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In the context of an ageing population, many healthcare professionals have limited experience and confidence in having necessary advance care planning (ACP) conversations.We conducted nine half-day simulation sessions, using professional actors. One-hundred and thirty-two participants attended from multidisciplinary backgrounds across primary and secondary care.Following the course, 90.2% felt confident or very confident initiating conversations, compared with 14.4% beforehand. Understanding of when ACP is appropriate also increased from 70% to 100%. Post-course, 98% of participants stated that they would be more likely to initiate an ACP. Three months later, 86% had a sustained change in practice. All participants said they would recommend this simulation course and multidisciplinary approach.Multidisciplinary simulation training is an effective way to teach ACP to doctors, nurses and allied healthcare professionals. The simulation was shown to improve participant understanding, confidence and reduce barriers to discussions, both immediately and 3 months later.

We applied dimensionality reduction algorithms and pattern classifiers to functional neuroimaging data collected as participants listened to a story, temporally scrambled versions of the story, or underwent a resting state scanning session. These experimental conditions were intended to require different depths of processing and inspire different levels of cognitive engagement. We considered two primary aspects of the data. First, we treated the maximum achievable decoding accuracy across participants as an indicator of the “informativeness” of the recorded patterns. Second, we treated the number of features (components) required to achieve a threshold decoding accuracy as a proxy for the “compressibility” of the neural patterns (where fewer components indicate greater compression). Overall, we found that the peak decoding accuracy (achievable without restricting the numbers of features) was highest in the intact (unscrambled) story listening condition. However, the number of features required to achieve comparable classification accuracy was also lowest in the intact story listening condition. Taken together, our work suggests that our brain networks flexibly reconfigure according to ongoing task demands, and that the activity patterns associated with higher-order cognition and high engagement are both more informative and more compressible than the activity patterns associated with lower-order tasks and lower levels of engagement.

Aims To repurpose a silver-based antimicrobial textile coating product (Micro-Fresh 1911) as a dual-function antimicrobial laundry additive and textile coating. Methods and Results Survival of Escherichia coli or Staphylococcus aureus type and clinical isolates in a domestic 40°C wash was assessed with and without soiling and biological detergent. Washing with 2% w/v silver additive (wash phase) reduced E. coli and S. aureus by 7·14–8·08 log10 and no cross-contamination was observed. Under dirty conditions, 0·5% silver additive in the rinse phase of a wash with biological detergent reduced E. coli and S. aureus by 7·98–8·40 log10 (0·00–1·42 log10 cross contamination). BS EN ISO 20645:2004 and BS EN ISO 20743:2013 methods were used to assess the antimicrobial activity of polycotton washed with 2% w/v silver additive against S. aureus and E. coli. The treated polycotton was antimicrobial against E. coli and S. aureus type and clinical isolates and remains active after at least one further wash cycle at 40 or 73°C. Conclusions The silver additive exhibits antimicrobial activity in a 40°C domestic wash, preventing cross contamination onto clean textiles and depositing an antimicrobial coating onto polycotton. Significance and Impact of the Study The survival of micro-organisms on healthcare uniforms during domestic laundering presents a potential risk of contaminating the home, cross-contamination of other clothing within the wash and transmitting potential pathogens back into healthcare settings via contaminated uniforms. Silver may be useful as an antimicrobial laundry additive to decontaminate healthcare laundry washed at low temperatures in domestic and industrial settings, to therefore reduce the potential risk of transmitting micro-organisms within the domestic and clinical environments.

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link. Background: The COVID-19 pandemic raised concerns towards domestic laundering of healthcare worker (HCW) uniforms; this is common practice in countries such as the United Kingdom (UK) and United States. Previous research suggested 4-32% of nurses did not adhere to laundry policies, which could be an infection control risk. This study aimed to investigate the knowledge and attitudes of UK healthcare workers towards domestic laundering of uniforms during the COVID-19 pandemic. Methods: Online and paper questionnaires were distributed to HCWs and nursing students who regularly wear uniforms. Differences in knowledge between HCWs were analysed by Chi-squared tests and attitudes were examined using exploratory factor analysis. Results: 86% of participants (n=1099 of 1277) laundered their uniforms domestically. Respondents were confident in laundering their uniforms appropriately (71%), however 17% failed to launder at the recommended temperature (60°C). Most participants (68%) would prefer their employer launder their uniforms, with mixed negative emotions towards domestic laundering. Limited provision of uniforms and changing/storage facilities were a barrier to following guidelines. Conclusion: Most HCWs domestically launder their uniforms, despite a preference for professional laundering. One-fifth of HCWs deviated from the UK National Health Service uniform guidelines; onsite changing facilities were the most significant barrier towards adherence.

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link. There is need for new effective antivirals, particularly in response to the development of antiviral drug resistance and emerging RNA viruses such as SARS-CoV-2. Plants are a significant source of structurally diverse bioactive compounds for drug discovery suggesting that plant-derived natural products could be developed as antiviral agents. This article reviews the antiviral activity of plant-derived natural products against RNA viruses, with a focus on compounds targeting specific stages of the viral life cycle. A range of plant extracts and compounds have been identified with antiviral activity, often against multiple virus families suggesting they may be useful as broad-spectrum antiviral agents. The antiviral mechanism of action of many of these phytochemicals is not fully understood and there are limited studies and clinical trials demonstrating their efficacy and toxicity in vivo. Further research is needed to evaluate the therapeutic potential of plant-derived natural products as antiviral agents.

open access article The role of indirect contact in the transmission of SARS-CoV-2 is not clear. SARS-CoV-2 persists on dry surfaces for hours to days; published studies have largely focused on hard surfaces with less research being conducted on different porous surfaces, such as textiles. Understanding the potential risks of indirect transmission of COVID-19 is useful for settings where there is close contact with textiles, including healthcare, manufacturing and retail environments. This article aims to review current research on porous surfaces in relation to their potential as fomites of coronaviruses compared to non-porous surfaces. Current methodologies for assessing the stability and recovery of coronaviruses from surfaces are also explored. Coronaviruses are often less stable on porous surfaces than non-porous surfaces, for example, SARS-CoV-2 persists for 0.5 h–5 days on paper and 3–21 days on plastic; however, stability is dependent on the type of surface. In particular, the surface properties of textiles differ widely depending on their construction, leading to variation in the stability of coronaviruses, with longer persistence on more hydrophobic materials such as polyester (1–3 days) compared to highly absorbent cotton (2 h–4 days). These findings should be considered where there is close contact with potentially contaminated textiles.

Introduction: The survival of the COVID-19 coronavirus (SARS-CoV-2) on textiles during laundering and in the presence of ozone is not well understood. In this study, the stability of a model human coronavirus (HCoV-OC43), on cotton textiles laundered using the OTEX validated ozone disinfection system was investigated. Method: Samples of cotton were contaminated with HCoV-OC43 and then washed using the Foul and Infected (40°C) cycle with laundry detergent and ozone. Sterile textile samples were washed in the same load to investigate potential cross contamination of HCoV-OC43. After washing, the number of infectious virus particles present on the cotton samples was determined. In a time-assay study, the stability of HCoV-OC43 in the presence of ozone over time was also investigated. Cotton samples contaminated with HCoV-OC43 were exposed to ozone in solution, for 3 and 6 minutes. The number of infectious virus particles remaining on the cotton after the wash was determined. For both the contamination tests and time-assay study, washes without detergent and ozone were included as controls. Results: No infectious virus was detected on contaminated cotton samples after washing using the OTEX Foul and Infected cycle, demonstrating at least 1.6 log10 reduction in HCoV-OC43 infectivity from the textile when using this wash cycle. No infectious virus was detected on sterile textile samples included in the washes, suggesting that there was no detectable cross-contamination occurring within the wash. In the time-assay study, HCoV-OC43 infectivity was reduced by at least 4.3 log10 within 6 minutes of washing in the presence of ozone – beyond that of the limit of detection. Discussion: These findings show that ozone contributes to the inactivation of HCoV-OC43. Overall, the results suggest that coronaviruses such as HCoV-OC43 are unlikely to persist within the OTEX laundering cycle.

Introduction: Advance care planning is the process by which patients can make decisions about their future health care should they lose capacity. Such conversations are shown to improve quality of life and reduce institutionalization. This article explores the preferences and wishes of patients in terms of advance care planning. Methods: CINAHL, Medline, Embase and Pubmed were searched. Key words included ‘elderly’, ‘advance care planning’, ‘advance directive’, ‘views’ and ‘opinions’. Results: A total of 64 abstracts were screened and 20 full text articles read; 11 articles were included in the final study. Individual and cultural differences influence the level of decision making that patients want. Most studies agreed that conversations should be carried out opportunistically by a trained health-care professional. Patients value honest and open conversations, without which they may make misinformed decisions. Conclusions: The level of shared decision making that individuals personally want should be established. Open and honest conversations should be initiated at the earliest opportunity.

open access article Aims: To develop an essential oil (EO)-loaded textile coating using an environmentally-friendly microemulsion technique to achieve both antimicrobial and mosquito repellent functionalities. Methods and Results: Minimum inhibitory concentrations and fractional inhibitory concentrations of litsea, lemon and rosemary EOs were determined against Staphylococcus aureus, Escherichia coli, Staphylococcus epidermidis, Pseudomonas aeruginosa and Trichophyton rubrum. A 1:2 mixture of litsea and lemon EOs inhibited all the microorganisms tested and was incorporated into chitosan-sodium alginate assembly by a microemulsification process. The EO-loaded microemulsions were applied to cotton and polyester fabrics using a soak-pad-dry method. The textile challenge tests demonstrated 7-8 log10 reductions of S. epidermidis, S. aureus and E. coli after 24 h and T. rubrum after 48 h. Aedes aegypti mosquito repellency was also assessed which demonstrated 71.43% repellency compared to 52.94% by neat EO-impregnated cotton. Conclusions: Textiles treated with the litsea and lemon EO microemulsion showed strong antimicrobial activity against the skin associated microorganisms E. coli, S. aureus, S. epidermidis and T. rubrum and potential mosquito repellent properties. Significance of Study: EOs could be useful for the development of natural, environmentally-friendly functional textiles to protect textiles and users from microbial contamination in addition to possessing other beneficial properties such as mosquito repellency.

Patients with Parkinson's disease, who lose the dopaminergic projections to the striatum, are impaired in certain aspects of motor learning. Recent evidence suggests that, in addition to its role in motor performance, the striatum plays a key role in the memory of motor learning. Whether Parkinson's patients have impaired motor memory and whether motor memory is modulated by dopamine at the time of initial learning is unknown. To address these questions, we measured memory of a learned motor sequence in Parkinson's patients who were either On or Off their dopaminergic medications at the time of initial learning. We compared them to a group of older and younger controls. Contrary to our predictions, motor memory was not impaired in patients compared to older controls, and was not influenced by dopamine state at the time of initial learning. To probe post-learning consolidation processes, we also tested whether learning a new sequence shortly after learning the initial sequence would interfere with later memory. We found that, in contrast to younger adults, neither older adults nor patients were susceptible to this interference. These findings suggest that motor memory is preserved in Parkinson's patients and raise the possibility that motor memory in patients is supported by compensatory non-dopamine sensitive mechanisms. Furthermore, given the similar performance characteristics observed in the patients and older adults and the absence of an effect of dopamine, these results raise the possibility that aging and Parkinson's disease affect motor memory in similar ways.

Healthcare-associated infections (HAIs) are a significant cause of morbidity and mortality and pose a major economic burden. Infection control is therefore important in healthcare environments to minimize the transmission of microorganisms. Personal Protective Equipment (PPE) is used to provide protection to both wearer and patient from contaminants in a healthcare setting. Reusable PPE such as healthcare worker uniforms are common; however microorganisms are able to survive on textiles for days, indicating that insufficient decontamination of reusable clothing could transmit HAIs. Adequate laundering of reusable items is therefore a necessary infection control measure. Antimicrobial coatings offer a potential solution to the contamination of reusable textile items. However, research is needed to validate their efficacy in healthcare settings and assurances of their durability are needed to support their use for infection control purposes.

Antibacterial efficacy of nanoscale silver, copper (II) oxide and zinc oxide were assessed against Pseudomonas aeruginosa and Staphylococcus aureus biofilms in solution and on surfaces. Using a Center for Disease Control biofilm reactor, minimum biofilm reduction concentrations, the coefficient of determination (R2) and log(10) reductions were determined. Atomic absorption spectroscopy, scanning electron microscopy and confocal laser scanning microscopy were used to assess the disruption of the biofilms. The efficacy of thin films of zinc oxide and silver deposited via magnetron sputtering and thermal evaporation respectively was also assessed. Minimum biofilm reduction concentrations of zinc oxide or silver nanoparticles were 256 or 50 µg/ml for P. aeruginosa and 16 or50 µg/ml for S. aureus respectively. When tested in combination the nanoparticles concentrations were at least halved resulting in significant (p ≤0.05) biofilm reductions of 3.77 log(10) - 3.91 log(10). Biofilm growth on thin films resulted in reductions of up to 1.82 log(10). The results suggest that nanoparticle suspensions and thin films of zinc oxide and may have potential as antimicrobial treatments for hard to eliminate biofilms in a clinical environment.

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link. Aims: To determine the survival of Escherichia coli and Staphylococcus aureus on cotton and polyester and the effectiveness of low temperature laundering and detergents on the removal of microorganism from healthcare laundry. Methods and Results: Survival of E. coli and S. aureus on polyester or cotton was assessed over 3 weeks and the efficacy of a domestic wash (40°C and 60°C) and a range of detergents was also determined. Both bacteria were able to survive on cotton (5 log(10)) and polyester (0.28 log(10)) for up to 3 weeks. Laundering at 40°C resulted in a 3.5 log(10) removal of the initial 7.7 log(10) inoculum and some cross contamination to sterile fabrics (3 log(10). Increasing the temperature to 60°C resulted in the complete removal of the initial inoculum. Conclusions: This study shows that most of the microorganisms are removed at 40°C however, those cells still remaining may have the potential for further contamination to the clinical environment and patients Significance and Impact of Study: National Health Service (NHS) nurses are required to domestically launder their uniforms at 60°C to ensure safe removal of microorganisms, 33% of NHS staff questioned said they launder their uniforms at 40°C, which could potentially result in transmission of Hospital Acquired Infections (HAIs).

Acne vulgaris, a chronic condition associated with overgrowth of Propionibacterium acnes and Staphylococcus epidermidis, is commonly treated with antibiotics. However, the emergence of antibiotic resistance has resulted in a need for alternative therapies. The aim of this study is to develop a topical preparation incorporating essential oils (EOs) for use against acne-associated bacteria and assess its efficacy against prescription therapies Dalacin T and Stiemycin. Antimicrobial screening of rosewood, clove bud and litsea EOs was conducted before interactions between binary and ternary combinations were determined against P. acnes and S. epidermidis (type and clinical isolates) using minimum inhibitory concentrations and fractional inhibitory concentrations. The EOs were characterised by both gas chromatography–mass spectrometry and nuclear magnetic resonance. A combination of 0.53 mg/mL litsea, 0.11 mg/mL rosewood and 0.11 mg/mL clove bud was formulated into herbal distillates and compared with Dalacin T and Stiemycin against antibiotic sensitive and resistant isolates (erythromycin). The distillate with EO had synergistic activity against P. acnes (7log10 reduction) and indifferent activity against S. epidermidis (6log10 reduction); antimicrobial activity was either significantly (p ≤ 0.05) more antimicrobial or equivalent to that of Dalacin T and Stiemycin. This formulation may serve as a valuable alternative for the control of acne vulgaris-associated bacteria. Copyright © 2017 John Wiley & Sons, Ltd.

The file attached to this record is the author's final peer reviewed version Vancomycin Resistant Enterococcus faecium (VRE) has become endemic in healthcare settings, reducing treatment options for enterococcal infections. New antimicrobials for VRE infections are a high priority, but the development of novel antibiotics is time-consuming and expensive. Essential Oils (EOs) synergistically enhance the activity of some existing antibiotics, suggesting that EO-antibiotic combinations could re-sensitise resistant bacteria and maintain the antibiotic repertoire. The mechanism of re-sensitisation of bacteria to antibiotics by EOs is relatively understudied. Here, the synergistic interactions between carvacrol (1.98 mM) and cuminaldehyde (4.20 mM) were shown to re-establish susceptibility to vancomycin (0.031 mg/L) in VRE, resulting in bactericidal activity (4.73 log10 CFU/mL reduction). Gene expression profiling, coupled with β-galactosidase leakage and salt tolerance assays suggested that cell envelope damage contributes to the synergistic bactericidal effect against VRE. The EO-vancomycin combination was also shown to kill clinical isolates of VRE (2.33-5.25 log10 CFU/mL reduction) and stable resistance did not appear to develop even after multiple passages. The in vivo efficacy of the EO-vancomycin combination was tested in a Galleria mellonella larvae assay; however no antimicrobial action was observed, indicating that further drug development is required for the EO-vancomycin combination to be clinically useful for treatment of VRE infections.

Background: Formulations employing synergistic combinations of antibiotics with Essential Oils (EOs) could help preserve the antibiotic repertoire by improving their activity against resistant bacteria. Objective: Antimicrobial interactions between double and triple combinations of EOs, EO components and antibiotics were determined using the checkerboard method. The most active triple combinations were then assessed by a time-kill assay. Methods: Two synergistic EO-antibiotic combinations and eight additive EO-antibiotic combinations reduced the antibiotic minimum inhibitory concentration below clinical sensitivity breakpoints according to the checkerboard method. However, all the tested combinations were additive according to the time-kill assay; while the combinations completely killed S. aureus, E. coli and P. aeruginosa cells in 2 h. At least one EO compound from the combination alone completely killed the cells of test species. Results: Two synergistic EO-antibiotic combinations and eight additive EO-antibiotic combinations reduced the antibiotic minimum inhibitory concentration below clinical sensitivity breakpoints according to the checkerboard method. However, all the tested combinations were additive according to the time-kill assay; while the combinations completely killed S. aureus, E. coli and P. aeruginosa cells in 2 h. At least one EO compound from the combination alone completely killed the cells of test species. Conclusion: Positive interactions support the use of EOs or EO components to enhance antibiotic efficacy against antibiotic resistant bacteria. The EO-antibiotic combinations tested by the time kill assay were indifferent; therefore, the observed antimicrobial activity did not arise from synergistic mechanisms as indicated by the checkerboard method. Investigation of other synergistic combinations identified by the checkerboard method could reveal more promising candidates.

The file attached to this record is the author's final peer reviewed version. Introduction: The antimicrobial activity of many Essential Oils (EOs) is well established, indicating that EOs may be a source of compounds for antimicrobial drug development. Thin Layer Chromatography-Direct Bioautography (TLC-DB) can quickly identify antimicrobial components in complex mixtures and can be applied to the screening of EOs for lead compounds. Objectives: This study aimed to identify antimicrobial components of oregano, rosewood and cumin EOs against antibiotic-sensitive and -resistant bacteria using TLC-DB and a multi-faceted approach of GC-MS, LC-MS and NMR techniques to characterise bioactive compounds. The study also aimed to quantify the antimicrobial activity of bioactive compounds in order to evaluate their potential for the development of therapies against antibiotic-resistant bacteria. Materials and Methods: EOs were eluted on TLC plates and sprayed with a suspension of Staphylococcus aureus, Enterococcus faecium, Escherichia coli or Pseudomonas aeruginosa (antibiotic-sensitive and -resistant isolates). Zones of inhibition, visualised with iodonitrotetrazolium chloride, were subject to GC-MS, LC-MS and NMR to characterise the bioactive compounds. Results: Seven compounds were identified from the three EOs using GC-MS, while LC-MS and NMR failed to detect the presence of any further non-volatile or heat labile compounds. Carvacrol was most antimicrobial compound identified, with minimum inhibitory concentrations ranging 0.99-31.62 mM. Conclusion: The identified antimicrobial compounds present in oregano, rosewood and cumin EOs including carvacrol may be candidates for the development of novel antimicrobial therapies against antibiotic-resistant bacteria.

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link Antibiotic resistance has increased dramatically in recent years, yet the antibiotic pipeline has stalled. New therapies are therefore needed to continue treating antibiotic resistant infections. One potential strategy currently being explored is the use of non-antibiotic compounds to potentiate the activity of currently-employed antibiotics. Many natural products including Essential Oils (EOs) possess broad spectrum antibacterial activity and so have been investigated for this purpose. This article aims to review recent literature concerning the antibacterial activity of EOs and their interactions with antibiotics, with consideration of dual mechanisms of action of EOs and antibiotics as a potential solution to antibiotic resistance. Synergistic interactions between EOs and their components with antibiotics have been reported, including several instances of antibiotic resensitization in resistant isolates, in support of this strategy to control antibiotic resistance. However, a lack of consistency in methods and interpretation criteria makes drawing conclusions of efficacy of studied combinations difficult. Synergistic effects are often not explored beyond preliminary identification of antibacterial interactions and mechanism of action is rarely defined, despite many hypotheses and recommendations for future study. Much work is needed to fully understand EO-antibiotic associations before they can be further developed into novel antibacterial formulations.

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link. Many essential oil components are known to possess broad spectrum antimicrobial activity, including against antibiotic resistant bacteria. These compounds may be a useful source of new and novel antimicrobials. However, there is limited research on the structure-activity relationship (SAR) of essential oil compounds, which is important for target identification and lead optimization. This study aimed to elucidate SARs of essential oil components from experimental and literature sources. Minimum Inhibitory Concentrations (MICs) of essential oil components were determined against Escherichia coli and Staphylococcus aureus using a microdilution method and then compared to those in published in literature. Of 12 essential oil components tested, carvacrol and cuminaldehyde were most potent with MICs of 1.98 and 2.10 mM, respectively. The activity of 21 compounds obtained from the literature, MICs ranged from 0.004 mM for limonene to 36.18 mM for α-terpineol. A 3D qualitative SAR model was generated from MICs using FORGE software by consideration of electrostatic and steric parameters. An r2 value of 0.807 for training and cross-validation sets was achieved with the model developed. Ligand efficiency was found to correlate well to the observed activity (r2 = 0.792), while strongly negative electrostatic regions were present in potent molecules. These descriptors may be useful for target identification of essential oils or their major components in antimicrobial/drug development.

Acne vulgaris, a chronic condition associated with overgrowth of Propionibacterium acnes and Staphylococcus epidermidis, is commonly treated with antibiotics. However, the emergence of antibiotic resistance has resulted in a need for alternative therapies. The aim of this study is to develop a topical preparation incorporating essential oils (EOs) for use against acne-associated bacteria and assess its efficacy against prescription therapies Dalacin T and Stiemycin. Antimicrobial screening of rosewood, clove bud and litsea EOs was conducted before interactions between binary and ternary combinations were determined against P. acnes and S. epidermidis (type and clinical isolates) using minimum inhibitory concentrations and fractional inhibitory concentrations. The EOs were characterised by both gas chromatography-mass spectrometry and nuclear magnetic resonance. A combination of 0.53 mg/mL litsea, 0.11 mg/mL rosewood and 0.11 mg/mL clove bud was formulated into herbal distillates and compared with Dalacin T and Stiemycin against antibiotic sensitive and resistant isolates (erythromycin). The distillate with EO had synergistic activity against P. acnes (7log

Aim: It has been claimed for a number of years that the urine of children with autism contains exogenously derived opioid peptides. This finding is said to reflect a disturbance in the integrity of the gut epithelium, act as a diagnostic marker for autism and predict treatment response to a diet excluding gluten and casein. The aim of the present study was to determine whether exogenous or endogenous peptides were present either in the urine of children with autism, or control children. Design: Case-control study Setting: Cases were recruited from two tertiary referral centres specialising in autistic spectrum disorders whilst controls were recruited from and mainstream primary and secondary schools in the same geographical area. Participants: 65 boys with autism mean age 7:4 years (5-11) and 158 control boys mean age 7:8 years (4:2-11). Investigations: Urine samples were examined by High Pressure Liquid Chromatography (HPLC) and Matrix Assisted Laser Desorbtion Ionisation-Time of Flight Mass Spectroscopy (MALDI-TOF MS) for the presence of a number of putative opioid peptides. Outcomes: There were no significant differences between the HPLC urinary profiles of the children affected by autism and the typically developing controls. In those cases where HPLC showed peaks in the locations at which opioid peptides might be expected to be found., MALDI-TOF established that these peaks did not, in fact, represent opioid peptides at all. Conclusions: Given the lack of evidence for any opioid peptiduria in children with autism it can neither serve as a biomedical marker for autism, nor be employed to predict or monitor response to a casein and gluten exclusion diet.

This article presents the findings of the first study to have followed up children conceived by in vitro fertilisation (IVF) to late adolescence. As close as possible to their eighteenth birthday, standardised interviews and questionnaires were administered to 26 adolescents conceived by IVF and comparison groups of 27 adolescents adopted in infancy and 56 adolescents conceived naturally by previously infertile parents. IVF adolescents were found to have good relationships with their parents that did not differ from those of adopted and natural conception adolescents. At age 18, no young person was distressed about having been conceived by IVF. The findings of this study indicate that as test-tube babies approach adulthood, they are generally functioning well.

This paper presents the findings of the third phase of a longitudinal study of families created by assisted reproduction. The quality of parent–child relationships was examined close to the adolescent's 18th birthday in 26 in vitro fertilization (IVF) families and 26 donor insemination (DI) families in comparison with 38 adoptive families and 63 natural conception families matched for demographic characteristics. A significantly higher level of mother–adolescent warmth was found between the assisted reproduction and the adoptive families, between the DI and natural conception families and between the DI and IVF families. IVF mothers showed significantly greater disciplinary indulgence than natural conception mothers, and significantly lower disciplinary aggression than DI mothers. No differences were identified between fathers for warmth or conflict. Only 2 DI children were aware of their donor conception.

Systematic data from a multidisciplinary clinical assessment of a large series of females with Rett syndrome (RS; n=87) is presented. Participants' ages ranged from 2 years 1 month to 44 years 10 months. Areas assessed included oromotor skills, feeding problems, growth, breathing abnormalities, mobility, postural abnormalities and joint deformities, epilepsy, hand use and stereotypies, self-care, and cognitive and communication skills. Many previously reported trends in the presentation of RS over time were confirmed, notably the increasingly poor growth and near pervasiveness of fixed joint deformities and scoliosis in adulthood. In contrast, there was a slight trend towards improved autonomic function in adulthood, whereas feeding difficulties increased into middle childhood and then reached a plateau. Improvements in mobility into adolescence were followed by a decline in those skills in adulthood. Levels of dependency were high, confirming findings from previous studies. Despite the presence of repetitive hand movements, a range of hand-use skills was seen in individuals of all ages. Cognitive and communication skills were limited, but there was little evidence of deterioration of these abilities with age. These findings confirm that RS is not a degenerative condition and indicate that intervention and support to maintain and increase motor skills, daily living skills, and cognitive and communicative functioning are appropriate targets for individuals with RS.

Data on features of regression and pre-regression developmental history in a case series of 53 girls and women with Rett syndrome are presented. Consistent with the diagnostic criteria, hand skills and verbal or non-verbal communication skills were the most common skills lost during regression. Play and motor skills were also lost in half the cases. Regression most commonly occurred between 12 and 18 months of age but was noted in a few cases before 6 months or after 36 months. Pre-regression developmental delays or abnormalities were noted in over two-thirds of cases, increasing to 85% of the youngest cases where parental reporting was likely to be more accurate. Age at regression was not associated with severity of physical and growth symptoms, and thus did not appear to be an index of neurological severity. There is a continuing need to further elucidate the pre- and post-regression features of Rett syndrome in order to aid early identification, diagnosis and referral for genotype mutation analysis.

Objectives To compare the outcome of two methods of maternity care during the antenatal period and at delivery. One was to be midwife-led for both antenatal care and delivery, the latter taking place in rooms similar to those in one's own home to simulate home confinement. The other would be consultant-led with the mothers labouring in the delivery suite rooms with resuscitation equipment for both mother and baby in evidence, monitors present and a delivery bed on which both anaesthetic and obstetric procedures could be easily and safely carried out. Design Randomised controlled trial. Setting Leicester Royal Infirmary Maternity Hospital. Subjects Of 3510 women who were randomised, 2304 were assigned to the midwife-led scheme and 1206 were assigned to the consultant-led scheme. Main outcome measures Complications in the antenatal, intrapartum and postpartum periods were compared as was maternal morbidity and fetal mortality and morbidity. Satisfaction of the women with care over different periods of the pregnancy and birth were assessed. Results There were few significant differences in antepartum, intrapartum and postpartum events between the two groups. There was no difference in the percentage of mothers and babies discharged home alive and well. Generally higher levels of satisfaction with care antenatally and during labour and delivery were shown in those women allocated to midwife care.

5ffi TRI1CS who are disturbed by "problems" in Measure f Measure focus generally on inconsistencies of characterization or on a disparity between the ending of the play and the rest of its action. A. P. Rossiter, for example, concludes that the play is essentially cynical and pessimistic and that the happy ending and the forgiveness of Angelo are devices tacked on to it, not wholly successfully, to make it a comedy.' Such criticism fails to see that the notion of the gracelessness of man, so strongly conveyed by the failings of Angelo, Isabellk, and Claudio, as well as by the low moral tone of the minor characters, is paralleled throughout the play by the notions of divine redemption and human mercy and that the thrust of the whole play from its beginning is away from punishment for its own sake and toward forgiveness and self-knowledge. Forgiveness is central to the play; the "problems" which it seems to present are related to the dramatic problem of representing forgiveness on the stage and can be in part dealt with through comparison with other plays that emphasize forgiveness. In so far as mercy, forgiveness, and repentance are qualities or actions of the mind and spirit rather than external actions, they cannot be directly presented. In medieval plays a change of mind was represented allegorically or it was accounted for by the direct intervention of the divine in the action of the play.! Thus, in the early morality play The Castle of Perseverance, Mankind's sudden repentance of his worldly allegiance is represented on the stage by the figure of Penance, who touches him with the point of his lance. And in the Ludus Coventriae mystery play of The Woman Taken in Adultery, the presence of Christ and the simplicity of characterization make the woman's speeches of repentance a sufficient indication of her true remorse. Similarly, the fact that an angel announces Christ's birth to the shepherds in The Second Shepherds' Play and that the shepherds themselves see Christ with his mother, makes divine forgiveness real enough so that its human parallel in the shepherds' forgiveness of Mak needs no other explanation. But in Shakespeare's plays the problem of dramatizing this sort of change of mind is complicated by the absence of direct presentation of the divine and by the increased realism of the characters. In Measure for Measure we have a real exploration of the human meanings of repentance and forgiveness withoutthe use of explicitly divine or allegorical figures. There is no concrete representation of the supernatural, eternal world of spirit. But there are sug