Magnitude and variability of loading on the osseointegrated implant of transfemoral amputees during walking

This study directly measured the load acting on the abutment of the osseointegrated implant system of transfemoral amputees during level walking, and studied the variability of the load within and among amputees. Twelve active transfemoral amputees (age: 54±12 years, mass:84.3±16.3 kg, height: 17.8±0.10 m) fitted with an osseointegrated implant for over 1 year participated in the study. The load applied on the abutment was measured during unimpeded, level walking in a straight line using a commercial six-channel transducer mounted between the abutment and the prosthetic knee. The pattern and the magnitude of the three-dimensional forces and moments were revealed. Results showed a low step-to-step variability of each subject, but a high subject-to-subject variability in local extrema of body-weight normalized forces and moments and impulse data. The high subject-to-subject variability suggests that the mechanical design of the implant system should be customized for each individual, or that a fit-all design should take into consideration the highest values of load within a broad range of amputees. It also suggests specific loading regime in rehabilitation training are necessary for a given subject. Thus the loading magnitude and variability demonstrated should be useful in designing an osseointegrated implant system better able to resist mechanical failure and in refining the rehabilitation protocol.

Synthesis of 4-arm star poly(L-Lactide) oligomers using an in situ-generated calcium-based initiator

Using an in situ-generated calcium-based initiating species derived from pentaerythritol, the bulk synthesis of well-defined 4-arm star poly(L-lactide) oligomers has been studied in detail. The substitution of the traditional initiator, stannous octoate with calcium hydride allowed the synthesis of oligomers that had both low PDIs and a comparable number of polymeric arms (3.7 – 3.9) to oligomers of similar molecular weight. Investigations into the degree of control observed during the course of the polymerization found that the insolubility of pentaerythritol in molten L-lactide resulted in an uncontrolled polymerization only when the feed mole ratio of L-lactide to pentaerythritol was 13. At feed ratios of 40 and greater, a pseudo-living polymerization was observed. As part of this study, in situ FT-Raman spectroscopy was demonstrated to be a suitable method to monitor the kinetics of the ring-opening polymerization (ROP) of lactide. The advantages of using this technique rather than FT-IR-ATR and 1H NMR for monitoring L-lactide consumption during polymerization are discussed.

Development and validation of 3-Minute Nutrition Screening (3-MinNS) tool for acute hospital patients in Singapore

It is important to detect and treat malnutrition in hospital patients so as to improve clinical outcome and reduce hospital stay. The aim of this study was to develop and validate a nutrition screening tool with a simple and quick scoring system for acute hospital patients in Singapore. In this study, 818 newly admitted patients aged above 18 years old were screened using five parameters that contribute to the risk of malnutrition. A dietitian blinded to the nutrition screening score assessed the same patients using the reference standard, Subjective Global Assessment (SGA) within 48 hours. The sensitivity and specificity were established using the Receiver Operator Characteristics (ROC) curve and the best cutoff scores determined. The nutrition parameter with the largest Area Under the ROC Curve (AUC) was chosen as the final screening tool, which was named 3-Minute Nutrition Screening (3-MinNS). The combination of the parameters weight loss, intake and muscle wastage (3-MinNS), gave the largest AUC when compared with SGA. Using 3-MinNS, the best cutoff point to identify malnourished patients is three (sensitivity 86%, specificity 83%). The cutoff score to identify subjects at risk of severe malnutrition is five (sensitivity 93%, specificity 86%). 3-Minute Nutrition Screening is a valid, simple and rapid tool to identify patients at risk of malnutrition in Singapore acute hospital patients. It is able to differentiate patients at risk of moderate malnutrition and severe malnutrition for prioritization and management purposes.

Estimation and compensation of clipping noise in OFDMA systems

We propose an efficient and low-complexity scheme for estimating and compensating clipping noise in OFDMA systems. Conventional clipping noise estimation schemes, which need all demodulated data symbols, may become infeasible in OFDMA systems where a specific user may only know his own modulation scheme. The proposed scheme first uses equalized output to identify a limited number of candidate clips, and then exploits the information on known subcarriers to reconstruct clipped signal. Simulation results show that the proposed scheme can significantly improve the system performance.

Adjuvant use of nutritional and herbal medicines with antidepressants, mood stabilizers and benzodiazepines

Adjuvant use of nutritional and herbal medicines has potential to increase the efficacy of synthetic pharmaceuticals, and perhaps also decrease their side-effects by allowing lower doses to be prescribed. We evaluated current evidence for adjuvant use of nutritional and herbal medicines with antidepressants, mood stabilizers and benzodiazepines; and explored novel future areas of research. The paper also critiques current evidence for co-administration of St. John’s wort with synthetic antidepressants. We performed a systematic search of MEDLINE, CINAHL, PsycINFO, The Cochrane database, China National Knowledge Infrastructure and the Chinese Science Citation Database. Search results were supplemented by a review of reference lists and a forward search using the Web of Science. Where possible we calculated effect sizes. Encouraging evidence exists for the use of omega-3 fatty acids, SAMe, folic acid and l-tryptophan adjuvantly with antidepressants to enhance response and improve efficacy. Various nutrients also have emerging evidence as effective adjuncts with antipsychotics and mood stabilizers. While some evidence supports nutritional adjuvancy with various psychopharmacotherapies, adjuvant use of herbal therapies has not been sufficiently studied to warrant standard clinical application. This remains a promising area of research via robust, safety-conscious studies.

The Kava Anxiety Depression Spectrum Study (KADSS): A randomized, placebo-controlled, cross-over trial using an aqueous extract of Piper methysticum.

Rationale: Piper methysticum (Kava) has been withdrawn in European, British, and Canadian markets due to concerns over hepatotoxic reactions. The WHO recently recommended research into “aqueous” extracts of Kava. Objective: The objective of this study was to conduct the first documented human clinical trial assessing the anxiolytic and antidepressant efficacy of an aqueous extract of Kava. Design and participants: The Kava Anxiety Depression Spectrum Study was a 3-week placebo-controlled, double-blind crossover trial that recruited 60 adult participants with 1 month or more of elevated generalized anxiety. Five Kava tablets per day were prescribed containing 250 mg of kavalactones/day. Results: The aqueous extract of Kava reduced participants' Hamilton Anxiety Scale score in the first controlled phase by −9.9 (CI = 7.1, 12.7) vs. −0.8 (CI = −2.7, 4.3) for placebo and in the second controlled phase by −10.3 (CI = 5.8, 14.7) vs. +3.3 (CI = −6.8, 0.2). The pooled effect of Kava vs. placebo across phases was highly significant (p < 0.0001), with a substantial effect size (d = 2.24, η² [sub]p[sub] = 0.428). Pooled analyses also revealed highly significant relative reductions in Beck Anxiety Inventory and Montgomery–Asberg Depression Rating Scale scores. The aqueous extract was found to be safe, with no serious adverse effects and no clinical hepatotoxicity. Conclusions: The aqueous Kava preparation produced significant anxiolytic and antidepressant activity and raised no safety concerns at the dose and duration studied. Kava appears equally effective in cases where anxiety is accompanied by depression. This should encourage further study and consideration of globally reintroducing aqueous rootstock extracts of Kava for the management of anxiety.

Effectiveness of current treatment approaches for benzodiazepine discontinuation : a meta-analysis.

Aims: To assess the effectiveness of current treatment approaches to assist benzodiazepine discontinuation. Methods: A systematic review of approaches to benzodiazepine discontinuation in general practice and out-patient settings was undertaken. Routine care was compared with three treatment approaches: brief interventions, gradual dose reduction (GDR) and psychological interventions. GDR was compared with GDR plus psychological interventions or substitutive pharmacotherapies. Results: Inclusion criteria were met by 24 studies, and a further eight were identified by future search. GDR [odds ratio (OR) = 5.96, confidence interval (CI) = 2.08–17.11] and brief interventions (OR = 4.37, CI = 2.28–8.40) provided superior cessation rates at post-treatment to routine care. Psychological treatment plus GDR were superior to both routine care (OR = 3.38, CI = 1.86–6.12) and GDR alone (OR = 1.82, CI = 1.25–2.67). However, substitutive pharmacotherapies did not add to the impact of GDR (OR = 1.30, CI = 0.97– 1.73), and abrupt substitution of benzodiazepines by other pharmacotherapy was less effective than GDR alone (OR = 0.30, CI = 0.14–0.64). Few studies on any technique had significantly greater benzodiazepine discontinuation than controls at follow-up. Conclusions: Providing an intervention is more effective than routine care. Psychological interventions may improve discontinuation above GDR alone. While some substitutive pharmacotherapies may have promise, current evidence is insufficient to support their use.

Imagery and strength of craving for eating, drinking and playing sport

The elaborated intrusion (EI) theory of desire (Kavanagh, Andrade, & May, 2005) attributes the motivational force of cravings to cognitive elaboration, including imagery, of apparently spontaneous thoughts that intrude into awareness. We report a questionnaire study in which respondents rated a craving for food or drink. Questionnaire items derived from EI theory formed a single factor alongside factors for anticipated reward/relief, resistance, and opportunity. In a multiple regression predicting strength of craving, the first three factors accounted for 36% of the variance. Opportunity did not enter the model. In a second study, the difference between individuals' strong and weak cravings to take part in a sporting activity was shown to be related to visual, auditory, and general imagery, and to anticipated reward or relief from engaging in the activity. Implications for treatment of craving-related disorders are discussed in the light of these results and of other research indicating that interference with imagery can reduce the strength of craving.

The reliability and validity of the Severity of Dependence Scale for detecting cannabis dependence in psychosis.

Aims: To determine the reliability and validity of the Severity of Dependence Scale (SDS) for detecting cannabis dependence in a large sample of in-patients with a schizophrenia spectrum disorder. Design: Cross-sectional study. Participants: Participants were 153 in-patients with a schizophrenia spectrum disorder in Brisbane, Australia. Measurements: Participants were administered the SDS for cannabis dependence in the past 12 months. The presence of Diagnostic and Statistical Manual Version-IV (DSM-IV) cannabis dependence in the previous 12 months was assessed using the Comprehensive International Diagnostic Interview (CIDI). Findings: The SDS had high levels of internal consistency and strong construct and concurrent validity. Individuals with a score of ≥2 on the SDS were nearly 30 times more likely to have DSM-IV cannabis dependence. The SDS was the strongest predictor of DSM-IV cannabis dependence after controlling for other predictor variables. Conclusions: The SDS is a brief, valid and reliable screen for cannabis dependence among people with psychosis

Crossing boundaries: Implications of advances in basic sciences for the management of addiction.

This set of papers in this issue of "Addictive Behaviors" was presented at the 2004 'Addictions' conference, which, for the first time, was held in the Southern Hemisphere, on the Sunshine Coast of Queensland, Australia. The theme of the conference, Crossing Boundaries: Implications of Advances in Basic Sciences for the Management of Addiction, speaks for itself. The papers derive from a wide range of empirical paradigms and cover issues with relevance to the development of addiction, to the maintenance of problematic use, and to assessment, treatment, and relapse. Research from Europe and the United States is represented, as well as work from Australia. An international perspective is strongly emphasized from the initial paper by Obot, Poznyak, and Moneiro, (see record 2004-19599-015) which describes the WHO Report on the Neuroscience of Psychoactive Substance Use and Dependence, and summarises some of the report's implications for policy and practice. Hall, Carter, and Morley (see record 2004-19599-014) close the issue with a paper on the wide-ranging ethical implications of advances in neuroscience research, including issues arising from the identification of high risk for addiction, the potential for coercive pharmacotherapy, use of medications to enhance function, and risks to privacy.

Prevention of postnatal distress or depression : an evaluation of an intervention at preparation for parenthood classes.

Determined the effectiveness of a psychosocial intervention, provided to expectant couples in routine antenatal classes, on the postpartum psychosocial adjustment of women and men. Preparation for Parenthood programs were randomly allocated to one of three conditions: usual service ('control'), experimental ('empathy'), or non-specific control ('baby-play'). The latter condition controlled for the non-specific effects of the intervention, these being: the provision of an extra class; asking couples to consider the early postpartum weeks; and receiving booster information after the antenatal class, and again shortly after the birth. Women and men were categorised into three levels of self-esteem, as measured antenatally: low, medium and high. 268 participants were recruited antenatally. Interview data and self-report information was collected from 202 of these women at 6 weeks postpartum, and 180 women at 6 months postpartum. The intervention consisted of a session focusing on psychosocial issues related to becoming first-time parents. Participants discussed possible postpartum concerns in separate gender groups for part of the session, and then discussed these issues with their partners

Being stoned : a review of self-reported cannabis effects.

Although there has been considerable research into the adverse effects of cannabis, less attention has been directed toward subjective effects that may be associated with ongoing cannabis use. Examination of self-reported cannabis effects is an important issue in understanding the widespread use of cannabis. While reviews have identified euphoria as a primary factor in maintaining cannabis use, relaxation is the effect reported most commonly in naturalistic studies of cannabis users, irrespective of the method used. Self-reported effects in 12 naturalistic and 18 laboratory studies were compared. Regardless of methodology there was considerable variation in the effects experienced. Variation has been reported in terms of opposite effects being experienced by different individuals, variation of effects by individuals within a single occasion and between occasions of use. Factors that might explain this variation are outlined. Limitations of the available literature and suggested directions for future research are discussed.

Event-related potential (ERP) correlates of impaired visuospatial memory in schizophrenia

Previous studies have reported that patients with schizophrenia demonstrate impaired performance during working memory (WM) tasks. The current study aimed to determine whether WM impairments in schizophrenia are accompanied by reduced slow wave (SW) activity during on-line maintenance of mnemonic information. Event-related potentials were obtained from patients with schizophrenia and well controls as they performed a visuospatial delayed response task. On 50% of trials, a distractor stimulus was introduced during the delay. Compared with controls, patients with schizophrenia produced less SW memory negativity, particularly over the right hemisphere, together with reduced frontal enhancement of SW memory negativity in response to distraction. The results indicate that patients with schizophrenia generate less maintenance phase neuronal activity during WM performance, especially under conditions of distraction.

Human brain regions required for the dividing and switching of attention between two features of a single object

This combined PET and ERP study was designed to identify the brain regions activated in switching and divided attention between different features of a single object using matched sensory stimuli and motor response. The ERP data have previously been reported in this journal [64]. We now present the corresponding PET data. We identified partially overlapping neural networks with paradigms requiring the switching or dividing of attention between the elements of complex visual stimuli. Regions of activation were found in the prefrontal and temporal cortices and cerebellum. Each task resulted in different prefrontal cortical regions of activation lending support to the functional subspecialisation of the prefrontal and temporal cortices being based on the cognitive operations required rather than the stimuli themselves.

A re-examination of the Ghrelin and Ghrelin receptor genes

The last few years have seen dramatic advances in genomics, including the discovery of a large number of non-coding and antisense transcripts. This has revolutionised our understanding of multifaceted transcript structures found within gene loci and their roles in the regulation of development, neurogenesis and other complex processes. The recent and continuing surge of knowledge has prompted researchers to reassess and further dissect gene loci. The ghrelin gene (GHRL) gives rise to preproghrelin, which in turn produces ghrelin, a 28 amino acid peptide hormone that acts via the ghrelin receptor (growth hormone secretagogue receptor/GHSR 1a). Ghrelin has many important physiological and pathophysiological roles, including the stimulation of growth hormone (GH) release, appetite regulation, and cancer development. A truncated receptor splice variant, GHSR 1b, does not bind ghrelin, but dimerises with GHSR 1a, and may act as a dominant negative receptor. The gene products of ghrelin and its receptor are frequently overexpressed in human cancer While it is well known that the ghrelin axis (ghrelin and its receptor) plays a range of important functional roles, little is known about the molecular structure and regulation of the ghrelin gene (GHRL) and ghrelin receptor gene (GHSR). This thesis reports the re-annotation of the ghrelin gene, discovery of alternative 5’ exons and transcription start sites, as well as the description of a number of novel splice variants, including isoforms with a putative signal peptide. We also describe the discovery and characterisation of a ghrelin antisense gene (GHRLOS), and the discovery and expression of a ghrelin receptor (growth hormone secretagogue receptor/GHSR) antisense gene (GHSR-OS). We have identified numerous ghrelin-derived transcripts, including variants with extended 5' untranslated regions and putative secreted obestatin and C-ghrelin transcripts. These transcripts initiate from novel first exons, exon -1, exon 0 and a 5' extended 1, with multiple transcription start sites. We used comparative genomics to identify, and RT-PCR to experimentally verify, that the proximal exon 0 and 5' extended exon 1 are transcribed in the mouse ghrelin gene, which suggests the mouse and human proximal first exon architecture is conserved. We have identified numerous novel antisense transcripts in the ghrelin locus. A candidate non-coding endogenous natural antisense gene (GHRLOS) was cloned and demonstrates very low expression levels in the stomach and high levels in the thymus, testis and brain - all major tissues of non-coding RNA expression. Next, we examined if transcription occurs in the antisense orientation to the ghrelin receptor gene, GHSR. A novel gene (GHSR-OS) on the opposite strand of intron 1 of the GHSR gene was identified and characterised using strand-specific RT-PCR and rapid amplification of cDNA ends (RACE). GHSR-OS is differentially expressed and a candidate non-coding RNA gene. In summary, this study has characterised the ghrelin and ghrelin receptor loci and demonstrated natural antisense transcripts to ghrelin and its receptor. Our preliminary work shows that the ghrelin axis generates a broad and complex transcriptional repertoire. This study provides the basis for detailed functional studies of the the ghrelin and GHSR loci and future studies will be needed to further unravel the function, diagnostic and therapeutic potential of the ghrelin axis.