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Cells need to act upon the elastic extracellular matrix and against steric constraints when proliferating in a confined environment, leading to the build-up, at the population level, of a compressive, growth-induced, mechanical stress. Compressive mechanical stresses are ubiquitous to any cell population growing in a spatially-constrained environment, such as microbes or most solid tumors. They remain understudied, in particular in microbial populations, due to the lack of tools available to researchers. Here, we present various mechano-chemostats: microfluidic devices developed to study microbes under pressure. A mechano-chemostat permits researchers to control the intensity of growth-induced pressure through the control of cell confinement, while keeping cells in a defined chemical environment. These versatile devices enable the interrogation of physiological parameters influenced by mechanical compression at the single cell level and set a standard for the study of growth-induced compressive stress.

Background The Xarelto for Prevention of Stroke in Patients with Atrial Fibrillation (XANTUS) registry investigated the safety and efficacy of the factor Xa inhibitor rivaroxaban. We studied the Dutch XANTUS cohort to a ssess drug safety and prescription patterns in the Netherlands.Methods The XANTUS registry was designed as a European prospective, observational study among patients with non-valvular atrial fibrillation. Major bleeding and all-cause mortality were assessed every three months during a 1-year follow-up period. In this Dutch sub-cohort we were also specifically interested in dosing regimens and the incidence and reasons for temporary or permanent discontinuation.Results Patients (n = 899) had a mean age of 69 (SD +/- 9) years and 64.8% were male. The median CHA2DS2-VASc score was 2 (IQR 2-4) and the median HAS-BLED score was 2 (IQR 1-2). Major bleeding occurred in 19 patients (2.4 per 100 patient-years) and 8 patients (1.0 per 100 patient- years) died during the 1-year follow-up period. According to renal function, label-discordant dosing was observed in 48 (8.3%) patients. Finally, 124 patients (13.8%) reported a temporary interruption of rivaroxaban treatment and 11.8% switched to another oral anticoagulant therapy after permanent discontinuation of rivaroxaban.Conclusion In the Dutch subset of the XANTUS registry, we observed low rates of major bleeding and label-discordant dosing and high persistence rates during one year of follow-up in patients receiving rivaroxaban in routine clinical practice. However, documenting the motivation of novel oral anticoagulant (NOAC) type and dose is essential to study label-discordant prescription, a potential safety paradox and identify patient characteristics to optimise NOAC use and adherence.

Construction projects, by their very nature, impose significant financial risks on all stakeholders. Changes to the scope of work are contemplated by the contracts. Time is of the essence, and commencing construction (and sometimes equipment procurement) before design is complete has become the industry norm. Changes, delays, unanticipated events, and disruptions, regardless of their root cause, can exponentially increase the cost incurred by the stakeholders in completion of the project. Disputes among the stakeholders are inevitable, and an effective dispute resolution process is critical to the financial success of the project. Dispute resolution boards, project neutrals, partnering, mandatory negotiation among project executives, and other creative mechanisms as a prerequisite to any more formal dispute resolution process can be very effective in promptly resolving disputes. Reaching a successful resolution becomes significantly more difficult, however, as the complexity of the project and the number of stakeholders in the process increases. Rather than (or in conjunction with) submitting disputes to a binding resolution process such as arbitration or litigation, stakeholders often utilize mediation. Mediation gives the stakeholders the opportunity to work with an experience neutral facilitator in crafting an acceptable resolution of the dispute. In addition to retaining control of the outcome of the process, mediation is cost-effective and minimizes the transaction and opportunity costs associated with resolving the underlying disputes. This article focuses on effectively mediating large and complex construction disputes, with an emphasis on the dynamics associated with multiparty mediation. To demonstrate the complexity of a construction mediation involving multiple parties, consider the following hypothetical situation, with the diverse interests of the various stakeholders.

Aim: To determine the prognostic value of reversible myocardial perfusion defects on myocardial perfusion scintigraphy (MPS) in patients with type 2 diabetes mellitus and mild anginal complaints.Methods and results: In the MERIDIAN trial, patients with diabetes mellitus type 2, stable, mild anginal symptoms (Canadian Cardiovascular Society classification (CCS) I-II/IV) and reversible perfusion defects were randomized to either continued pharmacological treatment or early invasive treatment. In this sub analysis, the severity of the myocardial perfusion defect was related to the occurrence of cardiac death and non-fatal myocardial infarction, in 319 patients (63% male, 65 ± 9 years). During follow-up (2.2 ± 0.6 years), 14 patients had a cardiac event: 3 in 171 patients without myocardial ischemia and 11 in 148 patients with myocardial ischemia. Annual event rates rose from 0.8% to 5.8% with increasing severity of myocardial ischemia. Multivariable analysis identified the presence of severe myocardial ischemia (hazard ratio (HR) 5.45, 95%CI 1.89-15.71) and insulin use (HR 4.00, 95%CI 1.25-12.75) as independent predictors of cardiac events.Conclusions: Type 2 diabetics with mild anginal symptoms with no or moderate myocardial ischemia have a low annual cardiac event rate. In patients with severe myocardial ischemia event rate increased 3-6 fold.

The use of liquid chromatography (LC) coupled with tandem mass spectrometry (MS/MS) or single-stage mass spectrometry (MS) is making significant inroads in the analyst's compendium of instrumentation available for the analysis of drugs in biological fluids, tissues, and other specimens of interest. LC/MS(/MS) has the unique capability of analyzing substances frequently not analyzable by any other means. Furthermore, LC/MS(/MS), particularly LC/MS/MS instrumentation, has shown a precipitous drop in cost, making it more accessible to the smaller laboratories. As such, an increasing number of methods for the analysis of drugs of abuse have been published using LC/MS(/MS) - in particular, those methods associated with LC/MS/MS. However, these methods are not without certain endemic problems/limitations such as ion source selection, matrix effects, endogenous interferences, and interlibrary matching of spectra. This review seeks to show what progress is being made to circumvent the perceived limitations of LC/MS(/MS). It presents methodologies for selected drugs of abuse (opioids, benzodiazepines, cannabinoids, cocaine, and the amphetamines) that have been developed in recent years for analysis in blood, urine, hair, and oral fluids, as well as certain other specimens. Emphasis is primarily directed toward those methodologies that have been developed recently for LC/MS/MS, but LC/MS methods are also addressed where appropriate.

This article is concerned with penalty methods for solving optimal Dirichlet control problems governed by the steady-state and time-dependent Navier-Stokes equations. We present, in two different versions, the penalized methods for solving the steady-slate Dirichlet control problems. These approaches are implemented and compared numerically. We also generalize the penalty methods to the time-dependent case. Scmidiscrete and fully discrete approximations of time-dependent Dirichlet control problems are discussed and implemented. Numerical results for solving both the steady-state and the time dependent Dirichlet control problems are reported.

AIMS--A new sign of florid xanthelasmata is described in four male patients with orbital manifestations of Wegener's granulomatosis. METHODS--The case notes of four patients with Wegener's granulomatosis, with orbital involvement accompanied by yellow lid lesions, are reviewed. RESULTS--All the patients had active Wegener's granulomatosis at the time the lid lesions were most florid. The lesions gradually resolved as the inflammatory disease was controlled with immunosuppressive agents. The lesions displayed marked asymmetry and predominantly involved the side with the most severe inflammation. Abnormalities of lipid metabolism were not identified and it is believed that the lesions developed in a susceptible anatomical region affected by a vasculitic process. CONCLUSION--A 'yellow lid' associated with orbital inflammation and is a strong pointer to the clinical diagnosis of Wegener's granulomatosis.

The effects of prolonged release recombinant porcine somatotropin (rpST) and dietary protein were tested in 108 Lacombe pigs, allocated to control or rpST treatments at 70 kg and fed isoenergetic diets containing one of three protein levels (14, 17 or 20% CP). Recombinant derived porcine somatotropin was implanted in the ear weekly (Monsanto Agricultural Co., St. Louis, #CP 115409, 12 mg wk−1). The control animals were given a weekly sham injection for a minimum of 4 wk. The prolonged release rpST had no effect on average daily gain (ADG, P > 0.05), but did reduce both the feed:gain ratio (F:G, P −1 reduction, P −1 (P −1 for every 3% increase in crude protein. Simultaneous reductions in carcass fat, marbling and drip loss were observed (P

In the preparation of plant samples for 15N analysis, it is often necessary to digest the samples for long periods in the presence of H2SO4 and catalysts. As an alternative, a recently developed H2O2 digestion procedure for total N was tested for use in 15N analysis of plant tissue. As tested, the digestion period was 13 min, and the procedure resulted in good recoveries of total N (98.7%) and atom % 15N (99.6%) from eight 15N‐enriched plant standards.

To present several modifications of the standard sit-and-reach protocol.Many exercises designed to increase strength and aerobic capacity tend to decrease the flexibility of the erector spinae and hamstrings musculature. Less-than-ideal flexibility in these soft tissues may increase the risk of injury during training, competition, or activities of daily living. The most widely used measures of flexibility have been either the stand-and-reach or the sit-and-reach, but both are limited to a single measure.Using the new multitest flexometer, we were able to take 6 flexibility measures beyond the stand-and-reach test: standard active sit-and-reach, standard passive sit-and-reach, modified active sit-and-reach with external rotators slackened, modified passive sit-and-reach with external rotators slackened, modified active sit-and-reach with the hamstrings, gastrocnemii, and external rotators slackened, and modified passive sit-and-reach with the hamstrings, gastrocnemii, and external rotators slackened.This modified sit-and-reach protocol allows the indirect assessment of the influence of the 4 major muscle groups that affect sit-and-reach scores: erector spinae, hip rotators, hamstrings, and gastrocnemii.

PURPOSE: To determine the prevalence and predictors of reversible myocardial perfusion defects, indicative of myocardial ischaemia, in patients with mild, stable anginal complaints [Canadian Cardiovascular Society classification (CCS) I-II/IV] and diabetes mellitus type 2 (T2DM). METHODS: A total of 329 patients with T2DM and stable, mild anginal symptoms (CCS I-II/IV) underwent myocardial perfusion scintigraphy. Perfusion images were assessed using a five-point (semi)-quantitative scoring system according to a 17-segment myocardial model. RESULTS: One-hundred and fifty-six (47%) patients showed reversible myocardial perfusion defects defined as a summed difference score of >/=3. Male gender [odds ratio (OR) 2.28, 95% CI 1.4-3.71, p=0.001], previous myocardial infarction (MI) without revascularisation (OR 3.04, 95% CI 1.28-7.24, p=0.01), and the use of two or more classes of anti-anginal medication (OR 2.36, 95% CI 1.48-3.76, p

A distinct body of literature supports the association between clinical postures of the dental practitioner and work-related musculoskeletal disorders (WRMD). Several aids or devices have been tested to improve clinical posture in the interest of decreasing WRMD. The use of magnification lenses while performing dental procedures may increase the quality of work and decrease the likelihood of musculoskeletal problems. To date, only anecdotal and personal opinions had existed regarding the benefits of using magnification lenses, and no empirical evidence had authenticated the contention that use of magnification lenses exerts a positive change in operator posture. The objective of this study was to assess the effect magnification lenses had on the posture of dental hygiene students. Using a randomized crossover design, researchers videotaped nineteen senior dental hygiene students performing an intra-oral procedure with and without the use of magnification lenses. The tapes were then evaluated by a panel of five dental hygiene educators calibrated in the use of Branson's Posture Assessment Instrument (PAI). Results of a paired t-test indicate that the posture of the students while wearing magnification lenses was more acceptable (p=.019) than when wearing traditional safety glasses. Results of this study indicate a quantifiable change in acceptability of posture for clinicians wearing magnification lenses and suggest that the use of such lenses in dental education may be warranted.

Recently, Holt and Lotto [Hear. Res. 167, 156-169 (2002)] reported that preceding speech sounds can influence phonetic identification of a target syllable even when the context sounds are presented to the opposite ear or when there is a long intervening silence. These results led them to conclude that phonetic context effects are mostly due to nonperipheral auditory interactions. In the present paper, similar presentation manipulations were made with nonspeech context sounds. The results agree qualitatively with the results for speech contexts. Taken together, these findings suggest that the same nonperipheral mechanisms may be responsible for effects of both speech and nonspeech context on phonetic identification. (C) 2003 Acoustical Society of America.

To this point in time, acupuncture has been used primarily as an analgesic, a therapeutic intervention that controls pain under pathological conditions. Although some of the mechanisms of acupuncture as it applies to pain relief have been studied, little is known of the positive and/or negative effects of this procedure on the physical performance parameters of healthy people, particularly highly trained athletes. After introducing acupuncture from historical and technique viewpoints, preliminary studies of the effects of acupuncture on strength, aerobic conditioning, flexibility, and sport performance are discussed, as well as concerns regarding the direction of research investigating the potential benefit and/ or adverse effects of this practice. Finally, an argument is put forward for the establishment of guidelines for the use of acupuncture in the sports community.

Since the discovery that oral ingestion of creatine leads to an increase in intramuscular creatine, its supplementation has become widespread. However, the dosage necessary to maximize retention and create significant increases in intramuscular creatine is poorly understood. In this study, 24-hour urinary creatine and creatinine levels of 20 university men's football players and 20 university men's hockey players involved in a resistance-exercise program and supplementing with creatine were collected and analyzed. In a double-blind, randomized design, 10 football players and 10 hockey players were randomly assigned to either the supplement or placebo group. Subjects provided a 24-hour urine sample twice during the study: once prior to supplementation (baseline) and the second 7 days after daily supplementation and resistance exercise. Creatine dosage was 0.1 g x kg(-1) lean body mass. The quantity of creatine ingested was compared with the amount excreted in the urine of those subjects supplementing with creatine and with placebo. Creatinine levels were compared between the first and second urine collection and between groups. Creatine and creatinine concentrations were determined using high-performance liquid chromatography. In 24-hours, 46% of the ingested creatine was excreted. There was no change in creatine levels for placebo subjects. Creatinine levels remained the same within groups at the first and second collection times (p0.05). Our findings indicate that when supplementing with dosages of 0.1 g x kg(-1) lean body mass or between 6 and 8 g at a time, approximately half of the ingested creatine gets excreted. Because there was no change in urinary creatinine, it can be assumed that enhanced degradation of creatine did not occur.

Ever since DNA microarrays were first applied to the quantitation of RNA levels, there has been considerable interest in generating a protein homolog that can be used to assay cellular protein expression. A recent paper describes the first microarray that can be used for such protein profiling.

Cerebrovascular disease is the most common cause of neurological disability in Western countries. Patients who survive cerebrovascular accidents exclusive to the occipital lobe often have no significant neurological deficits other than visual-field loss. Visual-field defects from occipital lobe stroke typically include congruous homonymous hemianopsias or quadranopsias, with or without macular sparing.A 61-year-old white man came to us with symptoms of sudden loss of vision and difficulty reading. Visual-field testing revealed a bilateral inferior altitudinal defect with normal optic nerve and fundus appearance in both eyes. On radiological examination, he was found to have had a bioccipital lobe cerebrovascular accident secondary to complete occlusion of the left vertebral artery. An embolic event causing the artery occlusion, in combination with bilaterally compromised cerebellar and posterior cerebral arteries, presumably caused the bilateral stroke. After appropriate medical and neurological consultation, optometric management consisted of maximizing the patient's remaining vision with a prismatic spectacle correction.Patients with infarction exclusive to the occipital lobe typically have no other neurological deficits except visual-field loss and are often easier to manage than patients with infarctions to other areas of the cerebral cortex or multiple infarctions. Visual-field loss from occipital lobe damage can be successfully managed with optical systems and/or visual rehabilitation. Factors related to management include location and extent of visual-field damage, functional visual needs, and both personal and health concerns of the patient. A discussion is presented on cerebrovascular disease, occipital lobe infarction, imaging techniques, and visual rehabilitation.

We described two elderly patients with severe hyponatremia that was probably caused by inappropriate secretion of antidiuretic hormone. The hyponatremia arose during fluoxetine (Prozac) antidepressant therapy. (Arch Intern Med. 1996;156:681-682)

Training methods used in competitive flatwater paddling often lead to a common pattern of soft tissue injuries that affect the upper limb. Of particular frequency is paddler's shoulder, a condition that can become chronic and may result in permanent damage. The authors suggest that the cumulative effect of poorly structured resistance training initiates the deteriorative process and together with the repetitiveness of on-water training results in the pathologies referred to as paddler's shoulder.

In a 78-year-old female with hyponatraemia, the syndrome of inappropriate ADH secretion as a side effect of fluoxetine, a relatively new antidepressive drug, was tentatively diagnosed. In the literature 14 cases of this adverse reaction have been described. One should be careful when prescribing fluoxetine to elderly persons, notably when a diuretic is prescribed as well.

A greenhouse experiment was conducted to measure nitrous oxide (N2O) emissions from a soil, which had been planted to flooded transplanted rice, as it was rewetted to simulate the end of a dry season fallow period. The pots of soil had been cropped to transplanted rice with two commonly used nitrogen (N) fertilizer treatments and a control, and the soil had been puddled before transplanting. Large amounts of nitrate N accumulated in the soils during the dry season fallow, and the N fertilizers applied to the previous crop had little effect on nitrate accumulation. There was little N2O emission during the nitrification period. With water additions meant to simulate rainfall events at the beginning of a wet season, the soil redox dropped slightly, and large amounts of N2O began to be emitted. Large emissions began 5 days after each of the two simulated rainy season watering events and stopped abruptly at soil saturation, even though considerable amounts of nitrate still remained in the soil after saturation. Total measured emissions amounted to 6 to 7 kg N2O-N ha−1 for the period. Although these measurements were made in a system which may have favored nitrate accumulation, they are the first known measurements of N2O made from a rice soil as it is wetted. Nitrous oxide emitted from the flooding of rice soils that have accumulated nitrate during a dry season fallow may be a major source of N2O additions to the atmosphere.