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During the COVID-19 pandemic, many advocacy groups and individuals criticized governments on social media for doing either too much or too little to mitigate the pandemic. In this article, we review advocacy for COVID-19 elimination or "zero-covid" on the social media platform X (Twitter). We present a thematic analysis of tweets by 20 influential co-signatories of the World Health Network letter on ten themes, covering six topics of science and mitigation (zero-covid, epidemiological data on variants, long-term post-acute sequelae (Long COVID), vaccines, schools and children, views on monkeypox/Mpox) and four advocacy methods (personal advice and promoting remedies, use of anecdotes, criticism of other scientists, and of authorities). The advocacy, although timely and informative, often appealed to emotions and values using anecdotes and strong criticism of authorities and other scientists. Many tweets received hundreds or thousands of likes. Risks were emphasized about children's vulnerability, Long COVID, variant severity, and Mpox, and via comparisons with human immunodeficiency viruses (HIV). Far-reaching policies and promotion of remedies were advocated without systematic evidence review, or sometimes, core field expertise. We identified potential conflicts of interest connected to private companies. Our study documents a need for public health debates to be less polarizing and judgmental, and more factual. In order to protect public trust in science during a crisis, we suggest the development of mechanisms to ensure ethical guidelines for engagement in "science-based" advocacy, and consideration of cost-benefit analysis of recommendations for public health decision-making., Competing Interests: Declarations. Competing interests: The authors do research in public health, epidemiology, biochemistry, virology, biostatistics, policy, politics, education and student experience, pediatrics, mathematical modeling, data science, and psychology relevant to the claims made by the studied advocacy in the paper but with no direct association to the studied advocacy. Kasper P. Kepp has unpaid research affiliations with METRICS, Stanford, and Epistudia, Bern, has published or submitted a dozen papers on COVID-19-related research (SARS-CoV-2 mutation evolution, public health, and epidemiology), has been engaged in the pandemic debate in Danish media and social media, where he has been critical of the studied zero-covid groups, and is without any financial conflicts of interests. Kevin Bardosh is Director of Collateral Global, a UK-based research and education charity that is focused on understanding the impact of COVID policies around the world, and has been active in the pandemic debate on social media and in the popular press. Tijl De Bie was an active participant in the pandemic debate in the Belgian media, on social media, and in personal conversations, and is without any financial conflicts of interests. He has co-led the writing of the so-called Wintermanifesto, a public call for a more sustainable pandemic policy in Belgium, supported by around 100 Belgian academics and other public figures and published in January 2022. Also in January 2022, he was heard as an expert in the Belgian federal parliament regarding a possible Covid19-vaccination mandate. During the pandemic, he took part in exploratory conversations with Johnson & Johnson about a possible academic collaboration unrelated to COVID-19, for which he received no compensation of any kind. Louise Emilsson works as head and senior consultant at a primary care practice in Region Värmland, Sweden. She is also Associate Professor at Oslo University, affiliated to Karolinska Institutet and has published several papers on COVID. She has no financial conflict of interest. Justin Greaves is Director of Student Experience and Progression in the Department of Politics and International Studies at the University of Warwick. He has engaged in the pandemic debate on social media. His research background includes work on a Rural Economy and Land Use (RELU) funded project on the Governance of Livestock Diseases (2007-2010). The Principal Investigator of this project was Graham Medley, currently Chair of the SPI-M modelling sub-committee of the Scientific Advisory Group for Emergencies (Sage), in the UK. Tea Lallukka has provided an invited report for the Committee for the Future (an established, standing committee in the Parliament of Finland) in late 2022, where she was asked to describe the future of public health. Her report covered e.g. inequalities in health, population aging, oral health, mental health, COVID-19 and potential new pandemics. Taulant Muka is co-founder, co-owner, and CEO at Epistudia GmbH, acts as unpaid advisor for the Academic Parity Movement, a non-profit organization uprooting academic bullying, discrimination, and violence and has written systematic reviews and meta-analyses on Covid-19 related topics. He received research funds from Merz Aesthetics not related to this work. In addition, he has written a book on academic silencing and mobbing during the Covid-19 pandemic (ISBN-13. ‎979-8801214009). J. Cristian Rangel, PhD. is the PI in a Social Sciences and Humanities Research Council (SSHRC) funded project mapping scientific networks influencing Public Health pandemic response in Ontario, Canada. He’s also a co-PI in a New Frontiers SSHRC grant studying the social effects of pandemic response in Canada and selected countries. He has been engaged in public critique on the role of academics in pandemic response. Michaéla Schippers is founder of Ikigaitv.nl: positive psychology interventions for the general public, to enhance mental wellbeing and co-founder of Great Citizens Movement (greatcitizensmovement.org). She also served as expert witness of extra-parliamentary inquiry regarding the COVID-19 crisis handling in the Netherlands (2020); she signed the Great Barrington declaration and owns the podcast followthescience.nl and does contract research on improving study success: https://www.erim.eur.nl/erasmus-centre-for-study-and-career-success/ . Jonas Schmidt-Chanasit declares that the following conflicts of interest may exist, which may result from an employment relationship, a shareholding, a consultancy activity or grants for research projects, lectures or other activities: Blusense Diagnostics, Mahidol University, Vietnam Military Medical University, Deutsche Forschungsgemeinschaft (DFG), Bundesministerium für Bildung und Forschung (BMBF), Bundesministerium für Gesundheit (BMG), Bundesministerium für Ernährung und Landwirtschaft (BMEL), Instand e.V., Auswärtiges Amt, QCMD, Takeda, AstraZeneca, Pfizer, Wynn Macau, Sonic Healthcare, Chulalongkorn University, Valneva, Bavarian Nordic, Hermes Arzneimittel, CRM - Centrum für Reisemedizin, Johnson & Johnson, EUROIMMUN, BASF, Siemens, Roche, Bangkok Bank, China Construction Bank, Deutsche Bank, Diasorin, Sanofi, and Mikrogen. He is an active participant in the pandemic debate in the German media, on social media (X), and advised the Government of the City of Hamburg during the COVID-19 pandemic. Tracy Vaillancourt is the Chair of the COVID-19 Task Force for the Royal Society of Canada (RSC). She also chaired the RSC’s Children and Schools Policy Report which covered all aspects of education during the COVID-19 pandemic. She is the current chair of the Canada Learning Loss Policy Report in partnership with the RSC and the Canadian Commission UNESCO, which is funded by the Social Sciences and Humanities Research Council (Canada). She provided consultation to the Canadian government on education, child development, and behavioural sciences during the pandemic. She is the president of the International Society for Research on Aggression, a Senior Fellow of the Centre for International Governance Innovation, a member of the National Expert Committee on Countering Radicalization to Violence, Government of Canada, and the Chief Editor, Frontiers in Child and Adolescent Psychiatry – Child Mental Health and Interventions Ethics approval: No ethics approval was obtained as all data studied in the paper are fully available in public., (© 2024. The Author(s) under exclusive licence to Monash University.)

This cross-sectional study aimed to explore the incidence of impostor phenomenon among 79 nurses in specialist roles in a single NHS trust in England, using an online anonymous questionnaire that included the Clance Imposter Phenomenon Scale and free-text responses. Results indicated a high prevalence of impostor phenomenon, with no specific variables predicting its occurrence. Four main themes emerged: self-doubt, role expectations, fear of exposure as an impostor, and factors leading to burnout. The study highlights the need for targeted support and training for this cohort, particularly as impostor phenomenon was found to be prevalent during career transitions and was not limited by gender. The findings have implications for nursing management and education, offering the opportunity to develop specific support mechanisms to alleviate impostor phenomenon and potentially reduce attrition rates in specialist nursing roles.

12-Thiazole abietanes are highly selective reversible inhibitors of hABHD16A that could potentially alleviate neuroinflammation. In this study, we used synthetic chemistry, competitive activity-based protein profiling, and computational methodologies to try to establish relevant structural determinants of activity and selectivity of this class of compounds for inhibiting ABHD16A over ABHD12. Five compounds significantly inhibited hABHD16A but also very efficiently discriminated between inhibition of hABHD16A and hABHD12, with compound 35 being the most effective, at 100 μM (55.1 ± 8.7%; p < 0.0001). However, an outstanding switch in the selectivity toward ABHD12 was observed in the presence of a ring A ester, if the C2' position of the thiazole ring possessed a 1-hydroxyethyl group, as in compound 28 . Although our data were inconclusive as to whether the observed enzyme inhibition is allosteric or not, we anticipate that the structure-activity relationships presented herein will inspire future drug discovery efforts in this field., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Background/objective: The purpose of this qualitative study was to provide insight into the changes and barriers to leisure experienced by people with scleroderma., Method: Twenty-five people with scleroderma consented to be interviewed via telephone using a semi-structured interview. The conversations were audio recorded and transcribed verbatim. Thorne's Interpretive Description informed the analysis process., Results: Three themes emerged from the analysis: barriers to leisure participation (impact of Raynaud's Phenomenon symptoms, fatigue, changes in body structures and functions, unpredictability of daily symptoms and selection of leisure activities), decreases in leisure participation (less time outdoors, reduction in time spent in active leisure, more time spent in passive leisure) and experiences of losing a valued leisure activity (depressed mood, identity change, fear of loss and sense of isolation)., Conclusions: The changes in leisure participation found in this study were reported to be due to the rate of disease progression and the severity of disease symptoms, particularly, Raynaud symptoms and fatigue. Health professionals should work with people with SSc to facilitate participation in valued leisure activities., (© 2023 John Wiley & Sons Ltd.)

Purpose: Children experience painful invasive procedures very intensely. The aim of health professionals is to help children minimize this traumatic experience. The Simplified Faces Pain Scale (S-FPS) and Simplified Concrete Ordinal Pain Scale (S-COS) tools offer children the possibility of self-assessing their pain. This can then be the basis for tailoring pain relief to the child's individual need. The aim of this study is to present the validation procedure of the S-FPC, S-COS methods., Design and Methods: 135 children aged 3-6 years assessed their pain using the self-reported S-FPS and S-COS methods at three consecutive times, and their results were compared with the commonly used Face, Legs, Activity, Cry, Consolability assessment scale. Intra-class correlations (ICC) were used to assess inter-rater agreement. Convergent validity was verified using Spearman's correlation coefficient., Results: This study demonstrated good validity for both the S FPS and S-COS assessment tools. The ICC coefficient showed good inter-rater correlation. Spearman's correlation coefficient showed a strong correlation between the scales., Practice Implications: It is not possible to clearly select a best method of pain assessment in preschool children. To choose the most appropriate method, it is necessary to take into account the child's cognitive development and preferences., (© 2023 Wiley Periodicals LLC.)

A mixed-methods approach was used to explore the acceptability of the Mantram Repetition Program (MRP) to reduce stress in adolescents with a history of pediatric cancer or brain tumor. Five male participants diagnosed at ages 1-14 years and currently, ages 13-18 years, completed assessments of stress, anxiety, and sleep disturbance and were interviewed about the acceptability of a mantram repetition intervention. Adolescent survivors reported low to moderate levels of stress, anxiety, and sleep disturbance. Data indicate that the MRP is acceptable among adolescent survivors of pediatric cancer and brain tumors, and face-to-face intervention delivery is preferred.

Digital polymerase chain reaction (dPCR) is emerging as a reliable platform for quantifying microorganisms in the field of water microbiology. This paper reviews the fundamental principles of dPCR and its application for health-related water microbiology. The relevant literature indicates increasing adoption of dPCR for measuring fecal indicator bacteria, microbial source tracking marker genes, and pathogens in various aquatic environments. The adoption of dPCR has accelerated recently due to increasing use for wastewater surveillance of Severe Acute Respiratory Coronavirus 2 (SARS-CoV-2) - the virus that causes Coronavirus Disease 2019 (COVID-19). The collective experience in the scientific literature indicates that well-optimized dPCR assays can quantify genetic material from microorganisms without the need for a calibration curve and often with superior analytical performance (i.e., greater sensitivity, precision, and reproducibility) than quantitative polymerase chain reaction (qPCR). Nonetheless, dPCR should not be viewed as a panacea for the fundamental uncertainties and limitations associated with measuring microorganisms in water microbiology. With dPCR platforms, the sample analysis cost and processing time are typically greater than qPCR. However, if improved analytical performance (i.e., sensitivity and accuracy) is critical, dPCR can be an alternative option for quantifying microorganisms, including pathogens, in aquatic environments., 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 © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Much of what is known and theorized concerning passive sampling techniques has been developed considering chemical analytes. Yet, historically, biological analytes, such as Salmonella typhi, have been collected from wastewater via passive sampling with Moore swabs. In response to the COVID-19 pandemic, passive sampling is re-emerging as a promising technique to monitor SARS-CoV-2 RNA in wastewater. Method comparisons and disease surveillance using composite, grab, and passive sampling for SARS-CoV-2 RNA detection have found passive sampling with a variety of materials routinely produced qualitative results superior to grab samples and useful for sub-sewershed surveillance of COVID-19. Among individual studies, SARS-CoV-2 RNA concentrations derived from passive samplers demonstrated heterogeneous correlation with concentrations from paired composite samples ranging from weak (R 2 = 0.27, 0.31) to moderate (R 2 = 0.59) to strong (R 2 = 0.76). Among passive sampler materials, electronegative membranes have shown great promise with linear uptake of SARS-CoV-2 RNA observed for exposure durations of 24 to 48 h and in several cases RNA positivity on par with composite samples. Continuing development of passive sampling methods for the surveillance of infectious diseases via diverse forms of fecal waste should focus on optimizing sampler materials for the efficient uptake and recovery of biological analytes, kit-free extraction, and resource-efficient testing methods capable of rapidly producing qualitative or quantitative data. With such refinements passive sampling could prove to be a fundamental tool for scaling wastewater surveillance of infectious disease, especially among the 1.8 billion persons living in low-resource settings served by non-traditional wastewater collection infrastructure., 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 © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

COVID-19 Oximetry@Home services have been commissioned nationally. This allows higher-risk patients with mild COVID-19 symptoms to remain at home, being supplied with a Pulse Oximeter to measure their oxygen saturation (SpO 2 ) two to three times daily for two weeks. Patients record their readings manually or electronically which are monitored by a clinical team. Clinical decisions, using an algorithm, are based on SpO 2 readings in a narrow range with 1-2 point changes potentially affecting care. In this article, we discussed the problem that multiple factors affect SpO 2 readings, and that some "normal" individuals will have "low-normal" scores at the threshold of clinical management, without any known respiratory problem. We discuss the potential magnitude of this problem based on the associated literature and consider how this will have an impact on the use of the Oximetry@home services, potentially partially confounding their purpose; to reduce face-to-face medical care., (© 2021 The Authors. Nursing Open published by John Wiley & Sons Ltd.)

Infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has the potential to be collected in wastewater from mucus, sputum, and feces of infected individuals, raising questions about the appropriate handling and treatment of the resulting wastewater. Current evidence indicates the likelihood of waterborne SARS-CoV-2 transmission is low; nonetheless, confirming the efficacy of disinfection against SARS-CoV-2 is prudent to ensure multiple barriers of protection for infectious SARS-CoV-2 that could be present in municipal and hospital wastewater. Sodium hypochlorite (free chlorine) is widely used for pathogen control in water disinfection applications. In the current study, we investigated the inactivation of SARS-CoV-2 in DI water and municipal wastewater primary influent by sodium hypochlorite (free chlorine) addition. Our results showed rapid disinfection of SARS-CoV-2, with less than 1 mg-min/L required for >3 log 10 TCID 50 reduction in DI water. More than 5 mg-min/L was required for 3 log 10 TCID 50 reduction in primary influent, suggesting potential shielding of the virus by suspended solids. These results are consistent with expected virus inactivation by free chlorine and suggest the adequacy of free chlorine disinfection for inactivation of infectious SARS-CoV-2 in water matrices., 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 © 2021. Published by Elsevier B.V.)

Aim: Early warning scores are commonly used in hospital settings, but little is known about their use in care homes. This study aimed to evaluate the impacts of National Early Warning Scores alongside other measures in this setting., Design: Convergent parallel design., Methods: Quantitative data from 276 care home residents from four care homes were used to analyse the relationship between National Early Warning Scores score, resident outcome and functional daily living (Barthel ADL (Barthel Index for Activities of Daily Living)) and Rockwood (frailty). Interviews with care home staff (N = 13) and care practitioners (N = 4) were used to provide qualitative data., Results: A statistically significant link between National Early Warning Scores (p = .000) and Barthel ADL (p = .013) score and hospital admissions was found, while links with Rockwood were insignificant (p = .551). Care home staff reported many benefits of National Early Warning Scores, including improved communication, improved decision-making and role empowerment. Although useful, due to the complexity of the resident population's existing health conditions, National Early Warning Scores alone could not act as a diagnostic tool., (© 2021 The Authors. Nursing Open published by John Wiley & Sons Ltd.)

Background: The Royal College of Pathologists of Australasia Quality Assurance Programs (RCPAQAP) is a world leader in the provision of external quality assurance (EQA) for pathology laboratories. The development and delivery of new programmes are designed to meet the evolving needs of our participants and pathology practice. A cytopathology technical programme was established in 2018 to provide proficiency testing in routine cytopreparatory techniques. The cytopathology technical pilot focused on standard operating procedures and laboratory performance during rapid on-site evaluation (ROSE). The exercise aimed to assess the diagnostic adequacy and provide technical recommendations on each of the whole slide images from four fine-needle aspiration biopsy (FNAB) samples of the thyroid in a setting of ROSE., Methods: Four whole slide imaging cases, each comprising one Diff-QuikTM stained preparation of an FNAB of the thyroid, were provided to all laboratories currently enrolled in the RCPAQAP Cytopathology diagnostic programmes. Each scanned image represented one slide from the first pass collected by a radiologist under ultrasound guidance. Participating laboratories were encouraged to distribute the exercise to individual staff members who attend ROSE procedures. A laboratory practice questionnaire was also conducted., Results: There were a total of 186 submissions received for the assessment across the four virtual cases provided. Although the assessment of on-site adequacy by participants showed high concordance across some of the cases, there was variation in the initial diagnostic evaluation and technical recommendation., Conclusions: ROSE has been adopted as a standard procedure in many laboratories worldwide. A peer comparison of participating laboratories in an EQA exercise has highlighted ROSE as susceptible to variation across standard operating procedures, the provision of diagnostic adequacy, diagnostic feedback to the attending clinician, and technical recommendation., (© 2022 S. Karger AG, Basel.)

Resuspension of dust from flooring is a major source of human exposure to microbial contaminants, but the persistence of viruses on dust and carpet and the contribution to human exposure are often unknown. The goal of this work is to determine viability of MS2 and Phi6 bacteriophages on cut carpet, looped carpet, and house dust both over time and after cleaning. Bacteriophages were nebulized onto carpet or dust in artificial saliva. Viability was measured at 0, 1, 2, 3, 4, 24, and 48 h and after cleaning by vacuum, steam, hot water extraction, and disinfection. MS2 bacteriophages showed slower viability decay rates in dust (-0.11 hr -1 ), cut carpet (-0.20 hr -1 ), and looped carpet (-0.09 hr -1 ) compared to Phi6 (-3.36 hr -1 , -1.57 hr -1 , and -0.20 hr -1 , respectively). Viable viral concentrations were reduced to below the detection limit for steam and disinfection for both MS2 and Phi6 (p < 0.05), while vacuuming and hot water extraction showed no significant changes in concentration from uncleaned carpet (p > 0.05). These results demonstrate that MS2 and Phi6 bacteriophages can remain viable in carpet and dust for several hours to days, and cleaning with heat and disinfectants may be more effective than standard vacuuming., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

We revisit the hypothesis that there is life in the venusian clouds to propose a life cycle that resolves the conundrum of how life can persist aloft for hundreds of millions to billions of years. Most discussions of an aerial biosphere in the venusian atmosphere temperate layers never address whether the life-small microbial-type particles-is free floating or confined to the liquid environment inside cloud droplets. We argue that life must reside inside liquid droplets such that it will be protected from a fatal net loss of liquid to the atmosphere, an unavoidable problem for any free-floating microbial life forms. However, the droplet habitat poses a lifetime limitation: Droplets inexorably grow (over a few months) to large enough sizes that are forced by gravity to settle downward to hotter, uninhabitable layers of the venusian atmosphere. (Droplet fragmentation-which would reduce particle size-does not occur in venusian atmosphere conditions.) We propose for the first time that the only way life can survive indefinitely is with a life cycle that involves microbial life drying out as liquid droplets evaporate during settling, with the small desiccated "spores" halting at, and partially populating, the venusian atmosphere stagnant lower haze layer (33-48 km altitude). We, thus, call the venusian lower haze layer a "depot" for desiccated microbial life. The spores eventually return to the cloud layer by upward diffusion caused by mixing induced by gravity waves, act as cloud condensation nuclei, and rehydrate for a continued life cycle. We also review the challenges for life in the extremely harsh conditions of the venusian atmosphere, refuting the notion that the "habitable" cloud layer has an analogy in any terrestrial environment.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA is frequently detected in the feces of infected individuals. While infectious SARS-CoV-2 has not previously been identified in wastewater, infectious SARS-CoV-2 has been isolated from the feces of at least one patient, raising concerns about the presence of infectious SARS-CoV-2 in wastewater. The fate and inactivation characteristics of SARS-CoV-2 in water and wastewater are unknown, with current inactivation estimates based on surrogate models. In this study, the persistence of SARS-CoV-2 infectivity and RNA signal was determined in water and wastewater. The times for 90% reduction ( T 90 ) of viable SARS-CoV-2 in wastewater and tap water at room temperature were 1.5 and 1.7 days, respectively. In high-starting titer (10 5 TCID 50 mL -1 ) experiments, infectious virus persisted for the entire 7-day sampling time course. In wastewater at 50 and 70 °C, the observed T 90 values for infectious SARS-CoV-2 were decreased to 15 and 2 min, respectively. SARS-CoV-2 RNA was found to be significantly more persistent than infectious SARS-CoV-2, indicating that the environmental detection of RNA alone does not substantiate risk of infection., Competing Interests: The authors declare no competing financial interest.

Fecal indicator bacteria (FIB) are typically used to monitor microbial water quality but are poor representatives of viruses due to different environmental fate. Viral fecal indicators have been proposed as alternatives to FIB; however, data evaluating the persistence of emerging viral fecal indicators under realistic environmental conditions is necessary to evaluate their potential application. In this study, we examined the persistence of five viral fecal indicators, including crAssphage and pepper mild mottle virus (PMMoV), and three bacterial fecal indicators ( E. coli , enterococci and HF183/BacR287) in large-scale experimental ponds and freshwater mesocosms. Observed inactivation rate constants were highly variable and ranged from a minimum of -0.09 d -1 for PMMoV to a maximum of -3.5 d -1 for HF183/BacR287 in uncovered mesocosms. Overall, viral fecal indicators had slower inactivation than bacterial fecal indicators and PMMoV was inactivated more slowly than all other targets. These results demonstrate that bacterial fecal indicators inadequately represent viral fate following aging of sewage contaminated water due to differential persistence, and that currently used fecal indicator monitoring targets demonstrate highly variable persistence that should be considered during water quality monitoring and risk assessment., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: K.B. is a co-inventor on a patent application entitled “Cross-Assembly Phage DNA Sequences, Primers and Probes for PCR-based Identification of Human Fecal Pollution Sources” (Application Number: 62/386,532). Universities and non-profit researchers interested in using this technology must obtain a research license from the USEPA. To apply for a research license, please request additional information from ftta@epa.gov. The authors declare no other conflict of interest., (© 2020 The Authors.)

The significant decrease in the incidence of cervical cancer in Australian women since the implementation of an organised approach to cervical screening through the National Cervical Screening Program (NSCP) can be largely attributed to high-quality cervical cytology reporting by Australian laboratories. Performance measures for Australian laboratories reporting cervical cytology are a well-established and an integral part of monitoring and maintaining this high standard by facilitating interlaboratory comparison of performance. This study summarises the aggregate data collected annually by Royal College of Pathologists of Australasia Quality Assurance Programs (RCPAQAP) over the decade from 2009 until 30 November 2017, when the NCSP was revised and the cervical screening test replaced the Pap test as the primary mode of screening women for preinvasive disease. Overall, laboratories continued to perform to a high standard over this period. However, the introduction of a national school and GP based human papillomavirus (HPV) vaccination program in 2006 had a significant impact on the reporting of possible and definite high-grade abnormalities. In the renewed cervical screening program which commenced in December 2017 and which is based on HPV testing and reflex liquid-based cytology, new performance benchmarks will need to be developed when sufficient data have been collected., (Copyright © 2020 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)

S -Acylation of the SNARE protein SNAP25 (synaptosome-associated protein of 25 kDa) is mediated by a subset of Golgi zinc finger DHHC-type palmitoyltransferase (zDHHC) enzymes, particularly zDHHC17. The ankyrin repeat domain of zDHHC17 interacts with a short linear motif known as the zDHHC ankyrin repeat-binding motif (zDABM) in SNAP25 ( 112 VVASQP 117 ), which is downstream of its S -acylated, cysteine-rich domain ( 85 CGLCVCPC 92 ). Here, we investigated the importance of a flexible linker region (amino acids 93-111, referred to hereafter as the "mini-linker" region) that separates the zDABM and S -acylated cysteines in SNAP25. Shortening the mini-linker did not affect the SNAP25-zDHHC17 interaction but blocked S -acylation. Insertion of additional flexible glycine-serine repeats had no effect on S -acylation, but extended and rigid alanine-proline repeats perturbed it. A SNAP25 mutant in which the mini-linker region was substituted with a flexible glycine-serine linker of the same length underwent efficient S -acylation. Furthermore, this mutant displayed the same intracellular localization as WT SNAP25, indicating that the amino acid composition of the mini-linker is not important for SNAP25 localization. Using the results of previous peptide array experiments, we generated a SNAP25 mutant predicted to have a higher-affinity zDABM. This mutant interacted with zDHHC17 more strongly but was S -acylated with reduced efficiency in HEK293T cells, implying that a lower-affinity interaction of the SNAP25 zDABM with zDHHC17 is optimal for S -acylation efficiency. These results show that amino acids 93-111 in SNAP25 act as a flexible molecular spacer that ensures efficient coupling of the SNAP25-zDHHC17 interaction and S -acylation of SNAP25., (© 2020 Salaun et al.)

Wastewater treatment plants are typically monitored using fecal indicator bacteria to ensure adequate microbial water quality of the treated effluent. Fecal indicator bacteria exhibit poor correlation with virus fate in the environment, including during wastewater treatment. Viral-based microbial source tracking methods have the potential to overcome this limitation. The recently discovered human gut bacteriophage crAssphage is a promising viral human fecal indicator. In this current study, primary influent, primary effluent, secondary effluent, and final effluent of a conventional activated sludge wastewater treatment plant were analyzed for a suite of fecal indicators to evaluate the suitability of crAssphage as a wastewater process indicator for virus removal. CrAssphage was the most abundant fecal indicator measured through the wastewater treatment process. Culturable and molecular bacterial fecal pollution indicators showed higher removal than viral fecal pollution indicators, including crAssphage, confirming the necessity of a viral-specific fecal monitoring target. CrAssphage was strongly correlated with adenovirus and polyomavirus molecular indicators through the wastewater treatment process. Literature comparison demonstrated site-specific removal of molecular fecal indicators during wastewater treatment highlighting the need for local performance validation. The high abundance of crAssphage and correlation with pathogenic viruses suggests the potential suitability of crAssphage as a viral fecal pollution process indicator during wastewater treatment., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: K.B. is a co-inventor on a US patent application entitled “Cross-Assembly Phage DNA Sequences, Primers and Probes for PCR-based Identification of Human Fecal Pollution Sources” (Application Number: 62/386,532). United States universities and non-profit researchers interested in using this technology must obtain a research license from the US EPA. To apply for a research license, please request additional information from ftta@epa.gov. The authors declare no other conflict of interest., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The Royal College of Pathologists of Australasia Quality Assurance Programs (RCPAQAP) offers a comprehensive range of External Quality Assurance programs for all disciplines of pathology and is committed to delivering programs to advance outcomes in patient care and promote excellence in laboratory diagnostic and technical proficiency. Proficiency testing in cytopreparatory techniques became available for formal enrolment in 2018. The 2019 technical program focused on the demonstration of a laboratory to troubleshoot problems encountered during staining and processing. The exercise provided a peer comparison of a laboratory's ability to (1) identify the problem viewed from a digital image and (2) describe the troubleshooting steps to rectify the problem using assessment guidelines., Methods: Ten troubleshooting exercises including whole-slide z-stacked virtual images, a reference slide, and an online Result Entry questionnaire were provided. Common staining and processing problems were demonstrated in these exercises. Multiple-choice responses were made available to participants for each case with 1 response requiring submission. Participants were then allowed free text to describe how they would rectify the problem., Results: Of the 72 participants who participated, 62 participants (86%) achieved a satisfactory assessment, 6 participants (8%) received a borderline assessment, and 4 participants (6%) received an unsatisfactory assessment. The average mark obtained was 32.7 out of a total of 45 marks, which equates to a satisfactory assessment. The highest mark obtained for this survey was 42.5., Conclusions: Quality cytopathology preparatory techniques are integral to mitigating the risk of diagnostic error. The digital pathology platform allowed homogeneity of samples for all participants and appeared to be a satisfactory mode for demonstrating the technical problems to participants. Laboratories participating in this survey showed good performance in identifying processing and staining problems on virtual images and working through the troubleshooting steps. The exercise also identified a method for troubleshooting formalin vapour-affected slides using citrate buffer which may be useful for laboratories following in-house validation., (© 2020 S. Karger AG, Basel.)

The use of synthetically synthesized azide and alkyne fatty acid analogs coupled with bioorthogonal Cu(I)-catalyzed Huisgen 1,3-dipolar cycloaddition reaction-based detection methods to study protein S-acylation reactions has replaced the traditional method of using in vivo metabolic radiolabeling with tritiated palmitic acid and has greatly facilitated our understanding of this essential cellular process. Here, we describe the chemical synthesis of myristic (C:14), palmitic (C16:0), and stearic (C18:0) acid-azide probes and detail how they may be utilized as chemical reporters for the analysis of S-acylation of exogenously expressed proteins in cells.

STX19 is an unusual Q a -SNARE as it lacks a C-terminal transmembrane domain. However, it is efficiently targeted to post-Golgi membranes. Here, we set out to determine the intracellular localisation of endogenous STX19 and elucidate the mechanism by which it is targeted to membranes. We have found that a pool of STX19 is localised to tubular recycling endosomes where it colocalises with MICAL-L1 and Rab8 (which has Rab8a and Rab8b forms). Using a combination of genetic, biochemical and cell-based approaches, we have identified that STX19 is S-acylated at its C-terminus and is a substrate for several Golgi-localised S-acyltransferases, suggesting that STX19 is initially S-acylated at the Golgi before trafficking to the plasma membrane and endosomes. Surprisingly, we have found that S-acylation is a key determinant in targeting STX19 to tubular recycling endosomes, suggesting that S-acylation may play a general role in directing proteins to this compartment. In addition, S-acylation also protects STX19 from proteosomal degradation, indicating that S-acylation regulates the function of STX19 at multiple levels.This article has an associated First Person interview with the first author of the paper., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2018. Published by The Company of Biologists Ltd.)

Actin-based protrusions are reinforced through positive feedback, but it is unclear what restricts their size, or limits positive signals when they retract or split. We identify an evolutionarily conserved regulator of actin-based protrusion: CYRI (CYFIP-related Rac interactor) also known as Fam49 (family of unknown function 49). CYRI binds activated Rac1 via a domain of unknown function (DUF1394) shared with CYFIP, defining DUF1394 as a Rac1-binding module. CYRI-depleted cells have broad lamellipodia enriched in Scar/WAVE, but reduced protrusion-retraction dynamics. Pseudopods induced by optogenetic Rac1 activation in CYRI-depleted cells are larger and longer lived. Conversely, CYRI overexpression suppresses recruitment of active Scar/WAVE to the cell edge, resulting in short-lived, unproductive protrusions. CYRI thus focuses protrusion signals and regulates pseudopod complexity by inhibiting Scar/WAVE-induced actin polymerization. It thus behaves like a 'local inhibitor' as predicted in widely accepted mathematical models, but not previously identified in cells. CYRI therefore regulates chemotaxis, cell migration and epithelial polarization by controlling the polarity and plasticity of protrusions.

Objectives: To review current methods for informing nurse workforce decisions in critical care. Many clinical outcomes are worse if staffing is inadequate. Workforce planning is usually according to guidelines developed from the opinions of expert groups. Objective systems for planning and distributing staff have been developed but their value is unclear., Design: A rapid review methodology was employed., Review Methods: The search included research studies, guidelines and surveys within and outside United Kingdom since 1995., Findings: Thirty-two studies met eligibility criteria. Studies originated worldwide, with considerable work undertaken in the United Kingdom and Brazil. Two were large multicentre studies. Tools examined fell into three groups: those focused on the condition and needs of the patient, those focused on the number and time for nursing activities and those that also took account of psycho-social factors. Many tools were not used beyond their country of origin., Conclusion: There is limited experience of using tools to determine nurse staffing. No one tool is likely to suit every application. More information is needed to clarify the practicalities of using the tools., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The cytokine leukaemia inhibitory factor (LIF) promotes self-renewal of mouse embryonic stem cells (ESCs) through activation of the transcription factor Stat3. However, the contribution of other ancillary pathways stimulated by LIF in ESCs, such as the MAPK and PI3K pathways, is less well understood. We show here that naive-type mouse ESCs express high levels of a novel effector of the MAPK and PI3K pathways. This effector is an isoform of the Gab1 (Grb2-associated binder protein 1) adaptor protein that lacks the N-terminal pleckstrin homology (PH) membrane-binding domain. Although not essential for rapid unrestricted growth of ESCs under optimal conditions, the novel Gab1 variant (Gab1β) is required for LIF-mediated cell survival under conditions of limited nutrient availability. This enhanced survival is absolutely dependent upon a latent palmitoylation site that targets Gab1β directly to ESC membranes. These results show that constitutive association of Gab1 with membranes through a novel mechanism promotes LIF-dependent survival of murine ESCs in nutrient-poor conditions., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2018. Published by The Company of Biologists Ltd.)

'Maintaining independence' is a core project for many older people; a project which has received critical attention within aging studies. In this paper, we extend the critique by exploring how aging intersects with disability and militarism as additional critical subjectivities. The empirical focus of the paper is the narratives of older military veterans who had lost a limb either during or post-service. Data reveal the long legacy of military experience in the lives of these veterans; a legacy which is manifested in both negative and positive outcomes. A dominant narrative of 'struggling against decline' is identified, while 'minimization', 'victimhood', and 'life-as-normal' emerged as further narrative types through which veterans articulated their experiences of aging with limb loss. Findings from this study highlight both resilience and vulnerability as features of older veterans' experiences of aging with limb loss. Building on previous critiques, we add further nuance to understandings of how older people might respond to the narrative of decline, and illustrate multiple possible meanings of claims to 'normality'. By sharing the stories of older limbless veterans, we aim to contribute to - and connect - several fields of study including aging studies, critical disability studies, and critical military studies. Findings are discussed in light of current trends in each of these fields., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: The Royal College of Pathologists of Australasia Quality Assurance Programs introduced virtual microscopy cases into its cytopathology non-gynaecological programme after a short pilot phase, to address the challenges of providing a purely glass slide-based external quality assurance programme to multiple participants both locally and internationally. The use of whole slide image (WSI) cases has facilitated a more robust programme in relation to standardised material and statistical analysis, with access to a wider variety of specimen types and diagnostic entities., Method: Diagnostic accuracy rates on 56 WSI were assessed against the reference diagnosis. A portion (12) of these WSI slides had been used in glass slide format in previous external quality assurance surveys, and the results of these were compared to the responses received as glass slide cases., Results: Overall diagnostic accuracy for the 56 WSI cases was acceptable in comparison to the reference diagnosis. When these 12 cases were analysed individually, for seven of the 12 cases, virtual format was found to be not inferior to glass slides for diagnostic accuracy. For one case, accuracy using WSI for diagnosis was superior to glass format., Conclusion: Diagnostic accuracy, using WSI for cases in our external quality assurance programme is acceptable. As the use of digital microscopy in a large scale external quality assurance programme offers extensive advantages over a glass slide-based format, our results encourage future comparison of diagnostic accuracy for virtual compared to glass slide format at a point in time where pathologists are becoming increasingly familiar with virtual microscopy in everyday practice., (© 2018 John Wiley & Sons Ltd.)

Annually, about 15 million preterm infants are born in the world. Of these, due to complications resulting from their premature birth, about 1 million would die before the age of five. Since the high incidence of preterm birth (PTB) is partially due to the lack of effective diagnostic modalities, methodologies are needed to determine risk of PTB. We propose a noninvasive tool based on polarized light imaging aimed at measuring the organization of collagen in the cervix. Cervical collagen has been shown to remodel with the approach of parturition. We used a full-field Mueller matrix polarimetric colposcope to assess and compare cervical collagen content and structure in nonpregnant and pregnant women in vivo. Local collagen directional azimuth was used and a total of eight cervices were imaged., ((2018) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).)

Intracellular uptake, distribution and metabolism of lipids are tightly regulated characteristics in healthy cells. An analytical technique capable of understanding these characteristics with a high level of species specificity in a minimally invasive manner is highly desirable in order to understand better how these become disrupted during disease. In this study, the uptake and distribution of three different alkyne tagged fatty acids in single cells were monitored and compared, highlighting the ability of Raman spectroscopy combined with alkyne tags for better understanding of the fine details with regard to uptake, distribution and metabolism of very chemically specific lipid species. This indicates the promise of using Raman spectroscopy directly with alkyne tagged lipids for cellular studies as opposed to subsequently clicking of a fluorophore onto the alkyne for fluorescence imaging., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Special consideration should be given when creating and selecting cytopathology specimens for digitization to maximize quality. Advances in scanning and viewing technology can also improve whole-slide imaging (WSI) output quality., Methods: Accumulated laboratory experience with digitization of glass cytopathology slides was collected., Results: This paper describes characteristics of a cytopathology glass slide that can reduce quality on resulting WSI. Important points in the glass cytopathology slide selection process, preparation, scanning, and WSI-editing process that will maximize the quality of the resulting acquired digital image are covered. The paper outlines scanning solutions which have potential to predict issues with a glass cytopathology slide before image acquisition, allowing for adjustment of the scanning approach. WSI viewing solutions that better simulate the traditional microscope experience are also discussed., Conclusion: In addition to taking advantage of technical advances, practical steps can taken to maximize quality of cytopathology WSI., Competing Interests: There are no conflicts of interest.

The S-acyltransferase zDHHC2 mediates dynamic S-acylation of PSD95 and AKAP79/150, which impacts synaptic targeting of AMPA receptors. zDHHC2 is responsive to synaptic activity and catalyses the increased S-acylation of PSD95 that occurs following action potential blockade or application of ionotropic glutamate receptor antagonists. These treatments have been proposed to increase plasma membrane delivery of zDHHC2 via an endosomal cycling pathway, enhancing substrate accessibility. To generate an improved understanding of zDHHC2 trafficking and how this might be regulated by neuronal activity, we searched for intramolecular signals that regulate enzyme localisation. Two signals were mapped to the C-terminal tail of zDHHC2: a non-canonical dileucine motif [SxxxLL] and a downstream NP motif. Mutation of these signals enhanced plasma membrane accumulation of zDHHC2 in both neuroendocrine PC12 cells and rat hippocampal neurons, consistent with reduced endocytic retrieval. Furthermore, mutation of these signals also increased accumulation of the enzyme in neurites. Interestingly, several threonine and serine residues are adjacent to these sorting motifs and analysis of phospho-mimetic mutants highlighted a potential role for phosphorylation in regulating the efficacy of these signals. This study offers new molecular insight into the signals that determine zDHHC2 localisation and highlights a potential mechanism to regulate these trafficking signals., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

S-acylation is a reversible lipid modification occurring on cysteine residues mediated by a family of membrane-bound 'zDHHC' enzymes. S-acylation predominantly results in anchoring of soluble proteins to membrane compartments or in the trafficking of membrane proteins to different compartments. Recent work has shown that although S-acylation of some proteins may involve very weak interactions with zDHHC enzymes, a pool of zDHHC enzymes exhibit strong and specific interactions with substrates, thereby recruiting them for S-acylation. For example, the ankyrin-repeat domains of zDHHC17 and zDHHC13 interact specifically with unstructured consensus sequences present in some proteins, thus contributing to substrate specificity of these enzymes. In addition to this new information on zDHHC enzyme protein substrate specificity, recent work has also identified marked differences in selectivity of zDHHC enzymes for acyl-CoA substrates and has started to unravel the underlying molecular basis for this lipid selectivity. This review will focus on the protein and acyl-CoA selectivity of zDHHC enzymes., (© 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.)

Objective: To assess both the feasibility and value of conducting an external quality assurance programme concerning technical aspects of cytopathology laboratory practice, and the interest by laboratories in enrolling in such a programme., Methods: Six technical surveys, comprising staining exercises and questionnaires relating to laboratory practice, were distributed over a 4-year period to the approximately 220 laboratories enrolled in the RCPAQAP Cytopathology slide survey modules. Staining exercises using the Papanicolaou and Romanowsky techniques, the preparation of urine and body fluid specimens and immunocytochemistry on the cell block material were assessed. Accompanying relevant questionnaires were included, and one survey comprised a questionnaire alone concerning the collection of urinary tract and body fluid samples., Results: Provision of an external cytopathology technical module was feasible for the RCPAQAP and participation rates (maximum of 87% per survey; average 68% for stained slides and 66% for questionnaires) were commendable, particularly considering these were optional undertakings with some exercises not applicable to all laboratories. The great majority of submitted slides were scored as satisfactory, and there was an especially high standard for the immunocytochemical staining exercise with 95% considered satisfactory, including 50.6% with a perfect score. Reasons for suboptimal scores were provided for potential quality improvement for interested laboratories. A wealth of information relating to laboratory practice was provided to the RCPAQAP which was collated and summarised for laboratory use., Conclusions: The provision of a technical module in cytopathology is both a feasible and valuable undertaking of interest to laboratories which should become standard practice for cytopathology external quality assurance providers., (© 2016 John Wiley & Sons Ltd.)

S-acylation is a major posttranslational modification, catalyzed by the zinc finger DHHC domain containing (zDHHC) enzyme family. S-acylated proteins can be modified by different fatty acids; however, very little is known about how zDHHC enzymes contribute to acyl chain heterogeneity. Here, we used fatty acid-azide/alkyne labeling of mammalian cells, showing their transformation into acyl-CoAs and subsequent click chemistry-based detection, to demonstrate that zDHHC enzymes have marked differences in their fatty acid selectivity. This difference in selectivity was apparent even for highly related enzymes, such as zDHHC3 and zDHHC7, which displayed a marked difference in their ability to use C18:0 acyl-CoA as a substrate. Furthermore, we identified isoleucine-182 in transmembrane domain 3 of zDHHC3 as a key determinant in limiting the use of longer chain acyl-CoAs by this enzyme. This study uncovered differences in the fatty acid selectivity profiles of cellular zDHHC enzymes and mapped molecular determinants governing this selectivity.

Autosomal-dominant adult-onset neuronal ceroid lipofuscinosis (ANCL) is caused by mutation of the DNAJC5 gene encoding cysteine string protein alpha (CSPα). The disease-causing mutations, which result in substitution of leucine-115 with an arginine (L115R) or deletion of the neighbouring leucine-116 (∆L116) in the cysteine-string domain cause CSPα to form high molecular weight SDS-resistant aggregates, which are also present in post-mortem brain tissue from patients. Formation and stability of these mutant aggregates is linked to palmitoylation of the cysteine-string domain, however the regions of the mutant proteins that drive aggregation have not been determined. The importance of specific residues in the cysteine-string domain was investigated, revealing that a central core of palmitoylated cysteines is essential for aggregation of ANCL CSPα mutants. Interestingly, palmitoylated monomers of ANCL CSPα mutants were shown to be short-lived compared with wild-type CSPα, suggesting that the mutants either have a faster rate of depalmitoylation or that they are consumed in a time-dependent manner into high molecular weight aggregates. These findings provide new insight into the features of CSPα that promote aggregation in the presence of L115R/∆L116 mutations and reveal a change in the lifetime of palmitoylated monomers of the mutant proteins.

Ozonolysis of alkenes is an important source of secondary organic aerosol (SOA) in the atmosphere. However, the mechanisms by which stabilized Criegee intermediates (SCI) react to form and grow the particles, and in particular the contributions from oligomers, are not well understood. In this study, ozonolysis of trans-3-hexene (C6H12), as a proxy for small alkenes, was investigated with an emphasis on the mechanisms of particle formation and growth. Ozonolysis experiments were carried out both in static Teflon chambers (18-20 min reaction times) and in a glass flow reactor (24 s reaction time) in the absence and presence of OH or SCI scavengers, and under different relative humidity (RH) conditions. The chemical composition of polydisperse and size-selected SOA particles was probed using different mass spectrometric techniques and infrared spectroscopy. Oligomers having SCI as the chain unit are found to be the dominant components of such SOA particles. The formation mechanism for these oligomers suggested by our results follows the sequential addition of SCI to organic peroxy (RO2) radicals, in agreement with previous studies by Moortgat and coworkers. Smaller particles are shown to have a relatively greater contribution from longer oligomers. Higher O/C ratios are observed in smaller particles and are similar to those of oligomers resulting from RO2 + nSCI, supporting a significant role for longer oligomers in particle nucleation and early growth. Under atmospherically relevant RH of 30-80%, water vapor suppresses oligomer formation through scavenging SCI, but also enhances particle nucleation. Under humid conditions, or in the presence of formic or hydrochloric acid as SCI scavengers, peroxyhemiacetals are formed by the acid-catalyzed particle phase reaction between oligomers from RO2 + nSCI and a trans-3-hexene derived carbonyl product. In contrast to the ozonolysis of trans-3-hexene, oligomerization involving RO2 + nSCI does not appear to be prevalent in the ozonolysis of α-cedrene (C15H24), indicating different particle formation mechanisms for small and large complex alkenes that need to be taken into account in atmospheric models.

The discovery of the zDHHC family of S-acyltransferase enzymes has been one of the major breakthroughs in the S-acylation field. Now, more than a decade since their discovery, major questions centre on profiling the substrates of individual zDHHC enzymes (there are 24 ZDHHC genes and several hundred S-acylated proteins), defining the mechanisms of enzyme-substrate specificity and unravelling the importance of this enzyme family for cellular physiology and pathology.

Background: Creating and maintaining a sustainable workforce is currently an international concern. Extensive literature suggest that students and staff need to be 'engaged', that is they need to interact with the health team if they are to maximise learning opportunities. Despite many studies since the 1970s into what creates a 'good' learning environment, ongoing issues continue to challenge healthcare organisations and educators. A 'good' learning environment has been an intangible element for many professions as learning is hindered by the complexity of practice and by limitations on practitioners' time available to assist and guide novices., Objectives: This study sought to explore the nature of the learning interactions and experiences in clinical nursing practice that enhance a 'good' workplace learning culture for both nursing students and qualified nurses., Design: An ethnomethodology study., Setting: A range of clinical settings in Victoria and Queensland, Australia., Participants: Students and registered nurses (n=95)., Methods: Fieldwork observations were carried out on student nurses and registered nurses, followed by an individual interview with each participant. An iterative approach to analysis was undertaken; field notes of observations were reviewed, interviews transcribed verbatim and entered into NVivo10. Major themes were then extracted., Results: Three central themes: learning by doing, navigating through communication, and 'entrustability', emerged providing insights into common practices potentially enhancing or detracting from learning in the workplace., Conclusions: Students' and registered nurses' learning is constrained by a myriad of interactions and embedded workplace practices, which can either enhance the individual's opportunities for learning or detract from the richness of affordances that healthcare workplace settings have to offer. Until the culture/or routine practices of the healthcare workplace are challenged, the trust and meaningful communication essential to learning in practice, will be achievable only serendipitously., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The surface chemistry of gold nanowires (AuNWs) has been systematically assessed in terms of contamination and cleaning processes. The nanomaterial's surface quality was correlated to its performance in the matrix-free laser desorption ionization mass spectrometry (LDI-MS) analysis of low molecular weight analytes. Arrays of AuNWs were deposited on glass slides by means of the lithographically patterned nanowire electrodeposition technique. AuNWs were then characterized in terms of surface chemical composition and morphology using X-ray photoelectron spectroscopy, scanning electron microscopy and atomic force microscopy. AuNWs were subjected to a series of well-known cleaning procedures with the aim of producing the best performing surfaces for the LDI-MS detection of leucine enkephalin, chosen as a model analyte with a molar mass below 1,000 g/mol. Prolonged cyclic voltammetry in 2 M sulfuric acid and, most of all, oxygen plasma cleaning for 5 min provided the best results in terms of simpler (interference-free) and more intense mass spectrometry spectra of the reference compound. The analyte always ionized as the sodiated adduct, and leucine enkephalin limits of detection of 0.5 and 2.5 pmol were estimated for the positive and negative analysis modes, respectively. This study points out the tight correlation existing between the chemical status of the nanostructure surface and the AuNW-assisted LDI-MS performance in terms of reproducibility of spectra, intensity of analyte ions and reduction of interferences.

S-acylation (also known as palmitoylation) is a major post-translational protein modification in all eukaryotic cells, involving the attachment of fatty acids onto cysteine residues. A variety of structural and signalling proteins are modified in this way, affecting their stability, membrane association and intracellular targeting. The enzymes that mediate S-acylation are encoded by genes belonging to the large (> 20 genes) ZDHHC family. The importance of these enzymes for normal physiological function is highlighted by their links to a diverse range of disease states, including neurological disorders, such as Huntington's disease, schizophrenia and intellectual disability, and diabetes and cancer. The recent study by Yeste-Velasco et al published in the Journal of Pathology highlights a novel tumour suppressor function for the zDHHC family: expression of zDHHC14 is decreased in testicular germ cell tumours, prostate cancer and a variety of other cancer types. This important finding further emphasizes the emerging clinical significance of the zDHHC family of S-acylation enzymes., (Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)

Many stars are surrounded by disks of dusty debris formed in the collisions of asteroids, comets, and dwarf planets, but is gas also released in such events? Observations at submillimeter wavelengths of the archetypal debris disk around β Pictoris show that 0.3% of a Moon mass of carbon monoxide orbits in its debris belt. The gas distribution is highly asymmetric, with 30% found in a single clump 85 astronomical units from the star, in a plane closely aligned with the orbit of the inner planet, β Pictoris b. This gas clump delineates a region of enhanced collisions, either from a mean motion resonance with an unseen giant planet or from the remnants of a collision of Mars-mass planets.