Technical and analytical approach to biventricular pressure-volume loops in swine including a completely endovascular, percutaneous closed-chest large animal model.

Pressure-volume (PV) loop analysis is a sophisticated invasive approach to quantifying load-dependent and independent measures of cardiac function. Biventricular (BV) PV loops allow left and right ventricular function to be quantified simultaneously and independently, which is important for conditions and certain physiologic states, such as ventricular decoupling or acute physiologic changes. BV PV loops can be performed in an entirely endovascular, percutaneous, and closed-chest setting. This technique is helpful in a survival animal model, as a percutaneous monitoring system during endovascular device experiments, or in cases where chest wall compliance is being tested or may be a confounder. In this article, we describe the end-to-end implementation of a completely endovascular, totally percutaneous, and closed-chest large animal model to obtain contemporaneous BV PV loops in 40 to 70 kg swine. We describe the associated surgical and technical challenges and our solutions to obtaining endovascular BV PV loops, closed-chest cardiac output, and stroke volume (including validation of the correction factor necessary for thermodilution), as well as how to perform endovascular inferior vena cava occlusion in this swine model. We also include techniques for data acquisition and analysis that are required for this method.

Researching big IT in the UK National Health Service: A systematic review of theory-based studies.

OBJECTIVE: To identify and discuss theory-based studies of large-scale health information technology programs in the UK National Health Service. MATERIALS AND METHODS: Using the PRISMA systematic review framework, we searched Scopus, PubMed and CINAHL databases from inception to March 2022 for theory-based studies of large-scale health IT implementations. We undertook detailed full-text analyses of papers meeting our inclusion criteria. RESULTS: Forty-six studies were included after assessment for eligibility, of which twenty-five applied theories from the information systems arena (socio-technical approaches, normalization process theory, user acceptance theories, diffusion of innovation), twelve from sociology (structuration theory, actor-network theory, institutional theory), while nine adopted other theories. Most investigated England's National Program for IT (2002-2011), exploring various technologies among which electronic records predominated. Research themes were categorized into user factors, program factors, process outcomes, clinical impact, technology, and organizational factors. Most research was qualitative, often using a case study strategy with a longitudinal or cross-sectional approach. Data were typically collected through interviews, observation, and document analysis; sampling was generally purposive; and most studies used thematic or related analyses. Theories were generally applied in a superficial or fragmentary manner; and articles frequently lacked detail on how theoretical constructs and relationships aided organization, analysis, and interpretation of data. CONCLUSION: Theory-based studies of large NHS IT programs are relatively uncommon. As large healthcare programs evolve over a long timeframe in complex and dynamic environments, wider adoption of theory-based methods could strengthen the explanatory and predictive utility of research findings across multiple evaluation studies. Our review has confirmed earlier suggestions for theory selection, and we suggest there is scope for more explicit use of such theoretical constructs to strengthen the conceptual foundations of health informatics research. Additionally, the challenges of large national health informatics programs afford wide-ranging opportunities to test, refine, and adapt sociological and information systems theories.

AMAnD: an automated metagenome anomaly detection methodology utilizing DeepSVDD neural networks.

The composition of metagenomic communities within the human body often reflects localized medical conditions such as upper respiratory diseases and gastrointestinal diseases. Fast and accurate computational tools to flag anomalous metagenomic samples from typical samples are desirable to understand different phenotypes, especially in contexts where repeated, long-duration temporal sampling is done. Here, we present Automated Metagenome Anomaly Detection (AMAnD), which utilizes two types of Deep Support Vector Data Description (DeepSVDD) models; one trained on taxonomic feature space output by the Pan-Genomics for Infectious Agents (PanGIA) taxonomy classifier and one trained on kmer frequency counts. AMAnD's semi-supervised one-class approach makes no assumptions about what an anomaly may look like, allowing the flagging of potentially novel anomaly types. Three diverse datasets are profiled. The first dataset is hosted on the National Center for Biotechnology Information's (NCBI) Sequence Read Archive (SRA) and contains nasopharyngeal swabs from healthy and COVID-19-positive patients. The second dataset is also hosted on SRA and contains gut microbiome samples from normal controls and from patients with slow transit constipation (STC). AMAnD can learn a typical healthy nasopharyngeal or gut microbiome profile and reliably flag the anomalous COVID+ or STC samples in both feature spaces. The final dataset is a synthetic metagenome created by the Critical Assessment of Metagenome Annotation Simulator (CAMISIM). A control dataset of 50 well-characterized organisms was submitted to CAMISIM to generate 100 synthetic control class samples. The experimental conditions included 12 different spiked-in contaminants that are taxonomically similar to organisms present in the laboratory blank sample ranging from one strain tree branch taxonomic distance away to one family tree branch taxonomic distance away. This experiment was repeated in triplicate at three different coverage levels to probe the dependence on sample coverage. AMAnD was again able to flag the contaminant inserts as anomalous. AMAnD's assumption-free flagging of metagenomic anomalies, the real-time model training update potential of the deep learning approach, and the strong performance even with lightweight models of low sample cardinality would make AMAnD well-suited to a wide array of applied metagenomics biosurveillance use-cases, from environmental to clinical utility.

Spatial variability of lightning intensity over the Mediterranean sea correlates with seawater properties.

The divergence of total alkalinity (TA) from conservation with salinity (S) and relatively acidic conditions (pH) in surface seawater was suggested to explain the high prevalence of lightning superbolts in the Mediterranean sea, North sea and upwelling regions of the oceans. In this study we tested the combined effects of changes in S, TA and pH of Mediterranean sea surface water on the intensity of laboratory generated electrical sparks, which are considered to be analogous to cloud to sea-surface intensity of lightning discharges. The experimental results were used to develop a multivariate linear equation (MLE) of Lightning Flash Intensity (LFI) as a function of S, TA/S and pH. This relation was validated with wintertime (DJF) LFI measurements along a Mediterranean sea zonal profile during the period 2009-2020 compared to corresponding climate model outputs of S, TA and pH. Based on the resulting MLE, the combined effects of climate change, ocean acidification and the damming of the Nile, may have increased LFI in the Levantine Sea by 16 ± 14% until now relative to the pre-Aswan Dam period. Furthermore, assuming that salinization and acidification of the Levantine Sea will continue at current trends, the LFI is predicted to increase by 25 ± 13% by the year 2050.

Effect of extremely low-frequency magnetic fields on light-induced electric reactions in wheat.

Magnetic field oscillations resulting from atmospheric events could have an effect on growth and development of plants and on the responsive reactions of plants to other environmental factors. In the current work, extremely low-frequency magnetic field (14.3 Hz) was shown to modulate light-induced electric reactions of wheat (Triticum aestivum L.). Blue light-induced electric reaction in wheat leaf comprises depolarization and two waves of hyperpolarization resulting in an increase of the potential to a higher level compared to the dark one. Fluorescent and inhibitory analysis demonstrate a key role of calcium ions and calcium-dependent H+-ATPase of the plasma membrane in the development of the reaction. Activation of H+-ATPase by the increased calcium influx is suggested as a mechanism of the influence of magnetic field on light-induced electric reaction.

Influence of Magnetic Field with Schumann Resonance Frequencies on Photosynthetic Light Reactions in Wheat and Pea.

Photosynthesis is an important target of action of numerous environmental factors; in particular, stressors can strongly affect photosynthetic light reactions. Considering relations of photosynthetic light reactions to electron and proton transport, it can be supposed that extremely low frequency magnetic field (ELFMF) may influence these reactions; however, this problem has been weakly investigated. In this paper, we experimentally tested a hypothesis about the potential influence of ELFMF of 18 µT intensity with Schumann resonance frequencies (7.8, 14.3, and 20.8 Hz) on photosynthetic light reactions in wheat and pea seedlings. It was shown that ELFMF decreased non-photochemical quenching in wheat and weakly influenced quantum yield of photosystem II at short-term treatment; in contrast, the changes in potential and effective quantum yields of photosystem II were observed mainly under chronic action of ELFMF. It is interesting that both short-term and chronic treatment decreased the time periods for 50% activation of quantum yield and non-photochemical quenching under illumination. Influence of ELFMF on pea was not observed at both short-term and chronic treatment. Thus, we showed that ELFMF with Schumann resonance frequencies could influence photosynthetic light processes; however, this effect depends on plant species (wheat or pea) and type of treatment (short-term or chronic).

Glossary on atmospheric electricity and its effects on biology.

There is an increasing interest to study the interactions between atmospheric electrical parameters and living organisms at multiple scales. So far, relatively few studies have been published that focus on possible biological effects of atmospheric electric and magnetic fields. To foster future work in this area of multidisciplinary research, here we present a glossary of relevant terms. Its main purpose is to facilitate the process of learning and communication among the different scientific disciplines working on this topic. While some definitions come from existing sources, other concepts have been re-defined to better reflect the existing and emerging scientific needs of this multidisciplinary and transdisciplinary area of research.

Challenges in coupling atmospheric electricity with biological systems.

The atmosphere is host to a complex electric environment, ranging from a global electric circuit generating fluctuating atmospheric electric fields to local lightning strikes and ions. While research on interactions of organisms with their electrical environment is deeply rooted in the aquatic environment, it has hitherto been confined to interactions with local electrical phenomena and organismal perception of electric fields. However, there is emerging evidence of coupling between large- and small-scale atmospheric electrical phenomena and various biological processes in terrestrial environments that even appear to be tied to continental waters. Here, we synthesize our current understanding of this connectivity, discussing how atmospheric electricity can affect various levels of biological organization across multiple ecosystems. We identify opportunities for research, highlighting its complexity and interdisciplinary nature and draw attention to both conceptual and technical challenges lying ahead of our future understanding of the relationship between atmospheric electricity and the organization and functioning of biological systems.

Natural ELF fields in the atmosphere and in living organisms.

Most electrical activity in vertebrates and invertebrates occurs at extremely low frequencies (ELF), with characteristic maxima below 50 Hz. The origin of these frequency maxima is unknown and remains a mystery. We propose that over billions of years during the evolutionary history of living organisms on Earth, the natural electromagnetic resonant frequencies in the atmosphere, continuously generated by global lightning activity, provided the background electric fields for the development of cellular electrical activity. In some animals, the electrical spectrum is difficult to differentiate from the natural background atmospheric electric field produced by lightning. In this paper, we present evidence for the link between the natural ELF fields and those found in many living organisms, including humans.

Increased Respiratory Viral Detection and Symptom Burden Among Patients with Primary Antibody Deficiency: Results from the BIPAD Study.

BACKGROUND: Patients with primary antibody deficiency (PAD) are at increased risk of respiratory tract infections, but our understanding of their nature and consequences remains limited. OBJECTIVE: To define the symptomatic and microbial burden of upper airway infection in adults with PAD relative to age-matched controls. METHODS: Prospective 12-month observational study consisting of a daily upper and lower airway symptom score alongside fortnightly nasal swab with molecular detection of 19 pathogen targets. RESULTS: A total of 44 patients and 42 controls (including 34 household pairs) were recruited, providing more than 22,500 days of symptom scores and 1,496 nasal swabs. Swab and questionnaire compliance exceeded 70%. At enrollment, 64% of patients received prophylactic antibiotics, with a 34% prevalence of bronchiectasis. On average, patients with PAD experienced symptomatic respiratory exacerbations every 6 days compared with 6 weeks for controls, associated with significant impairment of respiratory-specific quality-of-life scores. Viral detections were associated with worsening of symptom scores from a participant's baseline. Patients with PAD had increased odds ratio (OR) for pathogen detection, particularly viral (OR, 2.73; 95% CI, 2.09-3.57), specifically human rhinovirus (OR, 3.60; 95% CI, 2.53-5.13) and parainfluenza (OR, 3.06; 95% CI, 1.25-7.50). Haemophilus influenzae and Streptococcus pneumoniae were also more frequent in PAD. Young child exposure, IgM deficiency, and presence of bronchiectasis were independent risk factors for viral detection. Prophylactic antibiotic use was associated with a lower risk of bacterial detection by PCR. CONCLUSIONS: Patients with PAD have a significant respiratory symptom burden associated with increased viral infection frequency despite immunoglobulin replacement and prophylactic antibiotic use. This highlights a clear need for future therapeutic trials in the population with PAD, and informs future study design.

Ocean acidification may be increasing the intensity of lightning over the oceans.

The anthropogenic increase in atmospheric CO2 is not only considered to drive global warming, but also ocean acidification. Previous studies have shown that acidification will affect many aspects of biogenic carbon uptake and release in the surface water of the oceans. In this report we present a potential novel impact of acidification on the flash intensity of lightning discharged into the oceans. Our experimental results show that a decrease in ocean pH corresponding to the predicted increase in atmospheric CO2 according to the IPCC RCP 8.5 worst case emission scenario, may increase the intensity of lightning discharged into seawater by approximately 30 ± 7% by the end of the twenty-first century relative to 2000.

Clinical and laboratory characteristics of clozapine-treated patients with schizophrenia referred to a national immunodeficiency clinic reveals a B-cell signature resembling common variable immunodeficiency (CVID).

AIMS: An association between antibody deficiency and clozapine use in individuals with schizophrenia has recently been reported. We hypothesised that if clozapine-associated hypogammaglobulinaemia was clinically relevant this would manifest in referral patterns. METHODS: Retrospective case note review of patients referred and assessed by Immunology Centre for Wales (ICW) between January 2005 and July 2018 with extraction of clinical and immunological features for individuals with diagnosis of schizophrenia-like illness. RESULTS: 1791 adult patients were assessed at ICW during this period; 23 patients had a psychiatric diagnosis of schizophrenia or schizoaffective disorder. Principal indications for referral were findings of low calculated globulin and immunoglobulins. Clozapine was the single most commonly prescribed antipsychotic (17/23), disproportionately increased relative to reported use in the general schizophrenia population (OR 6.48, 95% CI: 1.79 to 23.5). Clozapine therapy was noted in 6/7 (86%) of patients subsequently requiring immunoglobulin replacement therapy (IgRT). Marked reduction of class-switched memory B cells (CSMB) and plasmablasts were observed in clozapine-treated individuals relative to healthy age-matched controls. Clozapine duration is associated with CSMB decline. One patient discontinued clozapine, with gradual recovery of IgG levels without use of IgRT. CONCLUSIONS: Our findings are consistent with enrichment of clozapine-treatment within schizophrenic individuals referred for ICW assessment over the last 13 years. These individuals displayed clinical patterns closely resembling the primary immunodeficiency common variable immunodeficiency, however appears reversible on drug cessation. This has diagnostic, monitoring and treatment implications for psychiatry and immunology teams and directs prospective studies to address causality and the wider implications for this patient group.

Twenty-five years of national health IT: exploring strategy, structure, and systems in the English NHS.

Objective: There is global interest in implementing national information systems to support healthcare, and the National Health Service in England (NHS) has a troubled 25-year history in this sphere. Our objective was to chronicle structural reorganizations within the NHS from 1973 to 2017, alongside concurrent national information technology (IT) strategies, as the basis for developing a conceptual model to aid understanding of the organizational factors involved. Materials and Methods: We undertook an exploratory, retrospective longitudinal case study by reviewing strategic plans, legislation, and health policy documents, and constructed schemata for evolving structure and strategy. Literature on multi-organizational forms, complexity, national-level health IT implementations, and mega-projects was reviewed to identify factors that mapped to the schemata. Guided by strong structuration theory, these factors were superimposed on a simplified structural schema to create the conceptual model. Results: Against a background of frequent NHS reorganizations, there has been a logical and emergent NHS IT strategy focusing progressively on technical and data standards, connectivity, applications, and consolidation. The NHS has a complex and hierarchical multi-organization form in which restructuring may impact a range of intra- and inter-organizational factors. Discussion: NHS-wide IT programs have generally failed to meet expectations, though evaluations have usually overlooked longer-term progress. Realizing a long-term health IT strategy may be impeded by volatility of the implementation environment as organizational structures and relationships change. Key factors influencing the strategy-structure dyad can be superimposed on the tiered NHS structure to facilitate analysis of their impact. Conclusion: Alignment between incremental health IT strategy and dynamic structure is an under-researched area. Lessons from organizational studies and the management of mega-projects may help in understanding some of the ongoing challenges.

Healthcare IT Strategic Alignment: Challenges and Recommendations.

Information technology (IT) has dramatically transformed business processes in many industries including healthcare, where electronic health records, electronic prescribing and computerized provider order entry systems have positively changed the practice of healthcare. Recently, King Faisal Specialist Hospital and Research Center, Saudi Arabia, implemented various IT systems in multiple clinical and administrative departments leading to major transformation in healthcare workflows and business processes. At the pharmacy department, many Healthcare-IT alignment challenges are still perceived. Information about challenges of strategic alignment were gathered using qualitative survey methods, through conducting semi-structures interviews, to collect opinions, experiences and suggestions. Findings were first validated, according to published literature and research work, then sorted into fourteen challenges categorized into four main areas and recommended solutions: 1) Improving organizational communication, 2) Enhancing organizational governance, 3) Specifying the alignment scope and building the architecture and 4) Developing organizational and human skills.

Synthetic phonics and decodable instructional reading texts: How far do these support poor readers?

This paper presents data from a quasi-experimental trial with paired randomisation that emerged during the development of a reading scheme for children in England. This trial was conducted with a group of 12 children, aged 5-6, and considered to be falling behind their peers in reading ability and a matched control group. There were two intervention conditions (A: using mixed teaching methods and a high percentage of non-phonically decodable vocabulary; P: using mixed teaching methods and low percentage of non-decodable vocabulary); allocation to these was randomised. Children were assessed at pre- and post-test on standardised measures of receptive vocabulary, phoneme awareness, word reading, and comprehension. Two class teachers in the same school each selected 6 children, who they considered to be poor readers, to participate (n = 12). A control group (using synthetic phonics only and phonically decodable vocabulary) was selected from the same 2 classes based on pre-test scores for word reading (n = 16). Results from the study show positive benefits for poor readers from using both additional teaching methods (such as analytic phonics, sight word vocabulary, and oral vocabulary extension) in addition to synthetic phonics, and also non-decodable vocabulary in instructional reading text.

Lightning Sensors for Observing, Tracking and Nowcasting Severe Weather.

Severe and extreme weather is a major natural hazard all over the world, oftenresulting in major natural disasters such as hail storms, tornados, wind storms, flash floods,forest fires and lightning damages. While precipitation, wind, hail, tornados, turbulence,etc. can only be observed at close distances, lightning activity in these damaging stormscan be monitored at all spatial scales, from local (using very high frequency [VHF]sensors), to regional (using very low frequency [VLF] sensors), and even global scales(using extremely low frequency [ELF] sensors). Using sensors that detect the radio wavesemitted by each lightning discharge, it is now possible to observe and track continuouslydistant thunderstorms using ground networks of sensors. In addition to the number oflightning discharges, these sensors can also provide information on lightningcharacteristics such as the ratio between intra-cloud and cloud-to-ground lightning, thepolarity of the lightning discharge, peak currents, charge removal, etc. It has been shownthat changes in some of these lightning characteristics during thunderstorms are oftenrelated to changes in the severity of the storms. In this paper different lightning observingsystems are described, and a few examples are provided showing how lightning may beused to monitor storm hazards around the globe, while also providing the possibility ofsupplying short term forecasts, called nowcasting.

Self-association of block copoly(oxyalkylene)s in aqueous solution. Effects of composition, block length and block architecture.

The article deals with the association behaviour in dilute aqueous solution of block copoly(oxyalkylene)s in which hydrophilic poly(ethylene oxide) is combined with hydrophobic poly(propylene oxide), poly(1,2-butylene oxide) or poly(styrene oxide). Polymers with three simple architectures are considered, i.e. copolymers of type EmAn, EmAnEm and AnEmAn, where E denotes an oxyethylene unit, A denotes a hydrophobic oxyalkylene unit, and the subscripts m and n denote number-average block lengths in repeat units. The aim is to examine how composition, block length and block architecture govern two fundamental properties, critical micelle concentration (cmc) and micelle association number (N), for systems which are in dynamic equilibrium. Copolymers with properties known to be greatly affected by heterogeneity in composition are excluded from consideration. A uniform pattern of behaviour emerges when log(cmc) is plotted against reduced hydrophobic block length (x), consistent with the micellisation equilibrium changing from one between unimers and multimolecular micelles at low values of x, to one between unimolecular micelles and multimolecular micelles at high values of x. Support for this model is provided by the enthalpy of micellisation, values of which fall effectively to zero as x is increased. Values of the micelle association number are used to define a critical hydrophobic block length for micellisation (n(cr)) for each class of diblock copolymers, values of which apply equally well to the half-length of the central block of corresponding EmAnEm triblock copolymers. Given these values, and irrespective of block architecture, the overall scaling law for the weight-average association number of the micelles is shown to be Nw = n'(1.07)m(-0.63) where m is the length (or half-length) of the hydrophilic block, and n' is the effective length of the hydrophobic block, equal to its length (or half-length) minus the critical length, i.e. n' = n-n(cr).

Analysis of temperature influences on the amplitude-frequency characteristics of Rn gas concentration.

The ventilation mechanism of Rn gas in underground environments is considered. Ventilation plays an important role in influencing the variability (harmonics) of Rn gas in the porous space below the earth's surface. We propose a new physical-environmental model of relating Rn gas concentrations to air temperature variations at the earth's surface. Applicability of this model was tested after searching for Rn gas indicators of geodynamic processes in two underground tunnels in central and southern Israel. The theoretical estimation of Rn gas concentrations shows a good agreement with the observed values. We demonstrate the possibility of Rn gas anomalies being caused by atmospheric temperature variations and the necessity to take these effects into account when investigating geodynamic processes.

Micelles and gels of mixed triblock copoly(oxyalkylene)s in aqueous solution.

The micellization in dilute aqueous solution of a 50/50 wt% mixture of two triblock copolymers, E45B14E45 and E62P39E62, and the gelation of concentrated micellar solutions have been investigated over a range of temperatures. Here E, B, and P denote oxyethylene, oxubutylene, and oxypropylene chain units. Comparison is made with aqueous solutions of the individual copolymers. The results of light scattering measurements are consistent with effectively separate micellization of the two copolymers in the mixture. Hard gel formed when the extent of micellization was high for both copolymers. Because of the relatively high critical micellization temperatures of copolymer E62P39E62, the low-temperature boundary of the hard gel was high for this copolymer and for the mixture. The minimum concentration for hard-gel formation was higher for the mixture than for either of the individual copolymers, as would be expected for packing of two distributions of micelles of different average size.

Evaluation of digital and geometric unsharpness in dental radiographs using an endodontic file model.

OBJECTIVE: We sought to compare the effects of geometric and digital unsharpness. STUDY DESIGN: Endodontic files of sizes 6, 8, 10, and 15 were placed in the root canal of an extracted lower incisor in 3 different positions at 2-mm increments. Radiographs were taken with a GE 100 x-ray unit at magnification factors of 1.0, 1.1, 1.2, and 1.3. With the use of a flatbed scanner, each radiograph was digitized at resolutions of 75, 150, 300, and 600 dpi. Ten observers viewed the digital images and identified the positions of the end of the files and the end of the roots, as well as assessed image quality. RESULTS: No significant differences were found between the resolutions of 300 and 600 dpi, nor between the magnifications of 1.0 and 1.1. Significant differences were found between the magnification of 1.3 and the others and the resolution of 75 dpi and the others for all of the files. CONCLUSION: Geometric unsharpness has little relevance in clinical dental radiography. Increasing scanning resolution to 600 dpi did not improve accuracy with respect to recognizing the position of endodontic files.