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Very slow growth of Escherichia coli.

A recycling fermentor (a chemostat with 100% biomass feedback) was used to study glucose-limited behavior of Escherichia coli B. The expectation from mass transfer analysis that growth would asymptotically approach a limit mass determined by the glucose provision rate (GPR) and the culture's maintenance requirement was not met. Instead, growth proceeded at progressively lower rates through three distinct phases. After the fermentor was seeded, but before glucose became limiting, growth followed the usual, exponential path (phase 1). About 12 h postseeding, residual glucose in the fermentor fell below 1 microgram . ml-1 and the growth rate (dx/dt) became constant and a linear function of GPR (phase 2). The specific growth rate, mu, therefore fell continuously throughout the phase. Biomass yield and glucose assimilation (13%) were near the level for exponential growth, however, and independent of GPR over a broad range. At a critical specific growth rate (0.04 h-1 for this strain), phase 2 ended abruptly and phase 3 commenced. In phase 3, the growth rate was again constant, although lower than in phase 2, so that mu continued to fall, but growth rates and yields were praboloid functions of GPR. They were never zero, however, at any positive value of GPR. By inference, the fraction of metabolic energy used for maintenance functions is constant for a given GPR, although different for phases 2 and 3, and independent of biomass. In both phases 2 and 3, orcinol, diphenylamine, and Lowry reactive materials were secreted at near-constant rates such that over 50% as much biosynthetic mass was secreted as was retained by the cells.

Adenosine Triphosphate↗

Comparison of clinical and pharmacokinetic profiles of etanercept 25 mg twice weekly and 50 mg once weekly in patients with psoriasis.

BACKGROUND: Etanercept is a tumour necrosis factor antagonist that is approved in the U.S.A., Canada and Europe for treating adult patients with chronic moderate to severe plaque psoriasis. OBJECTIVES: To assess whether clinical efficacy, safety and pharmacokinetic (PK) profiles of etanercept 50 mg once weekly are comparable to etanercept 25 mg twice weekly. METHODS: Patients from a U.S. phase 3 study and a global phase 3 study were subsequently enrolled in an open-label extension study (extension study) where they all received etanercept at a dose of 50 mg once weekly for an initial 12 weeks. Patients who had received at least 24 weeks of etanercept 25 mg twice weekly in the global phase 3 study and were enrolled in the extension study (n = 265) were assessed for efficacy and safety at extension study baseline and after 12 weeks of etanercept 50 mg once weekly. Efficacy endpoints included the Psoriasis Area and Severity Index (PASI), the Dermatology Life Quality Index and the Physician's Global Assessment of psoriasis. In addition, PK profiles from patients in the U.S. phase 3 study were compared with PK profiles from another set of patients in the extension study. Comparison was made between a subset of patients receiving etanercept 25 mg twice weekly dosing in the U.S. phase 3 study (n = 13) and those receiving etanercept 50 mg once weekly in the extension study (n = 84). RESULTS: The mean PASI score was 5.77 at extension study baseline after treatment with etanercept 25 mg twice weekly, which was sustained at 5.82 after 12 weeks of etanercept 50 mg once weekly. Similar results were observed in other efficacy endpoints. Etanercept 50 mg once weekly was generally well tolerated. No new safety findings were reported. PK profiles overlapped extensively between the two dosing regimens. CONCLUSIONS: In this report, we demonstrate that efficacy, safety and PK profiles were comparable between etanercept 25 mg twice weekly and 50 mg once weekly in patients who had received at least 24 weeks of etanercept 25 mg twice weekly prior to receiving etanercept 50 mg once weekly in the extension study.

Adult↗

Synaptic mechanisms of inspiratory off-switching evoked by pontine pneumotaxic stimulation in cats.

To elucidate synaptic mechanisms and the involvement of N-methyl-D-aspartate (NMDA) receptors in inspiratory off-switching (IOS) evoked by the stimulation of the nucleus parabrachialis medialis (NPBM), excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs) were recorded from bulbar augmenting inspiratory (aug-I) and postinspiratory (PI) neurons in vagotomized cats. Stimulation of NPBM produced either transient inhibition or premature termination of inspiration (reversible or irreversible IOS), depending on the stimulus intensity. Each neuron displayed four-phasic postsynaptic responses during the reversible IOS, i.e. Phase 1 EPSPs, Phase 2 IPSPs, Phase 3 EPSPs and Phase 4 IPSPs in aug-I neurons, and Phase 1 plus 2 EPSPs, Phase 3 IPSPs and Phase 4 EPSPs in PI neurons. During the irreversible IOS, Phase 4 responses were replaced by sustained hyperpolarization in aug-I neurons and decrementing depolarization in PI neurons. Blockade of NMDA receptors by dizocilpine (0.3 mg kg(-1) i.v.) selectively increased Phase 4 potentials in both types of neurons and decreased the thresholds for evoking the irreversible IOS. The NPBM-induced responses had a pattern and time-course similar to those induced by vagal stimulation. The present results suggest that pneumotaxic and vagal inputs converge on the common IOS circuit, and the effectiveness of both inputs is modulated by NMDA receptors.

Animals↗

Development of the physical therapy outpatient satisfaction survey (PTOPS).

BACKGROUND AND PURPOSE: The purposes of this 3-phase study were (1) to identify the underlying components of outpatient satisfaction in physical therapy and (2) to develop a test that would yield reliable and valid measurements of these components. SUBJECTS: Three samples, consisting of 177, 257, and 173 outpatients from 21 facilities, were used in phases 1, 2, and 3, respectively. METHODS AND RESULTS: In phase 1, principal component analyses (PCAs), reliability checks, and correlations with social desirability scales were used to reduce a pool of 98 items to 32 items. These analyses identified a 5-component model of outpatient satisfaction in physical therapy. The phase 2 PCA, with a revised pool of 48 items, indicated that 4 components rather than 5 components represented the best model and resulted in the 34-item Physical Therapy Outpatient Satisfaction Survey (PTOPS). Factor analyses conducted with phase 2 and phase 3 data supported this conclusion and provided evidence for the internal validity of the PTOPS scores. The 4-component scales were labeled "Enhancers," "Detractors," "Location," and "Cost." Responses from subsamples of phase 3 subjects provided evidence for validity of scores in that the PTOPS components of "Enhancers," "Detractors," and "Cost" appeared to differentiate overtly satisfied patients from overtly dissatisfied patients. "Location" and "Enhancer" scores discriminated subjects with excellent attendance at scheduled physical therapy sessions from those with poor attendance. CONCLUSION AND DISCUSSION: In this study, we identified components of outpatient satisfaction in physical therapy and used them to develop a test that would yield valid and reliable measurements of these components.

Adult↗

Contrasting effects of verapamil and procainamide on rate-dependent bundle branch block: pharmacologic evidence for the role of depressed sodium channel responses.

The mechanisms responsible for intermittent bundle branch block are still under debate. The role of the time-dependent behavior of the slow calcium channel has recently been emphasized. To test this hypothesis and ascertain the possible involvement of the fast sodium channel, the effects of the slow calcium channel blocker verapamil and the fast sodium channel blocker procainamide were compared in 10 patients with intermittent bundle branch block. All 10 patients showed bundle branch block during spontaneous sinus rhythm. Maneuvers to slow cardiac rate (that is, carotid sinus massage, Valsalva maneuver) were performed to identify normal conduction as well as phase 4 bundle branch block. Thus, the ranges of diastolic intervals (RR) resulting in phase 3 (tachycardia-dependent) bundle branch block, phase 4 (bradycardia-dependent) bundle branch block and normal conduction were measured in two control studies performed before intravenous administration of verapamil (control 1) and procainamide (control 2) and at the peak effect of both drugs. In the control studies, all 10 patients showed phase 3 bundle branch block, whereas phase 4 bundle branch block occurred in only 4 patients. The ranges of phase 3 bundle branch block, phase 4 bundle branch block and normal conduction were very similar in control studies 1 and 2. The phase 3 bundle branch block range was slightly shortened by verapamil (983 +/- 83.5 ms in control 1; 930 +/- 69.4 ms at the peak effect of verapamil), whereas phase 4 bundle branch block remained unchanged. In contrast, conduction was systematically worsened by procainamide.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Sustained benefit of a community and professional intervention to increase acute stroke therapy.

BACKGROUND: The ultimate test of an educational intervention is the sustainability of the effect after the intervention ceases. METHODS: The TLL Temple Foundation Stroke Project was a quasi-experimental study aimed at increasing Food and Drug Administration-approved acute stroke therapy in a nonurban community in east Texas. During the intensive community and professional intervention (phase 2), significantly more patients with acute stroke received intravenous tissue plasminogen activator (tPA) compared with the preintervention period (phase 1). In the comparison community, no change was noted. We present the results of tPA treatment in the 6 months after the intervention ended (phase 3). RESULTS: Two hundred thirty-eight patients had a validated stroke during phase 3. Among patients who experienced an ischemic stroke, 11.2% in the intervention group received intravenous tPA compared with 2.2% in phase 1 (P =.007). In the comparison group, 1.4% received intravenous tPA in phase 3 compared with 0.7% in phase 1 (P>.99). Among eligible candidates for treatment, 69.2% were treated in phase 3 in the intervention community compared with 13.6% in phase 1 (P =.002). In the comparison group, 20.0% were treated in phase 3 compared with 6.7% in phase 1 (P =.45). There was 1 protocol violation among the 9 patients treated in the intervention community in phase 3. CONCLUSIONS: There was a sustained benefit of the intervention in increasing tPA treatments in the intervention community even after cessation of the educational effort. Treatments in the control community remained few through all 3 phases of the study. A carefully planned multilevel intervention can improve community stroke treatments even in a nonurban community.

Drug Utilization↗

Hydrogen sulfide as an endogenous regulator of vascular smooth muscle tone in trout.

Hydrogen sulfide (H(2)S) is an endogenous vasodilator in mammals, but its presence and function in other vertebrates is unknown. We generated H(2)S from NaHS and examined the effects on isolated efferent branchial arteries from steelhead (stEBA) or rainbow (rtEBA) trout. H(2)S concentration was measured colorimetrically (CM) and with ion-selective electrodes (ISE) in rainbow trout plasma. NaHS produced a triphasic response consisting of a relaxation (phase 1), constriction (phase 2), and relaxation (phase 3) in both unstimulated vessels and in stEBA precontracted with carbachol (Carb). Phase 1 and phase 3 in stEBA were decreased and phase 2 increased in unstimulated vessels by K(+)(ATP) channel inhibition (glibenclamide), or a cocktail of inhibitors of cyclooxygenase, lipoxygenase, and cytochrome P-450 (indomethacin, esculetin, and clotrimazole). Inhibition of soluble guanylate cyclase with ODQ o NS-2028 inhibited phase 3 in stEBA, although NaHS decreased cGMP production by tEBA. stEBA phase 2 contractions were partially inhibited by the myosin light chain kinase inhibitor, ML-9, but unaffected by L-type calcium channel inhibition (methoxyverapamil), whereas contraction in tEBA was partially inhibited by nifedipine or removal of extracellular calcium. Phase 3 relaxations were more pronounced in stEBA precontracted with Carb and no epinephrine (NE) than those cont acted by KCl or K(2)SO(4). stEBA phase 2 and phase 3 responses were dose dependent (EC(50) = 1.1 +/- 1.2 x 10(-3) M and 6.7 +/- 0.9 x 10(-5) M, respectively; n = 7). NaHS was also vasoactive in steelhead bulbus arteriosus, celiac mesenteric arteries, and anterior cardinal veins. Rainbow trout plasma sulfide concentration was 4.0 +/- 0.3 x 10(-5) M, n = 4 (CM) and 3.8 +/- 0.4 x 10(-5) M, n = 9 (ISE); similar to phase 3 EC(50). Because NaHS has substantial vasoactive effects at physiological plasma concentrations, we propose that its soluble derivative, H(2)S, is a tonically active endogenous vasoregulator in trout.

Animals↗

Characterizing tolerance to trichloroethylene (TCE): effects of repeated inhalation of TCE on performance of a signal detection task in rats.

Previous work showed that rats develop tolerance to the acute behavioral effects of trichloroethylene (TCE) on signal detection if they inhale TCE while performing the task and that this tolerance depends more upon learning than upon changes in metabolism of TCE. The present study sought to characterize this tolerance by assessing signal detection in rats during three phases of TCE exposures. Tolerance was induced in Phase 1 (daily 1-h test sessions concurrent with TCE exposure), extinguished in Phase 2 (daily tests in air with intermittent probe tests in TCE), and reinduced in Phase 3. Original induction in Phase 1 required 2 weeks, whereas reinduction in Phase 3 required less than 1 week. Tolerance persisted for 2 (accuracy) or 8 weeks [response time] in Phase 2 and was resistant to changes in test conditions in Phase 3. The slow induction, gradual extinction, savings during reinduction and lack of disruption from altered test conditions suggest mediation by instrumental learning processes. These data and most other evidence for behavioral tolerance to solvents can be explained by solvent-induced loss of reinforcement.

Administration, Inhalation↗

Effects of pinacidil, verapamil, and heart rate on afterdepolarizations in the guinea-pig heart in vivo.

Recently, ionic current simulation in the Luo-Rudy model has elucidated putative mechanisms of afterdepolarizations under various experimental conditions. The present study was aimed at gaining insight into the differential mechanism of different types of afterdepolarizations in the guinea-pig heart in vivo. The effects of pharmacological and heart rate perturbations on early (EADs) and delayed (DADs) afterdepolarizations, induced by either digoxin, CsCl, or BayK 8644 were studied, using mid-myocardial left ventricular monophasic action potential (MAP) recordings. Digoxin insignificantly shortened sinus cycle length (SCL) and CsCl and BayK 8644 differentially prolonged SCL and MAP duration. Digoxin induced phase 3-EADs and DADs and CsCl or BayK 8644 induced phase 2- and phase 3-EADs. Pinacidil shortened MAP duration, suppressed almost all the phase 2-EADs and some of the phase 3-EADs, but not the DADs. In a few cases, DADs were manifested following the abolishment of phase 2-EADs by pinacidil, but this phenomenon did not occur in the presence of hexamethonium. Verapamil prolonged SCL, did not significantly affect phase 2-EADs, but suppressed almost all of the DADs, including those which appeared after pinacidil, and all but one of the phase 3-EADs. The effects of pinacidil and verapamil were independent of the mode of afterdepolarization induction. A pacing-induced heart rate increase, which shortened MAP duration, and vagal stimulation, which prolonged MAP duration, attenuated and enhanced phase 2-EADs, respectively. The amplitude of phase 3-EADs was inversely related to the heart rate. These data, taken together, are consistent with those obtained previously by others in a computer model and recent observations on CsCl-induced EADs in the guinea-pig Purkinje fibers in vitro which have indicated that the mechanism of phase 2-EADs is different from that of DADs and that late phase 3-EADs generated under conditions of Ca2+ overload and DADs share similar properties.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Plant sterol ester-enriched milk and yoghurt effectively reduce serum cholesterol in modestly hypercholesterolemic subjects.

BACKGROUND: The cholesterol-lowering efficacy of plant sterol esters (PSteE) or stanol esters (PStaE) in regular- and low-fat spreads has been consistently demonstrated, while their effectiveness in a low-fat, aqueous food carrier such as milk and yoghurt is less well established. AIM OF THE STUDY: Two studies were carried out to assess the cholesterol-lowering effect of PSteE-enriched low-fat milk and PSteE- and PStaE-enriched low-fat yoghurt in modestly hypercholesterolemic subjects (total cholesterol between 5-7.5 mmol/l). METHODS: Study one was a single blind crossover design with 4 phases of 3-week interventions. Subjects consumed 300 ml/d of placebo or PSteE-milk (2.0 g plant sterols/d) alone or combined with 25 g/d of placebo or PSteE-spread. Study two was a fully randomised, double blind crossover design with 3 phases of 3-week interventions. Subjects consumed 2 portions (150 g tubs each) of placebo, PSteE-yoghurt (1.8 g plant sterols/d) or PStaE-yoghurt (1.7 g plant stanols/d). In study one 39 subjects (21 men and 18 women) and in study two 40 subjects (17 men and 23 women) completed the dietary intervention. RESULTS: In study one, PSteE-milk and PSteE-spread were equally efficacious in lowering total and LDL-cholesterol as compared to placebo by 6-8% and 8-10%, respectively. No significant additional cholesterol-lowering was observed with the combination of PSteE-milk and PSteE-spread (4 g plant sterols/d). PSteE-enriched milk and the combination of PSteE-enriched milk plus spread both lowered lipid-adjusted serum beta-carotene concentrations by 10-14% (P < 0.02),while the PSteE-rich spread alone did not significantly alter serum beta-carotene levels. In study two, the PSteE- and PStaE-enriched yoghurts reduced LDL-cholesterol significantly compared to placebo by 0.27 +/- 0.05 mmol/l (6%) and 0.23 +/- 0.05 mmol/l (5%), respectively. In both studies, there was no effect on HDL-cholesterol and triacylglycerol concentrations. CONCLUSION: Plant sterols in the form of their esters when provided in lowfat milk and yoghurt are effective in lowering total and LDL-cholesterol.

Adult↗

Diabetes and cognitive function in a middle-aged cohort: findings from the Whitehall II study.

OBJECTIVE: To compare cognitive performance in those with diabetes, impaired glucose tolerance, and normoglycemia in a middle-aged cohort. METHODS: The authors analyzed data from a prospective occupational cohort study begun in 1985-1988 (baseline). Diabetes was classified from oral glucose tolerance tests that were performed in 1992-1993 (phase 3) and 1997-1999 (phase 5) and self reported diagnosis of diabetes from questionnaire at baseline, 1989 (phase 2), phase 3, 1995 (phase 4), and phase 5 of the study. A battery of cognitive tests (memory, Alice Heim 4 [AH 4], Mill Hill vocabulary test, phonemic fluency, and categorical fluency) were measured at phase 5 in 4,020 men and 1,627 women with a mean age of 56 and free of symptoms of stroke. RESULTS: At phase 5, a total of 208 (5%) men and 101 (6%) women had diabetes while 405 (10%) men and 192 (12%) women had impaired glucose tolerance. Those with diabetes were at increased risk of poor performance in AH 4 compared to those without (men: OR, 2.45; 95% CI, 1.77 to 3.38; women: OR, 1.83; 95% CI, 1.09 to 3.08). These effects were independent of age, social position, vascular problems, and health-related behaviors. Impaired glucose tolerance was not related to any measure of cognition. CONCLUSIONS: Type 2 diabetes is associated with poor performance in some aspects of cognition in middle-aged men and women.

Aged↗

Strontium ranelate: a new treatment for postmenopausal osteoporosis with a dual mode of action.

In vitro, strontium ranelate increases collagen and noncollagen protein synthesis by mature osteoblast-enriched cells. Its effects on bone formation were confirmed as the drug enhanced preosteoblastic cell replication. In the isolated osteoclast, preincubation of bone slices with strontium ranelate-induced dose-dependent inhibition of the bone-resorbing activity of treated rat osteoclast. Strontium ranelate dose-dependently inhibited preosteoclast differentiation. Its effect in postmenopausal women with established osteoporosis was assessed during an international, prospective, double-blind, randomized, placebo-controlled phase 3 program comparing strontium ranelate 2 g daily with placebo. The 3-year analysis of the phase 3 study, Spinal Osteoporosis Therapeutic Intervention, evaluating the effect of strontium ranelate 2 g/day on vertebral fracture rates, revealed a significant 41% reduction in the relative risk of patients experiencing new vertebral fracture with strontium ranelate over 3 years. A second phase 3 study showed a significant reduction in the relative risk of experiencing a nonvertebral fracture in the group treated with strontium ranelate over 3 years. These results show that strontium ranelate is a new, effective, and safe treatment for vertebral and hip osteoporosis, with a unique mode of action, increasing bone formation and decreasing bone resorption leading to a rebalance of bone turnover in favor of bone formation.

Animals↗

Clinical trials in cancer chemotherapy.

The success of cancer chemotherapy has increased greatly the potential areas for its inclusion in clinical trials and therefore has made the experimental design considerations more complex in these trials. New drugs still go through the three classic phases of clinical study beginning with clinical pharmacology (Phase I), efficacy screening (Phase 2) and role delineation (Phase 3). The Phase 2 and 3 trials now need to be considered within the overall therapeutic strategies which are required for each of the many diseases which are called cancer. The exigencies of a disease-oriented strategy which requires a blend of therapeutic modalities many times require a modification of what would be an ideal modality-oriented strategy geared solely to effectively testing a new agent. A new drug may need many Phase 2 and 3 trials in a variety of tumors before it can be considered adequately evaluated. Essential aspects of valid clinical trials include an adequate protocol which details the study and a design which is feasible for answering the question. Historical controls are advocated by many as a valid approach to clinical trials. Unless the numbers in the historical control are large and the prognostic variables well matches this approach should be viewed cautiously by the practicing physician.

Animals↗

An experimental uveitis induced by bovine serum albumin. A transmission and scanning electron microscopic study.

An acute experimental uveitis was produced by injecting bovine serum albumin (BSA) intravitreally into presensitized albino rabbits. Histopathological changes in the anterior uvea were followed during a period of 2 weeks using transmission and scanning electron microscopy. Both the ciliary body and the iris showed prominent ultrastructural changes. Based on the histopathological characteristics, the inflammatory reaction was divided into the 3 different phases: 1) a rapid and transient polymorphonuclear phase (3 h-day 1; 2) a slower and prolonged mononuclear phase (day 1-day 14) and 3) a phase which is characterized by tissue damage (day 7-). At the beginning of the mononuclear phase, inflammatory cells were seen to leak through the intercellular spaces of adjacent ciliary epithelial cells into the posterior chamber, later to cover large areas of the ciliary processes with fibrin. During the first 2 days, inflammatory changes were also detected in the ciliary body of the contralateral eye. The experiment was controlled using both unsensitized as well as presensitized rabbits which were intravitreally injected with sterile saline.

Animals↗

[Evaluation of middle cerebral artery blood flow velocity with transcranial Doppler in carotid endarterectomy].

Thirty patients, submitted to 34 carotid endarterectomies, from September, 1992 to April, 1996, on Hospital Albert Einstein, São Paulo, have been studied. In these surgeries, Middle Cerebral Artery (MCA) was miniaturized with Transcranial Doppler (TCD). The purpose of this study were to verify the relationship between MCA blood flow velocity with postoperative neurologic complications: studying the velocity variations with risk of cerebral low perfusion and carotid stump back pressure, during carotid clamping; confirming that the TCD information, could show when it is necessary to use shunting, and its efficiency; and to know whether the method could detect intraoperative embolization. The equipment used was a Transpect TCD-EME 2000. During surgery, when carotid stump back pressure was bellow of 54.4 mmHg, Pruitt-Inahara shunt was applied. The flow velocity value observed with TCD was divided in 3 parts: phase 1, basal, since anesthesy induction until carotid clamping; phase 2, clamping, during the period when the carotid artery was occluded; phase 3, post-declamping, from the time the carotid artery was declamping until the end of surgery. The MCA flow velocity was available on three phases, in cm/s and percentually on phases 2 and 3, in relation to basal phase. The embolizations, detected by TCD, were classified in: a) a few embolizations in less than 10 second period, b) many embolizations in more than 10 second period. Based on the results obtained, its possible to conclude that the MCA flow velocity is related to the risk of cerebral low perfusion during carotid clamping; it was not possible to stablish any relation of MCA flow velocity to carotid stump back pressure; the TCD informs when the use of shunt is necessary and its efficiency; the postoperative neurologic complications were caused by embolizations. The conclusion is that the TCD is useful and easily applicated on carotid endarterectomy.

Aged↗

Incremental treatment costs in national cancer institute-sponsored clinical trials.

CONTEXT: Concern about additional costs for direct patient care impedes efforts to enroll patients in clinical trials. But generalizable evidence substantiating these concerns is lacking. OBJECTIVE: To assess the additional cost of treating cancer patients in the National Cancer Institute (NCI)-sponsored clinical trials in the United States across a range of trial phases, treatment modalities, and patient care settings. DESIGN: Retrospective cost study using a multistage, stratified, random sample of patients enrolled in 1 of 35 active phase 3 trials or phase 1 or any phase 2 trials between October 1, 1998, and December 31, 1999. Unadjusted and adjusted costs were compared and related to trial phase, institution type, and vital status. SETTING AND PARTICIPANTS: A representative sample of 932 cancer patients enrolled in nonpediatric, NCI-sponsored clinical trials and 696 nonparticipants with a similar stage of disease not enrolled in a research protocol from 83 cancer clinical research institutions across the United States. MAIN OUTCOME MEASURES: Direct treatment costs as measured using a combination of medical records, telephone survey, and Medicare claims data. Administrative and other research costs were excluded. RESULTS: The incremental costs of direct care in trials were modest. Over approximately a 2.5-year period, adjusted costs were 6.5% higher for trial participants than nonparticipants (35,418 dollars vs 33,248 dollars; P =.11). Cost differences for phase 3 studies were 3.5% (P =.22), lower than for phase 1 or 2 trials (12.8%; P =.20). Trial participants who died had higher costs than nonparticipants who died (17.9%; 39,420 dollars vs 33,432 dollars, respectively; P =.15). CONCLUSIONS: Treatment costs for nonpediatric clinical trial participants are on average 6.5% higher than what they would be if patients did not enroll. This implies total incremental treatment costs for NCI-sponsored trials of 16 million dollars in 1999. Incremental costs were higher for patients who died and who were in early phase studies although these findings deserve further scrutiny. Overall, the additional treatment costs of an open reimbursement policy for government-sponsored cancer clinical trials appear minimal.

Adult↗

Surface soft phonon and the sqrt[3] x sqrt[3] <--> 3x3 phase transition in Sn/Ge(111) and Sn/Si(111).

Density functional theory calculations show that the reversible Sn/Ge(111) sqrt[3]xsqrt[3]<-->3x3 phase transition can be described in terms of a surface soft phonon. The isovalent Sn/Si(111) case does not display this transition since the sqrt[3]xsqrt[3] phase is the stable structure at low temperature, although it presents a partial softening of the 3x3 surface phonon. The rather flat energy surfaces for the atomic motion associated with this phonon mode in both cases explain the experimental similarities found at room temperature between these systems. The driving force underlying the sqrt[3]xsqrt[3]<-->3x3 phase transition is shown to be associated with the electronic energy gain due to the Sn dangling bond rehybridization.

Journal Article↗

Work characteristics predict psychiatric disorder: prospective results from the Whitehall II Study.

OBJECTIVES: The impact of work on the risk of future psychiatric disorder has been examined in few longitudinal studies. This was examined prospectively in a large epidemiological study of civil servants. METHODS: In the Whitehall II study, a longitudinal, prospective cohort study of 6895 male and 3413 female London based civil servants, work characteristics measured at baseline (phase 1: 1985-8) and first follow up (phase 2: 1989) were used to predict psychiatric disorder measured by a 30 item general health questionnaire (GHQ) at phase 2 and phase 3 follow up (phase 3: 1991-3). Work characteristics and GHQ were measured at all three phases. RESULTS: Low social support at work and low decision authority, high job demands and effort-reward imbalance were associated with increased risk of psychiatric disorder as assessed by the GHQ at follow up adjusting for age, employment grade, and baseline GHQ score. CONCLUSIONS: Social support and control at work protect mental health while high job demands and effort-reward imbalance are risk factors for future psychiatric disorder. Intervention at the level of work design, organisation, and management might have positive effects on mental health in working populations.

Adult↗