Critical Scale-invariance in Healthy Human Heart Rate

We demonstrate the robust scale-invariance in the probability density function (PDF) of detrended healthy human heart rate increments, which is preserved not only in a quiescent condition, but also in a dynamic state where the mean level of heart rate is dramatically changing. This scale-independent and fractal structure is markedly different from the scale-dependent PDF evolution observed in a turbulent-like, cascade heart rate model. These results strongly support the view that healthy human heart rate is controlled to converge continually to a critical state.Comment: 9 pages, 3 figures. Phys. Rev. Lett., to appear (2004

A mathematical model for the sequestering of chemical contaminants by magnetic particles

A mathematical model is developed and implemented to characterize the pickup of various liquid chemical contaminants by polyethylene-coated magnetic particles. The model and its associated experimental and analytical protocols were applied to a wide range of liquid chemicals in order to gain insights into the physical basis for the pickup phenomenon. The characteristics of the pickup isotherms range between “ideal” and “nonideal” behaviors that are reflected in the mathematical model by a single parameter, �0, where �0=1 corresponds to ideal behavior and �0�1 corresponds to a departure from idealized behavior that is directly quantified by the magnitude of �0. The parameter �0 is also related to the efficiency of pickup, and since most isotherms observed in the study deviate from ideality, the high efficiency of pickup observed in these systems has been attributed in part to this deviation. The proposed model and its associated experimental and analytical protocols demonstrate great potential for the systematic evaluation of the uptake of chemical contaminants using magnetic particle technology

Growing Environmental Activists: Developing Environmental Agency and Engagement Through Children’s Fiction.

We explore how story has the potential to encourage environmental engagement and a sense of agency provided that critical discussion takes place. We illuminate this with reference to the philosophies of John Macmurray on personal agency and social relations; of John Dewey on the primacy of experience for philosophy; and of Paul Ricoeur on hermeneutics, dialogue, dialectics and narrative. We view the use of fiction for environmental understanding as hermeneutic, a form of conceptualising place which interprets experience and perception. The four writers for young people discussed are Ernest Thompson Seton, Kenneth Grahame, Michelle Paver and Philip Pullman. We develop the concept of critical dialogue, and link this to Crick's demand for active democratic citizenship. We illustrate the educational potential for environmental discussions based on literature leading to deeper understanding of place and environment, encouraging the belief in young people that they can be and become agents for change. We develop from Zimbardo the key concept of heroic resister to encourage young people to overcome peer pressure. We conclude with a call to develop a greater awareness of the potential of fiction for learning, and for writers to produce more focused stories engaging with environmental responsibility and activism

An optimised protocol to generate high titre lentiviral vectors by extended HEK293T culture following transient transfection and suspension culture

Poster Presentation P291, presented at the ESGCT 29th Annual Congress In collaboration with BSGCT Edinburgh, UK October 11–14, 2022.HIV‐1 based lentiviral viruses are considered powerful and versatile gene therapy vectors to deliver therapeutic genes to patients with hereditary or acquired diseases. These vectors can efficiently transduce a variety of cell types when dividing or non‐dividing to provide permanent delivery and long‐term gene expression. Demand for scalable manufacturing protocols able to generate enough high titre vector for widespread use of this technology is increasing. Current methods for LV production either use transient transfection of producer cell lines or production from isolated clonal producer cells engineered to generate vector permanently. Cells can be grown at scale either in 2D relying on culturing producer cells in multi‐tray flasks or in roller bottles or cells can be adapted to grow in 3D suspensions in large batch fermenters. Transient transfection is, however, ideal to rapidly generate vector to test for efficacy. In this study, we compared cell survival and LV titres using three different transfection reagents: polyethyleneimine, Fugene® 6 and Genejuice®. LV was produced routinely at titres of 109 TU/ml by traditional monolayer conditions for up to 10 days instead of 72 hours using Genejuice® with little drop in titre due to low cellular toxicity. Genejuice® also enabled rapid conversion of HEK293T from 2D to 3D suspension cultures generating titres of 108 TU/ml in glass bottles. We propose, these simple changes in vector production enables the generation of larger volumes of high titre vector in a cost‐effective manner

Using EHRs to integrate research with patient care: promises and challenges

Clinical research is the foundation for advancing the practice of medicine. However, the lack of seamless integration between clinical research and patient care workflow impedes recruitment efficiency, escalates research costs, and hence threatens the entire clinical research enterprise. Increased use of electronic health records (EHRs) holds promise for facilitating this integration but must surmount regulatory obstacles. Among the unintended consequences of current research oversight are barriers to accessing patient information for prescreening and recruitment, coordinating scheduling of clinical and research visits, and reconciling information about clinical and research drugs. We conclude that the EHR alone cannot overcome barriers in conducting clinical trials and comparative effectiveness research. Patient privacy and human subject protection policies should be clarified at the local level to exploit optimally the full potential of EHRs, while continuing to ensure participant safety. Increased alignment of policies that regulate the clinical and research use of EHRs could help fulfill the vision of more efficiently obtaining clinical research evidence to improve human health

Optimised protocols to generate high titre lentiviral vectors using a novel transfection agent enabling extended HEK293T culture following transient transfection and suspension culture

Data availability statement: The data presented in this paper is available from the corresponding author upon reasonable request.Authors contributed equally to this work.Copyright © 2024 The Author(s). HIV-1 based lentiviral viruses are considered powerful and versatile gene therapy vectors to deliver therapeutic genes to patients with hereditary or acquired diseases. These vectors can efficiently transduce a variety of cell types when dividing or non-dividing to provide permanent delivery and long-term gene expression. Demand for scalable manufacturing protocols able to generate enough high titre vector for widespread use of this technology is increasing and considerable efforts to improve vector production cost-effectively, is ongoing. Current methods for LV production mainly use transient transfection of producer cell lines. Cells can be grown at scale, either in 2D relying on culturing producer cells in multi-tray flask cell culture factories or in roller bottles or can be adapted to grow in 3D suspensions in large batch fermenters. This suits rapid production and testing of new vector constructs pre-clinically for their efficacy, particle titre and safety. In this study, we sought to improve lentiviral titre over time by testing two alternative commercially available transfection reagents Fugene® 6 and Genejuice® with the commonly used polycation, polyethyleneimine. Our aim was to identify less cytotoxic transfection reagents that could be used to generate LV particles at high titre past the often used 72 h period when vector is usually collected before producer cell death is caused due to post transfection cytotoxicity. We show that LV could be produced in extended culture using Genejuice® and even by transfected cells in glass flasks in suspension. Because this delivery agent is less toxic to 293 T producer cells, following optimisation of transfection we found that LV can be harvested for more than 10 days at high titre. Using our protocol, titres of 109 TU/ml and 108 TU/ml were routinely reached via traditional monolayer conditions or suspension cultures, respectively. We propose, this simple change in vector production enables large volumes of high titre vector to be produced, cost effectively for non-clinical in vivo and in vitro applications or for more stringent downstream clinical grade vector purification

Ab Initio Study of Screw Dislocations in Mo and Ta: A new picture of plasticity in bcc transition metals

We report the first ab initio density-functional study of screw dislocations cores in the bcc transition metals Mo and Ta. Our results suggest a new picture of bcc plasticity with symmetric and compact dislocation cores, contrary to the presently accepted picture based on continuum and interatomic potentials. Core energy scales in this new picture are in much better agreement with the Peierls energy barriers to dislocation motion suggested by experiments.Comment: 3 figures, 3 table

The fetal mouse is a sensitive genotoxicity model that exposes lentiviral-associated mutagenesis resulting in liver oncogenesis

This article is available open access through the publisher’s website at the link below. Copyright @ 2013 The American Society of Gene & Cell Therapy.Genotoxicity models are extremely important to assess retroviral vector biosafety before gene therapy. We have developed an in utero model that demonstrates that hepatocellular carcinoma (HCC) development is restricted to mice receiving nonprimate (np) lentiviral vectors (LV) and does not occur when a primate (p) LV is used regardless of woodchuck post-translation regulatory element (WPRE) mutations to prevent truncated X gene expression. Analysis of 839 npLV and 244 pLV integrations in the liver genomes of vector-treated mice revealed clear differences between vector insertions in gene dense regions and highly expressed genes, suggestive of vector preference for insertion or clonal outgrowth. In npLV-associated clonal tumors, 56% of insertions occurred in oncogenes or genes associated with oncogenesis or tumor suppression and surprisingly, most genes examined (11/12) had reduced expression as compared with control livers and tumors. Two examples of vector-inserted genes were the Park 7 oncogene and Uvrag tumor suppressor gene. Both these genes and their known interactive partners had differential expression profiles. Interactive partners were assigned to networks specific to liver disease and HCC via ingenuity pathway analysis. The fetal mouse model not only exposes the genotoxic potential of vectors intended for gene therapy but can also reveal genes associated with liver oncogenesis.Imperial College London, the Wellcome Trust, and Brunel University

Effect of poly(lactic acid)/kenaf composites incorporated with thymol on the antimicrobial activity of processed meat

Bio-based composites comprised of poly(lactic acid) (PLA), kenaf fibers and thymol were developed and their antimicrobial (AM) properties and stability under different storage conditions investigated. The composite films containing 20-30% w/w thymol reduced E. coli in tryptone soy broth after two days at 37C and imparted a significant zone of inhibition in contact with E. coli inoculated plates. The composite films also reduced E. coli inoculated on the surface of processed sliced chicken samples after 30 days at 10C both in direct contact and in the vapour phase. The thymol additive was retained in the PLA/kenaf films that were wrapped with aluminium foil after 3 months of storage at ambient temperatures; however, unwrapped films lost some thymol to the atmosphere. The PLA/kenaf/thymol composite films show a strong potential for the development of active packaging systems in order to extend the shelf-life of some processed food products

Microvolt T-Wave Alternans and the Risk of Death or Sustained Ventricular Arrhythmias in Patients With Left Ventricular Dysfunction

ObjectivesThis study hypothesized that microvolt T-wave alternans (MTWA) improves selection of patients for implantable cardioverter-defibrillator (ICD) prophylaxis, especially by identifying patients who are not likely to benefit.BackgroundMany patients with left ventricular dysfunction are now eligible for prophylactic ICDs, but most eligible patients do not benefit; MTWA testing has been proposed to improve patient selection.MethodsOur study was conducted at 11 clinical centers in the U.S. Patients were eligible if they had a left ventricular ejection fraction (LVEF) ≤0.40 and lacked a history of sustained ventricular arrhythmias; patients were excluded for atrial fibrillation, unstable coronary artery disease, or New York Heart Association functional class IV heart failure. Participants underwent an MTWA test and then were followed for about two years. The primary outcome was all-cause mortality or non-fatal sustained ventricular arrhythmias.ResultsIschemic heart disease was present in 49%, mean LVEF was 0.25, and 66% had an abnormal MTWA test. During 20 ± 6 months of follow-up, 51 end points (40 deaths and 11 non-fatal sustained ventricular arrhythmias) occurred. Comparing patients with normal and abnormal MTWA tests, the hazard ratio for the primary end point was 6.5 at two years (95% confidence interval 2.4 to 18.1, p < 0.001). Survival of patients with normal MTWA tests was 97.5% at two years. The strong association between MTWA and the primary end point was similar in all subgroups tested.ConclusionsAmong patients with heart disease and LVEF ≤0.40, MTWA can identify not only a high-risk group, but also a low-risk group unlikely to benefit from ICD prophylaxis