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Background A person with an infection is considered a reservoir for a pathogen and capable of facilitating its ongoing transmission to others. Within health ethics, an infected person is understood as posing a risk of harm to others whilst needing healthcare to protect their wellbeing. This creates a potential ethical discord if control measures are not proportional to the risk, or if harms outweigh benefits. Public health policymakers are committed to controlling incidence of antibiotic resistant pathogens in hospitals. Control measures (now known as Contact Precautions) were developed in the late 1970’s however multi-resistant organisms (MROs) continue to occur in hospitals and antimicrobial resistance remains a global health risk. Negative consequences of Contact Precautions on patients, including psychological harm and compromised healthcare delivery, are recognised. Authors reporting these negative consequences have called for evidence-based change, but these appeals have been countered by researchers reporting conflicting findings. Evidence wars have resulted in an inertia of practice despite acknowledgement that the evidence supporting Contact Precautions efficacy is poorly constructed. The aim of this research was to explore the experience of Contact Precautions within a framework of bioethical principles which includes: respect for autonomy, justice, non-maleficence, and beneficence. The objectives were to understand the impact of Contact Precautions on patients and on health professionals, to discuss these findings within a bioethical framework with a view to exploring the ethical implications, and to make recommendations for an ethically sound framework for the management of hospital patients colonised with a multi-resistant organism (MRO). The research question asked: ‘Are Contact Precautions ethically justifiable in contemporary hospital care?’ Method Interpretive description, a methodological approach recognised as having practical application in improving nursing knowledge and practice, was used. The ethos of this qualitative approach mirrors recognised strengths of empirical ethical inquiry. Both have the power to discover the reality of a given situation, and to use the findings to develop insights into improved policy and practice. Theories of planned behaviour, principles of bioethics, and prior experience in infection prevention and control nursing provided the theoretical scaffold. The study was conducted in a publicly funded health system in regional Australia, with Human Research Ethics Committee (HREC) approval. Thirty-three participants (9 patients, 13 nurses, 7 doctors and 4 allied health professionals) were purposively recruited. Semi-structured interviews were recorded and transcribed for analysis. NVivo 12 was used to organise and manage the data. Data analysis of interview transcripts alongside research journal entries involved thematic and axial coding. Themed findings were explored in the context of the research question and theoretical scaffold alongside contemporary published research. Findings Four themes were identified, with sub-themes adding depth and texture. The first theme is ‘Powerlessness moving to acceptance’. Contributory sub-themes are communication, and healthcare hierarchies. Patients are denied the opportunity to provide informed consent prior to diagnostic testing. Additionally, patients colonised with an MRO are inadequately informed about Contact Precautions and do not consider themselves active partners in decision-making. Health professionals trust Contact Precautions but hold concerns that they stifle their personal autonomy as a health professional. Neither group feels able to affect change despite feeling uncomfortable about policy requirements. They tolerate Contact Precautions as a necessary part of hospital life. The second theme ‘You feel a bit of a pariah’ describes staff reluctance to enter the rooms of patients when Contact Precautions are implemented, and patients’ feelings of being untouchable. This was reinforced by staff wearing yellow gowns and other personal protective equipment (PPE), and signage displayed at doorways. Visual reminders of patient’s contaminated status were reinforced by auditory messaging such as the use of words such as ‘dirty’. The third theme is ‘Others need protection, but I need looking after too’. Patients are committed to following the rules despite noticing their care being compromised. Health professionals also recognised patient care might be compromised by Contact Precautions but remained committed to the policy as a means of protecting themselves, their family, or their career. The fourth theme is ‘Doing Contact Precautions is not easy’. Health professionals find Contact Precautions challenging because of confusing policy variations, and physical discomfort when wearing PPE. They experience negative emotions when balancing the need to follow a trusted policy with their professional and personal values when they notice associated harm for their patients, their workplace culture and professional relationships, or the environment. The findings corroborate other research reports, specifically those that describe the negative and harmful impact of Contact Precautions on hospital patients. Conflicts are identified with the bioethical principle of respect for personal and professional autonomy due to a lack of adherence to the requirements for informed consent, and sub-optimal communication to patients and health professionals. Patients are subjected to inequality of care provision and discriminatory practices, which breach the principle of justice. Contact Precautions potentially elicit stigma for patients, and moral distress and inter-personal conflict for staff, breaching the principle of non-maleficence. Under the principle of beneficence, a pluralistic cost–benefit assessment of Contact Precautions situates them as a low-value practice. Health professionals require training to develop skills and confidence in discussing antimicrobial resistance and hospital infection prevention measures with patients, and to improve their practice from an ethical standpoint. Overt leadership that supports staff in speaking out when they observe patient safety risks, and role modelling of expected exemplary practice, would reduce the stress and harm experienced by health professionals in relation to Contact Precautions. Further research into health professionals’ attitudes and beliefs around infection prevention policy, and the role of informed consent relating to clinical specimen collection and testing, would be beneficial. Conclusion Contact Precautions present a significant challenge to organisational culture, professional well-being, and the provision of person-centred ethical care. The identified negative impacts of Contact Precautions on patients and health professionals confirm they breach established ethical paradigms. The wider evidence base fails to confirm superiority of Contact Precautions over Standard Precautions in preventing MRO acquisition. In conclusion, the ethical costs of Contact Precautions outweigh the benefits, and Contact Precautions are confirmed as an example of low-value practice. It is time for the long-standing evidence wars to end as this study confirms that the use of Contact Precautions in the management of patients colonised with an MRO is not ethically justifiable in contemporary hospital care.

Chronic hepatitis B virus (HBV) infection is a global health problem that presents as a spectrum of liver disease, reflecting an interplay between the virus and the host immune system. HBV genomes exist as episomal covalently closed circular DNA (cccDNA) or chromosomal integrants. The relative contribution of these genomes to the viral transcriptome in chronic hepatitis B (CHB) is not well-understood. We developed a qPCR method to estimate the abundance of HBV cccDNA- and integrant-derived viral transcripts and applied this to a cohort of patients diagnosed with CHB in the HBe antigen negative phase of disease. We noted a variable pattern of HBV transcripts from both DNA templates, with preS1/S2 mRNAs predominating and a significant association between increasing age and the expression of integrant-derived mRNAs, but not with inflammatory status. In contrast, cccDNA-derived transcripts were associated with markers of liver inflammation. Analysis of the inflammatory hepatic transcriptome identified 24 genes significantly associated with cccDNA transcriptional activity. Our study uncovers an immune gene signature that associates with HBV cccDNA transcription and increases our understanding of viral persistence.

This work was supported by the Engineering and the Physical Sciences Research Council (EPSRC) under Grant EP/K503162/1. The misallocation of driver visual attention has been suggested as a major contributing factor to vehicle accidents. One possible reason is that the relatively high cognitive demands of driving limits the ability to efficiently allocate gaze. We present an experiment that explores the relationship between attentional function and visual performance when driving. Drivers performed two variations of a multiple object tracking task targeting aspects of cognition including sustained attention, dual-tasking, covert attention and visuomotor skill. They also drove a number of courses in a driving simulator. Eye movements were recorded throughout. We found that individuals who performed better in the cognitive tasks exhibited more effective eye movement strategies when driving, such as scanning more of the road, and they also exhibited better driving performance. We discuss the potential link between an individual's attentional function, effective eye movements and driving ability. We also discuss the use of a visuomotor task in assessing driving behaviour.The misallocation of driver visual attention has been suggested as a major contributing factor to vehicle accidents. One possible reason is that the relatively high cognitive demands of driving limit the ability to efficiently allocate gaze. We present an experiment that explores the relationship between attentional function and visual performance when driving. Drivers performed 2 variations of a multiple-object tracking task targeting aspects of cognition including sustained attention, dual-tasking, covert attention, and visuomotor skill. They also drove a number of courses in a driving simulator. Eye movements were recorded throughout. We found that individuals who performed better in the cognitive tasks exhibited more effective eye movement strategies when driving, such as scanning more of the road, and they also exhibited better driving performance. We discuss the potential link between an individual’s attentional function, effective eye movements, and driving ability. We also discuss the use of a visuomotor task in assessing driving behavior. Publisher PDF

This work was supported by the Engineering and the Physical Sciences Research Council (EPSRC) under Grant EP/K503162/1. Differences in eye movement patterns are often found when comparing passive viewing paradigms to actively engaging in everyday tasks. Arguably, investigations into visuomotor control should therefore be most useful when conducted in settings that incorporate the intrinsic link between vision and action. We present a study that compares oculomotor behaviour and hazard reaction times across a simulated driving task and a comparable, but passive, video-based hazard perception task. We found that participants scanned the road less during the active driving task and fixated closer to the front of the vehicle. Participants were also slower to detect the hazards in the driving task. Our results suggest that the interactivity of simulated driving places increased demand upon the visual and attention systems than simply viewing driving movies. We offer insights into why these differences occur and explore the possible implications of such findings within the wider context of driver training and assessment. Publisher PDF

Electrophoretic analysis of colloidal particles is adversely affected by a host of surface phenomena, including electroosmosis, phase wall wetting, and sample or air bubble adsorption. Neutral, hydrophilic polymer coatings control such phenomena on a variety of surfaces. Poly(ethylene glycol)-poly(ethylene imine) (PEG-PEI) conjugates significantly reduce electroosmosis and positively control adsorption and wetting in the glass sample chambers (5 mm × 3 mm × 1 mm i.d.) employed in a representative commercial electrophoresis apparatus (Coulter DELSA 440). The reduction in electroosmosis (e.g., 80% in 7.5 mM solution at pH 11) was similar to that exhibited by coated 2-mm-i.d. quartz capillaries in a Rank MK I manual apparatus. PEG-PEI coatings significantly reduce electroosmosis over a wide range of pH (2-11) and ionic strength (1-100 mM) and can be stable for weeks under normal laboratory conditions. They greatly enhance ease of operation and accuracy (sample mean electrophoretic mobility ± SD) of the DELSA 440. The latter results from reduced electroosmosis flow profile gradients near the chamber center-axis stationary levels, where particle mobility is typically measured. Such flow profiles may also be affected by chamber wall surface asymmetries. A hydrodynamic description of electroosmotic fluid flow in rectangular chambers was adapted in order to analyze the propagation of errors due to both nonideal focusing and chamber surface asymmetry. The analysis indicated that the accuracy of rectangular chambered devices may be improved by measuring particle mobility at stationary levels different than chamber center-axes. As a result, some rectangular chambers may confer accuracy advantages over cylindrical chambers.

The renin-angiotensin system (RAS) plays a key role in cardiovascular homeostasis through the interactions of angiotensin II with its receptors. All components of the RAS are developmentally regulated in the kidney. The functions of the system in the maturing kidney overlap those of the adult, but higher levels of expression and novel locations of expression in the fetus suggest that the RAS has alternate functions as well. Increasing evidence suggests that the RAS may regulate renal growth and development by initiating a complex cascade of events, involving growth factors and proto-oncogenes and other unidentified factors. These same cascades may also be important in renal disease states. Recent advances in the field of molecular and cell biology are providing new tools and strategies to elucidate the intimate mechanism whereby the RAS regulates growth processes and disease states.

We have previously shown that neurofilaments in enteric neurons are immunologically distinct from those found in the central nervous system. In particular, one monoclonal antibody to the medium molecular weight neurofilament subunit, called NN18, stained the perikarya of enteric neurons very weakly, if at all, although other medium molecular weight neurofilament subunit antibodies clearly showed the presence of significant amounts of medium molecular weight neurofilament subunit. We have since located the epitope for NN18 in a peptide sequence at the car☐y terminal tail of medium molecular weight neurofilament subunit and have now looked for further neurofilament antibodies that stain the same region. We found two monoclonal antibodies, RMO1 and RMO59, that recognize the same peptide. These antibodies also show much reduced staining in myenteric neurons compared to those in the central nervous system, suggesting that this region of the medium molecular weight neurofilament subunit is specifically modified in certain cells. In the developing enteric nervous system, we found that all the antibodies show strong staining of enteric neurons in the neonatal rat, but that with NN18, RMO1, and RMO59, the staining intensity decreases during further development, and by postnatal day 21 all three demonstrate decreased or absent staining identical to the adult. These results indicate that myenteric neurons, in contrast to the brain, have a developmentally regulated modification in a specific region of the medium molecular weight neurofilament subunit, which may reflect adaptation to structural stress by myenteric neurons.

The primary-secondary settlement hypothesis, that mussels first settle in algae and then move to mussel beds, was rejected as the only mode of recruitment for the brown mussel Perna perna in a previous study at one location over one year on the south coast of South Africa. We investigated recruitment of P. perna into mussel beds and algal turfs over a five-year period (1995–2000) at 3–4 sites at each of four locations on the South and East coasts. Attachment to the two substrata was significantly temporally synchronous at two of the four locations. The disparity among locations could be due to differences in the algal species present or to differences in the importance of turf algae as a facilitator of recruitment. At Zululand, on the East Coast, attachment to mussel beds and algae was measured monthly and found not to be temporally synchronous. At this location, primary settlement into algae was significantly correlated with an increase in the density of juveniles in the mussel beds 2–3 months later, indicating that turf algae can act as irregular but important facultative facilitators of mussel recruitment, supplementing direct input into the mussel beds. However, as amounts of settlers and recruits in mussel beds exceeded those found in algal turfs most years and places, the primary-secondary settlement hypothesis is inapplicable to P. perna under most circumstances. Keywords: Perna perna, primary-secondary settlement hypothesis, recruitment, rocky intertidal, turf algaeAfrican Journal of Marine Science 2007, 29(3): 545–549

Any attempt to reconstruct the life of André Beauneveu is reliant on a series of documents largely discovered in the course of nineteenth-century archival research and published in many different contexts over the past hundred and fifty years. This material is collected here in date order so as to make possible a full overview of Beauneveu’s career.

This chapter examines the historiography of André Beauneveu and his co-option into the national art histories of nineteenth and twentieth century Belgium, England and France.

The use of liposomal carriers and the modification of therapeutic molecules through the attachment of poly(ethylene glycol) [PEG] moieties ('pegylation') are the most common approaches for enhancing the delivery of parenteral agents. Although 'classical' liposomes (i.e. phospholipid bilayer vehicles) have been effective in decreasing the clearance of encapsulated agents and in passively targeting specific tissues, they are associated with considerable limitations. Pegylation may be an effective method of delivering therapeutic proteins and modifying their pharmacokinetic properties, in turn modifying pharmacodynamics, via a mechanism dependent on altered binding properties of the native protein. Pegylation reduces renal clearance and, for some products, results in a more sustained absorption after subcutaneous administration as well as restricted distribution. These pharmacokinetic changes may result in more constant and sustained plasma concentrations, which can lead to increases in clinical effectiveness when the desired effects are concentration-dependent. Maintaining drug concentrations at or near a target concentration for an extended period of time is often clinically advantageous, and is particularly useful in antiviral therapy, since constant antiviral pressure should prevent replication and may thereby suppress the emergence of resistant variants. Additionally, PEG modification may decrease adverse effects caused by the large variations in peak-to-trough plasma drug concentrations associated with frequent administration and by the immunogenicity of unmodified proteins. Pegylated proteins may have reduced immunogenicity because PEG-induced steric hindrance can prevent immune recognition. Two PEG-modified proteins are currently approved by the US Food and Drug Administration; several others, including cytokines such as interferon-alpha (IFNalpha), growth factors and free radical scavengers, are under development. Careful assessment of various pegylated IFNalpha products suggests that pegylated molecules can be differentiated on the basis of their pharmacokinetic properties and related changes in pharmacodynamics. Because the size, geometry and attachment site of the PEG moiety play a crucial role in determining these properties, therapeutically optimised agents must be designed on a protein-by-protein basis.

In early 1989 we surveyed by questionnaire Alabama primary care physicians (N = 1800) concerning their attitudes toward and use of mammography. There were 681 respondents (37.8%). The majority (83%) recommend mammograms for their patients according to the American Cancer Society guidelines and obtain baseline studies in asymptomatic women between the ages of 35 and 40 years. It appears that the cost of mammograms is decreasing in Alabama; a screening study was available for $50 or less to 34% of responding physicians. Almost one half (48%) of the physician respondents believe that more than 50% of their patients have had at least one mammogram.