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Study Objectives: Post hoc analysis to evaluate the effect of daridorexant on sleep architecture in people with insomnia, focusing on features associated with hyperarousal., Methods: We studied sleep architecture in adults with chronic insomnia disorder from two randomized phase 3 clinical studies (Clinicaltrials.gov: NCT03545191 and NCT03575104) investigating 3 months of daridorexant treatment (placebo, daridorexant 25 mg, daridorexant 50 mg). We analyzed sleep-wake transition probabilities, EEG spectra, and sleep spindle properties including density, dispersion, and slow oscillation phase coupling. The wake EEG similarity index (WESI) was determined using a machine learning algorithm analyzing the spectral profile of the EEG., Results: At month 3, daridorexant 50 mg decreased wake-to-wake transition probabilities (p < .05) and increased the probability of transitions from wake-to-N1 (p < .05), N2 (p < .05), and REM sleep (p < .05), as well as from N1-to-N2 (p < .05) compared to baseline and placebo. Daridorexant 50 mg decreased relative beta power during wake (p = .011) and N1 (p < .001) compared to baseline and placebo. During the wake, relative alpha power decreased (p < .001) and relative delta power increased (p < .001) compared to placebo. Daridorexant did not alter EEG spectra bands in N2, N3, and REM stages or in sleep spindle activity. Daridorexant decreased the WESI score during wake compared to baseline (p = .004). Effects with 50 mg were consistent between months 1 and 3 and less pronounced with 25 mg., Conclusions: Daridorexant reduced EEG features associated with hyperarousal as indicated by reduced wake-to-wake transition probabilities and enhanced spectral features associated with drowsiness and sleep during wake and N1., Clinical Trials: ClinicalTrials.gov NCT03545191: study to assess the efficacy and safety of ACT-541468 (daridorexant) in adult and elderly participants with insomnia disorder. URL: Study Details | study to assess the efficacy and safety of ACT-541468 (daridorexant) in adult and elderly participants with insomnia disorder | ClinicalTrials.gov ClinicalTrials.gov NCT03575104:study to assess the efficacy and safety of ACT-541468 (daridorexant) in adult and elderly participants who experience difficulties sleeping. URL: study details | study to assess the efficacy and safety of ACT-541468 (daridorexant) in adult and elderly participants who experience difficulties sleeping | ClinicalTrials.gov., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society.)

Background and Objectives: Current practice in clinical neurophysiology is limited to short recordings with conventional EEG (days) that fail to capture a range of brain (dys)functions at longer timescales (months). The future ability to optimally manage chronic brain disorders, such as epilepsy, hinges upon finding methods to monitor electrical brain activity in daily life. We developed a device for full-head subscalp EEG (Epios) and tested here the feasibility to safely insert the electrode leads beneath the scalp by a minimally invasive technique (primary outcome). As secondary outcome, we verified the noninferiority of subscalp EEG in measuring physiologic brain oscillations and pathologic discharges compared with scalp EEG, the established standard of care., Methods: Eight participants with pharmacoresistant epilepsy undergoing intracranial EEG received in the same surgery subscalp electrodes tunneled between the scalp and the skull with custom-made tools. Postoperative safety was monitored on an inpatient ward for up to 9 days. Sleep-wake, ictal, and interictal EEG signals from subscalp, scalp, and intracranial electrodes were compared quantitatively using windowed multitaper transforms and spectral coherence. Noninferiority was tested for pairs of neighboring subscalp and scalp electrodes with a Bland-Altman analysis for measurement bias and calculation of the interclass correlation coefficient (ICC)., Results: As primary outcome, up to 28 subscalp electrodes could be safely placed over the entire head through 1-cm scalp incisions in a ∼1-hour procedure. Five of 10 observed perioperative adverse events were linked to the investigational procedure, but none were serious, and all resolved. As a secondary outcome, subscalp electrodes advantageously recorded EEG percutaneously without requiring any maintenance and were noninferior to scalp electrodes for measuring (1) variably strong, stage-specific brain oscillations (alpha in wake, delta, sigma, and beta in sleep) and (2) interictal spikes peak-potentials and ictal signals coherent with seizure propagation in different brain regions (ICC >0.8 and absence of bias)., Discussion: Recording full-head subscalp EEG for localization and monitoring purposes is feasible up to 9 days in humans using minimally invasive techniques and noninferior to the current standard of care. A longer prospective ambulatory study of the full system will be necessary to establish the safety and utility of this innovative approach., Trial Registration Information: clinicaltrials.gov/study/NCT04796597.

Sleep architecture encodes relevant information on the structure of sleep and has been used to assess hyperarousal in insomnia. This study investigated whether polysomnography-derived sleep architecture displays signs of hyperarousal in individuals with insomnia compared with individuals without insomnia. Data from Phase 3 clinical trials, private clinics and a cohort study were analysed. A comprehensive set of sleep architecture features previously associated with hyperarousal were retrospectively analysed focusing on sleep-wake transition probabilities, electroencephalographic spectra and sleep spindles, and enriched with a novel machine learning algorithm called the Wake Electroencephalographic Similarity Index. This analysis included 1710 individuals with insomnia and 1455 individuals without insomnia. Results indicate that individuals with insomnia had a higher likelihood of waking from all sleep stages, and showed increased relative alpha during Wake and N1 sleep and increased theta power during Wake when compared with individuals without insomnia. Relative delta power was decreased and Wake Electroencephalographic Similarity Index scores were elevated across all sleep stages except N3, suggesting more wake-like activity during these stages in individuals with insomnia. Additionally, sleep spindle density was decreased, and spindle dispersion was increased in individuals with insomnia. These findings suggest that insomnia is characterized by a dysfunction in sleep quality with a continuous hyperarousal, evidenced by changes in sleep-wake architecture., (© 2024 Idorsia Pharmaceuticals Ltd. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

Tri-beam microscopes comprising a fs-laser beam, a Xe+ plasma focused ion beam (PFIB) and an electron beam all in one chamber open up exciting opportunities for site-specific correlative microscopy. They offer the possibility of rapid ablation and material removal by fs-laser, subsequent polishing by Xe-PFIB milling and electron imaging of the same area. While tri-beam systems are capable of probing large (mm) volumes providing high resolution microscopical characterisation of 2D and 3D images across exceptionally wide range of materials and biomaterials applications, presenting high quality/low damage surfaces to the electron beam can present a significant challenge, especially given the large parameter space for optimisation. Here the optimal conditions and artefacts associated with large scale volume milling, mini test piece manufacture, serial sectioning and surface polishing are investigated, both in terms of surface roughness and surface quality for metallic, ceramic, mixed complex phase, carbonaceous, and biological materials. This provides a good starting place for those wishing to examine large areas or volumes by tri-beam microscopy across a range of materials., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Research in human volunteers and surgical patients has shown that unconsciousness under general anesthesia can be reliably tracked using real-time electroencephalogram processing. Hence, a closed-loop anesthesia delivery (CLAD) system that maintains precisely specified levels of unconsciousness is feasible and would greatly aid intraoperative patient management. The US Federal Drug Administration has approved no CLAD system for human use due partly to a lack of testing in appropriate animal models. To address this key roadblock, we implement a nonhuman primate (NHP) CLAD system that controls the level of unconsciousness using the anesthetic propofol. The key system components are a local field potential (LFP) recording system; propofol pharmacokinetics and pharmacodynamic models; the control variable (LFP power between 20 and 30 Hz), a programmable infusion system and a linear quadratic integral controller. Our CLAD system accurately controlled the level of unconsciousness along two different 125-min dynamic target trajectories for 18 h and 45 min in nine experiments in two NHPs. System performance measures were comparable or superior to those in previous CLAD reports. We demonstrate that an NHP CLAD system can reliably and accurately control in real-time unconsciousness maintained by anesthesia. Our findings establish critical steps for CLAD systems' design and testing prior to human testing., (© The Author(s) 2023. Published by Oxford University Press on behalf of National Academy of Sciences.)

Background: Sleep spindle activity is commonly estimated by measuring sigma power during stage 2 non-rapid eye movement (NREM2) sleep. However, spindles account for little of the total NREM2 interval and therefore sigma power over the entire interval may be misleading. This study compares derived spindle measures from direct automated spindle detection with those from gross power spectral analyses for the purposes of clinical trial design., Methods: We estimated spindle activity in a set of 8,440 overnight electroencephalogram (EEG) recordings from 5,793 patients from the Sleep Heart Health Study using both sigma power and direct automated spindle detection. Performance of the two methods was evaluated by determining the sample size required to detect decline in age-related spindle coherence with each method in a simulated clinical trial., Results: In a simulated clinical trial, sigma power required a sample size of 115 to achieve 95% power to identify age-related changes in sigma coherence, while automated spindle detection required a sample size of only 60., Conclusions: Measurements of spindle activity utilizing automated spindle detection outperformed conventional sigma power analysis by a wide margin, suggesting that many studies would benefit from incorporation of automated spindle detection. These results further suggest that some previous studies which have failed to detect changes in sigma power or coherence may have failed simply because they were underpowered., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Lentinula is a broadly distributed group of fungi that contains the cultivated shiitake mushroom, L. edodes . We sequenced 24 genomes representing eight described species and several unnamed lineages of Lentinula from 15 countries on four continents. Lentinula comprises four major clades that arose in the Oligocene, three in the Americas and one in Asia-Australasia. To expand sampling of shiitake mushrooms, we assembled 60 genomes of L. edodes from China that were previously published as raw Illumina reads and added them to our dataset. Lentinula edodes sensu lato (s. lat.) contains three lineages that may warrant recognition as species, one including a single isolate from Nepal that is the sister group to the rest of L. edodes s. lat., a second with 20 cultivars and 12 wild isolates from China, Japan, Korea, and the Russian Far East, and a third with 28 wild isolates from China, Thailand, and Vietnam. Two additional lineages in China have arisen by hybridization among the second and third groups. Genes encoding cysteine sulfoxide lyase ( lecsl ) and γ-glutamyl transpeptidase ( leggt ), which are implicated in biosynthesis of the organosulfur flavor compound lenthionine, have diversified in Lentinula . Paralogs of both genes that are unique to Lentinula ( lecsl 3 and leggt 5b) are coordinately up-regulated in fruiting bodies of L. edodes . The pangenome of L. edodes s. lat. contains 20,308 groups of orthologous genes, but only 6,438 orthogroups (32%) are shared among all strains, whereas 3,444 orthogroups (17%) are found only in wild populations, which should be targeted for conservation.

The electromyography (EMG) cocontraction index (CCI) given by the antagonistic/agonistic Root Mean Square (RMS) amplitude ratio of the same muscle is a qualified biomarker used for spastic cocontraction quantification and management in cerebral palsy children. However, this normative EMG ratio is likely subject to a potential source of errors with biased estimates when measuring the gastrocnemius plantar flexors activity. Due to the uneven distribution of electrical activity within the muscle volume, cocontraction levels can be misestimated, if EMGs are obtained from the sole traditional bipolar sensor location recommended by SENIAM. This preliminary study, on 10 healthy children (mean age 10 yr), investigated whether surface EMG detected proximally and distally via two pairs of bipolar electrodes, within the medial gastrocnemius (MG), provides a significant difference in CCI estimates during non-dynamic (isometric dorsiflexion) and dynamic (swing phases of gait) conditions. Gait cycles were extracted from Inertial Measurement Unit sensors. Medial gastrocnemius activity was greater distally than proximally during plantar flexion when it acts as an agonist (~24±18%) and it was greater proximally during dorsiflexion (~23±9%) when it is acting as an antagonist. As a direct consequence, CCI estimates from the conventional sensor location were significantly different (~36%) from the CCIs computed by considering broader MG regions. This difference arose in all subjects during isometric efforts and in two of 10 healthy children during the swing phase of gait who presented cocontraction patterns ( [Formula: see text]). EMG bipolar sampling encompassing proximal and distal gastrocnemius muscle regions may reduce bias in CCI computation and provide a more representative and accurate cocontraction index that is especially important for comparisons to the diseased state.

Objective: Muscle clinical metrics are crucial for spastic cocontraction management in children with Cerebral Palsy (CP). We investigated whether the ankle plantar flexors cocontraction index (CCI) normalized with respect to the bipedal heel rise (BHR) approach provides more robust spastic cocontraction estimates during gait than those obtained through the widely accepted standard maximal isometric plantar flexion (IPF)., Methods: Ten control and 10 CP children with equinus gait pattern performed the BHR and IPF testing and walked barefoot 10-m distance. We compared agonist medial gastrocnemius EMG during both testing and CCIs obtained as the ratios of antagonist EMG during swing phase of gait and either BHR or IPF agonist EMG., Results: Agonist EMG values from the BHR were: (i) internally reliable (Cronbach's α = 0.993), (ii) ~50 ± 0.4% larger than IPF, (iii) and positively correlated. Derived CCIs were significantly smaller (p < 0.05) in both populations., Conclusion: The bipedal heel rise approach may be accurate enough to reveal greater agonist activity of plantar flexors than the maximal isometric plantar flexion and seems to be more appropriate to obtain cocontraction estimates during swing of gait., Significance: This modified biomarker may represent a step forward towards improved accuracy of spastic gait management in pediatric., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Ketamine is an NMDA receptor antagonist commonly used to maintain general anesthesia. At anesthetic doses, ketamine causes high power gamma (25-50 Hz) oscillations alternating with slow-delta (0.1-4 Hz) oscillations. These dynamics are readily observed in local field potentials (LFPs) of non-human primates (NHPs) and electroencephalogram (EEG) recordings from human subjects. However, a detailed statistical analysis of these dynamics has not been reported. We characterize ketamine's neural dynamics using a hidden Markov model (HMM). The HMM observations are sequences of spectral power in seven canonical frequency bands between 0 to 50 Hz, where power is averaged within each band and scaled between 0 and 1. We model the observations as realizations of multivariate beta probability distributions that depend on a discrete-valued latent state process whose state transitions obey Markov dynamics. Using an expectation-maximization algorithm, we fit this beta-HMM to LFP recordings from 2 NHPs, and separately, to EEG recordings from 9 human subjects who received anesthetic doses of ketamine. Our beta-HMM framework provides a useful tool for experimental data analysis. Together, the estimated beta-HMM parameters and optimal state trajectory revealed an alternating pattern of states characterized primarily by gamma and slow-delta activities. The mean duration of the gamma activity was 2.2s([1.7,2.8]s) and 1.2s([0.9,1.5]s) for the two NHPs, and 2.5s([1.7,3.6]s) for the human subjects. The mean duration of the slow-delta activity was 1.6s([1.2,2.0]s) and 1.0s([0.8,1.2]s) for the two NHPs, and 1.8s([1.3,2.4]s) for the human subjects. Our characterizations of the alternating gamma slow-delta activities revealed five sub-states that show regular sequential transitions. These quantitative insights can inform the development of rhythm-generating neuronal circuit models that give mechanistic insights into this phenomenon and how ketamine produces altered states of arousal., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: ENB has licensed IP to Masimo for the analysis of EEG under anesthesia. ENB is a cofounder of PASCALL, a company constructing control systems for anesthesia.

Upper limb motor deficits in severe stroke survivors often remain unresolved over extended time periods. Novel neurotechnologies have the potential to significantly support upper limb motor restoration in severely impaired stroke individuals. Here, we review recent controlled clinical studies and reviews focusing on the mechanisms of action and effectiveness of single and combined technology-aided interventions for upper limb motor rehabilitation after stroke, including robotics, muscular electrical stimulation, brain stimulation and brain computer/machine interfaces. We aim at identifying possible guidance for the optimal use of these new technologies to enhance upper limb motor recovery especially in severe chronic stroke patients. We found that the current literature does not provide enough evidence to support strict guidelines, because of the variability of the procedures for each intervention and of the heterogeneity of the stroke population. The present results confirm that neurotechnology-aided upper limb rehabilitation is promising for severe chronic stroke patients, but the combination of interventions often lacks understanding of single intervention mechanisms of action, which may not reflect the summation of single intervention's effectiveness. Stroke rehabilitation is a long and complex process, and one single intervention administrated in a short time interval cannot have a large impact for motor recovery, especially in severely impaired patients. To design personalized interventions combining or proposing different interventions in sequence, it is necessary to have an excellent understanding of the mechanisms determining the effectiveness of a single treatment in this heterogeneous population of stroke patients. We encourage the identification of objective biomarkers for stroke recovery for patients' stratification and to tailor treatments. Furthermore, the advantage of longitudinal personalized trial designs compared to classical double-blind placebo-controlled clinical trials as the basis for precise personalized stroke rehabilitation medicine is discussed. Finally, we also promote the necessary conceptual change from 'one-suits-all' treatments within in-patient clinical rehabilitation set-ups towards personalized home-based treatment strategies, by adopting novel technologies merging rehabilitation and motor assistance, including implantable ones., (© The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Subthalamic deep brain stimulation (DBS) for Parkinson disease (PD) currently requires laborious open-loop programming, which can mitigate the benefits of this treatment. Experimental closed-loop DBS systems are emerging that can sense the electrophysiological surrogates of PD motor signs and respond with delivery of an automatically adapted stimulation. Such biomarker-based neural interfaces constitute a major advance towards improving the outcomes of patients treated with DBS and enhancing our understanding of the pathophysiological mechanisms underlying PD. In this Perspectives article, we argue that closed-loop DBS, in addition to offering advantages in patients with PD, might extend the current indications for DBS to include selected psychiatric disorders in which the symptoms are similarly driven by pathological brain circuit activity. The success of closed-loop DBS in such settings will depend on the identification of symptom-specific biomarkers, which ideally should reflect causal mechanisms of the underlying pathology.

A methodology has been demonstrated to consolidate Ti-6Al-4V powder without taking it to the liquid state by novel combination of the electron beam melting additive manufacture and hot isostatic pressing processes. This results in improved static mechanical properties (both strength and yield) in comparison to standard EBM processed material. In addition, the ability to generate microstructurally graded components has been demonstrated by generating a component with a significant change in both microstructure and mechanical properties. This is revealed by the use of electron backscattered diffraction and micro hardness testing to produce maps showing a clear distinction between materials consolidated in different ways. The variation in microstructure and mechanical properties is attributed to the different thermal history experienced by the material at different locations. In particular, it is found that the rapid cooling experienced during EBM leads to a typical fine α lath structure, whereas a more equiaxed α grains generated by diffusion is found in HIP consolidated powder.

Atomically thin films of III-VI post-transition metal chalcogenides (InSe and GaSe) form an interesting class of two-dimensional semiconductors that feature a strong variation of their band gap as a function of the number of layers in the crystal and, specifically for InSe, an expected crossover from a direct gap in the bulk to a weakly indirect band gap in monolayers and bilayers. Here, we apply angle-resolved photoemission spectroscopy with submicrometer spatial resolution (μARPES) to visualize the layer-dependent valence band structure of mechanically exfoliated crystals of InSe. We show that for one-layer and two-layer InSe the valence band maxima are away from the Γ-point, forming an indirect gap, with the conduction band edge known to be at the Γ-point. In contrast, for six or more layers the band gap becomes direct, in good agreement with theoretical predictions. The high-quality monolayer and bilayer samples enable us to resolve, in the photoluminescence spectra, the band-edge exciton (A) from the exciton (B) involving holes in a pair of deeper valence bands, degenerate at Γ, with a splitting that agrees with both μARPES data and the results of DFT modeling. Due to the difference in symmetry between these two valence bands, light emitted by the A-exciton should be predominantly polarized perpendicular to the plane of the two-dimensional crystal, which we have verified for few-layer InSe crystals.

Hepatocellular carcinoma (HCC) is highly refractory to current therapeutics used in the clinic. DX-2647, a recombinant human antibody, potently neutralizes the action of insulin-like growth factor-II (IGF-II), a ligand for three cell-surface receptors (IGF-IR, insulin receptor A and B isoforms, and the cation-independent mannose-6-phosphate receptor) which is overexpressed in primary human HCC. DX-2647 impaired the growth of tumor xenografts of the HCC cell line, Hep3B; however, xenografts of the HCC cell line, HepG2, were largely unresponsive to DX-2647 treatment. Analysis of a number of aspects of the IGF signaling axis in both cell lines did not reveal any significant differences between the two. However, while DX-2647 abolished phospho (p)-IGF-IR, p-IR and p-AKT signaling in both cell lines, HepG2 showed high levels of p-STAT3, which was unaffected by DX-2647 treatment and was absent from the Hep3B cell line. The driver of p-STAT3 was found to be a secreted cytokine, and treatment of HepG2 cells with a pan- JAK kinase inhibitor resulted in a loss of p-STAT3. These findings implicate the activation of STAT3 as one pathway that may mediate resistance to IGF-II-targeted therapy in HCC., (Copyright © 2018 BAYLOR COLLEGE OF MEDICINE. Published by Elsevier Inc. All rights reserved.)

Endometrial cancer contributes to significant morbidity and mortality in women with advanced stage or recurrent disease. IL11 is a cytokine that regulates cell cycle, invasion, and migration, all hallmarks of cancer. IL11 is elevated in endometrial tumors and uterine lavage fluid in women with endometrial cancer, and alters endometrial epithelial cancer cell adhesion and migration in vitro, but its role in endometrial tumorigenesis in vivo is unknown. We injected mice subcutaneously with human-derived Ishikawa or HEC1A endometrial epithelial cancer cells (ectopic), or HEC1A cells into the uterus (orthotopic) to develop endometrial cancer mouse models. Administration of anti-human IL11 receptor (R) α blocking antibody dramatically reduced HEC1A-derived tumor growth in both models and reduced peritoneal metastatic lesion spread in the orthotopic model, compared with IgG. Anti-human IL11Rα retained a well-differentiated, endometrial epithelial phenotype in the HEC1A ectopic mice, suggesting it prevented epithelial-to-mesenchymal transition. Blockade of mouse IL11Rα with anti-mouse IL11Rα antibody did not alter tumor growth, suggesting that cancer epithelial cell IL11 signaling is required for tumor progression. In vitro, anti-human IL11Rα antibody significantly reduced Ishikawa and HEC1A cell proliferation and invasion and promoted apoptosis. Anti-human, but not anti-mouse, IL11Rα antibody reduced STAT3, but not ERK, activation in HEC1A cells in vitro and in endometrial tumors in xenograft mice. We demonstrated that targeted blockade of endometrial cancer epithelial cell IL11 signaling reduced primary tumor growth and impaired metastasis in ectopic and orthotopic endometrial cancer models in vivo Our data suggest that therapeutically targeting IL11Rα could inhibit endometrial cancer growth and dissemination. Mol Cancer Ther; 15(4); 720-30. ©2016 AACR., (©2016 American Association for Cancer Research.)

This paper will focus on the provision of community aged care services via 'direct payments' and 'social enterprise'. These are two solutions that were not fully considered by the Productivity Commission as a way to make the provision of community aged care more sustainable in Australia. The empowerment component of social enterprise activities and 'direct payments' have the potential to generate improvements in the community aged care system., (© 2015 AJA Inc.)

Aims and Objectives: To identify factors that motivate older nurses to leave the workforce., Background: As many older nurses are now reaching retirement age and will be eligible for government-funded pensions, governments are concerned about the impending financial burden. To prepare for this scenario, many are looking at increasing the age of retirement to 67 or 70 years. Little is known about how this will affect the continuing employment of older nurses and the consequences for employers and the nurses themselves if they remain longer in the workforce., Design: Prospective randomised quantitative survey study., Methods: The Mature Age Workers Questionnaire, Job Descriptive Index and Job in General Scale were used to measure job satisfaction, intention to retire and factors encouraging retirement in registered nurses aged 45 years and over (n = 352) in Australia (July-August 2007)., Results: There were 319 respondents. The mean age proposed for leaving the workforce was 61·7 years. Key motivators were: financial considerations (40·1%), primarily financial security; nurse health (17·4%) and retirement age of partner (13·3%)., Conclusions: Older nurses are leaving the workforce prior to retirement or pension age, primarily for financial, social and health reasons, taking with them significant experience and knowledge. As financial considerations are important in older nurses decisions to continue to work, increasing the age of retirement may retain them. However, consideration will need to be given to ensure that they continue to experience job satisfaction and are physically and mentally able to undertake demanding work., Relevance to Clinical Practice: Increasing retirement age may retain older nurses in the workforce, however, the impact on the health of older nurses is not known, nor is the impact for employers of older nurses continuing to work known. Employers must facilitate workplace changes to accommodate older nurses., (© 2014 John Wiley & Sons Ltd.)

Mitochondrial DNA (mtDNA) copy number is strictly regulated during differentiation so that cells with a high requirement for ATP generated through oxidative phosphorylation have high mtDNA copy number, whereas those with a low requirement have few copies. Using immunoprecipitation of DNA methylation on 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC), which distinguish between de novo DNA methylation and demethylation, respectively, we set out to determine whether DNA methylation at exon 2 of the human mtDNA-specific polymerase (DNA polymerase gamma A (POLGA)) regulates cell-specific mtDNA copy number in highly proliferative and terminally differentiated cells. Highly proliferative cancer and pluripotent and multipotent cells possessed low mtDNA copy number and were highly methylated at exon 2 of POLGA in contrast to post-mitotic cells. Unlike neural stem cells, cancer cells were unable to differentiate and remained extensively DNA methylated at exon 2 of POLGA. However, mtDNA depletion of cancer cells reduced DNA methylation at exon 2 of POLGA as they replenished mtDNA to form tumours in mice. Glioblastoma cells treated with the DNA demethylation agent 5-azacytidine over 28 days of astrocyte-induced differentiation demethylated exon 2 of POLGA leading to increased mtDNA copy number and expression of the astrocyte endpoint marker glial fibrillary acidic protein (GFAP). However, the demethylation agent vitamin C (VitC) was unable to sustain increased mtDNA copy number and differentiation, as was the case when VitC was withdrawn after short-term treatment. These data demonstrate that DNA demethylation of POLGA is an essential regulator of mtDNA copy number and cellular fate and that cancer cells are only able to modulate DNA methylation of POLGA and mtDNA copy number in the presence of a DNA demethylation agent that inhibits de novo methyltransferase 1 activity.

This article describes the context and development of the new Nurse Practitioner Standards for Practice in Australia, which went into effect in January 2014. The researchers used a mixed-methods design to engage a broad range of stakeholders who brought both political and practice knowledge to the development of the new standards. Methods included interviews, focus groups, surveys, and work-based observation of nurse practitioner practice. Stakeholders varied in terms of their need for detail in the standards. Nonetheless, they invariably agreed that the standards should be clinically focussed attributes. The pillars common in many advanced practice nursing standards, such as practice, research, education, and leadership, were combined and expressed in a new and unique clinical attribute., (© The Author(s) 2015.)

Terminal deletions in the long arm of chromosome 1 result in a postnatally recognizable disorder described as 1q43q44 deletion syndrome. The size of the deletions and the resulting phenotype varies among patients. However, some features are common among patients as the chromosomal regions included in the deletions. In the present case, ultrasonography at 22 weeks of gestation revealed choroid plexus cysts (CPCs) and a single umbilical artery (SUA) and therefore amniocentesis was performed. Chromosomal analysis revealed a possible terminal deletion in 1q and high resolution array CGH confirmed the terminal 1q43q44 deletion and estimated the size to be approximately 8 Mb. Following termination of pregnancy, performance of fetopsy allowed further clinical characterization. We report here a prenatal case with the smallest pure terminal 1q43q44 deletion, that has been molecularly and phenotypically characterized. In addition, to our knowledge this is the first prenatal case reported with 1q13q44 terminal deletion and Pierre-Robin sequence (PRS). Our findings combined with review data from the literature show the complexity of the genetic basis of the associated syndrome.

Objective: To identify the reasons older RNs (≥45 years) remain in the healthcare workforce., Background: Despite predictions of early retirements of older nurses, many continue to work past the age when they can gain access to their retirement funds., Methods: The authors surveyed nurses older than 45 years in New South Wales, Australia., Results: The need for income was the most common reason for staying in nursing (61.9%; n = 210), with nearly 43% (n = 130) identifying this as the main reason for staying., Conclusions: Retaining older nurses in the workforce is an important strategy for managing workforce shortages. Nurse executives will need to consider strategies that will enhance retention of older nurses and focus on the reasons older nurses want to keep working.

Background: In recent years, there has been a substantial increase in the number of nurses holding advanced practice nursing positions. However, the lack of clarity regarding key terms such as 'advanced practice nursing', 'advanced nursing practice', 'scope of practice' and 'extended practice', and international variability in how these terms are used has created significant confusion. This lack of clarity is problematic for nurses, other health professionals, health service consumers, educators and policy makers, particularly given the global mobility of the nursing workforce., Objectives: 1) To highlight the significant international variability in how advanced practice nursing, and associated terms such as extended and expanded practice, are defined and regulated across a variety of different English speaking countries, including the US, UK, New Zealand, Canada and Australia. 2) To propose innovative formulations for how the nursing profession may attempt to ensure greater precision and agreement around advanced practice terminology., Design: Discursive paper., Results: It was found that there is a considerable lack of clarity regarding the precise definitions of key terms surrounding the discussion of advanced practice. Additionally, there are large disparities in how the five chosen countries regulate advanced practice nursing, and roles such as that of the nurse practitioner., Conclusions: It is suggested that the confusion regarding advanced practice terminology can be reduced definitionally by minimising the use of the term 'expanded practice'; defining advanced practice nursing to refer to the type of practice in defined and regulated advanced practice nursing scopes; and defining advanced nursing practice as expert practice within a regulated nursing scope., (© 2013.)

As stem cells undergo differentiation, mitochondrial DNA (mtDNA) copy number is strictly regulated in order that specialized cells can generate appropriate levels of adenosine triphosphate (ATP) through oxidative phosphorylation (OXPHOS) to undertake their specific functions. It is not understood whether tumor-initiating cells regulate their mtDNA in a similar manner or whether mtDNA is essential for tumorigenesis. We show that human neural stem cells (hNSCs) increased their mtDNA content during differentiation in a process that was mediated by a synergistic relationship between the nuclear and mitochondrial genomes and results in increased respiratory capacity. Differentiating multipotent glioblastoma cells failed to match the expansion in mtDNA copy number, patterns of gene expression and increased respiratory capacity observed in hNSCs. Partial depletion of glioblastoma cell mtDNA rescued mtDNA replication events and enhanced cell differentiation. However, prolonged depletion resulted in impaired mtDNA replication, reduced proliferation and induced the expression of early developmental and pro-survival markers including POU class 5 homeobox 1 (OCT4) and sonic hedgehog (SHH). The transfer of glioblastoma cells depleted to varying degrees of their mtDNA content into immunocompromised mice resulted in tumors requiring significantly longer to form compared with non-depleted cells. The number of tumors formed and the time to tumor formation was relative to the degree of mtDNA depletion. The tumors derived from mtDNA depleted glioblastoma cells recovered their mtDNA copy number as part of the tumor formation process. These outcomes demonstrate the importance of mtDNA to the initiation and maintenance of tumorigenesis in glioblastoma multiforme.

Duplications of the X chromosome are rare cytogenetic findings, and have been associated with an abnormal phenotype in the male offspring of apparently normal or near normal female carriers. We report on the prenatal diagnosis of a duplication on the long arm of chromosome X from chromosomal band Xq13.2 to q21.31 in a male fetus with increased nuchal translucency in the first trimester and polyhydramnios at 22 weeks of gestation. Amniocentesis was undertaken and cytogenetic analysis revealed additional chromosomal material in the long arm of chromosome X at position Xq13. Analysis with high resolution array CGH revealed the additional material is in fact a duplication of the region Xq13.2-q21.13. The duplication is 14.8 Mb in size and includes fourteen genes: SLC16A2, KIAA2022, ABCB7, ZDHHC15, ATRX, MAGT1, ATP7A, PGK1, TBX22, BRWD3, POU3F4, ZNF711, POF1B and CHM. Analysis of the parents revealed the mother to be a carrier of the same duplication. After elected termination of the pregnancy at 28 weeks a detailed autopsy of the fetus allowed for genotype-phenotype correlations., (© 2013.)

Objective: Many patients undergoing percutaneous coronary intervention (PCI) experience symptoms of anxiety; however, it is unclear whether anxiety is an issue in the early recovery period and the types of factors and patient concerns that are associated. This study set out to determine the patterns of anxiety and concerns experienced by patients undergoing PCI and the contributing factors in the time period surrounding PCI., Methods: A convenience sample of patients undergoing PCI (n = 100) were recruited, and anxiety was measured using the Spielberger State Anxiety Inventory immediately before the PCI, the first day postprocedure, and 1 week postdischarge. Patients were also asked to identify their most important concern at each time. Independent predictors of anxiety at each time were determined by multiple regression analysis., Results: Anxiety scores were highest pre-procedure (35.72, standard deviation [SD] 11.75), decreasing significantly by the postprocedure time (31.8, SD 10.20) and further still by the postdischarge time (28.79, SD 9.78) (repeated-measures analysis of variance: F = 39.72, P < .001). The concerns patients identified most frequently as most important were the outcome of the PCI and the possibility of surgery pre-procedure (37%) and postdischarge (31%), and the limitations and discomfort arising from the access site wound and immobility postprocedure (25%). The predictor of anxiety at the pre-procedure time was taking medication for anxiety and depression (b = 7.12). The predictors of anxiety at the postprocedure time were undergoing first-time PCI (b = 4.44), experiencing chest pain (b = 7.63), and experiencing pre-procedural anxiety (b = .49). The predictors of anxiety at the postdischarge time were reporting their most important concern as the future progression of CAD (b = 7.51) and pre-procedural anxiety (b = .37)., Conclusion: Symptoms of anxiety were common, particularly before PCI. These symptoms are important to detect and treat because pre-procedural anxiety is predictive of anxiety on subsequent occasions. Patients who have had chest pain or their first PCI should be targeted for intervention during the early recovery period after PCI, and information on CAD should be provided postdischarge., (Copyright © 2011 Elsevier Inc. All rights reserved.)

This discursive paper examines recent research on career progression for nurse executives in Australia. In particular, it focuses on the personal, work-related and professional factors which influence progression. The role of gender, location and the provision of mentoring are also considered. It is suggested that family friendly policies (such as the option to job share or to perform an executive role on a part-time basis), the availability of a mentor, and the opportunity to pursue further education/training are vital in assisting nurses to progress in their executive careers.

Abstract Purpose. The use of benzodiazepines remains a source of controversy. Some prescribers believe that they are beneficial and espouse their use; others regard their risk:benefit ratio as too adverse for any but occasional use. This review considers these viewpoints based on the appropriate literature. Survey. The recent English-language literature relating to this topic was surveyed. The publications proved too heterogeneous for a formal meta-analysis, so a descriptive review is provided. Overview. Surveys of benzodiazepine use provide data mainly from the UK, Europe and North America. Prescribing patterns varied widely but long-term usage is common and sometimes the norm. Conclusions. Long-term prescription of benzodiazepines still takes place despite general warnings from the medical and other professions and drug regulatory bodies that long-term use is unjustified both from the lack of a systemic database establishing such efficacy and a large literature documenting the risks of long-term usage, such as dependence. The young and the old are particularly at risk. Continued monitoring is essential, but the regulatory authorities may need to take a more active role in curbing such undesirable practice.

This paper examines the impact of direct payments on social isolation. We define what social isolation means, and then evaluate the role of direct payments in the provision of social services in the United Kingdom. Social isolation is a particular problem for older people. In Australia there are an increasing number of older residents who are isolated, but would benefit from having greater choice in terms of how they access and receive social services. Increased access to direct payments could help to reduce waiting lists for traditional social services and address gaps in service provision.

Background: Patients with anxiety prior to coronary angiography and percutaneous coronary intervention (PCI), may have negative physical and psychological consequences., Aim: To identify patients factors associated with anxiety and assess the validity of the Faces Anxiety Scale (FAS) in this sample., Methods: Patients (n=159) were surveyed preprocedure using the Spielberger State Anxiety Inventory (SAI) and the FAS and asked to identify their major concern., Results: The sample was aged an average 66.73 years (sd 10.12) and predominantly male (72%). Anxiety was low to moderate (SAI mean 36.44, sd 11.23; FAS median 2, range 1-5). There was a moderate correlation between the SAI and the FAS (r=.521, p=or<.001), with the FAS having low sensitivity (27%) and high specificity (95%). Patients' most common concern (37%) was uncertainty about the outcome from the procedure. Predictors of higher anxiety were taking medication for anxiety or depression (beta=5.84), experiencing angina (beta=4.96) or having a major concern about the procedural outcome (beta=4.00)., Conclusions: Many patients have moderate anxiety before coronary angiography and PCI; therefore, routine assessment and management of anxiety are justified. The FAS is not as useful as the SAI for this purpose., (Copyright (c) 2009 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.)

Neurons in higher cortical areas appear to become active during action observation, either by mirroring observed actions (termed mirror neurons) or by eliciting mental rehearsal of observed motor acts. We report the existence of neurons in the primary motor cortex (M1), an area that is generally considered to initiate and guide movement performance, responding to viewed actions. Multielectrode recordings in monkeys performing or observing a well-learned step-tracking task showed that approximately half of the M1 neurons that were active when monkeys performed the task were also active when they observed the action being performed by a human. These 'view' neurons were spatially intermingled with 'do' neurons, which are active only during movement performance. Simultaneously recorded 'view' neurons comprised two groups: approximately 38% retained the same preferred direction (PD) and timing during performance and viewing, and the remainder (62%) changed their PDs and time lag during viewing as compared with performance. Nevertheless, population activity during viewing was sufficient to predict the direction and trajectory of viewed movements as action unfolded, although less accurately than during performance. 'View' neurons became less active and contained poorer representations of action when only subcomponents of the task were being viewed. M1 'view' neurons thus appear to reflect aspects of a learned movement when observed in others, and form part of a broadly engaged set of cortical areas routinely responding to learned behaviors. These findings suggest that viewing a learned action elicits replay of aspects of M1 activity needed to perform the observed action, and could additionally reflect processing related to understanding, learning or mentally rehearsing action.

The use of benzodiazepine anxiolytics and hypnotics continues to excite controversy. Views differ from expert to expert and from country to country as to the extent of the problem, or even whether long-term benzodiazepine use actually constitutes a problem. The adverse effects of these drugs have been extensively documented and their effectiveness is being increasingly questioned. Discontinuation is usually beneficial as it is followed by improved psychomotor and cognitive functioning, particularly in the elderly. The potential for dependence and addiction have also become more apparent. The licensing of SSRIs for anxiety disorders has widened the prescribers' therapeutic choices (although this group of medications also have their own adverse effects). Melatonin agonists show promise in some forms of insomnia. Accordingly, it is now even more imperative that long-term benzodiazepine users be reviewed with respect to possible discontinuation. Strategies for discontinuation start with primary-care practitioners, who are still the main prescribers.This review sets out the stratagems that have been evaluated, concentrating on those of a pharmacological nature. Simple interventions include basic monitoring of repeat prescriptions and assessment by the doctor. Even a letter from the primary-care practitioner pointing out the continuing usage of benzodiazepines and questioning their need can result in reduction or cessation of use. Pharmacists also have a role to play in monitoring the use of benzodiazepines, although mobilizing their assistance is not yet routine. Such stratagems can avoid the use of specialist back-up services such as psychiatrists, home care, and addiction and alcohol misuse treatment facilities.Pharmacological interventions for benzodiazepine dependence have been reviewed in detail in a recent Cochrane review, but only eight studies proved adequate for analysis. Carbamazepine was the only drug that appeared to have any useful adjunctive properties for assisting in the discontinuation of benzodiazepines but the available data are insufficient for recommendations to be made regarding its use. Antidepressants can help if the patient is depressed before withdrawal or develops a depressive syndrome during withdrawal. The clearest strategy was to taper the medication; abrupt cessation can only be justified if a very serious adverse effect supervenes during treatment. No clear evidence suggests the optimum rate of tapering, and schedules vary from 4 weeks to several years. Our recommendation is to aim for withdrawal in <6 months, otherwise the withdrawal process can become the morbid focus of the patient's existence. Substitution of diazepam for another benzodiazepine can be helpful, at least logistically, as diazepam is available in a liquid formulation.Psychological interventions range from simple support through counselling to expert cognitive-behavioural therapy (CBT). Group therapy may be helpful as it at least provides support from other patients. The value of counselling is not established and it can be quite time consuming. CBT needs to be administered by fully trained and experienced personnel but seems effective, particularly in obviating relapse.The outcome of successful withdrawal is gratifying, both in terms of improved functioning and abstinence from the benzodiazepine usage. Economic benefits also ensue.Some of the principles of withdrawing benzodiazepines are listed. Antidepressants may be helpful, as may some symptomatic remedies. Care must be taken not to substitute one drug dependence problem for the original one.

Aim: The aim of this study is to assess the replacement of chromosomal analysis of chorionic villi (CV) direct preparation samples (DIR) by quantitative fluorescence PCR (QF-PCR) and to determine its advantages in routine prenatal diagnosis., Methods: From a total of 4,020 CV samples, rapid results were obtained either by conventional cytogenetic analysis of DIR in 2,770 samples, or by QF-PCR analysis in 1,250 samples. The final results were given after long-term culture (LTC)., Results: The frequencies of unbalanced fetal karyotypes were not significantly different, being 4.8% by DIR-LTC and 4.3% by QF-PCR-LTC. No false-negative or false-positive results were obtained from either approach., Conclusion: QF-PCR can replace chromosomal analysis of CV-DIR in most cases during routine prenatal diagnosis, requiring smaller CV samples and being more labor effective. Coupled with LTC, it is a robust diagnostic approach with high predictive value for the most frequent fetal trisomies., (2009 S. Karger AG, Basel.)

The Respiratory Coordinated Care Program (RCCP) based at St George Hospital, is a specialised community program designed to assist people with advanced COPD (DRG groupings E65A/E65B) to live optimally well at home. The aim of the program is to reduce hospital admission rates, readmission rates, and hospital length of stay (LOS). Additional components of RCCP include a Pulmonary Rehabilitation program and an early discharge service. An improvement in patient outcomes over subsequent years 1998-2006, is demonstrated when compared to the national peer DRG with regards to LOS, readmission rates and hospital admissions per patient per year, pre and post recruitment to the RCCP. The chronic long term component of the RCCP shows that the mean LOS and the number of hospital admissions was significantly lower when compared to the national DRG average. Since its inception, the RCCP has consistently demonstrated a cost effective reduction in hospital admission rates, LOS and reduced readmission.

Objective: To identify the healing rates, wound hygiene practices, types of primary wound dressings used, antibiotics prescribed, pain intensity and embarrassment levels in patients with pilonidal sinus., Method: A prospective descriptive design was used. We followed 55 patients for three months following excision of pilonidal sinus. Digital photographs were taken and the wound area was calculated using the Alfred and Medseed Wound Imaging System on the first postoperative day, at 2-3 weeks and again at 12 weeks. Data were collected from the nurses and patients using piloted questionnaires., Results: Sixty per cent of the participants had closed wounds within 12 weeks of surgery. Various dressing types were used. There was no significant correlation between dressing type and healing, or wound size and healing. There was no significant association between antibiotic usage and faster healing rates. A mean pain intensity score of 4.8 on a 0-10 scale was reported at the first dressing change for saline gauze dressings, which was the most painful experience with this wound. Average levels of embarrassment were low and decreased over time., Conclusion: Forty per cent of participants who had unhealed wounds at 12 weeks had other factors involved, which were not measured in this study.

Chronic illness causes the majority of disease burden and health costs in developed countries; however, this could be substantially reduced by optimal patient self-management. This study examined the levels of self-management in patients (n = 300) with chronic illness (chronic heart failure, chronic respiratory disease, Parkinson's disease and chronic schizophrenia) of moderate severity who had experienced an illness exacerbation in the last month. Patient's perceptions of self-efficacy in relation to their self-management and their sense of coherence were also assessed at baseline and 1 month later. No changes occurred in self-perceptions or self-management from baseline to follow-up. Patients at risk of poor self-management included people with low self-efficacy, poor sense of coherence, older age and a primary diagnosis of chronic schizophrenia. As self-efficacy is the only predictor known to be amenable to intervention, self-efficacy enhancing support should be promoted.

Aim.  To identify the factors associated with better self-management in people with moderate to high levels of Parkinson's disease following an acute illness event. Design and methods.  A prospective, descriptive study conducted with 75 persons with Parkinson's disease over the age of 55, collected twice: within a week of an acute event and 1 month later, after resuming usual life at home. Participants completed a questionnaire on self-rated health status, self-efficacy, sense of coherence, symptom monitoring and medication and general self-management. Background.  Parkinson's disease is a chronic neurological condition that affects many dimensions of life, including threats to self-identity and confidence in self-management. Self-management has the potential to reduce costs through decreased hospital admissions, disease progression and avoidance of complications. While evidence for the relationships between self-management and self-efficacy and sense of coherence has been demonstrated in some chronic illness groups, this has not previously been demonstrated in Parkinson's disease. Results.  The independent predictors of better self-management were not being hospitalized in the last 6 months, more frequent symptom checking and better self-efficacy for self-management. The influence of other factors on self-management, such as sense of coherence, was mediated through self-efficacy. Support of family and others was associated with better self-efficacy both directly and through an improved sense of coherence. Conclusions and relevance to nursing practice.  The presence of informal support plays an important role in sustaining self-efficacy and sense of coherence and hence self-management in persons with Parkinson's disease. Since these attributes are amenable to change, nurses are in a good position to encourage participation in Parkinson's support groups, teach self-management skills through regular symptom monitoring and to assess and promote self-efficacy and sense of coherence., (© 2008 The Authors. Journal compilation © 2008 Blackwell Publishing Ltd.)

An initial profile of the demographics and current practice of Australian trauma nurse coordinators (TNCs) was conducted in 2003. The study identified common and differing role components, provided information to assist with establishing national parameters for the role, and identified the resources perceived necessary to enable the role to be performed effectively. This article compares the findings of the 2003 study with a 2007 survey, expanded to include New Zealand trauma coordinators. Forty-nine people, identified as working in a TNC capacity in Australia and New Zealand, were invited to participate in February 2007. The survey consisted of a 3-part questionnaire of respondents' demographics, the percentage of time allocated to 10 defined role functions (components), and the TNCs' perceived required resources to fulfill their role effectively. Feedback from the 2003 survey was incorporated in the redesign. Participation in the research enabled an update of the previously compiled Australia/New Zealand trauma network list. Thirty-six surveys (71.5% response rate) were returned. Descriptive statistics were undertaken for each item, and comparisons were made among states, territories, and countries. The mean age of respondents was 41+/-7.7, range 27 to 57, and 92% were female. They averaged 11.1 years of postregistration critical care or trauma experience, and 50% (n=18) reported working unpaid overtime (decreased from 56% (n=19) since 2003). Participants reported that most of their time was spent fulfilling the trauma registry component of the role (27% of total hours), followed by quality and clinical activities (19% of total hours), education, and administration. The component associated with the least amount of time was outreach (3% of total hours). Although the proportion of time has almost halved since 2003, TNCs still spend the most time maintaining trauma registries. Compared to the 2003 survey, Australian and New Zealand TNCs are working more unpaid overtime, spending more time performing quality and clinical activities and less time doing data entry. Despite where one works, the role components identified are fulfilled to a certain extent. However, trauma centers need to provide the TNC with adequate resources if trauma care systems are to be optimally effective.

Since the 1988 Bicentennial and the 2001 centenary of federation celebrations colonial images have flourished in Australia, highlighting the roles of convicts and free settlers during early colonization. Old sites, such as Port Arthur have been re-invigorated, and in 2004 Tasmanians celebrated the bicentenary of 'white' settlement. However, social scientists have given little attention to the role of colonial and post-colonial figures and myths as aspects of Australian national identity. We seek to address this issue by examining how convicts, free settlers, bushrangers and ANZACs are associated with contemporary identity in Australia. We examine evidence from the 2003 Australian Survey of Social Attitudes and find that historical figures such as the ANZACs and post-World War II immigrants comprise important aspects of national identity. A substantial majority of Australians judged ANZACs to be important, countering recent claims of the 'demise of the digger'. Sporting heroes are also at the core of Australian identity. Colonial figures appear to be far less important, although views on national identity vary according to social location. In particular, left-wing, university educated, younger, postmaterialist Australians view convicts and bushrangers as relatively important, indicating the salience of the larrikin in Australian identity.

Objective: The objective of this study was to examine whether the position of 'after hours clinical support enrolled nurse' is embracing clinical skill extension in the acute surgical area., Design: Experienced enrolled nurses employed in a supernumerary capacity documented all activities with which they were engaged over a six-month period., Setting: Six surgical wards within a tertiary referral hospital, Sydney, Australia., Subjects: Enrolled nurses working after hours in an extended support role in a supernumerary capacity., Results: Data demonstrated that, in this study, the 'after hours clinical support enrolled nurse' was primarily performing routine nursing activities. Although the number of extended skills (n=13) performed could be considered diverse for an enrolled nurse, many were seldom performed. The most frequently performed extended skills were patient escorts and undertaking bladder ultrasounds with a mobile scanner. Medication administration was rarely performed., Conclusion: The role primarily incorporates basic nursing care with minimal scope for extended skills. The paper recommends that basic nursing practices be delegated to assistants in nursing to enable the 'after hours clinical support enrolled nurse' to effectively support registered nurses and extend their own practice.

The increasing number of inexperienced graduates, as well as other levels of nurse such as the enrolled nurse and assistant-in-nursing, requires health service and nursing managers in the acute care sector to rethink the long-preferred "patient allocation" model of care provision. As well, the escalating shortage of registered nurses and subsequent low morale among those remaining in the workforce require hospitals to re-examine skills mix and staffing ratios. This paper presents the results of two work-sampling studies conducted in a major metropolitan private hospital, the first of which was to provide a rationale for changing from the patient allocation model to a team model of care. The second study aimed to evaluate and provide data on the impact of the change. Staff were heavily involved in both studies as well as the change process. The findings highlight how effective the new model has been in redistributing certain aspects of care to make better use of each nurse level's knowledge and skills.

Background: Activin is a well-characterised growth and differentiation factor and an important inflammatory mediator. Activin is secreted by normal endometrial glands and stroma and is expressed by endometrial leucocytes. It is also known that the eutopic endometrium from women with endometriosis is functionally different to that from women without endometriosis. In this study, we hypothesise that the endometrial secretion of activin is altered in women with endometriosis., Aims: To determine whether the expression of inhibin/activin subunits and the secretion of activin-A is different in eutopic endometrium from women with and without endometriosis., Methods: Endometrial biopsies were obtained from premenopausal, regularly menstruating women with and without endometriosis. Staining intensity for the different inhibin/activin subunits was compared in endometrial and endometriotic biopsies. Activin-A secretion was studied using endometrial explants and endometrial glandular and stromal monolayer cell cultures., Results: The alpha- and betaA-subunits of inhibin/activin were more abundant in eutopic glandular cells from patients with minimal to mild endometriosis compared to women without endometriosis. In patients with endometriosis, the betaB-subunit was more abundant in eutopic stromal cells and endometrial leucocytes. Comparison of paired endometrial and endometriotic biopsies from the same patient did not reveal significant differences for any of the inhibin/activin subunits or activin receptors. Activin-A secretion by glandular and stromal endometrial cells was sevenfold and threefold higher, respectively, in women with endometriosis compared to women without endometriosis., Conclusions: The expression of inhibin/activin subunits in eutopic endometrium is altered in women with endometriosis, leading to higher levels of activin-A secretion by both glandular cells and stromal cells.