identify possible selective forces for the evolution of viviparity), and (ii) comparing morphological, reproductive and ecological traits of L. bougainvilliiwith those of other sympatric scincid species (to identify traits that may have predisposed this taxon to the evolution of viviparity). The areas occupied by viviparous L. bougainvilliiare significantly colder than those occupied by both their intermediate and oviparous conspecifics, in accord with the “cold‐climate” hypothesis for reptilian viviparity. Rainfall is similar over the ranges of the three forms. Climatic unpredictability (as assessed by the magnitude of year‐to‐year thermal variation) is lower for viviparous animals, in contradiction to published speculations. Comparison with 31 sympatric scincid species showed that L. bougainvilliiis not atypical for most of the traits we measured (e.g., body size, clutch size, thermal preferenda and tolerances). However, oviparous L. bougainvilliido display several traits that have been suggested to facilitate the evolution of viviparity. For example, pregnancy does not reduce locomotor ability of females; the lizards are semi‐fossorial; even the oviparous females produce only a single clutch of eggs per year; and they ovulate relatively late in summer, so that the time available for incubation is limited.

Abstract: We studied rats with a hemi-Parkinsonian model created by lesions of mesostriatal dopaminergic neurons. Correlation between the extent of lesions and intensity of forced rotation movements (apomorphine (APO)-induced rotations, i.e., exercise) was investigated. The levels of endothelins (ET) in the circulation after rotation under normoxic and hypoxic conditions were measured. In normoxia, the rotation sessions were associated with significant decreases in circulating ET levels, from 21.32±4.06 to 9.32±1.08 pg/ml. Although hypoxia had no effect on the frequency of rotations induced by APO, it significantly attenuated a decrease in the ET levels in the circulation of rats with the most extensive lesions. We suggest that the mesostriatal dopaminergic system modulates endothelial function by an active process. This may have relevance for some clinical manifestations of disordered striatal function observed in humans.

Cell adhesion molecules are glycoproteins expressed on the cell surface and play an important role in inflammatory as well as neoplastic diseases. There are four main groups: the integrin family, the immunoglobulin superfamily, selectins, and cadherins. The integrin family has eight subfamilies, designated as β1, through β8. The most widely studied subfamilies are β1(CD29, very late activation [VLA] members), β2(leukocyte integrins such as CDlla/CD18, CDllb/CD18, CDllc/CD18, and αdβ2), β3(CD61, eytoadhesions), and β7(α4β7and αEβ7). The immunoglobulin superfamily includes leukocyte function antigen-2 (LFA-2 or CD2), leukocyte function antigen-3 (LFA-3 or CD58), intercellular adhesion molecules (ICAMs), vascular adhesion molecule-1 (VCAM-1), platelet-endothelial cell adhesion molecule-1 (PE-CAM-1), and mucosal addressin cell adhesion molecule-1 (MAdCAM-1). The selectin family includes E-selectin (CD62E), P-selectin (CD62P), and L-selectin (CD62L). Cadherins are major cell-cell adhesion molecules and include epithelial (E), placental (P), and neural (N) subclasses. The binding sites (ligands/receptors) are different for each of these cell adhesion molecules (e.g., ICAM binds to CD11/CD18; VCAM-1 binds to VLA-4). The specific cell adhesion molecules and their ligands that may be involved in pathologic conditions and potential therapeutie strategies by modulating the expression of these molecules will be discussed.

Patterns of sexual arousal were examined for eight male and eight female homosexuals. Comparisons were made in terms of physiological and subjective arousal. The results indicate that for each group there exists very distinct arousal responses, with each group showing the greatest response to same-gender homosexual activity. Results are discussed in relationship to establishing normative data for assessment and clinical function.

Brain glucose metabolism is impaired during hypoglycemia, but, if sustained, brain metabolism reverts to normal in animal models--data in man are lacking. We tested the hypothesis that adaptations occur to allow maintenance of normal rates of brain glucose uptake (BGU) following recurrent hypoglycemia in man. Twelve normal humans were studied over 4 days. On the initial day, arterial plasma glucose concentrations were decreased from 4.72 to 2.50 mmol/liter in five 0.56 mmol/liter steps. Cerebral blood flow, brain arteriovenous glucose difference, BGU, and cognitive function were quantitated at each step. BGU was initially impaired at the 3.61 mmol/liter glucose step (P = 0.04) and was antedated by increments in epinephrine that began at 4.16 mmol/liter (P = 0.03). The onset of hypoglycemic symptoms occurred during the 3.61 mmol/liter glucose step (P = 0.02), whereas tests of cognitive function generally deteriorated at the 3.05 mmol/liter step (P < 0.05). During the next 56 hr, mean glucose concentrations were kept at 2.9 +/- 0.1 mmol/liter and reached normal only during meals. The stepped clamp protocol was repeated beginning at 4.16 mmol/liter on the last day. No decrement in BGU was observed at any step; cognitive function was preserved until significantly lower glucose concentrations on the final day relative to the first (P = 0.04). Subjects remained asymptomatic of hypoglycemia until they reached a glucose concentration of 2.50 mmol/liter (P < 0.001 vs. day 1), while initial increments in all counterregulatory hormones were forestalled to lower glucose steps than on day 1. Therefore, adaptations occur that allow normal BGU and cerebral function to be maintained during recurrent systemic hypoglycemia. Counterregulatory events that should result in symptoms of hypoglycemia and increments in endogenous glucose production are prevented until extremely subnormal glucose concentrations.

The cumulative number of cases of acquired immunodeficiency syndrome (AIDS) in the United States has grown as the cube of time rather than exponentially. We explain this by interactions involving partner choice and sexual frequency in a risk-behavior model with biased mixing. This leads to a saturation wave of infection moving from high- to low-risk groups. If this description is correct, then the decreasing growth rate of AIDS cases is not due to behavior changes; rather it is due to the intrinsic epidemiology of the disease.

To define the quantitative relationship between peripheral nerve structure and function imposed by endoneurial oedema in the diabetic state, we determined values for sural nerve hydration structure as measured by magnetic resonance spectroscopy, and for neurological function with scores for nerve conduction properties (NCV-score), neuropathic symptoms (NS-score), and examination signs (NE-score). The coefficient of sural nerve hydration was elevated to 30±6% (p<0.05) in 79 symptomatic neuropathic diabetic subjects with an average of 15 years of diabetes mellitus, compared to a value of 25±3% in 72 non-diabetic control subjects. In contrast, in 75 asymptomatic diabetic subjects with an average of 6 additional years of diabetes, the mean hydration coefficient was only 28±5% (p<0.05). A nerve hyperhydration state was identified with a prevalence of 25% within the asymptomatic group characterized by nerve hydration greater than the 95th percentile, early changes in nerve electrophysiology and neurological examination, but with no symptomatology of neuropathy. Stratification of the symptomatic neuropathic group by worsening nerve electrophysiology, demonstrates a coincident deterioration in neurological examination (RR=5.39 at maximum NCV-score), and neuropathy symptomatology (RR=4.80 at maximum NE-score). The present data are consistent with the hypothesis that endoneurial oedema initiates deterioration sequentially in nerve electrophysiology, followed by abnormal findings on neurological examination, preceding the patient's final perception of symptomatic stocking-glove peripheral diabetic neuropathy.

We investigate a number of methods of measuring convergence rates of sequences. We clarify the relationships between these different measures of convergence rates. We present eight such measurement methods and demonstrate almost all relations among them (with two open problems remaining). We also present the notion of convergence-order profiles for sequences.

Many factors, both environmental and biotic, have been suggested to facilitate or hinder the evolution of viviparity (live‐bearing) in reptiles. Viviparity has evolved recently withinthe Australian scincid lizard Lerista bougainvilliiand the species includes oviparous, viviparous, and reproductively intermediate (with prolonged egg retention) populations; thus, it offers an exceptional opportunity to evaluate the validity of these hypotheses. We carried out such tests by (i) comparing environmental conditions over the geographic ranges occupied by oviparous, viviparous, and intermediate populations (to identify possible selective forces for the evolution of viviparity), and (ii) comparing morphological, reproductive and ecological traits of L. bougainvilliiwith those of other sympatric scincid species (to identify traits that may have predisposed this taxon to the evolution of viviparity). The areas occupied by viviparous L. bougainvilliiare significantly colder than those occupied by both their intermediate and oviparous conspecifics, in accord with the “cold‐climate” hypothesis for reptilian viviparity. Rainfall is similar over the ranges of the three forms. Climatic unpredictability (as assessed by the magnitude of year‐to‐year thermal variation) is lower for viviparous animals, in contradiction to published speculations. Comparison with 31 sympatric scincid species showed that L. bougainvilliiis not atypical for most of the traits we measured (e.g., body size, clutch size, thermal preferenda and tolerances). However, oviparous L. bougainvilliido display several traits that have been suggested to facilitate the evolution of viviparity. For example, pregnancy does not reduce locomotor ability of females; the lizards are semi‐fossorial; even the oviparous females produce only a single clutch of eggs per year; and they ovulate relatively late in summer, so that the time available for incubation is limited.

This paper establishes a new upper bound on the failure probability of linear structures excited by an earthquake. From Drenick’s inequality max|y(t)| ≤ MN, where N2 = ∫h2, M2, = ∫x2, x(t) is a nonstationary Gaussian stochastic process representing the excitation of the earthquake, and y(t) is the stochastic response of the structure with impulse response function h(τ), we obtain an exponential bound computable in terms of the mean and variance of the energy M2. A numerical example is given.

Two double-blind, randomized, placebo-controlled feasibility trials of minocycline in ALS were conducted. In Trial 1, 19 subjects received 200 mg/day or placebo for 6 months; there were no significant differences in adverse events (AE). In Trial 2, 23 subjects received up to 400 mg/day in an 8-month crossover trial. The mean tolerated dose was 387 mg/day, there was a trend toward more gastrointestinal AE (p 0.057), and blood urea nitrogen and liver enzymes became elevated (p< 0.05). Using these data, the authors have designed and launched a phase III trial.

• The dexamethasone suppression test (DST) as now commonly carried out in psychiatric settings yields "abnormal" results in many conditions including the healthy state. To determine whether the DST accurately identifies patients with physiologically meaningful increases in pituitary-adrenocortical activity, we compared DST results to baseline urinary cortisol level. Thirty-four psychiatric inpatients underwent a 24-hour urine collection and then a DST using 1 or 2 mg of dexamethasone. With the common 1-mg DST, 24-hour urinary cortisol levels in nonsuppressors and suppressors did not differ. With the 2-mg DST, however, nonsuppressors had significantly higher urinary cortisol levels than suppressors, and all nonsuppressors had urinary cortisol levels above the normal range. Thus, the 1-mg DST may not identify the heuristically important subgroup of psychiatric patients who have a pathophysiologically meaningful alteration in pituitary-adrenal regulation.

The Benton Judgment of Line Orientation Test (BJLOT) is a widely used neuropsychological test measuring visuospatial judgment. The present study developed two 15-item short forms using data from 100 neurologic patients. The new short forms are equivalent in test construction and retain the stimulus properties of the original test. Correlational analyses revealed that each short form score related significantly to the original BJLOT (p < 001). The short forms were found to be internally consistent, with alpha reliability coefficients exceeding 82. Although kappa coefficient analyses found the short forms to lack sufficient accuracy in categorizing the cases via the BJLOT diagnostic classifications, the short forms were accurate in detecting the presence of impairment. These results suggest that the two short forms can be utilized as screening instruments for detecting the presence or absence of visuospatial impairment.