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Background: The Sydney Health Partners Emergency Department (SHaPED) trial targeted ED clinicians and evaluated a multifaceted strategy to implement a new model of care. The objective of this study was to investigate attitudes and experiences of ED clinicians as well as barriers and facilitators for implementation of the model of care., Design: A qualitative study., Methods: The EDs of three urban and one rural hospital in New South Wales, Australia participated in the trial between August and November 2018. A sample of clinicians was invited to participate in qualitative interviews via telephone and face-to-face. The data collected from the interviews were coded and grouped in themes using thematic analysis methods., Results: Non-opioid pain management strategies (i.e., patient education, simple analgesics, and heat wraps) were perceived to be the most helpful strategy for reducing opioid use by ED clinicians. However, time constraints and rotation of junior medical staff were seen as the main barriers for uptake of the model of care. Fear of missing a serious pathology and the clinicians' conviction of a need to provide something for the patient were seen as barriers to reducing lumbar imaging referrals. Other barriers to guideline endorsed care included patient's expectations and characteristics (e.g., older age and symptoms severity)., Conclusions: Improving knowledge of non-opioid pain management strategies was seen as a helpful strategy for reducing opioid use. However, clinicians also raised barriers related to the ED environment, clinicians' behaviour, and cultural aspects, which should be addressed in future implementation efforts., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests. GM, CM, and KM report grants from the Australian National Health and Medical Research Council during the conduct of this trial (grant numbers: not applicable)., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Microplastic particles are ubiquitous in the environment. However, little is known about their uptake and effects in humans or mammalian model organisms. Here, we studied the effects of pristine polyamide (15-20 µm) and polyethylene (40-48 µm) particles after oral ingestion in rats. The animals received feed containing microplastic particles (0.1% polyamide or polyethylene, or a mixture of both polymers) or a control diet without microplastic particles, for 5 weeks. The permeability of the duodenum was investigated in an Ussing chamber, whereas gene expression and concentration of tight junction proteins were measured in gut tissue and plasma. Microplastic particles were quantified by pyrolysis-gas chromatography/mass spectrometry in rats' feces. Rats fed with microplastic particles had higher duodenal permeability. Expression of gene coding for the tight junction protein occludin (OCLN) was higher in PE treated animals compared to control or the PA group. No changes in the expression of the gene coding for zonula occludens protein 1 were detected. Occludin protein concentrations were below the limit of detection of the applied method in both gut and plasma. Zonula occludens protein 1 concentrations in the gut were significantly higher in groups exposed to PA and PE as compared to control, while zonula occludens protein 1 concentrations in plasma did not show significant changes. These results demonstrated that short-term exposure to a dose of 0.1% (w/w) microplastic particles in feed had limited effects on duodenal permeability, expression of pro-inflammatory protein genes and tight junction protein genes in the duodenum., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Tanja Koegel reports a relationship with Netherlands Organisation for Health Research and Development that includes: consulting or advisory., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Question: What are the effects of diagnostic labels and advice, and interactions between labels and advice, on perceived need for shoulder surgery for rotator cuff disease?, Design: 2×2 factorial online randomised experiment., Participants: People with shoulder pain., Intervention: Participants read a scenario describing a patient with rotator cuff disease and were randomised to bursitis label plus guideline-based advice, bursitis label plus treatment recommendation, rotator cuff tear label plus guideline-based advice, and rotator cuff tear label plus treatment recommendation. Guideline-based advice included encouragement to stay active and positive prognostic information. Treatment recommendation stressed that treatment is needed for recovery., Outcome Measures: Perceived need for surgery (primary outcome), imaging, an injection, a second opinion and to see a specialist; and perceived seriousness of the condition, recovery expectations, impact on work performance and need to avoid work., Results: A total of 2,024 responses (99.8% of 2,028 randomised) were analysed. Labelling as bursitis (versus rotator cuff tear) decreased perceived need for surgery (mean effect -0.5 on a 0-to-10 scale, 98.3% CI -0.7 to -0.2), imaging and to see a specialist, and perceived seriousness of the condition and need to avoid work. Guideline-based advice (versus treatment recommendation) decreased perceived need for surgery (mean effect -1.0, 98.3% CI -1.3 to -0.7), imaging, an injection, a second opinion and to see a specialist, and perceived seriousness of the condition and recovery expectations. There was little to no evidence of an advice label interaction for any outcome., Conclusion: Labels and advice influenced perceived need for surgery and other secondary outcomes in people with rotator cuff disease, with larger effects for advice. There was evidence of little or no interaction between labels and advice for any outcome, but the additive effect of labels and advice appeared large for some outcomes (eg, perceived need for imaging and perceived seriousness of the condition)., Trial Registration: ACTRN12621001370897., (Copyright © 2022 Australian Physiotherapy Association. Published by Elsevier B.V. All rights reserved.)

Objective: To evaluate the effects of a patient decision aid for people considering shoulder surgery., Methods: Participants with shoulder pain considering shoulder surgery (n = 425) were recruited online and randomised to (i) a decision aid outlining the benefits and harms of shoulder surgery and non-surgical options (then randomised to a side-by-side vs. top-and-bottom display of options); and (ii) general information about shoulder pain from the NHS. Outcomes included treatment intention (primary), knowledge, attitudes, informed choice, and decisional conflict. Linear and logistic regression models were used to evaluate between-groups differences in outcomes., Results: 409 participants (96%) had post-intervention data. Mean age was 41.3 years, 44.2% were female. There was no between-group difference in post-intervention treatment intention (MD -0.2, 95% CI: -3.3 to 2.8) and likelihood of intending to have shoulder surgery (OR 0.7, 95% CI: 0.3-1.5). The decision aid slightly improved knowledge (MD 4.4, 95% CI: 0.2-8.6), but not any other secondary outcomes. The display of options did not influence any outcome., Conclusions: In this online trial, a co-designed patient decision aid had no effect on treatment intention, attitudes, informed choice, and decisional conflict, but a small effect on improving knowledge., Practice Implications: Research is needed to understand reasons for the lack of anticipated effects., Trial Registration: Australia New Zealand Clinical Trials Registry (ACTRN12621000992808)., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Most people who suffer an anterior cruciate ligament (ACL) injury search for information online., Objectives: Summarise the proportion of webpages on ACL rupture management that present evidence-based information., Design: Content analysis., Methods: We examined webpage information on ACL ruptures identified through (1) Google searches using terms synonymous with 'anterior cruciate ligament rupture' and searching 'knee surgeon' linked to each Australian capital city, and (2) websites of professional associations. The primary outcome was the proportion of webpages that suggest people can return to at least some form of sport with non-surgical management. Secondary outcomes included webpage information on return to sport with ACL reconstruction (ACLR) and non-surgical management, benefits, harms, and risk of osteoarthritis related to these options, and activity modification., Results: Out of 115 webpages analysed, 48% suggested people can return to at least some form of sport with non-surgical management. Almost half of webpages suggested most people will return to some form of sport following ACLR (41%) and mentioned benefits of ACLR (43%). Fewer webpages mentioned benefits of non-surgical management (14%), approximately two in three people return to pre-injury level of sport following ACLR (4%), risk of re-injury following ACLR (23%), most people return to sport within 9 months of ACLR (27%), activity modification as a management approach (20%), and ACLR will reduce the risk of osteoarthritis (23%)., Conclusion: Most online information on ACL rupture management isn't aligned with the best available evidence. Inaccurate information could mislead patients' treatment choices and create unrealistic expectations for return to sport., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background & Aims: The physical and functional outcomes of lifelong treatment with a phenylalanine restricted diet for the management of Phenylketonuria (PKU) remain unknown. Given that the mainstay of dietary management consists of modifying the sources of ingested protein, various aspects of body protein status could be compromised., Objectives: To examine the existing evidence regarding the protein status of people with PKU and identify nutritional and lifestyle variables that influence protein status., Eligibility Criteria: Studies reporting anthropometric, biochemical and/or functional measurements of body protein status in people with PKU were eligible., Source of Evidence: MEDLINE (Ovid), Embase (Ovid), CENTRAL, Web of Science and Scopus, and conference abstracts., Results: Seventy studies were included in the review. The majority of studies assessing protein status based on anthropometric measurements observed no differences between people with PKU and controls, although deficits in muscle mass were reported within PKU cohorts. Findings for biochemical assessment of protein status were mixed and limited studies assessed protein status using functional measures. Factors such as participant age, sex, metabolic control, protein source, type of protein substitute, and pharmacological treatments were found to modulate protein status of people with PKU., Conclusions: Findings were inconclusive regarding body protein status in people with PKU. The relationship between diet and protein status outcomes remains unclear and further research is warranted to determine the impact of dietary regimens on physical and functional outcomes, and to understand the best clinical assessments to reliably monitor the protein status in people with PKU., Competing Interests: Conflict of interest Sarah Firman has received funding to attend conferences and study days from Nutricia, Vitaflo International and Dr. Schär UK Ltd, and consulting fees from Vitaflo International and Meta Healthcare Ltd. Kevin Whelan is in receipt of research funding from Danone and has acted as a consultant for Danone., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Lifelong dietary treatment is recommended in the management of phenylketonuria (PKU). Accordingly, an increasing adult population require age-specific PKU guidelines on protein requirements to support changing metabolic demands across the lifespan. Given that protein intake for dietary management of PKU is primarily (52-80%) derived from protein substitutes, the prescribing practice of protein substitutes must be underpinned by robust evidence. Whilst dietary guidelines for PKU management is evolving to incorporate adult specific protein recommendations, the scientific evidence underpinning these guidelines is currently limited. Instead, the determination of protein requirements for people with PKU have previously been extrapolated from estimates derived from the general healthy population, based on arguably outdated nitrogen balance methodology. Furthermore, a compensatory factor of 20-40% has been incorporated to account for the reduced uptake and utilisation of the elemental amino acids contained in protein substitutes. However, research informing this compensatory factor has been conducted in younger adults, with the majority of studies in non-PKU individuals. Given extensive evidence that the muscle anabolic response to ingested protein is impaired in older vs. young adults, the validity of current dietary protein recommendations for adults and older adults with PKU has been challenged. This narrative review aims to critically evaluate the existing scientific evidence underpinning current guidelines on protein requirements for adults with PKU, highlighting existing gaps in knowledge and directions for future research. We argue that current guidelines on protein requirements need updating to optimise long-term physical and functional outcomes in older adults with PKU., Competing Interests: Conflict of interest SF has received funding to attend conferences and study days from Nutricia, Vitaflo International and Dr. Schär UK Ltd, and consulting fees from Vitaflo International and Meta Healthcare Ltd., (Copyright © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Objective: To evaluate the effects of information format on intentions to request diagnostic imaging for non-specific low back pain in members of the public., Methods: We performed a three arm, 1:1:1, superiority randomised trial on members of the public. Participants were randomised to one of the three groups: a Standard Care Leaflet group (standard information on low back pain), a Neutral Leaflet group (balanced information on the benefits and harms of imaging) and a Nudge Leaflet group (with behavioural cues to emphasise the harms of unnecessary imaging). Our primary outcome was intention to request imaging for low back pain., Results: 418 participants were randomised. After reading the leaflet, intention to request imaging (measured on an 11-point scale (0 = definitely would not request to 10 = definitely would request) was lower in the Nudge Leaflet group (mean = 4.6, SD = 3.4) compared with the Standard Care Leaflet group (mean = 5.3, SD = 3.3) and the Neutral Leaflet group (mean = 5.3, SD = 3.0) (adjusted mean difference between Nudge and Neutral, -1.0 points, 95%CI -1.6 to -0.4)., Conclusion: Framing information to emphasise potential harms from overdiagnosis reduced intention to request diagnostic imaging for low back pain., Practice Implications: Nudge leaflets could help clinicians manage patient pressure for unnecessary tests., Competing Interests: Declaration of Competing Interest Prof Chris Maher is supported by a Principal Research Fellowship from Australia’s National Health and Medical Research Council (APP1103022) as well as a Program grant (APP1113532) and two Centre for Research Excellence grants (APP1134856, APP1171459). He has received research grants from various government and not for profit agencies. Flexeze provided heat wraps at no cost for the SHaPED trial that he is an investigator on. His expenses have been covered by professional associations hosting conferences he has spoken at., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Question: Do program and participant characteristics influence people's willingness to undertake exercise programs to prevent recurrence of low back pain?, Design: Discrete choice experiment., Participants: Six hundred and forty-seven people with a recent history of low back pain., Data Collection: Recruitment and participation occurred online. Participants were randomised to a block of 10 choice tasks, where the characteristics of the exercise program varied systematically. The characteristics that were presented for each exercise program were mode of exercise delivery, mode of supervision, setting, duration, weekly frequency, travel time, risk of recurrence, and costs. For each choice task, participants chose between no program or an exercise program with the characteristics as presented., Data Analysis: Choices were analysed using mixed logit models. Latent class models examined preference heterogeneity and identified participant-level characteristics predictive of preferences., Results: There appeared to be an underlying preference for exercise compared with no exercise, all else being equal. Preferences for programs were significantly influenced by the characteristics of the programs. Participants were less likely to choose exercise when programs were of a longer duration (OR 0.92, 95% CI 0.89 to 0.96 per extra month), but more likely to prefer programs offering greater reduction in the risk of recurrence of low back pain (OR 3.91, 95% CI 3.20 to 4.79 per 10% reduction in risk of recurrence). Preferences for engaging in exercise programs to prevent recurrent of low back pain were influenced by the characteristics of the programs themselves. However, there was mismatch between the preferred characteristics of exercise programs and the characteristics of known effective programs., Conclusion: People who have had low back pain should be advised explicitly about which exercise programs reduce recurrence. Understanding low back pain patients' preferences can help inform the implementation of existing prevention programs and guide the design of new prevention programs., (Copyright © 2020 Australian Physiotherapy Association. Published by Elsevier B.V. All rights reserved.)

Background & Aims: Malnutrition in older adults results in significant personal, social, and economic burden. To combat this complex, multifactorial issue, evidence-based knowledge is needed on the modifiable determinants of malnutrition. Systematic reviews of prospective studies are lacking in this area; therefore, the aim of this systematic review was to investigate the modifiable determinants of malnutrition in older adults., Methods: A systematic approach was taken to conduct this review. Eight databases were searched. Prospective cohort studies with participants of a mean age of 65 years or over were included. Studies were required to measure at least one determinant at baseline and malnutrition as outcome at follow-up. Study quality was assessed using a modified version of the Quality in Prognosis Studies (QUIPS) tool. Pooling of data in a meta-analysis was not possible therefore the findings of each study were synthesized narratively. A descriptive synthesis of studies was used to present results due the heterogeneity of population source and setting, definitions of determinants and outcomes. Consistency of findings was assessed using the schema: strong evidence, moderate evidence, low evidence, and conflicting evidence., Results: Twenty-three studies were included in the final review. Thirty potentially modifiable determinants across seven domains (oral, psychosocial, medication and care, health, physical function, lifestyle, eating) were included. The majority of studies had a high risk of bias and were of a low quality. There is moderate evidence that hospitalisation, eating dependency, poor self-perceived health, poor physical function and poor appetite are determinants of malnutrition. Moderate evidence suggests that chewing difficulties, mouth pain, gum issues co-morbidity, visual and hearing impairments, smoking status, alcohol consumption and physical activity levels, complaints about taste of food and specific nutrient intake are not determinants of malnutrition. There is low evidence that loss of interest in life, access to meals and wheels, and modified texture diets are determinants of malnutrition. Furthermore, there is low evidence that psychological distress, anxiety, loneliness, access to transport and wellbeing, hunger and thirst are not determinants of malnutrition. There appears to be conflicting evidence that dental status, swallowing, cognitive function, depression, residential status, medication intake and/or polypharmacy, constipation, periodontal disease are determinants of malnutrition., Conclusion: There are multiple potentially modifiable determinants of malnutrition however strong robust evidence is lacking for the majority of determinants. Better prospective cohort studies are required. With an increasingly ageing population, targeting modifiable factors will be crucial to the effective treatment and prevention of malnutrition., (Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background & Aims: Malnutrition is widespread among older people and related to poor outcome. Reported prevalences vary widely, also because of different diagnostic criteria used. This study aimed to describe prevalences in several populations of older persons in different settings using harmonized definitions., Methods: Available studies within the Joint Programming Initiative (JPI) Knowledge Hub 'Malnutrition in the Elderly' (MaNuEL) were used to calculate and compare prevalences of malnutrition indicators: low BMI (<20 kg/m 2 ; age-specific BMI <20 if age 65-<70 and <22 kg/m 2 if age ≥70 years), previous weight loss (WL), moderate and severe decrease in food intake, and combined BMI <20 kg/m 2 and/or WL in participants aged ≥65 years., Results: Fifteen samples with in total 5956 participants (59.3% women) were included: 7 consisting of community-dwelling persons, 2 studies in geriatric day hospitals, 3 studies in hospitalized patients and 3 in nursing homes. Mean age of participants ranged between 67 and 87 years. Up to 4.2% of community-dwelling persons had a BMI <20 kg/m 2 , 1.6 and 9% of geriatric day hospital patients, 4.5-9.4% of hospital patients and 3.8-18.2% of nursing home residents. Using age-specific cut-offs doubled these prevalences. WL was reported in 2.3-10.5% of community-dwelling persons, 6% and 12.6% of geriatric day hospital patients, 5-14% of hospitalized patients and 4.5-7.7% of nursing home residents. Severe decrease in food intake was recorded in up to 9.6% of community-dwelling persons, 1.5% and 12% of geriatric day hospital patients, 3.4-34.2% of hospitalized patients and 1.5-8.2% of nursing home residents. The criteria age-specific BMI and WL showed opposing prevalences across all settings. Compared to women, low BMI and moderate decrease in food intake showed low prevalences in men but similar prevalences were observed for weight loss and severe decrease in food intake. In half of the study samples, participants in a younger age group had a higher prevalence of WL compared to those of an older age group. Prevalence of BMI <20 kg/m 2 and WL at the same time did not exceed 2.6% in all samples. The highest prevalences were observed based on combined definitions when only one of the three criteria had to be present., Conclusions: Prevalences for different criteria vary between and within the settings which might be explained by varying functional status. The criteria used strongly affect prevalence and it may be preferable to look at each criterion separately as each may indicate a nutritional problem., (Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Adolescent low back pain has received limited research attention despite its potentially considerable impact on quality of life. The role of diagnostic triage to identify serious or specific pathology and/or order relevant investigations is considered. An overview of contemporary pain mechanisms is provided, with specific reference to the wide range of risk factors for persistent low back pain. Education and exercise framed within a biopsychosocial framework are the cornerstones of treatment. There is a lack of data on more comprehensive personalized treatment approaches among adolescents. One such approach - Cognitive Functional Therapy - which has shown promise in adults and active adolescents with low back pain, is described and illustrated using a case study. The most promising avenues, in practice and research, may be those that view adolescent low back pain as less of a local structural spinal issue and more of an indication of the general health of the adolescent., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Question: What are staff and patients' perceptions of physiotherapists working in the emergency department (ED)?, Design: Systematic review of qualitative studies., Participants: Staff working in EDs and patients presenting to the ED and managed by ED physiotherapists., Outcome Measures: Perceptions of ED staff and patients were synthesised using a three-stage thematic analysis consisting of extraction, grouping (codes), and abstraction of findings., Results: Eight studies, which had sought the perceptions of 138 patients and 122 ED staff members, were included. Three main themes emerged: role of physiotherapists in the ED, positive perceptions of ED physiotherapists, and concerns about physiotherapists in the ED. Patients and ED staff both considered physiotherapists to be experts in musculoskeletal care. The role of ED physiotherapists was seen as providing thorough patient education, non-pharmacological pain management and activity resumption, especially through exercise therapy. Having broad knowledge to assess and treat different health conditions was seen as facilitating the work of physiotherapists in the ED. Patients and ED staff felt that ED physiotherapists had good interpersonal communication skills. ED staff expressed concerns regarding the additional time that physiotherapists spent with patients. Some patients felt that performing exercises in the ED was inappropriate and painful., Conclusions: ED physiotherapists were mostly well accepted by patients and ED staff, and their work was perceived to improve the ED. Concerns included restricted availability, lack of awareness of the role undertaken by physiotherapists in the ED, and increased treatment time in some settings. [Ferreira GE, Traeger AC, O'Keeffe M, Maher CG (2018) Staff and patients have mostly positive perceptions of physiotherapists working in emergency departments: a systematic review. Journal of Physiotherapy 64: 229-236]., (Copyright © 2018 Australian Physiotherapy Association. Published by Elsevier B.V. All rights reserved.)

Introduction: Excessive thoracic kyphosis is considered a predisposing factor for shoulder pain, though there is uncertainty about the nature of the relationship between shoulder pain and thoracic spine posture. The aim of this systematic review was to investigate the relationship between thoracic kyphosis and shoulder pain, shoulder range of motion (ROM) and function., Methods: Two reviewers independently searched eight electronic databases and identified relevant studies by applying eligibility criteria. Sources of bias were assessed independently by two reviewers using a previously validated tool (Ijaz et al., 2013). Data were synthesised using a level of evidence approach (van Tulder et al., 2003)., Results: Ten studies were included. Four studies were rated as low risk of bias, three at moderate risk of bias and three at high risk of bias. There is a moderate level of evidence of no significant difference in thoracic kyphosis between groups with and without shoulder pain. One study at high risk of bias demonstrated significantly greater thoracic kyphosis in people with shoulder pain (p < 0.05). There is a strong level of evidence that maximum shoulder ROM is greater in erect postures compared to slouched postures (p < 0.001), in people with and without shoulder pain., Conclusions: Thoracic kyphosis may not be an important contributor to the development of shoulder pain. While there is evidence that reducing thoracic kyphosis facilitates greater shoulder ROM, this is based on single-session studies whose long-term clinical relevance is unclear. Higher quality research is warranted to fully explore the role of thoracic posture in shoulder pain., (Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.)

Question: What are physiotherapists' perspectives on managing the cognitive, psychological and social dimensions of chronic low back pain after intensive biopsychosocial training?, Design: Qualitative study design using semi-structured interviews to explore physiotherapists' perceptions of their identification and treatment of the biopsychosocial dimensions of chronic low back pain after intensive Cognitive Functional Therapy (CFT) training., Participants: Thirteen qualified physiotherapists from four countries who had received specific CFT training. The training involved supervised implementation of CFT in clinical practice with patients. Interviews were audio-recorded and transcribed verbatim. An interpretive descriptive analysis was performed using a qualitative software package., Results: Four main themes emerged from the data: self-reported changes in understanding and attitudes; self-reported changes in professional practice; altered scope of practice; and increased confidence and satisfaction. Participants described increased understanding of the nature of pain, the role of patient beliefs, and a new appreciation of the therapeutic alliance. Changes in practice included use of new assessments, changes in communication, and adoption of a functional approach. Since undertaking CFT training, participants described a greater awareness of their role and scope of practice as clinicians in identifying and addressing these factors., Conclusion: Physiotherapists expressed confidence in their capacity and skill set to manage the biopsychosocial dimensions of chronic low back pain after CFT training, and identified a clear role for including these skills within the physiotherapy profession. Despite this, further clinical trials are needed to justify the time and cost of training, so that intensive CFT training may be made more readily accessible to clinicians, which to date has not been the case. [Synnott A, O'Keeffe M, Bunzli S, Dankaerts W, O'Sullivan P, Robinson K, O'Sullivan K (2016) Physiotherapists report improved understanding of and attitude toward the cognitive, psychological and social dimensions of chronic low back pain after Cognitive Functional Therapy training: a qualitative study.Journal of Physiotherapy62: 215-221]., (Copyright © 2016 Australian Physiotherapy Association. All rights reserved.)

Question: What are physiotherapists' perceptions about identifying and managing the cognitive, psychological and social factors that may act as barriers to recovery for people with low back pain (LBP)?, Design: Systematic review and qualitative metasynthesis of qualitative studies in which physiotherapists were questioned, using focus groups or semi-structured interviews, about identifying and managing cognitive, psychological and social factors in people with LBP., Participants: Qualified physiotherapists with experience in treating patients with LBP., Outcome Measures: Studies were synthesised in narrative format and thematic analysis was used to provide a collective insight into the physiotherapists' perceptions., Results: Three main themes emerged: physiotherapists only partially recognised cognitive, psychological and social factors in LBP, with most discussion around factors such as family, work and unhelpful patient expectations; some physiotherapists stigmatised patients with LBP as demanding, attention-seeking and poorly motivated when they presented with behaviours suggestive of these factors; and physiotherapists questioned the relevance of screening for these factors because they were perceived to extend beyond their scope of practice, with many feeling under-skilled in addressing them., Conclusion: Physiotherapists partially recognised cognitive, psychological and social factors in people with LBP. Physiotherapists expressed a preference for dealing with the more mechanical aspects of LBP, and some stigmatised the behaviours suggestive of cognitive, psychological and social contributions to LBP. Physiotherapists perceived that neither their initial training, nor currently available professional development training, instilled them with the requisite skills and confidence to successfully address and treat the multidimensional pain presentations seen in LBP., Registration: CRD 42014009964. [Synnott A, O'Keeffe M, Bunzli S, Dankaerts W, O'Sullivan P, O'Sullivan K (2015) Physiotherapists may stigmatise or feel unprepared to treat people with low back pain and psychosocial factors that influence recovery: a systematic review.Journal of Physiotherapy61: 68-76]., (Copyright © 2015. Published by Elsevier B.V.)

Physiotherapists perceive upright, lordotic sitting postures to be important in the management of non-specific chronic low back pain (NSCLBP). Little is known about the perceptions of the wider community about seated posture, despite this being an important consideration before attempting to change seated posture. This study investigated perceptions of the best and worst sitting postures among members of the community, both with (n = 120) and without (n = 235) NSCLBP. Participants with NSCLBP perceived posture to be more important (p < 0.001), and reported thinking about their posture significantly more frequently (p < 0.001), than those without NSCLBP. 54% of participants selected a "neutral" lordotic sitting posture as their best posture, which was more frequent than any other posture (p < 0.001). Sitting postures which were "straight", and were perceived to keep the head, neck and shoulders in good alignment were preferred. However, what people considered "straight" varied considerably. 78% selected a slumped sitting posture as their worst posture, which was more frequent than any other posture (p < 0.001). The choice of best and worst sitting postures was not significantly influenced by gender, the presence of NSCLBP, or measures of pain, disability or back pain beliefs. Interestingly, a very upright sitting posture was the second most popular selection as both the best (19%) and worst (15%) posture. Overall, lordotic lumbar postures were strongly favoured among members of the community, which is broadly in line with the previously reported perceptions of physiotherapists., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Evidence suggests a relation between short sleep duration and obesity., Objective: We assessed energy balance during periods of short and habitual sleep in normal-weight men and women., Design: Fifteen men and 15 women aged 30-49 y with a body mass index (in kg/m(2)) of 22-26, who regularly slept 7-9 h/night, were recruited to participate in this crossover inpatient study. All participants were studied under short (4 h/night) and habitual (9 h/night) sleep conditions, in random order, for 5 nights each. Food intake was measured on day 5, and energy expenditure was measured with the doubly labeled water method over each period., Results: Participants consumed more energy on day 5 during short sleep (2813.6 ± 593.0 kcal) than during habitual sleep (2517.7 ± 593.0 kcal; P = 0.023). This effect was mostly due to increased consumption of fat (20.7 ± 37.4 g; P = 0.01), notably saturated fat (8.7 ± 20.4 g; P = 0.038), during short sleep. Resting metabolic rate (short sleep: 1455.4 ± 129.0 kcal/d; habitual sleep: 1486.5 ± 129.5 kcal/d; P = 0.136) and total energy expenditure (short sleep: 2589.2 ± 526.5 kcal/d; habitual sleep: 2611.1 ± 529.0 kcal/d; P = 0.832) did not differ significantly between sleep phases., Conclusions: Our data show that a reduction in sleep increases energy and fat intakes, which may explain the associations observed between sleep and obesity. If sustained, as observed, and not compensated by increased energy expenditure, the dietary intakes of individuals undergoing short sleep predispose to obesity. This trial is registered at clinicaltrials.gov as NCT00935402.

Measurement of steroid esters in bovine hair samples, using sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS), provides a powerful tool for identifying animals treated illicitly with growth promoters. The successful application of such testing requires appropriate sampling of hair from treated animals. This paper describes the results of hair analysis by LC-MS/MS for two animal studies in which animals were treated with estradiol-3-benzoate and nortestosterone decanoate. The results from the first animal study indicate that animals treated with these anabolic steroids may not always be identified from analysis of hair samples; positive test results occur sporadically and only for some of the treated animals. The results from the second animal study identify conditions attaching to positive hair samples, such as, that concentrations of steroid esters in hair are related to distance of sampling from point of injection and to time post-treatment, that concentrations of steroid esters in hair are related to dose given to the animal but that this relationship may vary over time post-treatment, and that steroid esters may be measured in regrowth hair taken some weeks after treatment. Steroid esters are determined along the length of the hair, confirming that accumulation of steroid esters into hair occurs from various sources, including blood, sweat and sebum. The reported research provides some useful insights into the mechanisms governing the persistence of steroid esters in bovine hair following illicit treatment with growth promoters.

The detection of steroid residues in hair is a powerful strategy to demonstrate long-term administration of these growth promoters in meat production animals. Analysis of the ester form of administered steroids is an unambiguous approach to prove the illegal use of natural hormones. For detection, gas chromatography-mass spectrometry (GC-MS/MS) was generally used. However, recent advances in liquid chromatography-tandem mass spectrometry (LC-MS/MS) technology have improved the robustness and potential sensitivity of this method. This paper describes development and validation, according to Commission Decision 2002/657/EC, of LC-MS/MS and GC-MS/MS methods, in two separate laboratories, for determination of steroid esters in bovine hair. Bovine hair samples taken from animals treated with estradiol-3-benzoate and nortestosterone decanoate, as well as from an untreated animal, were used to evaluate the comparability of the results of the two validated methods. The results of the inter-comparison demonstrate that both the LC-MS/MS and the GC-MS/MS methods are fit for purpose and capable of determining steroid esters in hair samples from treated bovine animals.

The critical importance of plasmacytoid dendritic cells (pDCs) in viral infection, autoimmunity, and tolerance has focused major attention on these cells that are rare in blood and immune organs of humans and mice. The recent development of an Flt-3 ligand (FL) culture system of bone marrow cells has led to the simple generation of large numbers of pDCs that resemble their in vivo steady-state counterparts. The FL system has allowed unforeseen insight into the biology of pDCs, and it is assumed that FL is the crucial growth factor for these cells. Surprisingly we have found that a cell type with high capacity for interferon-alpha (IFN-alpha) production in response to CpG-containing oligonucleotides, a feature of pDCs, develop within macrophage-colony-stimulating factor (M-CSF)-generated bone marrow cultures. Analysis of this phenomenon revealed that M-CSF is able to drive pDCs as well as conventional DCs (cDCs) from BM precursor cells in vitro. Furthermore, application of M-CSF to mice was able to drive pDCs and cDCs development in vivo. It is noteworthy that using mice deficient in FL indicated that the M-CSF-driven generation of pDCs and cDCs in vitro and in vivo was independent of endogenous FL.

The capacity of mouse spleen conventional dendritic cells (cDCs) and plasmacytoid dendritic cells (pDCs) to produce interferon-gamma (IFN-gamma) or IFN-alpha was assessed, and compared with that of natural killer (NK) cells and the recently identified interferon-producing killer dendritic cells (IKDCs), both of which are frequent contaminants in DC preparations. Fully developed cDCs or pDCs, if free of NK cells or IKDCs, showed little capacity for IFN-gamma production. However, an early developmental form of the CD4-8+ cDC subtype, and the Ly6C- Ly49Q- pDC subtype, both were able to produce moderate amounts of IFN-gamma, although less than IKDCs. In response to toll-like receptor 9 stimuli, both the Ly6C+ Ly49Q+ and the Ly6C- Ly49Q- pDC subtypes were effective producers of IFN-alpha. However, IKDCs, which efficiently produced IFN-gamma and showed immediate cytotoxicity on NK target cells, did not produce IFN-alpha under these conditions.

Benzimidazoles are anthelmintic agents widely used in the treatment of parasitic infections in a range of species and as fungicidal agents in the control of spoilage of crops during storage and transport. In this paper, the more important benzimidazoles are introduced and their pharmacological effects and physiochemical properties discussed. The metabolism of these drugs is described relating to the occurrence and persistence of residues in biological matrices, providing information for selection of suitable matrices and target residues for testing. Methods for determination of benzimidazoles are reviewed for a range of biological matrices. The importance of selecting suitable extraction and clean-up procedures is discussed, along with the difficulties encountered in adapting single residue methods to multi-residue methods. The importance of suitable detection systems for determination of benzimidazoles, namely, screening, HPLC, GC and confirmatory methods is described in detail. The future for benzimidazole residue analysis is discussed, focusing on selection of appropriate residues for screening methods and protocols for confirmation of benzimidazole residues.

The macrocyclic lactones (MLs) are probably the anti-parasitic agents most widely used in the treatment of food producing animals, poultry, aquaculture and crops. Ivermectin was the first macrocyclic lactone product to be licensed for use about 20 years ago. A number of alternative products such abamectin, doramectin, emamectin, eprinomectin, moxidectin, milbemycin and selamectin, have been marketed since. Because of the increase in the number of ML drugs, there has been a steady increase in the number of published analytical methods for determination of their residues. In this paper, the structure and properties of the different ML drugs available on the market are described. The occurrence and persistence of ML residues in food is discussed in relation to marker residues and current maximum residue limits (MRLs) as defined in the European Union (EU). Methodologies for determination of ML residues in biological matrices are described in terms of extraction and clean-up methods used for different matrices. Detection systems for determination of ML residues are discussed with a particular emphasis placed on new developments in screening technologies and liquid chromatography with fluorescence or mass spectrometry.

Reticuloendotheliosis viral oncogene homolog/nuclear factor of kappa light polypeptide gene enhancer in B cells 1 (Rel/NF-kappaB) activation is a ubiquitous outcome of engaging Toll-like receptors (TLRs), yet the cell-type-specific functions of this pathway in response to particular microbial signals remain poorly defined. Here we show that NF-kappaB1 and C-Rel, Rel/NF-kappaB proteins induced in conventional dendritic cells (cDCs) and plasmacytoid dendritic cells (pDCs) by cytosine-phosphate-guanosine (CpG) DNA, a TLR-9 ligand, serve markedly different functions in these DC subsets. With the exception of impaired interleukin-12 (IL-12) production, cultured Nfkb1(-/-)C-Rel(-/-) cDCs responded relatively normally to CpG DNA. In contrast, CpG-treated Nfkb1(-/-)C-Rel(-/-) pDCs, which were still able to produce type I interferon and regulated on activation normal T-cell expressed and secreted (RANTES), but not IL-6 or IL-12, failed to acquire an activated dendritic phenotype and underwent apoptosis. Although the TLR-9-mediated death of Nfkb1(-/-)C-Rel(-/-) pDCs, which coincided with a failure to up-regulate the prosurvival proteins B-cell lymphoma apoptosis regulator xL (Bcl-x(L)) and A1, was blocked by Bcl-2 transgene expression, this inhibition of apoptosis still failed to rescue the differentiation defects. This indicated that these NF-kappaB transcription factors independently regulate TLR-9-mediated pDC morphogenesis and survival. Collectively, these findings establish that NF-kappaB1 and c-Rel, while largely dispensable for TLR-9-induced cDC activation, are critical for regulating differentiation and survival programs during pDC activation.

A simple, fast and reliable HPLC-UV method has been developed for the determination of dinitrocarbanilide residues in broiler liver. Liver samples (2 g) were extracted with two portions of acetonitrile (10 and 5 ml), defatted with hexane and evaporated to dryness under nitrogen. Extracts were reconstituted in acetonitrile-water (70/30, v/v, 500 microl), loaded onto C18 solid phase (SPE) cartridges and eluted with acetonitrile-water (70/30, v/v, 2.5 ml) into clean test-tubes. Extracts were evaporated to dryness and reconstituted in acetonitrile-water (80/20, v/v, 500 microl). An aliquot of the extract was assayed by high performance liquid chromatography (HPLC) with UV detection at 350 nm. The method was validated according to EU guidelines using liver tissues fortified at levels of 100, 200 and 300 microg/kg, with dinitrocarbanilide. The decision limit (CC(alpha)) and the detection capability (CC(beta)) were calculated from the within laboratory repeatability data to be 228 and 266 microg/kg, respectively. The mean recovery was typically >70% and the limits of quantitation was 12.5 microg/kg (based on the lowest standard on the calibration curve).

Dendritic cells (DC) are efficient antigen presenting cells with the ability to activate naïve T cells. Murine DC represent a heterogeneous population that can be subdivided into distinct subsets, including the conventional DC (cDC) which are either CD4(-)CD8(-) (DN), CD4(+)CD8(-) (CD4+) or CD4(-)CD8(+) (CD8+) subsets and the plasmacytoid DC (pDC), which have different immune regulatory functions. In this study, we investigated the differential expression of genes encoding the inflammatory chemokines Mip-1alpha, Mip-1beta and Rantes, and the secretion of these chemokines, among splenic DC subsets. These chemokine genes were expressed at higher levels by the splenic CD4+ and DN cDC subsets compared with the CD8+ cDC, in both the resting and activated states in vivo. Both the pDC and cDC subsets displayed increases in chemokine secretion in response to a range of toll-like receptor (TLR) stimuli in vitro. Whilst the pDC were the highest producers of Mip-1alpha and Mip-1beta in response to some TLR stimuli, the DN and CD4+ cDC subsets were the superior producers of Rantes. Overall, of the cDC, the CD4+ cDC produced all chemokines most efficiently, both at a basal level, and in response to most TLR stimuli. Thus, we report a new functional difference between the murine splenic cDC subsets, with the CD4+ cDC demonstrating the most efficient production of the inflammatory chemokines Mip-1alpha, Mip-1beta and Rantes.

A new brittle hydrocarbon has been successfully synthesized in polycrystalline form, and its crystal structure solved by quantitative electron diffraction. By 3D tilting of the nano-crystals, the lattice type and unit cell parameters were determined. (Triclinic, [Formula: see text] A, [Formula: see text] A, [Formula: see text] A, [Formula: see text] degrees, [Formula: see text] degrees, and [Formula: see text] degrees.) Spot diffraction patterns were obtained at -165 degrees C using the Koehler selected-area mode on a LEO 912 TEM fitted with an omega in-column elastic energy filter. The direct methods algorithm was then applied to merged intensities and a trial structure obtained assuming single scattering. This was further refined to obtain good agreement with a small residual of about 10% using multiple scattering calculations. A diagram of the proposed structure is given.

Although previous studies had indicated that the CD8alpha- and CD8alpha+ subtypes of murine dendritic cells (DCs) differ in immediate origin, a recent study found that intravenous transfer of CD8alpha- DCs led to CD8alpha+ DCs in the spleen several days later, suggesting a direct precursor-product relationship. We have repeated these experiments with a balance sheet approach. We find that though a few CD8alpha+ DCs can be generated in such experiments, this is a rare event and could be the result of a contaminant precursor. Most of the immediate precursors of CD8alpha+ DCs are cells that lack the phenotype of a recognizable DC. CD8alpha- DCs and CD8alpha+ DCs are not precursor-product related, though these sublineages may be connected further upstream.

A lateral flow immunoassay (LFIA) device was developed and applied to testing urine samples for residues of the antimicrobial sulphamethazine (SMZ). This report describes the preparation of a rat monoclonal antibody to SMZ and its characterisation in an ELISA format. Apart from SMZ, the antibody showed high (> or =50%) cross-reactivity to N4-acetyl-sulphamethazine (55%), sulphamerazine (59%) and sulphisoxazole (50%) and lower cross-reactivity of 18% to sulphachlorpyridazine and sulphadiazine. The LFIA device consisted of a nitrocellulose membrane spotted with SMZ-ovalbumin and goat anti-mouse antibody as capture line and control line, respectively. Mouse anti-rat IgG F(ab')2 fragment specific antibody, adsorbed to colloidal carbon, was used as the detection ligand in the LFIA. The LFIA device had a cut-off value of 6.3 ng/ml in diluted (1/10) urine. Urine samples from SMZ-treated pigs, and bovine and porcine urine samples fortified with SMZ were used for a blind, four-laboratory evaluation of the performance of the LFIA device. Concentrations of SMZ in the test samples (n=29), as determined by LC-MS/MS, ranged from 0 (<3) to 1174 ng/ml. The evaluation of the LFIA device showed an overall sensitivity of 100%, a specificity of 71%, and positive and negative prediction values of 73% and 100%, respectively. The LFIA device has been fabricated as a test kit for determining SMZ residues in animals produced for slaughter.

Immature and predendritic cells (pre-DCs) of human blood are the most readily accessible human DC sources available for study ex vivo. Murine homologues of human blood DCs have not been described. We report the isolation and characterization of 2 populations of precursor DCs in mouse blood. Mouse blood cells with the surface phenotype CD11c(lo)CD11b(-)CD45RA(hi) closely resemble human plasmacytoid cells (or pre-DC2) by morphology and function. On stimulation with oligonucleotides containing CpG motifs (CpG), these cells make large amounts of type 1 interferons and rapidly develop into DCs that bear CD8, though they may be distinct from the CD8(+) DCs in the unstimulated mouse. A second population of cells with the surface phenotype CD11c(+)CD11b(+)CD45RA(-) closely resembles the immediate precursors of pre-DC1, rapidly transforming into CD8(-) DCs after tumor necrosis factor-alpha (TNF-alpha) stimulation. These findings indicate the close relationship between human and mouse DCs, provided cells are obtained directly from equivalent source materials.

Drug-specific monoclonal antibodies (MAbs) were produced against the very small drug hapten (162.15 Da), 5-benzimidazolecarboxylic acid, an analogue of 2-(4-Thiazolyl)benzimidazole (TBZ) but lacking the thiol group. TBZ is widely used as a broad-spectrum anthelmintic in various animal species and humans and also as a food preservative and agricultural fungicide. The anti-5-benzimidazolecarboxylic acid antibodies produced have potential use for extraction and/or detection of protein-bound residue forms of TBZ. Three in vivo immunisation regimes (with combinations of two related small drug haptens and two different adjuvants/carrier molecules) and an in vitro immunisation procedure using a combination of three related unconjugated small drug haptens were investigated. Specificity for the hapten immunogen/s was initially determined using two different ELISA procedures. BIACORE analysis, in conjunction with drug binding inhibition studies, was used to confirm the specificity of a small number of selected clones. In vivo immunisation with a drug molecule conjugated to a lipopeptide/T-cell epitope, which acts both as a carrier molecule and an adjuvant was the most useful of the methods tested for the production of specific MAbs to a typically very small hapten with low immunogenic properties.

Introduction: The aims of this study were to determine, in a cohort of extremely premature infants, the prevalence of iron deficiency identified by zinc protoporphyrin/heme ratio (ZPP) testing, and its association with neurodevelopmental problems and dietary risk factors for iron deficiency., Methods: Infants of less than 29 weeks' gestation or less than 1000 g birth weight were studied prospectively at a multidisciplinary follow-up clinic. Assessments were made at a corrected age of either 12 months (n=72) or 2 years (n=69). Physical examination, Griffiths Developmental Scale, and neurosensory-motor assessment were administered, information on diet and behaviour was obtained by questionnaire, and a fingerprick ZPP ratio was performed to identify iron deficiency., Results: 18.4% of infants had positive ZPP tests. There was no significant association between a positive ZPP test result and dietary risk factors, or symptoms of lethargy, irritability or poor attention. In children without cerebral palsy, there was no difference on Griffiths scores or neurosensory-motor assessment between ZPP-positive and ZPP-negative groups. The diagnosis of cerebral palsy (n=12) was significantly associated with both a positive ZPP test and a lower Griffiths general quotient (GQ) score., Conclusions: Iron deficiency occurs commonly in extremely low birth weight (ELBW) children in early childhood, and is not predicted by dietary risk factors. The prevalence of iron deficiency is increased in ELBW children with cerebral palsy. Non-anaemic iron deficiency (NAID) does not impair development or significantly affect behaviour of ELBW subjects who do not have cerebral palsy.

We studied the effects of administration of several cytokines, including progenipoietin-1 (ProGP-1), Flt-3 ligand (FL), granulocyte colony-stimulating factor (G-CSF), and granulocyte-macrophage colony-stimulating factor in a pegylated form (pGM-CSF), on dendritic cell (DC) populations in mouse spleen. ProGP-1 produced the most striking increase in overall DC numbers, apparently more than its constituent FL and G-CSF components. However, the expansion in DC numbers was strongly subpopulation selective, with ProGP-1 and FL producing selective expansion of CD8+ DCs, whereas pGM-CSF produced selective expansion of CD8- DCs. Surprising differences were observed between the effects of murine and human recombinant FL preparations on murine DCs. Many of the biologic functions of the DC subpopulations expanded by cytokines remained intact, including the capacity of the ProGP-1- and FL-expanded CD8+ DCs to produce the T-helper-1-biasing cytokine interleukin 12 (IL-12). However, the expanded DCs from all but G-CSF-treated mice were deficient in the ability to make interferon gamma, and the CD8+ DCs produced with pGM-CSF treatment had an abrogated capacity to form bioactive IL-12. Such selective expansion of DC populations and alterations in their cytokine-secretion capacity have implications for clinical use of the studied cytokines in immune modulation.

The antigen-presenting dendritic cells (DCs) found in mouse lymphoid tissues are heterogeneous. Several types of DCs have been identified on the basis of the expression of different surface molecules, including CD4, CD8alpha, and DEC-205. Previous studies by the authors showed that the mouse intrathymic lymphoid-restricted precursors (lin(-)c-kit(+)Thy-1(low)CD4(low)) can produce DCs in the thymus and spleen upon intravenous transfer, suggesting a lymphoid origin of these DCs. In the current study, the potential for DC production by the newly identified bone marrow (BM) common lymphoid precursors (CLPs), common myeloid precursors (CMPs), and committed granulocyte and macrophage precursors was examined. It was found that both the lymphoid and the myeloid precursors had the potential to produce DCs. All the different DC populations identified in mouse thymus and spleen could be produced by all these precursor populations. However, CLPs produced predominantly the CD4(-)CD8alpha(+) DCs, whereas CMPs produced similar numbers of CD4(-)CD8alpha(+) and CD4(+)CD8alpha(-) DCs, although at different peak times. On a per cell basis, the CLPs were more potent than the CMPs at DC production, but this may have been compensated for by an excess of CMPs over CLPs in BM. Overall, this study shows that the expression of CD8alpha does not delineate the hemopoietic precursor origin of DCs, and the nature of the early precursors may bias but does not dictate the phenotype of the DC product.

A multi-residue supercritical fluid extraction (SFE) method has been developed for the extraction and isolation of eprinomectin, moxidectin, abamectin, doramectin and ivermectin residues from animal liver. Liver samples are mixed with hydromatrix and packed into a vessel containing 2 g of basic alumina. The samples are extracted at 100 degrees C using unmodified supercritical carbon dioxide (SF-CO2) at a pressure of 300 bar and flow-rate of 5.0 l/min. The analytes are adsorbed in-line on the basic alumina trap, which is later eluted with 4 ml of methanol-ethyl acetate (70:30, v/v). After evaporating to dryness, sample extracts are derivatised using methylimidazole, trifluoroacetic anhydride and acetic acid at 65 degrees C for 30 min. Derivatised sample extracts are analysed by high-performance liquid chromatography (HPLC) with fluorescence detection. The method was validated using bovine liver fortified at levels of 4 and 20 microg/kg with the drugs. The mean recovery ranged between 76 and 97%. The intra- and inter-assay variations showed RSD values <10 and <16%, respectively. The procedure was also applied to ovine and porcine liver, giving similar results. The limit of quantitation of the method is 2 microg/kg.

A method is described for the analysis of beta-agonists in urine of cattle. The method uses solid-phase extraction (SPE), followed by analysis of the resulting extract by flow injection thermospray tandem mass spectrometry (TSP-MS-MS). Sample preparation is performed using a mixed-bed SPE procedure using a sorbent having both hydrophobic and ionic properties. MS-MS analysis following thermospray ionization, is performed in single-reaction monitoring parent mode. In that way isotope dilution can be used for quantitation of clenbuterol. Data are presented on precision and accuracy for clenbuterol and related compounds. Furthermore, data acquisition was performed in full-scan neutral loss mode to indicate the suitability of flow injection analysis (FIA)-TSP-MS-MS for exploratory analysis. Detection of beta-agonists in this mode is based on the presence of the N-tert.-butyl-beta-ethanolamino moiety and, in that respect, detection of known as well as unknown compounds having this moiety will take place. This feature is exemplified by the analysis of samples containing several compounds.