Like Frying Multiple Eggs in One Pan: a Qualitative Study Exploring the Understanding of Inter-speciality Training in Cancer Care.

H igh-quality cancer care is a key priority worldwide. Caring for people affected by cancer requires a range of specific knowledge, skills and experience to deliver the complex care regimens both within the hospital and within the community environment. In June 2022, the European Cancer Organisation along with 33 European cancer societies began working together to develop a curriculum for inter-speciality training for healthcare professionals across Europe. As part of the project, this research consisted of a qualitative survey distributed to the European Union societies via email. The aim of this paper is to disseminate the qualitative findings from healthcare professionals across Europe. Questionnaires were sent out to a convenience sample of 219 healthcare professionals and patient advocates with a response rate of 55% (n = 115). The findings identified that there were four key themes: 'What is inter-speciality training?', 'Barriers and challenges', 'Support throughout the cancer journey' and 'New ways of working'. These results are part of a larger needs analysis and scoping review to inform the development of a core competency framework which will be part of an inter-speciality curriculum for specialist cancer doctors, nurses and other healthcare professionals across Europe. Healthcare professionals will be able to access education and training through the virtual learning environment and workshops and by clinical rotations to other specialties.

Twenty Years of Collaboration to Sort out Phage Mu Replication and Its Dependence on the Mu Central Gyrase Binding Site.

For 20 years, the intricacies in bacteriophage Mu replication and its regulation were elucidated in collaboration between Ariane Toussaint and her co-workers in the Laboratory of Genetics at the Université Libre de Bruxelles, and the groups of Martin Pato and N. Patrick Higgins in the US. Here, to honor Martin Pato's scientific passion and rigor, we tell the history of this long-term sharing of results, ideas and experiments between the three groups, and Martin's final discovery of a very unexpected step in the initiation of Mu replication, the joining of Mu DNA ends separated by 38 kB with the assistance of the host DNA gyrase.

An evaluation of a video magnification-based system for respiratory rate monitoring in an acute mental health setting.

CONTEXT: One of the most important goals of inpatient psychiatric care is to provide a safe and therapeutic environment for both patients and staff. A small number of aggressive or agitated patients are difficult to sedate, even after multiple doses of sedating antipsychotics. Adverse effects can result in harm to the patient and staff and that observations are conducted without touching the patient. AIM: This study aims to determine if motion magnification can improve the feasibility of non-contact respirations monitoring over a video feed. METHODS: Registered nurses were invited to view seven pairs of pre-recorded footage of healthy volunteers and count the number of breaths that they observe over a period of one minute for each. One of the paired videos was unprocessed and the other magnified the motion of chest rise and fall. RESULTS: Nursing observation of respirations showed an improvement in reduction of count error from 15.7 % to 1.5 % after video magnification of respiratory movement. Nurses also stated that viewing the processed video was much easier to make their observations from. CONCLUSION: It is possible to use magnified video to monitor respirations of patients during circumstances where it is potentially difficult to obtain. Further observational studies should be conducted on a larger scale with this type of technique and is urgently needed to inform practice.

Anaesthetic management of emergency caesarean section with isolated cortical vein thrombosis and subacute intracerebral haemorrhage.

We report the case of an emergency caesarean section 5 days following the onset of a right-sided hemiparesis due to an intracerebral haemorrhage. Computerised tomography imaging in the postoperative period revealed an isolated cortical vein thrombosis as the likely cause. The caesarean section was conducted under general anaesthesia following consideration of the risks and benefits and discussion of these with the patient. No peri-operative complications occurred and neuro-rehabilitation was commenced as an inpatient. This case highlights the importance of maintaining a targeted systolic blood pressure whilst avoiding increased intracranial pressure in the obstetric patient with an intracerebral haemorrhage, and that the mode and conduct of anaesthesia can have a profound impact on these measurements. To our knowledge, this is the first reported case of a patient having an emergency caesarean section after subacute intracerebral haemorrhage caused by an isolated cortical vein thrombosis and it demonstrates that general anaesthesia can be used safely in this context. In this complex obstetric case, the role of multidisciplinary team collaboration in the peri-operative period was essential to optimising the patient's outcome.

Neural correlates of perceptual switching while listening to bistable auditory streaming stimuli.

Understanding the neural underpinning of conscious perception remains one of the primary challenges of cognitive neuroscience. Theories based mostly on studies of the visual system differ according to whether the neural activity giving rise to conscious perception occurs in modality-specific sensory cortex or in associative areas, such as the frontal and parietal cortices. Here, we search for modality-specific conscious processing in the auditory cortex using a bistable stream segregation paradigm that presents a constant stimulus without the confounding influence of physical changes to sound properties. ABA_ triplets (i.e., alternating low, A, and high, B, tones, and _ gap) with a 700 ms silent response period after every third triplet were presented repeatedly, and human participants reported nearly equivalent proportions of 1- and 2-stream percepts. The pattern of behavioral responses was consistent with previous studies of visual and auditory bistable perception. The intermittent response paradigm has the benefit of evoking spontaneous perceptual switches that can be attributed to a well-defined stimulus event, enabling precise identification of the timing of perception-related neural events with event-related potentials (ERPs). Significantly more negative ERPs were observed for 2-streams compared to 1-stream, and for switches compared to non-switches during the sustained potential (500-1000 ms post-stimulus onset). Further analyses revealed that the negativity associated with switching was independent of switch direction, suggesting that spontaneous changes in perception have a unique neural signature separate from the observation that 2-stream percepts evoke more negative ERPs than 1-stream. Source analysis of the sustained potential showed activity associated with these differences originating in anterior superior temporal gyrus, indicating involvement of the ventral auditory pathway that is important for processing auditory objects.

Supercoil Levels in E. coli and Salmonella Chromosomes Are Regulated by the C-Terminal 35⁻38 Amino Acids of GyrA.

Prokaryotes have an essential gene-gyrase-that catalyzes negative supercoiling of plasmid and chromosomal DNA. Negative supercoils influence DNA replication, transcription, homologous recombination, site-specific recombination, genetic transposition and sister chromosome segregation. Although E. coli and Salmonella Typhimurium are close relatives with a conserved set of essential genes, E. coli DNA has a supercoil density 15% higher than Salmonella, and E. coli cannot grow at the supercoil density maintained by wild type (WT) Salmonella. E. coli is addicted to high supercoiling levels for efficient chromosomal folding. In vitro experiments were performed with four gyrase isoforms of the tetrameric enzyme (GyrA2:GyrB2). E. coli gyrase was more processive and faster than the Salmonella enzyme, but Salmonella strains with chromosomal swaps of E. coli GyrA lost 40% of the chromosomal supercoil density. Reciprocal experiments in E. coli showed chromosomal dysfunction for strains harboring Salmonella GyrA. One GyrA segment responsible for dis-regulation was uncovered by constructing and testing GyrA chimeras in vivo. The six pinwheel elements and the C-terminal 35⁻38 acidic residues of GyrA controlled WT chromosome-wide supercoiling density in both species. A model of enzyme processivity modulated by competition between DNA and the GyrA acidic tail for access to ß-pinwheel elements is presented.

Effect of companion presence on maternal satisfaction during neuraxial catheter placement for labor analgesia: a randomized clinical trial.

BACKGROUND: Neuraxial labor analgesia is frequently achieved after placing an epidural catheter under sterile conditions. There is no consensus on the risk versus benefit of allowing a parturient's companion to remain during the procedure. We sought to assess the effect of the presence of a companion on maternal satisfaction and anxiety during neuraxial catheter placement for labor analgesia. METHODS: Healthy nulliparous parturients planning to receive neuraxial labor analgesia after admission to labor, and who had a companion with them at the time of interview, were randomized to having a companion present or not present in the labor and delivery room during neuraxial catheter placement. Participants completed questionnaires to assess maternal anxiety, pain catastrophizing and health literacy. Satisfaction was scored on 5-point Likert scale (1- highly dissatisfied, 2- dissatisfied, 3- neutral, 4- satisfied, 5- highly satisfied). RESULTS: A total of 143 participants completed the study. The Wilcoxon-Mann-Whitney odds ratio for a random pair of satisfaction scores for a woman with her companion present compared with companion not present was 1.93 (95% CI 1.30 to 2.81, P=0.001). Anxiety scores were decreased following the procedure (P=0.39) in both groups. Eighty-nine percent of women randomized to companion not present would have preferred to have a companion present (P <0.001) compared with only one with their companion present who would have preferred her companion to be not present (P=0.99). CONCLUSION: Maternal satisfaction can be improved with the presence of a companion in the labor and delivery room at the time of neuraxial catheter placement for labor analgesia.

A randomised comparison of bolus phenylephrine and ephedrine for the management of spinal hypotension in patients with severe preeclampsia and fetal compromise.

BACKGROUND: Studies in healthy patients undergoing elective caesarean delivery show that, compared with phenylephrine, ephedrine used to treat spinal hypotension is associated with increased fetal acidosis. This has not been investigated prospectively in women with severe preeclampsia. METHODS: Patients with preeclampsia requiring caesarean delivery for a non-reassuring fetal heart tracing were randomised to receive either bolus ephedrine (7.5-15mg) or phenylephrine (50-100µg), to treat spinal hypotension. The primary outcome was umbilical arterial base excess. Secondary outcomes were umbilical arterial and venous pH and lactate concentration, venous base excess, and Apgar scores. RESULTS: Among 133 women, 64 who required vasopressor treatment were randomised into groups of 32 with similar patient characteristics. Pre-delivery blood pressure changes were similar. There was no difference in mean [standard deviation] umbilical artery base excess (-4.9 [3.7] vs -6.0 [4.6] mmol/L for ephedrine and phenylephrine respectively; P=0.29). Mean umbilical arterial and venous pH and lactate concentrations did not significantly differ between groups (7.25 [0.08] vs 7.22 [0.10], 7.28 [0.07] vs 7.27 [0.10], and 3.41 [2.18] vs 3.28 [2.44] mmol/L respectively). Umbilical venous oxygen tension was higher in the ephedrine group (2.8 [0.7] vs 2.4 [0.62]) kPa, P=0.02). There was no difference in 1- or 5-min Apgar scores, numbers of neonates with 1-min Apgar scores <7 or with a pH <7.2. CONCLUSIONS: In patients with severe preeclampsia and fetal compromise, fetal acid-base status is independent of the use of bolus ephedrine versus phenylephrine to treat spinal hypotension.

Muprints and Whole Genome Insertion Scans: Methods for Investigating Chromosome Accessibility and DNA Dynamics using Bacteriophage Mu.

Bacteriophage Mu infects a broad range of gram-negative bacteria. After infection, Mu amplifies its DNA through a coupled transposition/replication cycle that inserts copies of Mu throughout all domains of the folded chromosome. Mu has the most relaxed target specificity of the known transposons (Manna et al., J Bacteriol 187: 3586-3588, 2005) and the Mu DNA packaging process, called "headful packaging", incorporates 50-150 bp of host sequences covalently bound to its left end and 2 kb of host DNA linked to its right end into a viral capsid. The combination of broad insertion coverage and easy phage purification makes Mu ideal for analyzing chromosome dynamics and DNA structure inside living cells. "Mu printing" (Wang and Higgins, Mol Microbiol 12: 665-677, 1994; Manna et al., J Bacteriol 183: 3328-3335, 2001) uses the polymerase chain reaction (PCR) to generate a quantitative fine structure map of Mu insertion sites within specific regions of a bacterial chromosome or plasmid. A complementary technique uses microarray platforms to provide quantitative insertion patterns covering a whole bacterial genome (Manna et al., J Bacteriol 187: 3586-3588, 2005; Manna et al., Proc Natl Acad Sci U S A 101: 9780-9785, 2004). These two methods provide a powerful complementary system to investigate chromosome structure inside living cells.

Measuring In Vivo Supercoil Dynamics and Transcription Elongation Rates in Bacterial Chromosomes.

DNA gyrase is the only topoisomerase that can catalytically introduce negative supercoils into covalently closed DNA. The enzyme plays a critical role in many phases of DNA biochemistry. There are only a few methods that allow one to measure supercoiling in chromosomal DNA and analyze the role of gyrase in transcription and its interaction with the other three bacterial topoisomerases. Here, we provide molecular tools for measuring supercoil density in the chromosome and for connecting the dots between transcription and DNA topology.

Efficient, ultra-high-affinity chromatography in a one-step purification of complex proteins.

Protein purification is an essential primary step in numerous biological studies. It is particularly significant for the rapidly emerging high-throughput fields, such as proteomics, interactomics, and drug discovery. Moreover, purifications for structural and industrial applications should meet the requirement of high yield, high purity, and high activity (HHH). It is, therefore, highly desirable to have an efficient purification system with a potential to meet the HHH benchmark in a single step. Here, we report a chromatographic technology based on the ultra-high-affinity (Kd ∼ 10-14-10-17 M) complex between the Colicin E7 DNase (CE7) and its inhibitor, Immunity protein 7 (Im7). For this application, we mutated CE7 to create a CL7 tag, which retained the full binding affinity to Im7 but was inactivated as a DNase. To achieve high capacity, we developed a protocol for a large-scale production and highly specific immobilization of Im7 to a solid support. We demonstrated its utility with one-step HHH purification of a wide range of traditionally challenging biological molecules, including eukaryotic, membrane, toxic, and multisubunit DNA/RNA-binding proteins. The system is simple, reusable, and also applicable to pulldown and kinetic activity/binding assays.

Enhancing OSCE preparedness with video exemplars in undergraduate nursing students. A mixed method study.

BACKGROUND: Objective structured clinical examinations (OSCEs) are designed to assess clinical skill performance and competency of students in preparation for 'real world' clinical responsibilities. OSCEs are commonly used in health professional education and are typically associated with high levels of student anxiety, which may present a significant barrier to performance. Students, including nursing students, have identified that flexible access to exemplar OSCEs might reduce their anxiety and enable them to better prepare for such examinations. AIM: To implement and evaluate an innovative approach to preparing students for OSCEs in an undergraduate (registration) acute care nursing course. METHOD: A set of digitized OSCE exemplars were prepared and embedded in the University-based course website as part of usual course learning activities. Use of the exemplars was monitored, pre and post OSCE surveys were conducted, and qualitative data were collected to evaluate the approach. OSCE grades were also examined. FINDINGS: The online OSCE exemplars increased self-rated student confidence, knowledge, and capacity to prepare and provided clarity around assessment expectations. OSCE exemplars were accessed frequently and positively received; but did not impact on performance. CONCLUSION: Video exemplars aid student preparation for OSCEs, providing a flexible, innovative and clear example of the assessment process. Video exemplars improved self-rated student confidence and understanding of performance expectations, leading to increased engagement and reduced anxiety when preparing for the OSCE, but not overall OSCE performance. Such OSCE exemplars could be used to increase staff capacity and improve the quality of the student learning experience.

Effect of Treatment With Tabalumab, a B Cell-Activating Factor Inhibitor, on Highly Sensitized Patients With End-Stage Renal Disease Awaiting Transplantation.

B cell-activation factor (BAFF) is critical for B cell maturation. Inhibition of BAFF represents an appealing target for desensitization of sensitized end-stage renal disease (ESRD) patients. We conducted a Phase 2a, single-arm, open-label exploratory study investigating the effect of tabalumab (BAFF inhibitor) in patients with ESRD and calculated panel reactive antibodies (cPRAs) >50%. The treatment period duration was 24 weeks. Eighteen patients received tabalumab, at doses of 240-mg subcutaneous (SC) at Week 0 followed by 120-mg SC monthly for 5 additional months. Patients were followed for an additional 52 weeks. Immunopharmacologic effects were characterized through analysis of blood for HLA antibodies, BAFF concentrations, immunoglobulins, T and B cell subsets, as well as pre- and posttreatment tonsil and bone marrow biopsies. Significant reductions in cPRAs were observed at Weeks 16 (p = 0.043) and 36 (p = 0.004); however, absolute reductions were small (<5%). Expected pharmacologic changes in B cell subsets and immunoglobulin reductions were observed. Two tabalumab-related serious adverse events occurred (pneumonia, worsening of peripheral neuropathy), while the most common other adverse events were injection-site pain and hypotension. Three patients received matched deceased donor transplants during follow-up. Treatment with a BAFF inhibitor resulted in statistically significant, but not clinically meaningful reduction in the cPRA from baseline (NCT01200290, Clinicaltrials.gov).

Species-specific supercoil dynamics of the bacterial nucleoid.

Bacteria organize DNA into self-adherent conglomerates called nucleoids that are replicated, transcribed, and partitioned within the cytoplasm during growth and cell division. Three classes of proteins help condense nucleoids: (1) DNA gyrase generates diffusible negative supercoils that help compact DNA into a dynamic interwound and multiply branched structure; (2) RNA polymerase and abundant small basic nucleoid-associated proteins (NAPs) create constrained supercoils by binding, bending, and forming cooperative protein-DNA complexes; (3) a multi-protein DNA condensin organizes chromosome structure to assist sister chromosome segregation after replication. Most bacteria have four topoisomerases that participate in DNA dynamics during replication and transcription. Gyrase and topoisomerase I (Topo I) are intimately involved in transcription; Topo III and Topo IV play critical roles in decatenating and unknotting DNA during and immediately after replication. RNA polymerase generates positive (+) supercoils downstream and negative (-) supercoils upstream of highly transcribed operons. Supercoil levels vary under fast versus slow growth conditions, but what surprises many investigators is that it also varies significantly between different bacterial species. The MukFEB condensin is dispensable in the high supercoil density (σ) organism Escherichia coli but is essential in Salmonella spp. which has 15 % fewer supercoils. These observations raise two questions: (1) How do different species regulate supercoil density? (2) Why do closely related species evolve different optimal supercoil levels? Control of supercoil density in E. coli and Salmonella is largely determined by differences encoded within the gyrase subunits. Supercoil differences may arise to minimalize toxicity of mobile DNA elements in the genome.

Oxfordshire Women and Their Children's Health (OxWATCH): protocol for a prospective cohort feasibility study.

INTRODUCTION: Some specific pregnancy disorders are known to be associated with increased incidence of long-term maternal ill health (eg, gestational diabetes with late onset type 2 diabetes; pre-eclampsia with arterial disease). To what degree these later health conditions are a consequence of the woman's constitution prior to pregnancy rather than pregnancy itself triggering changes in a woman's health is unknown. Additionally, there is little prospective evidence for the impact of pre-pregnancy risk factors on the outcome of pregnancy. To understand the importance of pre-pregnancy health requires the recruitment of women into a long-term cohort study before their first successful pregnancy. The aim of this feasibility study is to test recruitment procedures and acceptability of participation to inform the planning of a future large-scale cohort study. METHODS: The prospective cohort feasibility study will recruit nulliparous women aged 18-40 years. Women will be asked to complete a questionnaire to assess the acceptability of our recruitment and data collection procedures. Baseline biophysical, genetic, socioeconomic, behavioural and psychological assessments will be conducted and samples of blood, urine, saliva and DNA will be collected. Recruitment feasibility and retention rates will be assessed. Women who become pregnant will be recalled for pregnancy and postpregnancy assessments. ETHICS AND DISSEMINATION: The study protocol was approved by South Central Portsmouth REC (Ref: 12/SC/0492). The findings from the study will be disseminated through peer reviewed journals, national and international conference presentations and public events. TRIAL REGISTRATION NUMBER: http://www.clinicaltrials.gov; NCT02419898.

Topological Behavior of Plasmid DNA.

The discovery of the B-form structure of DNA by Watson and Crick led to an explosion of research on nucleic acids in the fields of biochemistry, biophysics, and genetics. Powerful techniques were developed to reveal a myriad of different structural conformations that change B-DNA as it is transcribed, replicated, and recombined and as sister chromosomes are moved into new daughter cell compartments during cell division. This article links the original discoveries of superhelical structure and molecular topology to non-B form DNA structure and contemporary biochemical and biophysical techniques. The emphasis is on the power of plasmids for studying DNA structure and function. The conditions that trigger the formation of alternative DNA structures such as left-handed Z-DNA, inter- and intra-molecular triplexes, triple-stranded DNA, and linked catenanes and hemicatenanes are explained. The DNA dynamics and topological issues are detailed for stalled replication forks and for torsional and structural changes on DNA in front of and behind a transcription complex and a replisome. The complex and interconnected roles of topoisomerases and abundant small nucleoid association proteins are explained. And methods are described for comparing in vivo and in vitro reactions to probe and understand the temporal pathways of DNA and chromosome chemistry that occur inside living cells.

Coping Styles, Pain Expressiveness, and Implicit Theories of Chronic Pain.

Whereas some individuals use active coping strategies and are able to adaptively cope with their pain, others use passive strategies and catastrophic appraisals, which are often associated with increased displays of pain behavior and negative pain-related outcomes. To investigate attribution-based implicit theories as a potential underlying mechanism that might affect coping success, we hypothesized that pain patients with an incremental implicit theory of pain (i.e., view pain as malleable) would have more active coping strategies, lower levels of pain expressiveness, and better pain-related outcomes than those with an entity implicit theory of pain (i.e., view pain as nonmalleable). Patients with chronic back pain undergoing a functional assessment completed a variety of self-report measures and participated in a pain-inducing physiotherapy procedure. The results revealed those with an incremental theory of pain used more active coping strategies, displayed less pain behavior, and reported better pain-related outcomes (e.g., lower levels of depression) than individuals with an entity theory of pain. The findings suggest implicit theories of pain may represent an underlying social-cognitive mechanism linked to important coping, emotional, and expressive reactions to chronic pain. Identifying such a mechanism may provide valuable information for the assessment and treatment of chronic pain.