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Radioactivity occurs in trithloroacetic acid (TCA)-soluble and precipitable, cytoplasm and salt-washed walls following germination of Lilium longiflorum, cv. 'Ace' pollen in medium containing [14C]-proline (Pro). Sephadex gel filtration on G-25 through G-100 was employed to determine whether radioactivity in cytoplasm, wall and growth medium from pollen fed [14C]-Pro or [3H]=Pro plus [14C]-arafbinose (Ara) was contained within molecules possessing molecular weights of 5,000 to 100,000 daltones or greater. G-25 elution profiles of a crude cytoplasmic fraction (15,000 X g supernatant) from [14C]-Pro labelled pollen yielded a radioctive void volume peak and a retarded peak. The void volume peak contained hydroxyproline (Hyp), and exhibited a coincidence of [3H]-Pro and [14C] -Ara labelling when pollen was double labelled with the two isotopes. This peak also contained radioactivity when pollen was germinated in 2-[3H]-myo-inositol. Germination in medium supplemented with 100 µM 2,2'-dipyridyl eliminated radioactivity from 2-[3H]-myo-inositol or [14C]-,Pro in the peak. Filtratian on G-25 of aTCA-soluble fraction of a salt-extract of walls from [14C]-Pro labelled pollen resulted in void volume and two retarded peaks. Void volume and two retarded peaks were also obtained upon G-25 filtration of a cellulase-digest of walls from [M]-Pro labeled pollen. The void volume peak contained Hyp, Lys, Gly, Ala, Ser, Glu and Asp acids, Val, Tyr, Leu or lieu and Pro. Sephadex G-90, 75, and 100 elution profiles of cellulasedigests of walls from [3H]-,Pro and [14C]-Ara labelled pollen yielded radioactive retarded and Hyp-containing void volume peaks with a coincidence of [3H] and [14C] labelling. Label in the void volume was obtained when either rhozyme P11- or pepsin-digests of walls from [14C]-Pro labelled pollen were gel filtered on G-50. Paper electrophoresis coupled with paper chromatography of acid hydrolyzates of salt-washed wall fractions demonstrated 15 of the common amino acids. Gel filtration on G-25 of growth medium in which pollen was germinated resulted in two peaks, one of which eluted in the void volume. contained Hyp and excluded during subsequent gel filtration on G-100.

Background: Previous studies have evidenced balance training for improving postural control in children with DCD, however none have examined how neuromuscular mechanisms controlling balance might be improved with training., Aims: To assess the neuromuscular control of balance before and after training in children with DCD., Methods and Procedures: Eleven children with DCD completed a six-week, game-based intervention to train balance, and lower-limb and core strength. Six children with DCD formed the control group. Stepping behaviour, centre of mass variability, centre of pressure area, and postural muscle onset latencies, using a continuous oscillating platform paradigm, were assessed at baseline, immediately-post and six-week-post intervention., Outcomes and Results: Both groups showed improvement in the oscillating platform task, indicating a learning effect. However, only the training group showed improvements in MABC-2 balance percentile scores from baseline (p = 0.008)., Conclusions and Implications: These findings suggest that children with DCD can learn through repeated exposure to challenging situations, regardless whether training is given. However, only the training group were able to transfer these improvements to the MABC-2 balance assessment. This may suggest the intervention exposed children to increased movement variations which could be transferred to a different task., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Most methods used to measure the thickness of thin liquid or solid surface films and coatings need access to the coated surface. In this work reflected ultrasonic pulses were used to measure a coating thickness from a solid back face. Piezoelectric transducers on the solid back face emitted ultrasound waves and received the waves that bounced off the front face. The magnitude of the reflected wave was dependent on the film thickness at the front face. Most pulse-echo ultrasonic approaches use the time-of-flight through the surface layer to determine its thickness. However, as the film becomes thinner, the reflected echoes overlap and there is often an acoustic mismatch between the solid and the surface film that reduces the signal strength. In this work, we propose the use of an ultrasonic continuously repeated chirp longitudinal wave to amplify the effect of the surface film. Multiple reflections interfere within the solid to form a superimposed standing wave whose amplitude spectrum is highly dependent on the surface film thickness thus overcoming the acoustic mismatch problem. Two bare 10 MHz piezoelectric elements were bonded to a 10 mm thick aluminium solid in a pitch-catch arrangement such that one continuously sends repeating chirp ultrasound waves and the other acts as the receiver. The transmitter was set to send a repeating chirp wave of 4 ms duration corresponding to the bandwidth of the transducer in order to maximise signal amplitude. The incident and reflected waves constructively and destructively interfere to form a superimposed standing wave within the solid. The solid/surface film to solid/air boundary condition frequency spectra ratio showed the film resonant frequency modes as minima. Using this technique epoxy coatings ranging from 70 μm to 350 μm were measured and showed a good correlation with independent measurements using a surface profilometer., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Galectin-3 is a beta-galactoside-binding mammalian lectin and part of the 15 member galectin family that are evolutionarily highly conserved. It is the only chimeric protein with a C-terminal carbohydrate recognition domain (CRD) linked to a proline, glycine, and tyrosine rich additional N-terminal domain. Galectin-3 binds several cell surface glycoproteins via its CRD domain as well as undergoing oligomerization, via binding at the N-terminal or the CRD, resulting in the formation of a galectin-3 lattice on the cell surface. The galectin-3 lattice has been regarded as being a crucial mechanism whereby extracellular galectin-3 modulates cellular signalling by prolonging retention time or retarding lateral movement of cell surface receptors in the plasma membrane. As such galectin-3 can regulate various cellular functions such as diffusion, compartmentalization and endocytosis of plasma membrane glycoproteins and glycolipids and the functionality of membrane receptors. In multiple models of organ fibrosis, it has been demonstrated that galectin-3 is potently pro-fibrotic and modulates the activity of fibroblasts and macrophages in chronically inflamed organs. Increased galectin-3 expression also activates myofibroblasts resulting in scar formation and may therefore impact common fibrotic pathways leading to fibrosis in multiple organs. Over the last decade there has been a marked increase in the scientific literature investigating galectin-3 in a range of fibrotic diseases as well as the clinical development of new galectin-3 inhibitors. In this review we will examine the role of galectin-3 in fibrosis, the therapeutic strategies for inhibiting galectin-3 in fibrotic disease and the clinical landscape to date., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Cyber-dependent offending, i.e. criminal behaviour reliant on computing and the online domain, has been reportedly associated with particular characteristics and motivations such as being young, male, autistic and motivated by challenge. These associations are anecdotal however and empirical evidence is limited. The present study investigated reasons for engaging or declining to commit cyber-dependent offending in cyber-skilled non-offenders (n = 175) and offenders (n = 7) via an online survey measuring cyber-dependent criminality. The potential role of autism and autistic traits was also considered. Qualitative interviews about motivations for offending were carried out with the offenders. The cyber-dependent offenders reported seven main reasons for engaging in cyber-dependent offending: (1) lack of understanding; (2) entertainment; (3) peer influence; (4) experience and career; (5) anonymity and risk perception; (6) life events; and (7) morals. Twenty-nine (approximately 17 %) of the non-offenders had been asked to engage in cyber-dependent offending but had declined. Their reasons and motivations for declining to commit cyber-dependent offences were compared with the cyber-dependent offenders reasons and motivations for engaging in cybercrime. Seven main reasons for declining to offend were identified: (1) moral principles; (2) perception of risk; (3) fear of consequences; (4) not wanting to; (5) wanting to adhere to the law; (6) behaviour being too complicated; and (7) price being too low. Implications for practise are discussed., (Copyright © 2020. Published by Elsevier Ltd.)

Household chaos and insecure parental attachment styles are associated with lower quality parenting behaviors. However, there is a paucity of evidence regarding fathers' parenting behaviors, and no studies examine if chaotic home environments moderate the attachment style-parenting behavior relationship. Using data from both mothers and fathers of 742 children (40.5% African American) living in rural, low-resource communities, the current study examined the individual and joint effects of self-reported adult attachment style and two domains of household chaos on observed maternal and paternal parenting behaviors during structured play with their 58-month old child (49.6% female). Multivariate models revealed that, even after controlling for confounders, attachment insecurity predicted lower quality parenting behavior for mothers and fathers. Further, for both mothers and fathers, the disorganized domain of household chaos, representing environments high in noise, clutter and disorder, predicted less sensitive and more intrusive parenting behavior. Finally, for mothers with dismissive attachment styles, high levels of disorganization appeared to exacerbate caregiving difficulties; this moderating relationship was not evident for fathers. These findings suggest that the stress of a chronically disorganized family environment may impact the expression of mothers' insecure tendencies in the context of parenting, thereby intensifying less sensitive and more intrusive parenting behaviors.

Background: Previous studies have found high rates of intellectual disabilities (ID) in prison. However, little is understood about prisoners with ID. This study aimed to identify prisoners with ID and compare their characteristics with prisoners without neurodevelopmental disorders with regard to demographic profile, mental health, suicide risk and offences., Method: This was a descriptive, cross-sectional study carried out using face-to-face interviews with 240 participants in a London Category C prison. Standardised tools were used to assess prisoners for ID and mental disorder., Results: The study identified 18 prisoners as having ID. Participants with ID were less likely to be from a black or minority ethnic background, be over 35 years of age or have any qualifications. They were more likely to have been single, homeless or unemployed before coming into prison. Prisoners with ID were significantly more likely to have mental health problems and 25% had thought about suicide in the last month and 63% had attempted suicide in the past. Prisoners with ID were also more likely to be housed in the vulnerable prisoners' wing and significantly more likely to have committed robbery than other prisoners., Conclusions: The findings confirm the presence of significant numbers of people with ID with high levels of mental illness in a male prison. Services across the CJS are required for this group, specifically, there is a need for raised awareness among those working in prison about ID and improved skills to recognise offenders with ID and address major gaps in current healthcare provision in prison., (© 2017 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.)

We present the design and operating characteristics of a vacuum furnace used for inelastic neutron scattering experiments on a time-of-flight chopper spectrometer. The device is an actively water cooled radiant heating furnace capable of performing experiments up to 1873 K. Inelastic neutron scattering studies performed with this furnace include studies of phonon dynamics and metallic liquids. We describe the design, control, characterization, and limitations of the equipment. Further, we provide comparisons of the neutron performance of our device with commercially available options. Finally we consider upgrade paths to improve performance and reliability.

Using propensity-matched controls, the present study examines the associations between maternal report of child-directed aggression and observed parenting behavior across early childhood for women with and without childhood sexual trauma histories. The moderating role of child sex was also examined. The sample (n=204) is from a longitudinal study of rural poverty exploring the ways in which child, family, and contextual factors shape development over time. After controlling for numerous factors including child and primary caregiver covariates, findings reveal that childhood sexual trauma is related to sensitive parenting behavior and child-directed aggression. Findings further revealed that child sex moderates the relation between sexual trauma history and maternal behavior towards children. Implications for interventions for mothers with childhood sexual trauma histories and directions for future study are proposed., Competing Interests: Conflict of Interest All authors declare that they have no competing interests

This study examines multiple pathways by which maternal childhood sexual trauma may be related to the behavioral development of children. Propensity score matching procedures were used to create matched groups (total N = 204) of mothers who retroactively did or did not self-report childhood sexual trauma in a longitudinal sample of families living in poor, rural communities. Using structural equation modeling, maternal characteristics and behaviors were examined as potential mediators of the relationship between maternal histories of childhood sexual trauma and children's conduct problems. After controlling for numerous socio-demographic factors, analyses indicate that maternal depressive symptoms, intimate partner violence, and maternal parenting were significant mediators and highlight the lasting impact of childhood sexual trauma on victims and their children.

Objectives: Stress control (SC), a brief psycho-education course, was implemented to increase access to psychological therapies in line with Northern Irish mental health service statutory drivers. The first aim of this study was to gauge the efficacy of SC in a robust manner with clinical significance testing. The second aim was to assess whether demographics traditionally 'hard-to-reach' - males, younger adults and those from deprived areas - accessed SC. The third aim was to elucidate what prompted their access and the experiences of attendees at SC., Methods: Attendees at SC were 170 adults over six iterations of the course. Pre- and post-questionnaires included the Depression Anxiety Stress Scales - 21, captured demographic details and qualitative feedback, which was subject to a mixed-methods analysis., Results: SC attendees reported significant decreases on depression, anxiety and stress sub-scales post-intervention. Moreover, 38.71% (n=36) of attendees who completed SC exhibited clinically significant improvement afterwards on one or more sub-scale. Attendance figures for males, younger adults and those classified as socioeconomically deprived were modest. Patterns within the data suggested prospective success for targeting these cohorts., Conclusions: SC attracted people in need of mental healthcare input and affected quantifiable change within those people's lives, while satisfying statutory demands for service delivery in an accessible community context. Recommendations to increase engagement with those traditionally 'hard-to-reach' for psychological services are provided, which, if implemented, have the potential to achieve further compliance with Northern Irish mental health statutory drivers.

The Queensland branch of the Royal Australasian College of Physicians (RACP) commissioned this study to update their workforce profile and examine rural practice. The present investigation aimed to describe characteristics of Queensland physicians and determine the influence of childhood and training locations on current rural practice. A cross-sectional online survey, conducted 4 July-4 November 2013, was administered to Fellows of The RACP, Queensland. Descriptive statistics report characteristics and logistic regression analyses identify associations and interactions. The outcome measure was current practice location using the Australian Standard Geographic Classification - Remoteness Area. Data were obtained for 633 physicians. Their average age was 49.5 years, a third was female and a quarter was in rural practice. Rural practice was associated with a rural childhood (odds ratio (OR) (95% confidence interval, CI) 1.89 (1.10, 3.27) P = 0.02) and any time spent as an intern (OR 4.07 (2.12, 7.82) P < 0.001) or registrar (OR 4.00 (2.21, 7.26) P < 0.001) in a rural location. Physicians with a rural childhood and rural training were most likely to be in rural practice. However, those who had a metropolitan childhood and a rural internship were approximately five times more likely to be working in rural practice than physicians with no rural exposure (OR 5.33 (1.61, 17.60) P < 0.01). The findings demonstrate the positive effect of rural vocational training on rural practice. A prospective study would determine if recent changes to the Basic Physician Training Pathway and the Basic Paediatric Training Network (more rural training than previous pathways) increases the rate of rural practice., (© 2016 Royal Australasian College of Physicians.)

Objectives: To gather and analyse information concerning the aetiology and pathology of otitis media with effusion in adults., Method: A review of the English language literature from 1970 to the present was conducted., Results: The available evidence suggests that otitis media with effusion in adult life is best viewed as a syndrome with a number of causes, including: infiltration of the eustachian tube by nasopharyngeal carcinoma and other local malignancies; changes in the middle ear and eustachian tube induced by radiotherapy; and systemic disease., Conclusion: There is now a body of evidence specifically related to the aetiology and pathology of otitis media with effusion in adult life. However, further research is required to fill in the gaps in our knowledge and understanding of this condition.

Background: Previous studies have found high rates of attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD) and intellectual disability (ID) within the criminal justice system (CJS). However, little is understood about prisoners with neurodevelopmental disorders and difficulties (NDD) or their needs. This study aimed to identify prisoners with NDD and compare their characteristics with prisoners without NDD on a range of socio-demographic and social functioning measures., Method: This was a descriptive, cross-sectional study carried out using face-to-face interviews with 240 participants in a London Category C prison. Standardised tools were used to assess prisoners for ADHD, ASD and ID., Results: The study identified 87 prisoners who screened positive for one or more type of NDD. Participants with NDD were significantly younger and more likely to be single [(odds ratio) OR = 2.1], homeless (OR = 3.4) or unemployed (OR = 2.6) before they came into prison. They also had poorer educational achievements that those without NDD. Over 80% of those with NDD had a previous conviction or imprisonment., Conclusions: The findings confirm the presence of significant numbers of people with NDD in a male prison. Services across the CJS are required for this group; specifically, there is a need for raised awareness among those working in the CJS to improve the recognition of offenders with NDD. Services in the community need to work with individuals with NDD who are at risk of offending, targeting those who are homeless, unemployed and have poor employment opportunities., (© 2015 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.)

A design for a sample cell system suitable for high temperature Quasi-Elastic Neutron Scattering (QENS) experiments is presented. The apparatus was developed at the Spallation Neutron Source in Oak Ridge National Lab where it is currently in use. The design provides a special sample cell environment under controlled humid or dry gas flow over a wide range of temperature up to 950 °C. Using such a cell, chemical, dynamical, and physical changes can be studied in situ under various operating conditions. While the cell combined with portable automated gas environment system is especially useful for in situ studies of microscopic dynamics under operational conditions that are similar to those of solid oxide fuel cells, it can additionally be used to study a wide variety of materials, such as high temperature proton conductors. The cell can also be used in many different neutron experiments when a suitable sample holder material is selected. The sample cell system has recently been used to reveal fast dynamic processes in quasi-elastic neutron scattering experiments, which standard probes (such as electrochemical impedance spectroscopy) could not detect. In this work, we outline the design of the sample cell system and present results demonstrating its abilities in high temperature QENS experiments.

This study describes the impact of pet dogs on stress of primary carers of children with Autism Spectrum Disorder (ASD). Stress levels of 38 primary carers acquiring a dog and 24 controls not acquiring a dog were sampled at: Pre-intervention (17 weeks before acquiring a dog), post-intervention (3-10 weeks after acquisition) and follow-up (25-40 weeks after acquisition), using the Parenting Stress Index. Analysis revealed significant improvements in the intervention compared to the control group for Total Stress, Parental Distress and Difficult Child. A significant number of parents in the intervention group moved from clinically high to normal levels of Parental Distress. The results highlight the potential of pet dogs to reduce stress in primary carers of children with an ASD.

Background: Genetic information, typically communicated in-person by genetic counselors, can be challenging to comprehend; delivery of this information online--as is becoming more common--has the potential of increasing these challenges., Methods: To address the impact of the mode of delivery of genomic risk information, 300 individuals were recruited from the general public and randomized to receive genomic risk information for type 2 diabetes mellitus in-person from a board-certified genetic counselor or online through the testing company's website., Results: Participants were asked to indicate their genomic risk and overall lifetime risk as reported on their test report as well as to interpret their genomic risk (increased, decreased, or same as population). For each question, 59% of participants correctly indicated their risk. Participants who received their results in-person were more likely than those who reviewed their results on-line to correctly interpret their genomic risk (72 vs. 47%, p = 0.0002) and report their actual genomic risk (69 vs. 49%, p = 0.002)., Conclusions: The delivery of personal genomic risk through a trained health professional resulted in significantly higher comprehension. Therefore, if the online delivery of genomic test results is to become more widespread, further evaluation of this method of communication may be needed to ensure the effective presentation of results to promote comprehension., (© 2014 S. Karger AG, Basel.)

Background: Genetic studies have identified numerous genes reproducibly associated with asthma, yet these studies have focussed almost entirely on single nucleotide polymorphisms (SNPs), and virtually ignored another highly prevalent form of genetic variation: Copy Number Variants (CNVs)., Objective: To survey the prevalence of CNVs in genes previously associated with asthma, and to assess whether CNVs represent the functional asthma-susceptibility variants at these loci., Methods: We genotyped 383 asthmatic trios participating in the Childhood Asthma Management Program (CAMP) using a competitive genomic hybridization (CGH) array designed to interrogate 20 092 CNVs. To ensure comprehensive assessment of all potential asthma candidate genes, we purposely used liberal asthma gene inclusion criteria, resulting in consideration of 270 candidate genes previously implicated in asthma. We performed statistical testing using FBAT-CNV., Results: Copy number variation in asthma candidate genes was prevalent, with 21% of tested genes residing near or within one of 69 CNVs. In six instances, the complete candidate gene sequence resides within the CNV boundaries. On average, asthmatic probands carried six asthma-candidate CNVs (range 1-29). However, the vast majority of identified CNVs were of rare frequency (< 5%) and were not statistically associated with asthma. Modest evidence for association with asthma was observed for 2 CNVs near NOS1 and SERPINA3. Linkage disequilibrium analysis suggests that CNV effects are unlikely to explain previously detected SNP associations with asthma., Conclusions and Clinical Relevance: Although a substantial proportion of asthma-susceptibility genes harbour polymorphic CNVs, the majority of these variants do not confer increased asthma risk. The lack of linkage disequilibrium (LD) between CNVs and asthma-associated SNPs suggests that these CNVs are unlikely to represent the functional variant responsible for most known asthma associations., (© 2012 Blackwell Publishing Ltd.)

Background: Sorafenib is currently the only approved systemic therapy shown to have efficacy in the treatment of advanced hepatocellular carcinoma (HCC). Recent studies suggest that hepatitis C (HCV)-related HCC patients derive more clinical benefit from sorafenib than other subgroups, but the mechanism for this effect is unknown. In vitro data suggest that sorafenib may exert anti-viral properties, and thus our aim in this study was to evaluate potential anti-viral activity of sorafenib in patients with HCV-related HCC., Aim: To evaluate potential anti-viral activity of sorafenib in patients with HCV-related HCC., Methods: We prospectively enrolled patients with HCV-related HCC treated with sorafenib for up to 6 months. Baseline clinical, viral and oncologic data were collected. Patients' HCV viral loads were obtained at various time points, and compared with their baseline viral levels. No patients received any known anti-viral therapy during this time., Results: Thirty-three patients were identified with baseline and subsequent HCV levels available for analysis. Six patients completed 6 months of full dose sorafenib, and comparisons of their HCV viral loads showed no significant change at week 24 (difference of means = 0.3500, CI: -0.1799-0.8799, P = 0.150), or the interim time points. Similarly, the HCV viral loads of all patients who received sorafenib and the viral loads of those patients who had tumour response to sorafenib showed no significant changes at any time point., Conclusion: Despite preclinical data and previous subgroup analyses suggesting that sorafenib has an anti-viral effect against HCV, this study suggests that sorafenib lacks significant anti-viral activity in HCV patients with HCC., (© 2012 Blackwell Publishing Ltd.)

It is anticipated that as the range of drugs for which pharmacogenetic testing becomes available expands, primary care physicians (PCPs) will become major users of these tests. To assess their training, familiarity, and attitudes toward pharmacogenetic testing in order to identify barriers to uptake that may be addressed at this early stage of test use, we conducted a national survey of a sample of PCPs. Respondents were mostly white (79%), based primarily in community-based primary care (81%) and almost evenly divided between family medicine and internal medicine. The majority of respondents had heard of PGx testing and anticipated that these tests are or would soon become a valuable tool to inform drug response. However, only a minority of respondents (13%) indicated they felt comfortable ordering PGx tests and almost a quarter reported not having any education about pharmacogenetics. Our results indicate that primary care practitioners envision a major role for themselves in the delivery of PGx testing but recognize their lack of adequate knowledge and experience about these tests. Development of effective tools for guiding PCPs in the use of PGx tests should be a high priority., (© 2012 John Wiley & Sons A/S.)

Pharmacogenetic (PGx) testing aims to improve therapeutic outcomes through tailoring treatment based on a patient's genetic risk for non-response and/or an adverse event. Given their expertise, geneticists could facilitate the use of PGx testing; however, the preparedness and perceived role of the clinical genetics community is unclear. To assess the attitudes, preparedness, and perceived roles of geneticists in the delivery of PGx testing, we conducted a survey of 1500 randomly selected board-certified genetic counselors and clinical geneticists in the United States [response rate: 37.8% (n = 516)]. Twelve percent of genetic counselors and 41% of clinical geneticists indicated that they had ordered or coordinated patient care for PGx testing, a seemingly high proportion at this early stage of adoption. Almost all respondents had some education on pharmacogenetics, although only 28% of counselors and 58% of clinical geneticists indicated they felt well-informed about PGx testing. About half of counselors (52%) and clinical geneticists (46%) felt they would play 'some' role in the delivery of PGx testing; 17 and 19%, respectively, felt that they would play 'no' or 'a little' role. At this early stage of PGx testing, the role of geneticists and genetic counselors is unclear. However, their experience may aid in readying PGx testing and informing delivery strategies into clinical practice., (© 2012 John Wiley & Sons A/S.)

Aim: The research question is: is it possible to predict, at the time of workers' compensation claim lodgement, which workers will have a prolonged return to work (RTW) outcome? This paper illustrates how a traditional analytic approach to the analysis of an existing large database can be insufficient to answer the research question, and suggests an alternative data management and analysis approach., Methods: This paper retrospectively analyses 9018 workers' compensation claims from two different workers' compensation jurisdictions in Australia (two data sets) over a 4-month period in 2007. De-identified data, submitted at the time of claim lodgement, were compared with RTW outcomes for up to 3 months. Analysis consisted of descriptive, parametric (analysis of variance and multiple regression), survival (proportional hazards) and data mining (partitioning) analysis., Results: No significant associations were found on parametric analysis. Multiple associations were found between the predictor variables and RTW outcome on survival analysis, with marked differences being found between some sub-groups on partitioning--where diagnosis was found to be the strongest discriminator (particularly neck and shoulder injuries). There was a consistent trend for female gender to be associated with a prolonged RTW outcome. The supplied data were not sufficient to enable the development of a predictive model., Conclusion: If we want to predict early who will have a prolonged RTW in Australia, workers' compensation claim forms should be redesigned, data management improved and specialised analytic techniques used., (© 2011 The Author. Internal Medicine Journal © 2011 Royal Australasian College of Physicians.)

Background: Health-related quality of life (HRQoL) is a rapidly growing area of expertise and the most commonly used patient-reported outcome (PRO). The impact of cystic fibrosis (CF) on HRQoL is liable to be great, making CF patients ideal candidates for the application of HRQoL instruments. The aims of this study were to assess the affect of CF on HRQoL, to ascertain the reliability and validity of the United Kingdom Sickness Impact Profile (UKSIP) and the Cystic Fibrosis Quality of Life Questionnaire (CFQoL) in the adult CF population, and to examine their role in the management of patients., Methods: Seventy participants were recruited from the All Wales Adult Cystic Fibrosis Centre at Llandough Hospital, UK. There were two stages to the study: self-report of the UKSIP and CFQoL; and completion of the same two questionnaires 7-10 days later., Results: The areas of HRQoL most impaired by CF were employment and concerns regarding the future. The UKSIP and CFQoL showed high internal consistency (rα = 0.89-0.93) and test-retest reliability (r(s) = 0.57-0.94, p < 0.005) in the CF population. Validity was variable with the UKSIP showing discrimination across socio-demographic factors, whilst the CFQoL showed increased sensitivity to clinical variables. Many parameters influenced patient-reported HRQoL, with the greatest correlations seen with the Borg score (p < 0.005). The use of a HRQoL instrument in CF annual reviews is recommended to provide holistic patient care. The results of this study underpin the value of HRQoL as a patient-reported outcome measure in the management of adult CF.

Background: Stapedotomy produces the best hearing results of any otological operation. However, in a small number of cases the air-bone gap is not successfully closed, or conductive hearing loss recurs., Objective: To investigate the proportion of cases in the senior author's series which required revision surgery and to determine the medium to long term success rate of surgery, taking into account the results of revision surgery., Methods: Review of a series of 233 primary stapedotomy operations and 100 revision procedures carried out by one surgeon over a 20-year period., Results: Closure of the air-bone gap to within 10 dB was achieved in 80 per cent of cases following the primary procedure. Fifteen per cent of patients developed a recurrence of conductive hearing loss. When the results of revision surgery were taken into account, the proportion of ears with a mean air-bone gap of less than 10 dB was 86 per cent. However, of the patients undergoing revision surgery, air-bone gap closure to within 10 dB was only achieved in 52 per cent of cases., Conclusion: The best chance of obtaining a successful outcome in stapedotomy is to achieve this for the first procedure. However, revision surgery does increase the medium to long term success rate.

Background: The role of further hormone therapy in castration-resistant prostate cancer (CRPC) remains unclear. We performed a multi-centre randomised phase III study comparing the use of Dexamethasone, Aspirin, and immediate addition of Diethylstilbestrol (DAiS) vs Dexamethasone, Aspirin, and deferred (until disease progression) addition of Diethylstilbestrol (DAdS)., Methods: From 2001 to 2008, 270 men with chemotherapy-naive CRPC were randomly assigned, in a 1 : 1 ratio, to receive either DAiS or DAdS. They were stratified for performance status, presence of bone metastases, and previous normalisation of prostate-specific antigen (PSA) to androgen deprivation. The study end points were the proportion of patients achieving a 50% PSA response, progression-free survival (PFS), overall survival, and quality of life. Intention-to-treat analysis was carried out. The effect of treatment was studied first by Kaplan-Meier curves and log-rank test, and finally through multivariable stratified Cox's proportional hazards model adjusting for the effects of possible baseline prognostic factors. Quality of life was analysed using multivariate analysis of variance., Results: At study entry, the median age was 76 years (inter-quartile range: 70-80 years), the median PSA was 79 ng ml(-1), and 76% of the cohort had metastatic disease. The response rates for DAiS (68%) and DAdS (64%) were not significantly different (P=0.49). Similar to the response rate, neither the PFS (median=8.1 months for both arms) nor the overall survival (19.4 vs 18.8 months) differed significantly between the DAiS and DAdS groups (P>0.20). However, the response rate for the DAiS (68%) was significantly higher than the response rate of DA (before adding Diethylstilbestrol) (50%) (P=0.002). Similarly, the median time to progression for DAiS (8.6 months) was significantly longer than that of DA (4.5 months) (P<0.001). Multivariable analysis showed that patients with previous haemoglobin ≥11 g dl(-1) decreased the risk of death significantly (hazard ratio: 0.44, 95% CI: 0.25-0.77). Patients treated with previous anti-androgens alone had more than 5 times more risk of death compared with patients treated with gonadorelin analogues throughout their castration-sensitive phase. Treatment sequencing did not affect the quality of life but pre-treatment performance status did. The incidence of veno-thromboembolic events was 22% (n=28) in DAiS and 11% (n=14) in the DA arm (P=0.02). Painful gynaecomastia occurred in only 1% on DA, whereas in 40% on DAiS (P=0.001)., Conclusion: Dexamethasone and immediate Diethylstilbestrol resulted in neither higher PSA response rate nor higher PFS compared with Dexamethasone with deferred Diethylstilbestrol. There was no suggestion of significantly improved overall survival or quality of life. Given the significantly higher toxicity of Diethylstilbestrol, deferring Diethylstilbestrol until failure of Dexamethasone is the preferred strategy when using these agents in CRPC.

Introduction: Despite advances in imaging and other diagnostic tests, it is often impossible to establish with confidence a pre-operative diagnosis in a patient with a conductive hearing loss., Methods: We studied a series of 340 exploratory tympanotomies for conductive hearing loss carried out by a single surgeon., Results: The most common operative diagnosis was otosclerosis (n = 164, 48.2 per cent). Ossicular discontinuity was found more commonly than previously reported (n = 103, 30.3 per cent). A small but significant number of patients were found to have cholesteatoma (n = 7.2 per cent)., Conclusions: This information is of value when discussing potential findings at surgery for conductive hearing loss. While otosclerosis is the commonest finding in such cases, a significant number of patients have defects of the ossicular chain.

Background: Congenital cholesteatoma occurring behind the tympanic membrane is typically located in the anterior middle ear., Objective: To investigate the location, clinical features and treatment of cholesteatomas located behind an intact tympanic membrane in adults., Methods: Review of a series of 265 consecutive, new, adult cases of previously untreated cholesteatoma seen by the author over a 22-year period., Results: Seventeen (6 per cent) cases were located behind an intact tympanic membrane without any evidence of a retraction pocket of the attic or pars tensa. Ten (59 per cent) of these patients had undergone previous ear surgery and therefore the disease could reasonably be considered to be iatrogenic. The most common presentation was conductive deafness with no other symptoms (71 per cent). In all of the cases, the disease was located in the posterior half of the middle-ear space. The most common surgical management was simple excision of the disease via a tympanotomy. Two cases (12 per cent) developed residual disease., Conclusion: The majority of the cases in this series were likely to be acquired cholesteatomas. This type of disease often presents with conductive hearing loss alone.

Automation of differentials is desirable for economic and time-saving reasons. Over the last 20 years, automated imaging processes have started to be introduced where stained blood films are scanned by a computer-driven microscope and leucocytes classified; however, early methods were slow and had difficulty in classifying abnormal cells. More recently the CellaVision DM96 (CellaVision AB, Lund, Sweden) has been introduced with added features such as continuous loading of slides and a faster throughput than previous instruments. The accuracy of CellaVision DM96 has been evaluated by comparing results to reference manual differentials. Results from different operators using the DM96 were compared with their own manual differential and to a 400-cell reference manual differential. Precision of the instrument was compared to the manual differential. The preclassification accuracy of the DM96 was 89.2%. Precision was similar to that of the 100-cell manual differential. The DM96 was faster than the manual method, even after reclassification by a laboratory scientist of any cells wrongly categorized by the instrument. The DM96 accuracy in morphological classification of leucocytes and red blood cells; depends upon both blood pathology and experience of the laboratory scientist using the instrument. For some cell types and operators, DM96 accuracy was better than the individual's 100 cell manual differential.

Introduction: Ménière's disease is a diagnosis requiring expert clinical judgment. There are several differences between the American Academy of Otolaryngology Head and Neck Surgery diagnostic guidelines and Prosper Ménière's original description of the disease., Methods: Six hundred and fifty patients attending a specialist balance clinic had their clinical profiles fully analysed according to each set of diagnostic criteria., Results: Application of the American Academy of Otolaryngology Head and Neck Surgery guidelines resulted in the diagnosis of three times more patients than did use of Ménière's diagnostic criteria. Treatment options for patients in both groups were similar. It is unlikely that the application of different diagnostic criteria would have an effect on the treatment of individual patients., Discussion: The American Academy of Otolaryngology Head and Neck Surgery guidelines are more sensitive and less specific in diagnosing Ménière's disease than Prosper Ménière's original description. Standardised criteria should be applied across published series, in order to make results accurate, comparable and useful in the long term. We would recommend the introduction of a stricter diagnostic category for definite Ménière's disease.

Introduction: The sacculo-collic reflex is believed to be a short latency, otolith-mediated myogenic response to sound. With the application of air-conducted sound, one would expect an absent response in stapes fixation, as a fixed stapes footplate will not transmit a pressure wave to the saccule., Methods: Fifty patients (70 stapes surgery ears, 26 otosclerotic ears and four normal ears) and 40 controls underwent repeated sacculo-collic tests., Results: The results support the proposed mechanism for the sacculo-collic response. The study also suggests that, whilst stapedotomy piston prostheses are effective in the reversal of conductive hearing loss, they produce an insufficient pressure wave to elicit a myogenic response to sound., Conclusion: The sacculo-collic test could be a useful tool for screening otolith function and inferior vestibular nerve integrity, but further work is needed to determine the effect of stapes surgery on saccular function.

Introduction: The objective of this study was to determine the value of routine urine cytology in the initial evaluation of patients presenting to a one-stop haematuria clinic., Patients and Methods: A total of 1000 consecutive patients who attended the haematuria clinic between June 2003 and November 2004 were studied prospectively. A standard protocol was used to investigate these patients. This included urine cytology, upper tract imaging and flexible cystoscopy., Results: Overall, 986 samples of urine were sent for cytology. In 126 patients, the report was abnormal; of these, 71 patients were found to have bladder transitional cell carcinoma by flexible cystoscopy and a further 3 had upper tract transitional cell carcinoma diagnosed radiologically. The remaining 52 patients with abnormal cytology were not found to have cancer on further investigations. The total cost for urine cytology and additional investigations was pound50,535., Conclusions: In this study of the initial evaluation of patients with haematuria, no case of urothelial malignancy was diagnosed on the basis of urine cytology alone. Therefore, urine cytology need not be used routinely in the initial diagnostic work-up for haematuria.

Introduction: A clear and detailed clinical history is essential in the assessment of patients with balance symptoms. The aim of this study was to assess the usefulness of open-ended questionnaires in the specialist balance clinic., Methods: Fifty-four consecutive new patients completed an open-ended questionnaire, prior to a consultation in which the clinical history was taken using a standardised proforma. The results of the two were compared., Results: The open-ended questionnaires provided patient-centred data, and did not provide clinicians with sufficient data for diagnosis. Patients were more likely to respond in the affirmative when asked about symptoms directly, than to report the same symptoms spontaneously on an open-ended questionnaire. When questions had a number of possible answers, patients were more likely to report them in full in an open-ended questionnaire than to provide a response during direct questioning.

We studied the transmission of heat to the vestibule during revision stapes surgery with a piston in situ, using a CO2 laser, in an in vitro model. A type K thermocouple was placed around the medial end of stainless steel and fluoroplastic wire pistons in a 'vestibule' filled with saline. The effect of laser hits on fluoroplastic wire and stainless steel stapes prostheses was investigated. The effect of introducing a vein graft to seal the stapedotomy was also examined. Greater temperature rises occurred with stainless steel than with fluoroplastic wire pistons. The addition of the vein graft reduced heat transmission. Application of the CO2 laser to fluoroplastic wire pistons, using the power settings suggested by the manufacturer, is not likely to damage the inner-ear structures. Application of 6 W laser energy to stainless steel pistons can potentially disturb the inner-ear function.

We describe two patients with stapes fixation, in both of whom Rosen mobilization seemed to be the most prudent surgical choice. In both cases, a useful hearing gain was achieved initially. In the patient with otosclerosis, the conductive hearing loss recurred and a stapedectomy was subsequently carried out. In the patient with congenital stapes fixation, the hearing gain was maintained for two years eight months. We believe that this technique still has a place in stapes surgery in rare instances.

We investigated the motion of the single ossicle found in the middle ears of four different species of birds. In the avian middle ear, the off centre attachment of the extracolumella to the tympanic membrane and the flexion of the joint between the extracolumella and columella results in rocking of the footplate rather than direct excursion in and out of the vestibule. We postulate that this is a protective mechanism to avoid excessive displacement of the footplate into the vestibule during changes in middle-ear pressure and that it is analogous to the ossicular 'decoupling' observed in the human middle ear in the same circumstances.

Stable, self-cleansing retraction pockets of the pars tensa are common incidental findings and require no treatment. In other cases, recurrent discharge occurs and there may also be associated conductive hearing loss. In a minority of cases, cholesteatoma may develop. This paper presents the results of surgery using a graft composed of cartilage and perichondrium for retraction pockets involving the posterior half of the tympanic membrane, as well as early results using a larger graft designed to manage retraction of the entire tympanic membrane. Data on 51 patients with posterior retraction pockets are presented. Forty-two (82 per cent) patients had no aural discharge one year following surgery and the tympanic membrane was not retracted in 43 (84 per cent). The larger 'Mercedes-Benz' graft was used in four patients and the results obtained suggested that it may prove a successful technique for extensive retraction pockets.

The objective was to assess the number of patients with acute oesophageal bolus obstruction that resolves spontaneously and to aid the identification of the best practice. This prospective and retrospective case series study at a teaching hospital and a district general hospital in Scotland, UK, involved 37 patients with acute oesophageal obstruction from a food bolus who were observed for 24 h from the beginning of symptoms. The bolus passed spontaneously in 54% of the patients during the observational period. A short observational period following the admission of patients with acute food bolus obstruction is reasonable as it may reduce exposure to surgical morbidity and decrease inpatient stay.

Central core disease and malignant hyperthermia (MH) are both associated with mutations in the RYR1 gene. We report the anaesthetic management of one such patient presenting for coronary artery bypass grafting. Her medication included aspirin 75 mg, atorvastatin 20 mg, isosorbide mononitrate 60 mg, atenolol 25 mg and glyceryl trinitrite sublingual spray as required. The use of aprotinin, statins and moderate hypothermia in patients with central core disease and known susceptibility to MH has not been documented.

Background: Young people with early psychosis are at particularly high risk of suicide. However, there is evidence that early intervention can reduce this risk. Despite these advances, first episode psychosis patients attending these new services still remain at risk. To address this concern, a program called LifeSPAN was established within the Early Psychosis Prevention and Intervention Centre (EPPIC). The program developed and evaluated a number of suicide prevention strategies within EPPIC and included a cognitively oriented therapy (LifeSPAN therapy) for acutely suicidal patients with psychosis. We describe the development of these interventions in this paper., Method: Clinical audit and surveys provided an indication of the prevalence of suicidality among first episode psychosis patients attending EPPIC. Second, staff focus groups and surveys identified gaps in service provision for suicidal young people attending the service. Third, a suicide risk monitoring system was introduced to identify those at highest risk. Finally, patients so identified were referred to and offered LifeSPAN therapy whose effectiveness was evaluated in a randomised controlled trial., Results: Fifty-six suicidal patients with first episode psychosis were randomly assigned to standard clinical care or standard care plus LifeSPAN therapy. Forty-two patients completed the intervention. Clinical ratings and measures of suicidality and risk were assessed before, immediately after the intervention, and 6 months later. Benefits were noted in the treatment group on indirect measures of suicidality, e.g., hopelessness. The treatment group showed a greater average improvement (though not significant) on a measure of suicide ideation., Conclusions: Early intervention in psychosis for young people reduces the risk of suicide. Augmenting early intervention with a suicide preventative therapy may further reduce this risk.

Delayed facial palsy following conventional stapes surgery is a rare event, but this complication appears to be more common when a laser is used. We have investigated the temperature in the facial canal during stapes surgery using a KTP laser or a microdrill in preserved human temporal bones. Thermocouples were placed in the facial canal and under the foot plate. The results show maximum rises in temperature of between 1.4 degrees C and 15.2 degrees C in the facial canal during laser surgery (mean 6.1 degrees C, SD 4.5 degrees C), but only between 0.45 degrees C and 2 degrees C during procedures in which a microdrill was used (mean 0.9 degrees C, SD 0.9 degrees C) (P = < 0.009). In addition, the facial nerve undergoes repeated heating and cooling cycles during the laser surgery. We conclude that heating of the facial nerve during laser surgery causes oedema, which in turn leads to compression of the nerve within its bony canal.

Optical imaging of cardiac electrical activity using a voltage-sensitive dye provides high spatial resolution maps of action potential propagation and repolarization. Charge-coupled-device (CCD) camera-based imaging systems, however, are limited by their low signal-to-noise ratio. We have developed an image processing method to enhance the quality of optical signals recorded using a CCD camera. The method is based on the observation that within a small neighborhood of adjacent pixels, the morphology of the optical action potential varies little except for a phase shift in time resulting from the propagation of the wavefront. The method uses a phase-correlation technique to first correct for this time shift before spatially filtering with a 5 x 5 Gaussian convolution kernel (sigma = 1.179). A length 5 median filter is then applied to further reduce noise by filtering in the temporal domain. The image-processing scheme allows for more accurate extraction of maps of electrical activation, repolarization, and action potential duration.

An ossicular prosthesis produced by making a mould from a cadaveric incus and injecting ionomeric cement into it (incus replica prosthesis, IRP) has been cemented to the malleus head and stapes head and evaluated in fresh human temporal bones using a laser vibrometer. Stapes velocity was recorded under acoustic stimulation and foot plate displacements were derived. Fourteen frequencies between 125 Hz and 8000 Hz have been used. Measurements were made with the ossicular chain intact, following removal of the incus, with the prosthesis cemented to the malleus, but not the stapes, and with the incudo-stapedial joint cemented. In a second series of experiments the performance of the IRP was compared with that of a Causse partial ossicular replacement prosthesis, using the same experimental set-up. The results indicate that the prosthesis performs almost as well as the intact ossicular chain and that cementing the incudo-stapedial joint gives better sound transmission than leaving it uncemented. In addition the IRP outperforms the conventional partial ossicular replacement prosthesis.

Purpose: We investigate fertility and sexual function in patients following orchiectomy and adjuvant cisplatin based chemotherapy for high risk, stage I nonseminomatous germ cell tumor of the testis., Materials and Methods: Between 1985 and 1994, 59 patients with stage I nonseminomatous germ cell tumor and poor prognostic factors were treated with 2 cycles of cisplatin, vinblastine and bleomycin, or bleomycin, etoposide and cisplatin after orchiectomy. At least 32 months following treatment all patients were contacted and asked to complete a questionnaire regarding fertility and sexual activity, and to volunteer for a semen and hormonal analysis., Results: Of the 59 patients 49 (83%) completed the questionnaire. Before chemotherapy 18 (37%) patients had fathered children, 6 (12%) were involuntarily childless and none had a major sexual dysfunction. After treatment 11 (22%) patients fathered children, and 5 (10%) were involuntarily childless, with 4 involuntarily childless before chemotherapy. There were no significant alterations in sexual function. Semen analysis in 27 patients was normal in 23, and revealed mild oligospermia in 2 and azoospermia in 2. In 18 patients with hormone analysis median values for luteinizing hormone and free testosterone were normal but median value for follicle-stimulating hormone was slightly increased., Conclusions: Two cycles of cisplatin based adjuvant chemotherapy do not seem to affect adversely fertility or sexual activity.

To assess the impact of the use of plain X-ray films and ultrasound examinations on clinical decision-making in patients referred with symptoms of bladder outflow obstruction. Patients with symptoms of bladder outflow obstruction were recruited prospectively. After clinical assessment they underwent standard investigations of plain X-ray of the kidneys, ureters and bladder, and upper and lower urinary tract ultrasound. A management decision was made on the basis of all results. These decisions were then reviewed with specific reference to radiological findings to assess the role of imaging in the decision-making process. A total of 320 men were recruited for the study. X-ray of the kidneys, ureters and bladder detected 10 upper tract calculi, none of which has required active intervention to date. Four bladder calculi were detected. Two of these were also seen on ultrasound scan: one was small and insignificant, the other had caused microscopic haematuria, necessitating cystoscopy regardless of the X-ray findings. Upper tract ultrasound revealed abnormalities and anatomical variants which did not affect management. Four patients had upper tract dilatation but these had already had surgery planned on the basis of other investigations, including residual urine volume determination by lower tract ultrasound. Lower urinary tract ultrasound should be the only routine imaging used in the initial assessment of patients with bladder outflow obstruction, with consequent implications of reduced patient stress and reduced investigation cost.

One hundred and ninety-one children who presented to the author's clinic with otitis media with effusion (OME) over a 2-year period (1986-1988) have been studied prospectively. Resolution of their OME was considered to have occurred when they had normal findings on pneumatic otoscopy, tympanometry and audiometry on at least two occasions 6 months apart and had subjectively normal hearing in between. The number of operations performed during the course of the disease was used as a surrogate for chronicity. Children with a history of previous aural discharge at presentation were significantly more likely to have chronic OME (P = < 0.02).