Attitudes and practices of general practitioners in the diagnosis and management of attention-deficit/hyperactivity disorder

Objective: To assess understanding of, and actual and potential roles in management of attention-deficit/hyperactivity disorder (ADHD) among GPs. Methods: A cross-sectional questionnaire survey of Queensland GPs selected randomly from the Royal Australian College of General Practitioners directory of members was carried out. Main outcome measures were knowledge levels of ADHD, current management practices, referral patterns and self-perceived information and training needs. Results: Three hundred and ninety-nine GPs returned a completed questionnaire (response rate 76%). Roles identified by GPs were: the provisional diagnosis of ADHD and referral to specialist services for confirmation of the diagnosis and initiation of management; assistance with monitoring progress once a management plan was in place; education of the child and their family regarding the disorder; and liaison with the school where necessary. Perceived barriers to increased involvement of GPs were: time and resource constraints of general practice; concerns regarding abuse and addiction liability of prescription stimulants; complex diagnostic issues associated with childhood behavioural problems; and lack of training and education regarding ADHD. Conclusions: General practitioners identify a role for themselves in ADHD care that is largely supportive in nature and involves close liaison with specialist services.

Acyl glucuronide reactivity in perspective: biological consequences

The metabolic conjugation of exogenous and endogenous carboxylic acid substrates with endogenous glucuronic acid, mediated by the uridine diphosphoglucuronosyl transferase (UGT) superfamily of enzymes, leads to the formation of acyl glucuronide metabolites. Since the late 1970s, acyl glucuronides have been increasingly identified as reactive electrophilic metabolites, capable of undergoing three reactions: intramolecular rearrangement, hydrolysis, and intermolecular reactions with proteins leading to covalent drug-protein adducts. This essential dogma has been accepted for over a decade. The key question proposed by researchers, and now the pharmaceutical industry, is: does or can the covalent modification of endogenous proteins, mediated by reactive acyl glucuronide metabolites, lead to adverse drug reactions, perhaps idiosyncratic in nature? This review evaluates the evidence for acyl glucuronide-derived perturbation of homeostasis, particularly that which might result from the covalent modification of endogenous proteins and other macromolecules. Because of the availability of acyl glucuronides for test tube/in vitro experiments, there is now a substantial literature documenting their rearrangement, hydrolysis and covalent modification of proteins in vitro. It is certain from in vitro experiments that serum albumin, dipeptidyl peptidase IV, tubulin and UGTs are covalently modified by acyl glucuronides. However, these in vitro experiments have been specifically designed to amplify any interference with a biological process in order to find biological effects. The in vivo situation is not at all clear. Certainly it must be concluded that all humans taking carboxylate drugs that form reactive acyl glucuronides will form covalent drug-protein adducts, and it must also be concluded that this in itself is normally benign. However, there is enough in vivo evidence implicating acyl glucuronides, which, when backed up by in vivo circumstantial and documented in vitro evidence, supports the view that reactive acyl glucuronides may initiate toxicity/immune responses. In summary, though acyl glucuronide-derived covalent modification of endogenous macromolecules is well-defined, the work ahead needs to provide detailed links between such modification and its possible biological consequences. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.

Coordinations in business interactions between Hong Kong Chinese, Mainland Chinese and western actors

Hong Kong firms continue to play an important role in the development of mainland China trade. This paper studies the nature of coordinations in triadic interactions between Hong Kong Chinese intermediaries and mainland Chinese sellers, and buyers from the West, and their impact on relationships development. Contrary to popular belief, the results presented here identify that interactions between Hong Kong intermediaries and mainland Chinese sellers tend to include relationships based on price and authority. These interactions tend to be classical in nature, and serve to hinder the development of relationships. On the other hand, interactions between buyers from the West and Hong Kong intermediaries tend to be relational in nature. They include different forms of personal relationships, which tends to be positive for the development of relationships. A new plural form of international business relationship triad is also identified.

Preserved obstacle avoidance during reaching in patients with left visual neglect

We asked 12 patients with left visual neglect to bisect the gap between two cylinders or to reach rapidly between them to a more distal target zone. Both tasks demanded a motor response but these responses were quite different in nature. The bisection response was a communicative act whereby the patient indicated the perceived midpoint. The reaching task carried no imperative to bisect the gap, only to maintain a safe distance from either cylinder while steering to the target zone. Optimal performance on either task could only be achieved by reference to the location of both cylinders. Our analysis focused upon the relative influence of the left and right cylinders on the lateral location of the response. In the bisection task, all neglect patients showed qualitatively the same asymmetry, with the left cylinder exerting less influence than the right. In the reaching task, the neglect group behaved like normal subjects, being influenced approximately equally by the two cylinders. This was true for all bar two of the patients, who showed clear neglect in both tasks. We conclude that the visuomotor processing underlying obstacle avoidance during reaching is preserved in most patients with left visual neglect. (C) 2004 Elsevier Ltd. All rights reserved.

Suitability of acoustic perturbation measures in analysing periodic and nearly periodic voice signals

In recent years, acoustic perturbation measurement has gained clinical and research popularity due to the ease of availability of commercial acoustic analysing software packages in the market. However, because the measurement itself depends critically on the accuracy of frequency tracking from the voice signal, researchers argue that perturbation measures are not suitable for analysing dysphonic voice samples, which are aperiodic in nature. This study compares the fundamental frequency, relative amplitude perturbation, shimmer percent and noise-to-harmonic ratio between a group of dysphonic and non-dysphonic subjects. One hundred and twelve dysphonic subjects ( 93 females and 19 males) and 41 non-dysphonic subjects ( 35 females and 6 males) participated in the study. All the 153 voice samples were categorized into type I ( periodic or nearly periodic), type II ( signals with subharmonic frequencies that approach the fundamental frequency) and type III ( aperiodic) signals. Only the type I ( periodic and nearly periodic) voice signals were acoustically analysed for perturbation measures. Results revealed that the dysphonic female group presented significantly lower fundamental frequency, significantly higher relative amplitude perturbation and shimmer percent values than the non-dysphonic female group. However, none of these three perturbation measures were able to differentiate between male dysphonic and male non-dysphonic subjects. The noise-to-harmonic ratio failed to differentiate between the dysphonic and non-dysphonic voices for both gender groups. These results question the sensitivity of acoustic perturbation measures in detecting dysphonia and suggest that contemporary acoustic perturbation measures are not suitable for analysing dysphonic voice signals, which are even nearly periodic. Copyright (C) 2005 S. Karger AG, Basel.

The occurrence of hopanoids in planctomycetes: implications for the sedimentary biomarker record

Hopanoids have generally been found in aerobic bacteria (i.e. methanotrophs, heterotrophs and cyanobacteria). Here we show that a variety of hopanoids (i.e. bacteriohopanetetrol, diplopterol, diploptene and a C-27 hopanoid ketone) occur in planctomycetes, including strictly anaerobic bacteria capable of anaerobic ammonium oxidation. Since planctomycetes have a widespread occurrence in Nature, this indicates that they may be an additional source for sedimentary hopanoids. (C) 2004 Elsevier Ltd. All rights reserved.

Characterization of a complex chemosensory signal transduction system which controls twitching motility in Pseudomonas aeruginosa

Virulence of the opportunistic pathogen Pseudomonas aeruginosa involves the coordinate expression of a wide range of virulence factors including type IV pili which are required for colonization of host tissues and are associated with a form of surface translocation termed twitching motility. Twitching motility in P. aeruginosa is controlled by a complex signal transduction pathway which shares many modules in common with chemosensory systems controlling flagella rotation in bacteria and which is composed, in part, of the previously described proteins PilG, PilH, PilI, PilJ and PilK. Here we describe another three components of this pathway: ChpA, ChpB and ChpC, as well as two downstream genes, ChpD and ChpE, which may also be involved. The central component of the pathway, ChpA, possesses nine potential sites of phosphorylation: six histidine-containing phosphotransfer (HPt) domains, two novel serine- and threonine-containing phosphotransfer (SPt, TPt) domains and a CheY-like receiver domain at its C-terminus, and as such represents one of the most complex signalling proteins yet described in nature. We show that the Chp chemosensory system controls twitching motility and type IV pili biogenesis through control of pili assembly and/or retraction as well as expression of the pilin subunit gene pilA. The Chp system is also required for full virulence in a mouse model of acute pneumonia.

Prevalence of rectocele in young nulliparous women

Background: It is generally assumed that fascial defects in the rectovaginal septum are the result of childbirth. However, rectoceles do occur in women who have never delivered vaginally. Aims: To determine the incidence of rectocele in a cohort of asymptomatic, young nulliparous women. Methods: Observational cohort study on 178 nulliparous caucasian women (aged 18-24) recruited for a twin study of pelvic floor dysfunction. All women were interviewed and examined by translabial ultrasound, supine and after voiding. In 52 women, 3D imaging was obtained and 171 datasets were complete and available for analysis. Ultrasound findings were reviewed for rectovaginal septal integrity by an assessor blinded against interview and demographic data for rectovaginal septal integrity. Results: A discontinuity of the anterior rectal wall with extrusion of rectal mucosa or contents (depth of ! 10 mm) was observed in 21/171 (12%). The depth of this herniation ranged from 10 to 25 mm and was filled with stool (n = 10) or rectal mucosa (n = 11). Defects were associated with a higher BMI (P = 0.049), with the complaint of constipation (P = 0.049) and non-significantly with straining at stool (P = 0.09). Descent of the ampulla to beyond the level of the symphysis pubis without fascial defect, that is, significant perineal relaxation, was observed in 23/171 (13%). Conclusions: Twelve percent of 171 young nulligravid caucasian women showed a defect of the rectovaginal septum. Associations were observed with higher body mass index and a history of constipation. It is hypothesised that in some women defects of the rectovaginal septum and perineal hypermobility may be congenital in nature.

Use of pulse transit time to distinguish respiratory events from tidal breathing in sleeping children

Study objectives: Currently, esophageal pressure monitoring is the "gold standard" measure for inspiratory efforts, hut its invasive nature necessitates a better tolerated and noninvasive method to be used on children. Pulse transit time (PTT) has demonstrated its potential as a noninvasive surrogate marker for inspiratory efforts. The principle velocity determinant of PTT is the change in stiffness of the arterial wall and is inversely correlated to BP. Moreover, PTT has been shown to identify changes in inspiratory effort via the BP fluctuations induced by negative pleural pressure swings. In this study, the capability of PTT to classify respiratory, events during sleep as either central or obstructive in nature was investigated. Setting and participants: PTT measure was used in adjunct to routine overnight polysomnographic studies performed on 33 children (26 boys and 7 girls; mean +/- SD age, 6.7 +/- 3.9 years). The accuracy of PTT measurements was then evaluated against scored corresponding respiratory events in the polysomnography recordings. Results: Three hundred thirty-four valid respiratory events occurred and were analyzed. One hundred twelve obstructive events (OEs) showed a decrease in mean PTT over a 10-sample window that had a probability of being correctly ranked below the baseline PTT during tidal breathing of 0.92 (p < 0.005); 222 central events (CEs) showed a decrease in the variance of PTT over a 10-sample window that had a probability of being ranked below the baseline PTT of 0.94 (p < 0.005). This indicates that, at a sensitivity of 0.90, OEs can be detected with a specificity of 0.82 and CEs can be detected with a specificity of 0.80. Conclusions: PTT is able to categorize CEs and OEs accordingly in the absence of motion artifacts, including hypopneas. Hence, PTT shows promise to differentiate respiratory, events accordingly and can be an important diagnostic tool in pediatric respiratory sleep studies.< 0.005); 222 central events (CEs) showed a decrease in the variance of PTT over a 10-sample window that had a probability of being ranked below the baseline PTT of 0.94 (p < 0.005). This indicates that, at a sensitivity of 0.90, OEs can be detected with a specificity of 0.82 and CEs can be detected with a specificity of 0.80. Conclusions: PTT is able to categorize CEs and OEs accordingly in the absence of motion artifacts, including hypopneas. Hence, PTT shows promise to differentiate respiratory, events accordingly and can be an important diagnostic tool in pediatric respiratory sleep studies.');"

Effects of adsorbed phase on diffusion of subcritical hydrocarbons in activated carbon at low pressures

Diffusions of free and adsorbed molecules of subcritical hydrocarbons in activated carbon were investigated to study the influence of adsorbed molecules on both diffusion processes at low pressures. A collision reflection factor, defined as the fraction of molecules undergoing collision to the solid surface over reflection from the surface, is incorporated into Knudsen diffusivity and surface diffusivity in meso/macropores. Since the porous structure of activated carbon is bimodal in nature, the diffusion of adsorbed molecules is contributed by that of weakly adsorbed molecules on the meso/macropore surfaces and that of strongly adsorbed molecules in the small confinement of micropores. The mobility of adsorbed molecules on the meso/macropore surface is characterized by the surface diffusivity D-mu 2, while that in the micropore is characterized by D-mu 1. In our study with subcritical hydrocarbons, we have found that the former increases almost linearly with pressure, while the latter exhibits a sharp increase at a very low-pressure region and then decreases beyond a critical pressure. This critical pressure is identified as a pressure at which the micropores are saturated.

Hierarchical organisation of neuro-anatomical constraints in interlimb coordination

Based on the observation that bimanual finger tapping movements tend toward mirror symmetry with respect to the body midline, despite the synchronous activation of non-homologous muscles, F. Mechsner, D. Kerzel, G. Knoblich, and W. Prinz (2001) [Perceptual basis of bimanual coordination. Nature, 414, 69-73] suggested that the basis of rhythmic coordination is purely spatial/perceptual in nature, and independent of the neuro-anatomical constraints of the motor system. To investigate this issue further, we employed a four finger tapping task similar to that used by F. Mechsner and G. Knoblich (2004) [Do muscle matter in bimanual coordination? Journal of Experimental Psychology: Human Perception and Performance, 30, 490-503] in which six male participants were required to alternately tap combinations of adjacent pairs of index (1), middle (M) and ring (R) fingers of each hand in time with an auditory metronome. The metronome pace increased continuously from 1 Hz to 3 Hz over the course of a 30-s trial. Each participant performed three blocks of trials in which finger combination for each hand (IM or MR) and mode of coordination (mirror or parallel) were presented in random order. Within each block, the right hand was placed in one of three orientations; prone, neutral and supine. The order of blocks was counterbalanced across the six participants. The left hand maintained a prone position throughout the experiment. On the basis of discrete relative phase analyses between synchronised taps, the time at which the initial mode of coordination was lost was determined for each trial. When the right hand was prone, transitions occurred only from parallel symmetry to mirror symmetry, regardless of finger combination. In contrast, when the right hand was supine, transitions occurred only from mirror symmetry to parallel but no transitions were observed in the opposite direction. In the right hand neutral condition, mirror and parallel symmetry are insufficient to describe the modes of coordination since the hands are oriented orthogonally. When defined anatomically, however, the results in each of the three right hand orientations are consistent. That is, synchronisation of finger tapping is deter-mined by a hierarchy of control of individual fingers based on their intrinsic neuro-mechanical properties rather than on the basis of their spatial orientation. (c) 2005 Elsevier B.V. All rights reserved.

Correlation between anammox activity and microscale distribution of nitrite in a subtropical mangrove sediment

The distribution of anaerobic ammonium oxidation (anammox) in nature has been addressed by only a few environmental studies, and our understanding of how anammox bacteria compete for substrates in natural environments is therefore limited. In this study, we measure the potential anammox rates in sediment from four locations in a subtropical tidal river system. Porewater profiles of NOx- (NO2- plus NO3-) and NO2- were measured with microscale biosensors, and the availability of NO2- was compared with the potential for anammox activity. The potential rate of anammox increased with increasing distance from the mouth of the river and correlated strongly with the production of nitrite in the sediment and with the average concentration or total pool of nitrite in the suboxic sediment layer. Nitrite accumulated both from nitrification and from NOx- reduction, though NOx- reduction was shown to have the greatest impact on the availability of nitrite in the suboxic sediment layer. This finding suggests that denitrification, though using NO2- as a substrate, also provides a substrate for the anammox process, which has been suggested in previous studies where microscale NO2- profiles were not measured.

Detecting finite bandwidth periodic signals in stationary noise using the signal coherence spectrum

All signals that appear to be periodic have some sort of variability from period to period regardless of how stable they appear to be in a data plot. A true sinusoidal time series is a deterministic function of time that never changes and thus has zero bandwidth around the sinusoid's frequency. A zero bandwidth is impossible in nature since all signals have some intrinsic variability over time. Deterministic sinusoids are used to model cycles as a mathematical convenience. Hinich [IEEE J. Oceanic Eng. 25 (2) (2000) 256-261] introduced a parametric statistical model, called the randomly modulated periodicity (RMP) that allows one to capture the intrinsic variability of a cycle. As with a deterministic periodic signal the RMP can have a number of harmonics. The likelihood ratio test for this model when the amplitudes and phases are known is given in [M.J. Hinich, Signal Processing 83 (2003) 1349-13521. A method for detecting a RMP whose amplitudes and phases are unknown random process plus a stationary noise process is addressed in this paper. The only assumption on the additive noise is that it has finite dependence and finite moments. Using simulations based on a simple RMP model we show a case where the new method can detect the signal when the signal is not detectable in a standard waterfall spectrograrn display. (c) 2005 Elsevier B.V. All rights reserved.

Engineered T cell receptors and their potential in molecular medicine

T cell receptors are among the most specific biological structures found in nature and are therefore excellent candidates for the molecular targeting of antigen. It is becoming increasingly apparent that common sets of T cell receptors are frequently used in humans to combat pathogen and cancer derived threats. Given that many of these conserved T cell receptors have high affinity for their target ligands, there is potential to amass virtual banks of “off-the-shelf” receptors for use in a wide range of immunotherapeutic strategies. Additionally, such T cell receptors could become basic blueprints for artificial enhancement through mutagenesis, thereby creating an even better 3-dimensional fit for their cognate targets. Indeed, preliminary approaches using both “natural” and “supernatural” T cell receptors have shown promise in treating autoimmunity and malignancy. This review will discuss these studies and other approaches through which T cell receptors can be exploited in immunodiagnostics, pathogen control and gene therapy.

Genome reduction in Leptospira borgpetersenii reflects limited transmission potential

Leptospirosis is one of the most common zoonotic diseases in the world, resulting in high morbidity and mortality in humans and affecting global livestock production. Most infections are caused by either Leptospira borgpetersenii or Leptospira interrogans, bacteria that vary in their distribution in nature and rely on different modes of transmission. We report the complete genomic sequences of two strains of L. borgpetersenii serovar Hardjo that have distinct phenotypes and virulence. These two strains have nearly identical genetic content, with subtle frameshift and point mutations being a common form of genetic variation. Starkly limited regions of synteny are shared between the large chromosomes of L. borgpetersenii and L. interrogans, probably the result of frequent recombination events between insertion sequences. The L. borgpetersenii genome is ≈700 kb smaller and has a lower coding density than L. interrogans, indicating it is decaying through a process of insertion sequence-mediated genome reduction. Loss of gene function is not random but is centered on impairment of environmental sensing and metabolite transport and utilization. These features distinguish L. borgpetersenii from L. interrogans, a species with minimal genetic decay and that survives extended passage in aquatic environments encountering a mammalian host. We conclude that L. borgpetersenii is evolving toward dependence on a strict host-to-host transmission cycle.