Optical barcoding of colloidal suspensions: applications in genomics, proteomics and drug discovery

The enormous amount of information generated through sequencing of the human genome has increased demands for more economical and flexible alternatives in genomics, proteomics and drug discovery. Many companies and institutions have recognised the potential of increasing the size and complexity of chemical libraries by producing large chemical libraries on colloidal support beads. Since colloid-based compounds in a suspension are randomly located, an encoding system such as optical barcoding is required to permit rapid elucidation of the compound structures. We describe in this article innovative methods for optical barcoding of colloids for use as support beads in both combinatorial and non-combinatorial libraries. We focus in particular on the difficult problem of barcoding extremely large libraries, which if solved, will transform the manner in which genomics, proteomics and drug discovery research is currently performed.

Pro re nata medication for psychoses: the knowledge and beliefs of doctors and nurses

Objective: To examine the knowledge and beliefs of doctors and nurses in inpatient psychiatric units about pro re nata (PRN) (as needed) medications for psychotic disorders. Methods: Medical (n = 44) and nursing (n = 80) staff in two metropolitan public hospital units completed a structured questionnaire about their use of PRN psychotropic medications on one occasion during the four months from March-June 1999. Results: Nurses selected more indications for PRN antipsychotics than doctors (3.49 vs 2.72, p < 0.05), whereas doctors selected more indications for PRN benzodiazepines (3.77 vs 3.19, p < 0.05). The groups did not differ in the number of selected indications for using anticholinergics. For agitation, the majority of nurses viewed both benzodiazepines (56%) and antipsychotics (86%) as effective, with 60% preferring an antipsychotic. For the acute control of psychotic symptoms, 99% of nurses believed antipsychotics were effective and 58% benzodiazepines, with 87% preferring an antipsychotic. A large majority of doctors viewed both PRN benzodiazepines, 94% ,and antipsychotics, 81%, as effective for agitation, and 55% preferred to use a benzodiazepine. For psychotic symptoms, 80% believed PRN antipsychotics were effective, but only 32% viewed benzodiazepines as effective, and 64% preferred to use an antipsychotic. Nursing staff identified more non-pharmacological techniques for managing both agitation and psychotic symptoms and reported using these more often than doctors. Junior staff, both nursing and medical, had less knowledge of non-pharmacological alternatives to PRN medication than senior staff. Conclusions: Disparities existed between doctors and nurses views on the indications for PRN medication in the acute management of psychoses, thus it is important for doctors to specify indications when writing PRN prescriptions. Despite evidence for the safety and effectiveness of benzodiazepines, there was widespread reluctance to use them as PRN medication in acute psychoses. Beliefs of some staff about PRN medications were at odds with the known properties of these medicines. Educational interventions for both nurses and doctors are required to achieve best practice in PRN medication.

Pro re nata medication for psychoses: an audit of practice in two metropolitan hospitals

Objective: To examine the use of pro re nata (PRN) (as needed) medication in hospitalized patients with psychotic disorders. Methods: Retrospective chart reviews were conducted at two large public psychiatry units situated in inner city general hospitals. Pro re nata medication prescription, administration and outcomes were examined during inpatient episodes of care for 184 consecutive admissions of patients diagnosed with a psychotic disorder. Patient demographics, diagnoses, and regularly prescribed medication were also recorded. All admissions were drawn from a three-month period from December 1998-February 1999. Results: The most prevalent diagnoses were schizophrenia related disorders (n = 111) and mania (n = 34). Substance use disorders (n = 49) were the most common comorbid dis-orders. Pro re nata medication was administered during the acute phase of 82% of admissions. Drugs prescribed Pro re nata were mostly typical antipsychotics, benzodiazepines and/or anti-cholinergics. Coprescription of typical antipsychotics PRN with regularly scheduled atypical antipsychotics was common (64%). Pro re nata medications accounted for 31% of the total antipsychotic dose and 28% of the total anxiolytic dose administered during acute treatment. Higher daily doses of PRN medication were given to manic patients, males, younger patients and those with substance use disorders. Pro re nata prescriptions usually specified a maximum daily dose (87%) but rarely gave indications for use (6%). Adminis-tration records frequently lacked a specified reason for use (48%) or a notation of outcome (64%). Unit staff noted medication-related morbidity in 37% of patients receiving PRN medication, compared to 3% of patients receiving only regularly scheduled medication. Extrapyramidal symptoms (EPS) were most frequently associated with administration of PRN haloperidol (Relative Risk vs other PRN medications = 5.61, 95% CI = 2.36-13.73). Conclusions: Pro re nata medications comprised a significant part of the treatment which psychotic patients received. The common practice of coprescribing PRN typical antipsychotics with scheduled atypical antipsychotics is potentially problematical since administration of PRN medication is associated with significant medication related morbidity. Preferential use of benzodiazepines as PRN agents may minimize this morbidity and foster subsequent compliance with regularly prescribed antipsychotics.

Control of chaotic instability in a dual-spin spacecraft with dissipation using energy methods

Control of chaotic instability in a rotating multibody system in the form of a dual-spin spacecraft with an axial nutational damper is achieved using an algorithm derived using energy methods. The control method is implemented on two realistic spacecraft parameter configurations which have been found to exhibit chaotic instability when a sinusoidally varying torque is applied to the spacecraft for a range of forcing amplitudes and frequencies. Such a torque, in practice, may arise under malfunction of the control system or from an unbalanced rotor. Chaotic instabilities arising from these torques could introduce uncertainties and irregularities into a spacecraft's attitude and consequently impair pointing accuracy. The control method is formulated from nutational stability results derived using an energy sink approximation for a dual-spin spacecraft with an asymmetric platform and axisymmetric rotor. The effectiveness of the control method is shown numerically and the results are studied by means of time history, phase space, Poincare map, Lyapunov characteristic exponents and Bifurcation diagrams.

A rapid screen of the severity of mild traumatic brain injury

This study investigated the sensitivity of information processing, recall and orientation tasks to the presence of mild Traumatic Brain Injury (mTBI). Fifty-six (40 male, 16 female) mTBI patients and 85 (57 male and 28 female) controls with orthopaedic injuries were tested within 24 hr of injury in the Department of Emergency Medicine. mTBI patients answered fewer orientation questions and recalled fewer words in delayed recall than orthopaedic patients. mTBI patients judged fewer sentences in 2 min than orthopaedic controls, and female mTBI patients judged fewer sentences than male mTBI patients. Male mTBI patients correctly recalled fewer words during immediate memory and learning than female mTBI patients and orthopaedic controls. Those mTBI patients with a history of previous head injuries did not perform more poorly than those mTBI patients without previous head injuries. These results indicate that tests of speed of information processing, word learning and orientation questions are sensitive to the acute effects of mTBI.

Improvements to peroxide oxidation methods for analysing sulfur in acid sulfate soils

Improvements to peroxide oxidation methods for analysing acid sulfate soils (ASS) are introduced. The soil solution ratio has been increased to 1 : 40, titrations are performed in suspension, and the duration of the peroxide digest stage is substantially shortened. For 9 acid sulfate soils, the peroxide oxidisable sulfur value obtained using the improved method was compared with the reduced inorganic sulfur result obtained using the chromium reducible sulfur method. Their regression was highly significant, the slope of the regression line was not significantly different (P = 0.05) from unity, and the intercept not significantly different from zero. A complete sulfur budget for the improved method showed there was no loss of sulfur as has been reported for earlier peroxide oxidation techniques. When soils were very finely ground, efficient oxidation of sulfides was achieved, despite the milder digestion conditions. Highly sulfidic and organic soils were shown to be the most difficult to analyse using either the improved method or the chromium method. No single analytical method can be universally applied to all ASS, rather a suite of methods is necessary for a thorough understanding of many ASS. The improved peroxide method, in combination with the chromium method and the 4 M HCl extraction, form a sound platform for informed decision making on the management of acid sulfate soils.

Predictor-corrector methods of Runge-Kutta type for stochastic differential equations

In this paper we construct predictor-corrector (PC) methods based on the trivial predictor and stochastic implicit Runge-Kutta (RK) correctors for solving stochastic differential equations. Using the colored rooted tree theory and stochastic B-series, the order condition theorem is derived for constructing stochastic RK methods based on PC implementations. We also present detailed order conditions of the PC methods using stochastic implicit RK correctors with strong global order 1.0 and 1.5. A two-stage implicit RK method with strong global order 1.0 and a four-stage implicit RK method with strong global order 1.5 used as the correctors are constructed in this paper. The mean-square stability properties and numerical results of the PC methods based on these two implicit RK correctors are reported.

The influence of preparedness on rapid stepping in young and older adults

Objective: To investigate the influence of age and preparation level on postural muscle activation and step completion time during a rapid step task. Design: Postural muscle onset times (EMG) and ground reaction forces were recorded from healthy young (n = 20, age 21 +/- 3 years) and older (n = 25, age 71 +/- 5 years) female adults during a choice reaction-time stepping paradigm. Main outcome measures: Onset times of six trunk and hip muscles, reaction time and components of the step (weight shift time, step time and task time) were recorded. Results: Muscle activation was delayed and movement time was lengthened in both young and older adults when poorly prepared for a stepping task. While reduced preparation did not influence older adults to a greater extent than young adults, the slowest step response and completion time was evident in older adults when poorly prepared to move. Conclusions: A late postural response when poorly prepared to move may be a contributing factor to an increased risk of overbalancing in older adults. Future assessment of and intervention to improve postural stability in older adults should be expanded to incorporate tasks performed at various levels of preparation.

New W-isotope evidence for rapid terrestrial accretion and very early core formation

The short-lived Hf-182-W-182-isotope system is an ideal clock to trace core formation and accretion processes of planets. Planetary accretion and metal/silicate fractionation chronologies are calculated relative to the chondritic Hf-182-W-182-isotope evolution. Here, we report new high-precision W-isotope data for the carbonaceous chondrite Allende that are much less radiogenic than previously reported and are in good agreement with published internal Hf-W chronometry of enstatite chondrites. If the W-isotope composition of terrestrial rocks, representing the bulk silicate Earth, is homogeneous and 2.24 epsilon(182W) units more radiogenic than that of the bulk Earth, metal/silicate differentiation of the Earth occurred very early. The new W-isotope data constrain the mean time of terrestrial core formation to 34 million years after the start of solar system accretion. Early terrestrial core formation implies rapid terrestrial accretion, thus permitting formation of the Moon by giant impact while Hf-182 was still alive. This could explain why lunar W-isotopes are more radiogenic than the terrestrial value. Copyright (C) 2002 Elsevier Science Ltd.

An atomistic simulation of solid state sintering using Monte Carlo methods

This paper presents results on the simulation of the solid state sintering of copper wires using Monte Carlo techniques based on elements of lattice theory and cellular automata. The initial structure is superimposed onto a triangular, two-dimensional lattice, where each lattice site corresponds to either an atom or vacancy. The number of vacancies varies with the simulation temperature, while a cluster of vacancies is a pore. To simulate sintering, lattice sites are picked at random and reoriented in terms of an atomistic model governing mass transport. The probability that an atom has sufficient energy to jump to a vacant lattice site is related to the jump frequency, and hence the diffusion coefficient, while the probability that an atomic jump will be accepted is related to the change in energy of the system as a result of the jump, as determined by the change in the number of nearest neighbours. The jump frequency is also used to relate model time, measured in Monte Carlo Steps, to the actual sintering time. The model incorporates bulk, grain boundary and surface diffusion terms and includes vacancy annihilation on the grain boundaries. The predictions of the model were found to be consistent with experimental data, both in terms of the microstructural evolution and in terms of the sintering time. (C) 2002 Elsevier Science B.V. All rights reserved.

Postural control and movement performance during upper limb tasks in children with developmental co-ordination disorder (DCD)

At least 6% of primary school aged children present with DCD, where co-ordination is substantially below the normal range for the child’s age and intelligence. Motor skill difficulties negatively affect academic achievement, recreation and activities of daily living. Poor upper-limb co-ordination is a common difficulty for children with DCD. A possible cause of this problem is deviant muscle timing in proximal muscle groups, which results in poor postural and movement control. While studies have been published investigating postural control in response to external perturbations, detail about postural muscle activity during voluntary movement is limited even in children with normal motor development. No studies have investigated the relationship between muscle timing, resultant arm motion and upper-limb coordination deficits. Objectives: To investigate the relationship between functional difficulties with upper-limb motor skills and neuromuscular components of postural stability and coordination. Specifically, to investigate onset-timing of muscle activity, timing of arm movement, and resultant three-dimensional (3D) arm co-ordination during rapid, voluntary arm movement and to analyse differences arising due to the presence of DCD. This study is part of a larger research program investigating postural stability and control of upper limb movement in children. Design: A controlled, cross-sectional study of differences between children with and without DCD. Methods: This study included 50 children aged eight to 10 years (25 with DCD and 25 without DCD). Children participated in assessment of motor skills according to the Movement ABC Test and a laboratory study of rapid, voluntary arm movements. Parameters investigated included muscle activation timing of shoulder and trunk muscles (surface electromyography), arm movement timing (light sensor) and resultant 3D arm motion (Fastrak). Results: A MANOVA is being used to analyse between-group differences. Preliminary results indicate children with DCD demonstrate altered muscle timing during a rapid arm raise when compared with the control group of children. Conclusion: Differences in proximal muscle timing in children with DCD support the hypothesis that altered proximal muscle activity may contribute to poor proximal stability and consequently poor arm movement control. This has implications for clinical physiotherapy.