Exceptionally long-lived nuclear RNAs.

RNA labeled in young mice is detected 2 years later in adult mouse brains.

Single-molecule analysis of solvent-responsive mechanically interlocked ring polymers and the effects of nanoconfinement from coarse-grained simulations.

In this study, we simulate mechanically interlocked semiflexible ring polymers inspired by the minicircles of kinetoplast DNA (kDNA) networks. Using coarse-grained molecular dynamics simulations, we investigate the impact of molecular topological linkage and nanoconfinement on the conformational properties of two- and three-ring polymer systems in varying solvent qualities. Under good-quality solvents, for two-ring systems, a higher number of crossing points lead to a more internally constrained structure, reducing their mean radius of gyration. In contrast, three-ring systems, which all had the same crossing number, exhibited more similar sizes. In unfavorable solvents, structures collapse, forming compact configurations with increased contacts. The morphological diversity of structures primarily arises from topological linkage rather than the number of rings. In three-ring systems with different topological conformations, structural uniformity varies based on link types. Extreme confinement induces isotropic and extended conformations for catenated polymers, aligning with experimental results for kDNA networks and influencing the crossing number and overall shape. Finally, the flat-to-collapse transition in extreme confinement occurs earlier (at relatively better solvent conditions) compared to non-confined systems. This study offers valuable insights into the conformational behavior of mechanically interlocked ring polymers, highlighting challenges in extrapolating single-molecule analyses to larger networks such as kDNA.

Is proton beam therapy always better than photon irradiation? Lessons from two cases.

Proton beam therapy (PBT) is increasingly used to treat cancers, especially in the paediatric and adolescent and young adult (AYA) population. As PBT becomes more accessible, determining when PBT should be used instead of photon irradiation can be difficult. There is a need to balance patient, tumour and treatment factors when making this decision. Comparing the dosimetry between these two modalities plays an important role in this process. PBT can reduce low to intermediate doses to organs at risk (OAR), but photon irradiation has its dosimetric advantages. We present two cases with brain tumours, one paediatric and one AYA, in which treatment plan comparison between photons and protons showed dosimetric advantages of photon irradiation. The first case was an 18-month-old child diagnosed with posterior fossa ependymoma requiring adjuvant radiotherapy. Photon irradiation using volumetric modulated arc therapy (VMAT) had lower doses to the hippocampi but higher doses to the pituitary gland. The second case was a 21-year-old with an optic pathway glioma. There was better sparing of the critical optic structures and pituitary gland using fractionated stereotactic radiation therapy over PBT. The dosimetric advantages of photon irradiation over PBT have been demonstrated in these cases. This highlights the role of proton-to-photon comparative treatment planning to better understand which patients might benefit from photon irradiation versus PBT.

Developing a comparative photon-proton planning service in Victoria: the experience at Peter MacCallum Cancer Centre.

Proton-beam therapy (PBT) is a cutting-edge radiation therapy modality that is currently not available in Australia. Comparative photon-proton (CPP) planning is required for the medical treatment overseas programme (MTOP) and will be required for access to PBT in Australia in the future. Comparative planning brings professional development benefits to all members of the radiation therapy team. This service was also created to support future proposals for a PBT facility in Victoria. We report our experience developing an in-house CPP service at Peter MacCallum Cancer Centre. A set of resources to support CPP planning was established. Training of relevant staff was undertaken after which an in-house training programme was developed. A standard protocol for PBT planning parameters was established. All CPP plans were reviewed. Future goals for the CPP planning programme were described. In total, 62 cases were comparatively planned over 54 months. Of these, 60% were paediatric cases, 14% were adolescents and young adults (15-25 years) and 26% were adults. The vast majority (over 75%) of patients comparatively planned required irradiation to the central nervous system including brain and cranio-spinal irradiation. A variety of proton plans were reviewed by international PBT experts to confirm their deliverability. Our team at Peter MacCallum Cancer Centre has gained significant experience in CPP planning and will continue to develop this further. Local expertise will help support decentralisation of patient selection for proton treatments in the near future and the PBT business case in Victoria.

Early-career general practitioners' antibiotic prescribing for acute infections: a systematic review.

BACKGROUND: Antimicrobial resistance is a worldwide threat, exacerbated by inappropriate prescribing. Most antibiotic prescribing occurs in primary care. Early-career GPs are important for the future of antibiotic prescribing and curbing antimicrobial resistance. OBJECTIVES: To determine antibiotic prescribing patterns by early-career GPs for common acute infections. METHODS: A systematic literature search was conducted using PubMed, Embase and Scopus. Two authors independently screened abstracts and full texts for inclusion. Primary outcomes were antibiotic prescribing rates for common acute infections by GPs with experience of 10 years or less. Secondary outcomes were any associations between working experience and antibiotic prescribing. RESULTS: Of 1483 records retrieved, we identified 41 relevant studies. Early-career GPs were less likely to prescribe antibiotics compared with their more experienced colleagues (OR range 0.23-0.67). Their antibiotic prescribing rates for 'any respiratory condition' ranged from 14.6% to 52%, and for upper respiratory tract infections from 13.5% to 33%. Prescribing for acute bronchitis varied by country, from 15.9% in Sweden to 26% in the USA and 63%-73% in Australia. Condition-specific data for all other included acute infections, such as sinusitis and acute otitis media, were limited to the Australian context. CONCLUSIONS: Early-career GPs prescribe fewer antibiotics than later-career GPs. However, there are still significant improvements to be made for common acute conditions, as their prescribing is higher than recommended benchmarks. Addressing antimicrobial resistance requires an ongoing worldwide effort and early-career GPs should be the target for long-term change.

Differences in Alu vs L1-rich chromosome bands underpin architectural reorganization of the inactive-X chromosome and SAHFs.

The linear DNA sequence of mammalian chromosomes is organized in large blocks of DNA with similar sequence properties, producing a pattern of dark and light staining bands on mitotic chromosomes. Cytogenetic banding is essentially invariant between people and cell-types and thus may be assumed unrelated to genome regulation. We investigate whether large blocks of Alu-rich R-bands and L1-rich G-bands provide a framework upon which functional genome architecture is built. We examine two models of large-scale chromatin condensation: X-chromosome inactivation and formation of senescence-associated heterochromatin foci (SAHFs). XIST RNA triggers gene silencing but also formation of the condensed Barr Body (BB), thought to reflect cumulative gene silencing. However, we find Alu-rich regions are depleted from the L1-rich BB, supporting it is a dense core but not the entire chromosome. Alu-rich bands are also gene-rich, affirming our earlier findings that genes localize at the outer periphery of the BB. SAHFs similarly form within each territory by coalescence of syntenic L1 regions depleted for highly Alu-rich DNA. Analysis of senescent cell Hi-C data also shows large contiguous blocks of G-band and R-band DNA remodel as a segmental unit. Entire dark-bands gain distal intrachromosomal interactions as L1-rich regions form the SAHF. Most striking is that sharp Alu peaks within R-bands resist these changes in condensation. We further show that Chr19, which is exceptionally Alu rich, fails to form a SAHF. Collective results show regulation of genome architecture corresponding to large blocks of DNA and demonstrate resistance of segments with high Alu to chromosome condensation.

Additive manufacturing of patient specific bolus for radiotherapy: large scale production and quality assurance.

Bolus is commonly used to improve dose distributions in radiotherapy in particular if dose to skin must be optimised such as in breast or head and neck cancer. We are documenting four years of experience with 3D printed bolus at a large cancer centre. In addition to this we review the quality assurance (QA) program developed to support it. More than 2000 boluses were produced between Nov 2018 and Feb 2023 using fused deposition modelling (FDM) printing with polylactic acid (PLA) on up to five Raise 3D printers. Bolus is designed in the radiotherapy treatment planning system (Varian Eclipse), exported to an STL file followed by pre-processing. After checking each bolus with CT scanning initially we now produce standard quality control (QC) wedges every month and whenever a major change in printing processes occurs. A database records every bolus printed and manufacturing details. It takes about 3 days from designing the bolus in the planning system to delivering it to treatment. A 'premium' PLA material (Spidermaker) was found to be best in terms of homogeneity and CT number consistency (80 HU +/- 8HU). Most boluses were produced for photon beams (93.6%) with the rest used for electrons. We process about 120 kg of PLA per year with a typical bolus weighing less than 500 g and the majority of boluses 5 mm thick. Print times are proportional to bolus weight with about 24 h required for 500 g material deposited. 3D printing using FDM produces smooth and reproducible boluses. Quality control is essential but can be streamlined.

Describing the acceptability and use of an opioid stewardship self-assessment tool in real-world settings.

BACKGROUND: The Stewardship Framework (Framework) was developed by an expert clinician group and was designed to provide a mechanism for continuous monitoring of improvement in opioid prescribing in acute hospitals. The aim of this study was to modify the Framework into an Opioid Stewardship Self-Assessment Tool (Self-Assessment Tool), and pilot test the acceptability and its use in a variety of acute hospital settings. METHODS: The Framework was converted into the Self-Assessment Tool to allow hospitals to undertake a gap analysis of their current opioid stewardship activities. To participate hospitals were required to establish a small team and complete the Self-Assessment Tool. Participating sites were recruited using purposive sampling. Responses were tabulated and coded to enable assessment. 'Acceptability' was defined as the completion of the Self-Assessment Tool (response rate, proportion of questions answered) and responder feedback relating to its content. The use of the Tool was categorised based on the level of detail of responses. RESULTS: Nineteen of the 20 facilities approached, agreed to participate. The 16 sites which established a small team to facilitate survey completion are included in the final analysis. The overall response rate was 96 % (413/432) for the (27 survey questions across 16 participating sites), 4 % (19/432) of questions were left unanswered or were not interpretable by the study team. Opportunities were identified to enhance the use of the Self-Assessment Tool, particularly to support its potential to assist reflection and planning of local strategies. CONCLUSION: This study demonstrated that the Self-Assessment Tool was an acceptable method of assessing a facility's opioid stewardship capabilities in a real-world setting. The next iteration will be modified using the insights on how the Tool was used by study participants.

Diagnosis and management of acute infections during telehealth consultations in Australian general practice: a qualitative study.

BACKGROUND: The use of telehealth has increased dramatically since the beginning of the COVID-19 pandemic. Little is known about how GPs manage acute infections during telehealth, and the potential impact on antimicrobial stewardship. AIM: To explore the experiences and perceptions of GP trainees' and supervisors' use of telehealth, and how it influences their management of acute infections. DESIGN & SETTING: Australian GP registrars (trainees) and supervisors were recruited via email through their training organisations. Semi-structured interviews with 18 participants were conducted between July and August 2022. METHOD: Interviews were transcribed verbatim and analysed using a reflexive thematic approach. RESULTS: We identified six overall themes. 1. Participants experienced impaired diagnostic capacity during telehealth consultations. 2. Attempts to improve diagnostic acuity included various methods, such as having patients self-examine. 3. The management of clinical uncertainty frequently entailed referring patients for in-person assessment, overinvestigating, or overtreating. 4. Antibiotic prescribing decisions during telehealth were informed by less information than were in-person consults, with varying impact. 5. Participants believed that other GPs improperly prescribed antibiotics during telehealth. 6. Supervisors believed that registrars hadn't developed the knowledge or skills to determine when conditions could be managed appropriately via telehealth. CONCLUSION: Telehealth has potential for reducing transmission of acute infections and increasing access to healthcare. However, the implications of GPs, especially less experienced GPs, making diagnoses with less certainty, and consequently compromising antimicrobial stewardship, are a concern. Patient self-assessment tools may improve outcomes of telehealth consultations for acute infections.

Reducing antibiotic prescribing in general practice in Australia: a cluster randomised controlled trial of a multimodal intervention.

BACKGROUND: The health and economic burden of antimicrobial resistance (in Australia is significant. Interventions that help guide and improve appropriate prescribing for acute respiratory tract infections in the community represent an opportunity to slow the spread of resistant bacteria. Clinicians who work in primary care are potentially the most influential health care professionals to address the problem of antimicrobial resistance, because this is where most antibiotics are prescribed. METHODS: A cluster randomised trial was conducted comparing two parallel groups of 27 urban general practices in Queensland, Australia: 13 intervention and 14 control practices, with 56 and 54 general practitioners (GPs), respectively. This study evaluated an integrated, multifaceted evidence-based package of interventions implemented over a 6-month period. The evaluation included quantitative and qualitative components, and an economic analysis. RESULTS: A multimodal package of interventions resulted in a reduction of 3.81 prescriptions per GP per month. This equates to 1280.16 prescriptions for the 56GPs in the intervention practices over the 6-month period. The cost per prescription avoided was A$148. The qualitative feedback showed that the interventions were well received by the GPs and did not impact on consultation time. Providing GPs with a choice of tools might enhance their uptake and support for antimicrobial stewardship in the community. CONCLUSIONS: A multimodal package of interventions to enhance rational prescribing of antibiotics is effective, feasible and acceptable in general practice. Investment in antimicrobial stewardship strategies in primary care may ultimately provide the important returns for public health into the future.

Implementing paediatric appropriate use criteria for endotracheal suction to reduce complications in mechanically ventilated children with respiratory infections.

BACKGROUND: Endotracheal suction is used to maintain endotracheal tube patency. There is limited guidance to inform clinical practice for children with respiratory infections. OBJECTIVE: The objective of this study was to determine whether implementation of a paediatric endotracheal suction appropriate use guideline Paediatric AirWay Suction (PAWS) is associated with an increased use of appropriate and decreased use of inappropriate suction interventions. METHODS: A mixed-method, pre-implementation-post-implementation study was conducted between September 2021 and April 2022. Suction episodes in mechanically ventilated children with a respiratory infection were eligible. Using a structured approach, we implemented the PAWS guideline in a single paediatric intensive care unit. Evaluation included clinical (e.g., suction intervention appropriateness), implementation (e.g., acceptability), and cost outcomes (implementation costs). Associations between implementation of the PAWS guideline and appropriateness of endotracheal suction intervention use were investigated using generalised linear models. RESULTS: Data from 439 eligible suctions were included in the analysis. Following PAWS implementation, inappropriate endotracheal tube intervention use reduced from 99% to 58%, an absolute reduction (AR) of 41% (95% confidence interval [CI]: 25%, 56%). Reductions were most notable for open suction systems (AR: 48%; 95% CI: 30%, 65%), 0.9% sodium chloride use (AR: 23%; 95% CI: 8%, 38%) and presuction and postsuction manual bagging (38%; 95% CI: 16%, 60%, and 86%; 95% CI: 73%, 99%), respectively. Clinicians perceived PAWS as acceptable and suitable for use. CONCLUSIONS: Implementation of endotracheal tube suction appropriate use guidelines in a mixed paediatric intensive care unit was associated with a large reduction in inappropriate suction intervention use in paediatric patients with respiratory infections.

Impact of Molecular-level Structural Disruption on Relaxation Dynamics of Polymers with End-on and Side-on Liquid Crystal Moieties.

In side-chain liquid crystal polymers (SCLCPs), short side chains are attached on a flexible polymer backbone, and each side chain can have a liquid crystal (LC) group attached at the final bead in either an end-on or a side-on configuration. SCLCPs with random sequences of end-on and side-on LC moieties exhibit nonmonotonic thermal behavior as a function of composition, with some mixed sequences having a lower isotropic to LC phase transition than either purely end-on or side-on configurations. The origin of this nonmonotonic thermal trend lies in the disruption of molecular-level positional ordering and alignment due to the different preferred types of ordering of the different LC attachment types. We compare coarse-grained molecular dynamics (MD) simulations and experiments on SCLCP systems with only one type of LC moiety and demonstrate qualitative agreement in the observed mesophases of end-on and side-on SCLCP systems. Specifically, end-on SCLCPs display a smectic B-like mesophase, with layers of polymer between LC layers, while side-on SCLCPs exhibit a quasi-hexagonal columnar structure of polymer and a nematic surrounding the LC mesophase. Detailed analysis of SCLCP systems with various compositions of these types of LC attachments via MD reveals structural disruption in systems with intermediate compositions. Simulation snapshots and anisotropy ratio measurements show how random SCLCP systems deviate from the expected behavior of prolate or oblate systems in terms of their conformation. This molecular disruption in random SCLCP systems, particularly with a high composition of side-on LC moieties, also significantly impacts the relaxation dynamics. Modifying the composition of the LC type of attachment (molecular structure) is a possible route to tuning both the phase behavior and mechanical response of these systems.

Metronidazole prescribing practices in Australian hospitals: Measuring guideline compliance and appropriateness to support antimicrobial stewardship.

BACKGROUND: Metronidazole is a commonly prescribed antimicrobial in Australian hospitals. Inappropriate use may increase risks to patient care, such as toxicities and antimicrobial resistance. To date, there is limited information on the quality of metronidazole prescriptions to inform antimicrobial stewardship and quality improvement initiatives. This study aims to describe the quality of metronidazole prescribing practices in Australian hospitals. METHODS: Retrospective data analysis of the Hospital National Antimicrobial Prescribing Survey (Hospital NAPS). Data were collected by auditors at each participating hospital using a standardised auditing tool. All data from 2013 to 2021 were de-identified and analysed descriptively. Variables included were antimicrobial prescribed, indication, guideline compliance and appropriateness. RESULTS: Metronidazole was the fifth most prescribed antimicrobial in the Hospital NAPS dataset (2013-2021), accounting for 5.7 % (n = 14,197) of all antimicrobial prescriptions (n = 250,863). The proportion of metronidazole prescriptions declined by 2 % from 2013 to 2021 (p < 0.001). The most common indications were surgical prophylaxis (15.3 %), diverticulitis (9.4 %), aspiration pneumonia (7.3 %). Over half (53.5 %) of metronidazole prescriptions were deemed compliant with prescribing guidelines and 67.8 % were deemed appropriate. These rates were comparatively lower than the overall results of all antimicrobials. The primary documented reason for inappropriateness was that the spectrum was too broad (34.2 %). Surgical prophylaxis had the lowest rates of guideline compliance (53.8 %) and appropriateness (54.3 %). CONCLUSIONS: Metronidazole remains widely used in Australian hospitals with suboptimal rates of guideline compliance and appropriateness. A noted area for improvement that we identified was using metronidazole when its spectrum was too broad, possibly when anaerobic therapy is unnecessary. With increasing international adoption of the Hospital NAPS programme, future comparative studies will be critical to identify global trends of antimicrobial prescribing quality. Antimicrobial stewardship (AMS) programmes have proven to be effective in improving prescribing quality and should be considered to specifically target improvements in metronidazole prescribing.

Surgical site infection prophylaxis: what have we learned and are we making progress?

PURPOSE OF REVIEW: This review aims to discuss the current state of surgical antimicrobial prophylaxis (SAP) evidence for surgical site infection prevention. Despite decades of research, knowledge gaps persist in identifying optimal SAP regimens. RECENT FINDINGS: Recent randomised controlled trials highlight ongoing heterogeneity in study design. Key new findings support the use of oral preoperative SAP for colorectal surgery and advise against the use of SAP for transperineal prostate biopsy. There is growing evidence for culture-based SAP over empiric use for transrectal prostate biopsy.Contentious issues remain regarding topical antimicrobials for cardiac procedures involving sternotomy, the necessity of SAP for wire lumpectomy and laparoscopic cholecystectomy for both mild or moderate acute cholecystitis. Procedures where SAP is not indicated, yet research is still being conducted on this topic include dental implants and clean orthopaedic procedures. SUMMARY: Research efforts continue with numerous trials published and registered to determine optimal SAP regimens. However, many efforts are suboptimal due to poor statistical design and redundant questions already answered by existing literature. To improve practice and influence surgeons prescribing behaviour future RCTs should be well powered, with large sample sizes across multiple sites, focusing on clinically relevant questions.

Ingroup Empathy, Help, and Blame After Anti-LGBT+ Hate Crime.

Crimes motivated by hatred toward a person's sexual orientation or gender identity typically cause greater physical and emotional harm than comparative crimes not motivated by hate. Compounding these impacts, hate crime victims receive less empathy, less support, and are blamed more for their victimization both by society in general and by criminal justice agencies. However, as hate crimes are the epitome of intergroup hostility, the crimes are also likely to engender an ingroup empathy bias in which fellow LGBT+ people provide greater empathy to hate crime victims, potentially motivating greater support and reducing victim blaming for these particularly marginalized victims. Across three studies, we examined LGBT+ participants' empathic reactions to hate crime victims, along with their willingness to help victims and blame victims. In the Pilot Study (N = 131) and Study 1 (N = 600), we cross-sectionally showed that indirect experiences of hate crimes predicted a stronger LGBT+ identity which, in turn, was associated with greater empathy that predicted greater willingness to help victims and blame the victim less. In Study 2 (N = 657), we experimentally manipulated the motivation of a crime (hate vs. non-hate) and the group membership of the victim (ingroup-LGBT+ vs. outgroup-heterosexual) and found that crimes that had one or more group elements (i.e., involved an ingroup member and/or was motivated by hate) elicited greater empathy that, in turn, increased the willingness to help the victim and reduced victim blaming. Together, the findings provide cogent evidence that LGBT+ communities respond to anti-LGBT+ hate crimes with overwhelming empathy, and this ingroup empathy bias motivates helping behaviors and reduces victim blame, thereby buffering the marginalizing consequences of hate crimes. Policy implications include acknowledging and harnessing the importance of shared identities when practitioners and criminal justice agencies respond to anti-LGBT+ hate crimes.

"Handing out non-prescribed antibiotics is storing up trouble for the next generation!" Unpacking multistakeholder views of drivers and potential solutions in Ethiopia.

BACKGROUND: Antibiotic resistance is a global health crisis, with inappropriate antibiotic use often being linked to non-prescribed antibiotic dispensing practices. This study aimed to examine the perspectives of multiple stakeholders on the drivers and potential solutions for non-prescribed antibiotic dispensing in Ethiopian community drug retail outlets (CDROs). Despite the prescription only use policies, the practice remains prevalent in Ethiopia. Many factors are thought to contribute to this issue, although little research is available for non-urban settings. METHODS: A phenomenological qualitative study was conducted. Pharmacy professionals (owners or employees) working in non-urban towns CDROs were selected through a simulated client study, which identified CDROs that had dispensed antibiotics without a prescription. Some high-level decision makers in the Ethiopian health system were also purposively selected. Interviews were conducted in-person and over the phone or via Zoom. The interview data were transcribed verbatim, translated to English, and thematically analysed. NVivo 12 software was used to assist with coding. RESULTS: CDRO pharmacy professionals (n = 18) and five decision makers were interviewed. Most professionals (61%) were pharmacists working in drug stores, with one to 11 years of work experience. Several contributing factors were identified at the level of patients, CDRO staff, and the healthcare system. These included economic interests, inadequate knowledge and inappropriate attitudes about antibiotic use or supply, and issues within the healthcare system included inaccessibility and insufficient capacity, absence of or a weak enforcement of prescription-only regulations or service supervision. Additionally, patient-related factors included a lack of knowledge and inappropriate attitudes about antibiotics use and their supply, previous successful treatment experience and a culture of seeking out antibiotics. CONCLUSIONS: A complex set of modifiable factors related to patients, CDRO staff and healthcare system were identified that contribute to the non-prescribed supply of antibiotics. Due to this complexity, a single solution will not resolve the issues. Therefore, a range of multifaceted solutions have been suggested, including stricter regulation, increasing availability and accessibility of healthcare services, collaboration, and local consensus-building among CDROs, regular training for CDRO staff, and using community social events to educate the public about responsible use of antibiotics.

Improving difficult peripheral intravenous access requires thought, training and technology (DART3): a stepped-wedge, cluster randomised controlled trial protocol.

BACKGROUND: Peripheral intravenous catheters (PIVCs) are the most used invasive medical device in healthcare. Yet around half of insertion attempts are unsuccessful leading to delayed medical treatments and patient discomfort of harm. Ultrasound-guided PIVC (USGPIVC) insertion is an evidence-based intervention shown to improve insertion success especially in patients with Difficult IntraVenous Access (BMC Health Serv Res 22:220, 2022), however the implementation in some healthcare settings remains suboptimal. This study aims to co-design interventions that optimise ultrasound guided PIVC insertion in patients with DIVA, implement and evaluate these initiatives and develop scale up activities. METHODS: A stepped-wedge cluster randomized controlled trial will be conducted in three hospitals (two adult, one paediatric) in Queensland, Australia. The intervention will be rolled out across 12 distinct clusters (four per hospital). Intervention development will be guided by Michie's Behavior Change Wheel with the aim to increase local staff capability, opportunity, and motivation for appropriate, sustainable adoption of USGPIVC insertion. Eligible clusters include all wards or departments where > 10 PIVCs/week are typically inserted. All clusters will commence in the control (baseline) phase, then, one cluster per hospital will step up every two months, as feasible, to the implementation phase, where the intervention will be rolled out. Implementation strategies are tailored for each hospital by local investigators and advisory groups, through context assessments, staff surveys, and stakeholder interviews and informed by extensive consumer interviews and consultation. Outcome measures align with the RE-AIM framework including clinical-effectiveness outcomes (e.g., first-time PIVC insertion success for DIVA patients [primary outcome], number of insertion attempts); implementation outcomes (e.g., intervention fidelity, readiness assessment) and cost effectiveness outcomes. The Consolidated Framework for Implementation Research framework will be used to report the intervention as it was implemented; how people participated in and responded to the intervention; contextual influences and how the theory underpinning the intervention was realised and delivered at each site. A sustainability assessment will be undertaken at three- and six-months post intervention. DISCUSSION: Study findings will help define systematic solutions to implement DIVA identification and escalation tools aiming to address consumer dissatisfaction with current PIVC insertion practices. Such actionable knowledge is critical for implementation of scale-up activities. TRIAL REGISTRATION: Prospectively registered (Australian and New Zealand Clinical Trials Registry; ACTRN12621001497897).

Coarse-grained modeling of polymers with end-on and side-on liquid crystal moieties: Effect of architecture.

Mesogens, which are typically stiff rodlike or disklike molecules, are able to self-organize into liquid crystal (LC) phases in a certain temperature range. Such mesogens, or LC groups, can be attached to polymer chains in various configurations including within the backbone (main-chain LC polymers) or at the ends of side-chains attached to the backbone in an end-on or side-on configuration (side-chain LC polymers or SCLCPs), which can display synergistic properties arising from both their LC and polymeric character. At lower temperatures, chain conformations may be significantly altered due to the mesoscale LC ordering; thus, when heated from the LC ordered state through the LC to isotropic phase transition, the chains return from a more stretched to a more random coil conformation. This can cause macroscopic shape changes, which depend significantly on the type of LC attachment and other architectural properties of the polymer. Here, to study the structure-property relationships for SCLCPs with a range of different architectures, we develop a coarse-grained model that includes torsional potentials along with LC interactions of a Gay-Berne form. We create systems of different side-chain lengths, chain stiffnesses, and LC attachment types and track their structural properties as a function of temperature. Our modeled systems indeed form a variety of well-organized mesophase structures at low temperatures, and we predict higher LC-to-isotropic transition temperatures for the end-on side-chain systems than for analogous side-on side-chain systems. Understanding these phase transitions and their dependence on polymer architecture can be useful in designing materials with reversible and controllable deformations.

Early chromosome condensation by XIST builds A-repeat RNA density that facilitates gene silencing.

XIST RNA triggers chromosome-wide gene silencing and condenses an active chromosome into a Barr body. Here, we use inducible human XIST to examine early steps in the process, showing that XIST modifies cytoarchitecture before widespread gene silencing. In just 2-4 h, barely visible transcripts populate the large "sparse zone" surrounding the smaller "dense zone"; importantly, density zones exhibit different chromatin impacts. Sparse transcripts immediately trigger immunofluorescence for H2AK119ub and CIZ1, a matrix protein. H3K27me3 appears hours later in the dense zone, which enlarges with chromosome condensation. Genes examined are silenced after compaction of the RNA/DNA territory. Insights into this come from the findings that the A-repeat alone can silence genes and rapidly, but only where dense RNA supports sustained histone deacetylation. We propose that sparse XIST RNA quickly impacts architectural elements to condense the largely non-coding chromosome, coalescing RNA density that facilitates an unstable, A-repeat-dependent step required for gene silencing.