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"Carr, Peter"
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Flushing peripheral intravenous catheters: A scoping review
Peripheral intravascular catheters (PIVCs) are indispensable vascular access devices in healthcare, facilitating the administration of intravenous therapies. Despite their vital role, PIVCs are frequently associated with complications such as occlusion, infection, and thrombosis, which contribute to catheter failure. Flushing catheters is one of the most common practices during PIVC maintenance, as it cleans the internal catheter lumen, ensuring patency and reducing the risk of complications. However, inconsistencies in flushing practices such as flushing technique, volume to use, frequency, and methods highlight a lack of consensus in the literature and clinical guidelines.
Following JBI scoping review methodology, a comprehensive search was conducted across PubMed, Embase, Scopus, CINAHL, and grey literature sources. Studies were included if they focused on PIVC flushing techniques, flushing methods (speed, volume, frequencies, interval), or their impact on catheter-related outcomes. Data were charted using the PAGER (Patterns, Advances, Gaps, Evidence, Research recommendations) framework.
Of the 4539 initial studies retrieved, 39 met the inclusion criteria. Key findings reveal significant variability in flushing practices, with no consensus on optimal technique (continuous, intermittent, or pulsatile), volume (commonly 5-10 mL), or frequency (ranging from every 6 hours to every 24 hours). Pulsatile flushing showed promise in laboratory studies for reducing bacterial colonization and maintaining catheter patency but lacked consistent clinical evidence. Fluid dynamics studies on the flushing process suggested potential endothelial injury from high flushing velocities and the need for standardized practices.
While some studies have investigated PIVC flushing, the existing research remains inconsistent, with a lack of clinical trials and mechanistic evidence on how flushing affects catheter patency, endothelial damage, and complication prevention.
Journal Article
The further adventures of Red Sonja
\"She lived in a savage world in an uncivilized age - a world ruled by men and governed by the sword. The[y] called her... Red Sonja - for her flame red hair, and for the smoldering fire of her pride, which gave her sword-arm a strength that few men could match, and none had ever defeated. This collection contains a variety of issues from the original Marvel Comics series 'The Savage Sword of Conan,' as well as Sonja Tales from 'Kull and the Barbarians,' with each page re-mastered for this volume. Also included is a gallery of pin-ups by Frank Thorne, Howard Chaykin, and more. These tales are where it all began, and set the stage for the current Red Sonja series from Dynamite Entertainment\"--back cover.
Book
Genomically Recoded Organisms Expand Biological Functions
We describe the construction and characterization of a genomically recoded organism (GRO). We replaced all known UAG stop codons in Escherichia coli MG1655 with synonymous UAA codons, which permitted the deletion of release factor 1 and reassignment of UAG translation function. This GRO exhibited improved properties for incorporation of nonstandard amino acids that expand the chemical diversity of proteins in vivo. The GRO also exhibited increased resistance to T7 bacteriophage, demonstrating that new genetic codes could enable increased viral resistance.
Journal Article
Inter- and Intra-Patient Heterogeneity of Response and Progression to Targeted Therapy in Metastatic Melanoma
MAPK inhibitors (MAPKi) are active in BRAF-mutant metastatic melanoma patients, but the extent of response and progression-free survival (PFS) is variable, and complete responses are rare. We sought to examine the patterns of response and progression in patients treated with targeted therapy.
MAPKi-naïve patients treated with combined dabrafenib and trametinib had all metastases ≥5 mm (lymph nodes ≥15 mm in short axis) visible on computed tomography measured at baseline and throughout treatment.
24 patients had 135 measured metastases (median 4.5/patient, median diameter 16 mm). Time to best response (median 5.5 mo, range 1.7-20.1 mo), and the degree of best response (median -70%, range +9 to -100%) varied amongst patients. 17% of patients achieved complete response (CR), whereas 53% of metastases underwent CR, including 42% ≥10 mm. Metastases that underwent CR were smaller than non-CR metastases (median 11 vs 20 mm, P<0.001). PFS was variable among patients (median 8.2 mo, range 2.6-18.3 mo), and 50% of patients had disease progression in new metastases only. Only 1% (1/71) of CR-metastases subsequently progressed. Twelve-month overall survival was poorer in those with a more heterogeneous initial response to therapy than less heterogeneous (67% vs 93%, P = 0.009).
Melanoma response and progression with MAPKi displays marked inter- and intra-patient heterogeneity. Most metastases undergo complete response, yet only a small proportion of patients achieve an overall complete response. Similarly, disease progression often occurs only in a subset of the tumor burden, and often in new metastases alone. Clinical heterogeneity, likely reflecting molecular heterogeneity, remains a barrier to the effective treatment of melanoma patients.
Journal Article
Derivation of a clinical decision-making aid to improve the insertion of clinically indicated peripheral intravenous catheters and promote vessel health preservation. An observational study
It is well established that the idle peripheral intravenous catheter (PIVC) provides no therapeutic value and is a clinical, economic and above all, patient concern. This study aimed to develop a decision aid to assist with clinical decision making to promote clinically indicated peripheral intravenous catheter (CIPIVC) insertion in the emergency department (ED) setting. Providing evidence for a uniform process could assist clinicians in a decision-making process for PIVC insertion. This could enable patients receive appropriate vascular access healthcare.
We performed a secondary analysis of data from a multicentre cohort of emergency department clinicians who performed PIVC insertion. We defined CIPIVC a priori as one used for a specific clinical treatment and or procedure such as prescribed intravenous (IV) fluids; prescribed IV medication; or IV contrast (for computerized tomography scans). We sought to refute or validate an assumption if the clinician performing or requesting the insertion decided the patient was >80% likely to need a PIVC. Using logistic regression, we derived a decision aid for CIPIVCs.
In 817 patients undergoing PIVC insertion, we observed 68% of these to be CIPIVCs. Admitted patients were significantly more likely to have a CIPIVC, Odds Ratio (OR) = 3.05, 95% confidence interval (CI) = 2.17-4.30, p = <0.0001. Before insertion, patients who definitely needed IV fluids/medicines OR = 3.30, 95% CI = 2.02-5.39, p = <0.0001 and who definitely needed a contrast scan OR = 3.04, 95% CI = 1.15-8.03, p = 0.0250 were significantly more likely to have a device inserted for a clinical indication. Patients who presented with an existing vascular access device were more likely to have a new CIPIVC inserted for use OR = 4.35, 95% CI = 1.58-11.95, p = 0.0043. The clinician's pre-procedural judgment of the likelihood of therapeutic use >80% was independently associated with CIPIVC; OR 3.16, 95% CI = 2.06-4.87, p<0.0001. The area under the receiver operating characteristic curve was 0.81, and at the best cut-off, the model had a specificity of 0.81, sensitivity of 0.71, a positive predictive value of 0.89 and negative predictive value of 0.57.
Using the derived decision aid, clinicians could ask:- \"Does this patient need A-PIVC?\" Clinicians can decide to insert a CIPIVCs when: (i) Admission to hospital is anticipated and when (ii) a Procedure requires a PIVC, e.g., computerised tomography scans and where an existing suitable vascular access device is not present and or; (iii) there is an indication for IV fluids and or medicines that cannot be tolerated enterally and are suitable for dilution in peripheral veins; and, (iv) the Clinician's perceived likelihood of use is greater than 80%.
Journal Article
Enabling Microfluidics: from Clean Rooms to Makerspaces
The traditional requirement for clean rooms and specialized skills has inhibited many biologists from pursuing new microfluidic innovations. Makerspaces provide a growing alternative to clean rooms: they provide low-cost access to fabrication equipment such as laser cutters, plotter cutters, and 3D printers; use commercially available materials; and attract a diverse community of product designers. This Opinion discusses the materials, tools, and building methodologies particularly suited for developing novel microfluidic devices in these spaces, with insight into biological applications and leveraging the maker community. The lower barrier to access of makerspaces ameliorates the otherwise poor accessibility and scalability of microfluidic prototyping.
The use of simple tools and materials to manufacture microfluidic devices provides an opportunity for makerspaces to serve as a hotbed for microfluidic device development.
Materials such as plastic, adhesive, and paper, along with tools such as plotter/laser cutters and 3D printers, enable building integrated microfluidic systems that are more easily translated to large-scale manufacturing.
Makerspaces provide low-cost access to prototyping tools and access to technically diverse human capital, and they enable those without advanced skills to participate in microfluidic device development.
Journal Article
Engineered Resistance to Tobamoviruses
Tobacco mosaic virus (TMV) was the first virus to be studied in detail and, for many years, TMV and other tobamoviruses, particularly tomato mosaic virus (ToMV) and tobamoviruses infecting pepper (Capsicum spp.), were serious crop pathogens. By the end of the twentieth and for the first decade of the twenty-first century, tobamoviruses were under some degree of control due to introgression of resistance genes into commercial tomato and pepper lines. However, tobamoviruses remained important models for molecular biology, biotechnology and bio-nanotechnology. Recently, tobamoviruses have again become serious crop pathogens due to the advent of tomato brown rugose fruit virus, which overcomes tomato resistance against TMV and ToMV, and the slow but apparently inexorable worldwide spread of cucumber green mottle mosaic virus, which threatens all cucurbit crops. This review discusses a range of mainly molecular biology-based approaches for protecting crops against tobamoviruses. These include cross-protection (using mild tobamovirus strains to ‘immunize’ plants against severe strains), expressing viral gene products in transgenic plants to inhibit the viral infection cycle, inducing RNA silencing against tobamoviruses by expressing virus-derived RNA sequences in planta or by direct application of double-stranded RNA molecules to non-engineered plants, gene editing of host susceptibility factors, and the transfer and optimization of natural resistance genes.
Journal Article
Genome engineering
For more than 50 years, those engineering genetic material have pursued increasingly challenging targets. During that time, the tools and resources available to the genetic engineer have grown to encompass new extremes of both scale and precision, opening up new opportunities in genome engineering. Today, our capacity to generate larger
de novo
assemblies of DNA is increasing at a rapid pace (with concomitant decreases in manufacturing cost). We are also witnessing potent demonstrations of the power of merging randomness and selection with engineering approaches targeting large numbers of specific sites within genomes. These developments promise genetic engineering with unprecedented levels of design originality and offer new avenues to expand both our understanding of the biological world and the diversity of applications for societal benefit.
Journal Article
Programming cells by multiplex genome engineering and accelerated evolution
Generating genomic diversity
Genomic diversity is difficult to generate in the laboratory in an efficient way. A new technique called MAGE (multiplex automated genome engineering), described here, simultaneously targets many locations on the chromosome for modification in a single cell or across a population of cells, thereby producing combinatorial genomic diversity. This is an automated and efficient approach that expedites the design and evolution of organisms with new and improved properties.
Genomic diversity is difficult to generate in the laboratory in an efficient way. Here, multiplex automated genome engineering (MAGE) is described for large-scale programming and evolution of cells. It is an automated and efficient approach that expedites the design and evolution of organisms with new and improved properties.
The breadth of genomic diversity found among organisms in nature allows populations to adapt to diverse environments
1
,
2
. However, genomic diversity is difficult to generate in the laboratory and new phenotypes do not easily arise on practical timescales
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. Although
in vitro
and directed evolution methods
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,
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,
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,
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,
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,
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have created genetic variants with usefully altered phenotypes, these methods are limited to laborious and serial manipulation of single genes and are not used for parallel and continuous directed evolution of gene networks or genomes. Here, we describe multiplex automated genome engineering (MAGE) for large-scale programming and evolution of cells. MAGE simultaneously targets many locations on the chromosome for modification in a single cell or across a population of cells, thus producing combinatorial genomic diversity. Because the process is cyclical and scalable, we constructed prototype devices that automate the MAGE technology to facilitate rapid and continuous generation of a diverse set of genetic changes (mismatches, insertions, deletions). We applied MAGE to optimize the 1-deoxy-
d
-xylulose-5-phosphate (DXP) biosynthesis pathway in
Escherichia coli
to overproduce the industrially important isoprenoid lycopene. Twenty-four genetic components in the DXP pathway were modified simultaneously using a complex pool of synthetic DNA, creating over 4.3 billion combinatorial genomic variants per day. We isolated variants with more than fivefold increase in lycopene production within 3 days, a significant improvement over existing metabolic engineering techniques. Our multiplex approach embraces engineering in the context of evolution by expediting the design and evolution of organisms with new and improved properties.
Journal Article