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Frontiers in Pediatrics 2024In contrast to significant declines in deaths due to lung cancer and cardiac disease in Westernised countries, the mortality due to 'chronic obstructive pulmonary... (Review)
Review
In contrast to significant declines in deaths due to lung cancer and cardiac disease in Westernised countries, the mortality due to 'chronic obstructive pulmonary disease' (COPD) has minimally changed in recent decades while 'the incidence of bronchiectasis' is on the rise. The current focus on producing guidelines for these two airway 'diseases' has hindered progress in both treatment and prevention. The elephant in the room is that neither COPD nor bronchiectasis is a disease but rather a consequence of progressive untreated airway inflammation. To make this case, it is important to review the evolution of our understanding of airway disease and how a pathological appearance (bronchiectasis) and an arbitrary physiological marker of impaired airways (COPD) came to be labelled as 'diseases'. Valuable insights into the natural history of airway disease can be obtained from the pre-antibiotic era. The dramatic impacts of antibiotics on the prevalence of significant airway disease, especially in childhood and early adult life, have largely been forgotten and will be revisited as will the misinterpretation of trials undertaken in those with chronic (bacterial) bronchitis. In the past decades, paediatricians have observed a progressive increase in what is termed 'persistent bacterial bronchitis' (PBB). This condition shares all the same characteristics as 'chronic bronchitis', which is prevalent in young children during the pre-antibiotic era. Additionally, the radiological appearance of bronchiectasis is once again becoming more common in children and, more recently, in adults. Adult physicians remain sceptical about the existence of PBB; however, in one study aimed at assessing the efficacy of antibiotics in adults with persistent symptoms, researchers discovered that the majority of patients exhibiting symptoms of PBB were already on long-term macrolides. In recent decades, there has been a growing recognition of the importance of the respiratory microbiome and an understanding of the ability of bacteria to persist in potentially hostile environments through strategies such as biofilms, intracellular communities, and persister bacteria. This is a challenging field that will likely require new approaches to diagnosis and treatment; however, it needs to be embraced if real progress is to be made.
PubMed: 38910961
DOI: 10.3389/fped.2024.1391290 -
Scientific Reports Jun 2024After obtaining an exact regular-AdS black hole resulting from the coupling of general relativity with nonlinear electrodynamics (NED), we explore the thermodynamics of...
After obtaining an exact regular-AdS black hole resulting from the coupling of general relativity with nonlinear electrodynamics (NED), we explore the thermodynamics of the extended phase space, treating the cosmological constant ( ) as the pressure (P) of the black holes and its conjugate as thermodynamic volume (V). Considering the NED parameter (g), we investigate the Hawking temperature, entropy, Gibb's free energy and specific heat at the horizon radius. Due to the presence of NED charge, the black hole exhibits van der Waals-like phase transition instead of Hawking-Page phase transition, which could be observed through the plots, which display a swallowtail pattern below the critical pressure, and it gives rise to second-order phase transitions when pressure attains its critical value. The first-order phase transition shares similarities with the liquid-gas phase transition. We determine the exact critical points and explore the influence of NED on criticality, revealing that the isotherms undergo a liquid-gas-like phase transition for temperatures below its critical value , especially at lower . The identical critical exponent to that of the van der Waals fluid suggests that the NED does not alter the critical exponents, as observed in other arbitrary AdS black holes.
PubMed: 38880829
DOI: 10.1038/s41598-024-62645-4 -
Journal of Bodywork and Movement... Jul 2024Cerebral palsy (CP) is the most common childhood motor disability, and the Cerebral Palsy Follow-Up Program (CPUP) in Nordic countries uses a traffic light system for...
Limited associations between passive range of motion and gross motor function in ambulant/semi-ambulant children and adolescents with cerebral palsy: A cross-sectional study.
BACKGROUND AND AIM
Cerebral palsy (CP) is the most common childhood motor disability, and the Cerebral Palsy Follow-Up Program (CPUP) in Nordic countries uses a traffic light system for passive range of motion (ROM) assessment to aid interpretation and guide decisions regarding interventions. However, the arbitrary chosen ROM threshold values and their potential clinical impact are uncertain. We investigated whether lower extremity ROM values were positively associated with gross motor function and whether gross motor function scores differ between the CPUP ROM thresholds.
METHODS
This was a cross-sectional analysis of CPUP data for 841 ambulatory children and adolescents with CP, at a mean (SD) age of 9 (3). Regression analyses were employed to explore the relationship between gross motor capacity and performance (using the Gross Motor Function Measure (GMFM-66) and the Functional Mobility Scale (FMS) 5/50/500 m, respectively) and lower extremity ROM, measured with a goniometer. ROM was assessed both as continuous and categorical variables.
RESULTS
We found that two out of ten continuous ROM measures were positively associated with gross motor function. Limited differences in gross motor function between the ROM thresholds were seen for seven out of ten ROM measures. The CPUP traffic light thresholds primarily differentiated gross motor function between the red and green categories, predominantly for the subgroup of participants with bilateral spastic CP.
CONCLUSION
Limited associations between passive ROM and gross motor function in children and adolescents with CP were observed, indicating that there is more to consider than ROM when identifying whether interventions are needed.
Topics: Humans; Cerebral Palsy; Cross-Sectional Studies; Child; Male; Female; Adolescent; Range of Motion, Articular; Lower Extremity; Motor Skills
PubMed: 38876622
DOI: 10.1016/j.jbmt.2024.02.030 -
Journal of Applied Crystallography Jun 2024This paper introduces a new 2D representation of the orientation distribution function for an arbitrary material texture. The approach is based on the isometric square...
This paper introduces a new 2D representation of the orientation distribution function for an arbitrary material texture. The approach is based on the isometric square torus mapping of the Clifford torus, which allows for points on the unit quaternion hypersphere (each corresponding to a 3D orientation) to be represented in a periodic 2D square map. The combination of three such orthogonal mappings into a single RGB (red-green-blue) image provides a compact periodic representation of any set of orientations. Square torus representations of five different orientation sampling methods are compared and analyzed in terms of the Riesz energies that quantify the uniformity of the samplings. The effect of crystallographic symmetry on the square torus map is analyzed in terms of the Rodrigues fundamental zones for the rotational symmetry groups. The paper concludes with example representations of important texture components in cubic and hexagonal materials. The new RGB representation provides a convenient and compact way of generating training data for the automated analysis of material textures by means of neural networks.
PubMed: 38846769
DOI: 10.1107/S160057672400219X -
Nature Communications Jun 2024We introduce Ultra-Flexible Tentacle Electrodes (UFTEs), packing many independent fibers with the smallest possible footprint without limitation in recording depth using...
We introduce Ultra-Flexible Tentacle Electrodes (UFTEs), packing many independent fibers with the smallest possible footprint without limitation in recording depth using a combination of mechanical and chemical tethering for insertion. We demonstrate a scheme to implant UFTEs simultaneously into many brain areas at arbitrary locations without angle-of-insertion limitations, and a 512-channel wireless logger. Immunostaining reveals no detectable chronic tissue damage even after several months. Mean spike signal-to-noise ratios are 1.5-3x compared to the state-of-the-art, while the highest signal-to-noise ratios reach 89, and average cortical unit yields are ~1.75/channel. UFTEs can track the same neurons across sessions for at least 10 months (longest duration tested). We tracked inter- and intra-areal neuronal ensembles (neurons repeatedly co-activated within 25 ms) simultaneously from hippocampus, retrosplenial cortex, and medial prefrontal cortex in freely moving rodents. Average ensemble lifetimes were shorter than the durations over which we can track individual neurons. We identify two distinct classes of ensembles. Those tuned to sharp-wave ripples display the shortest lifetimes, and the ensemble members are mostly hippocampal. Yet, inter-areal ensembles with members from both hippocampus and cortex have weak tuning to sharp wave ripples, and some have unusual months-long lifetimes. Such inter-areal ensembles occasionally remain inactive for weeks before re-emerging.
Topics: Animals; Neurons; Electrodes, Implanted; Brain; Hippocampus; Male; Rats; Signal-To-Noise Ratio; Action Potentials; Mice; Prefrontal Cortex
PubMed: 38844769
DOI: 10.1038/s41467-024-49226-9 -
Scientific Reports May 2024In this paper, an absorptive coding metasurface (ACM) is proposed for ultra-wideband radar cross section (RCS) reduction, the design process is presented in detail, in...
In this paper, an absorptive coding metasurface (ACM) is proposed for ultra-wideband radar cross section (RCS) reduction, the design process is presented in detail, in which a lossy polarization conversion metasurface (PCM) is proposed at first. The lossy PCM is an anisotropic resistive structure with both polarization conversion and absorption performances, so that its co-polarization reflection coefficients under u- and v-polarized incidences can be kept at less than - 10 dB in magnitude in the frequency range from 7.5 to 45.2 GHz. Though the magnitude of the cross-polarization reflection coefficient cannot be very small only due to the absorption, its phase will be changed by nearly 180° when the unit-cell structure of the lossy PCM is rotated by 90°. Thus, the lossy PCM can be used as one of the two types of lossy coding elements for an ACM when its unit-cell structure is rotated by 90° or not. Based on the lossy PCM, an ACM is proposed. The simulation and experimental results show that the ACM has an excellent RCS reduction performance under arbitrary polarized incidence, it can achieve effective RCS reduction under normal incidence in the ultra-wide frequency band from 7.4 to 45.5 GHz with a ratio bandwidth (f/f) of 6.15:1; moreover, an ultra-wideband RCS reduction can still be achieved when the incident angle is increased to 45°, which indicates that the ACM has good stealth performance under the detection of various radars working in X, Ku, K and Ka bands, it is very practical.
PubMed: 38811829
DOI: 10.1038/s41598-024-63260-z -
Briefings in Bioinformatics May 2024Tumor mutational signatures have gained prominence in cancer research, yet the lack of standardized methods hinders reproducibility and robustness. Leveraging colorectal...
Tumor mutational signatures have gained prominence in cancer research, yet the lack of standardized methods hinders reproducibility and robustness. Leveraging colorectal cancer (CRC) as a model, we explored the influence of computational parameters on mutational signature analyses across 230 CRC cell lines and 152 CRC patients. Results were validated in three independent datasets: 483 endometrial cancer patients stratified by mismatch repair (MMR) status, 35 lung cancer patients by smoking status and 12 patient-derived organoids (PDOs) annotated for colibactin exposure. Assessing various bioinformatic tools, reference datasets and input data sizes including whole genome sequencing, whole exome sequencing and a pan-cancer gene panel, we demonstrated significant variability in the results. We report that the use of distinct algorithms and references led to statistically different results, highlighting how arbitrary choices may induce variability in the mutational signature contributions. Furthermore, we found a differential contribution of mutational signatures between coding and intergenic regions and defined the minimum number of somatic variants required for reliable mutational signature assignment. To facilitate the identification of the most suitable workflows, we developed Comparative Mutational Signature analysis on Coding and Extragenic Regions (CoMSCER), a bioinformatic tool which allows researchers to easily perform comparative mutational signature analysis by coupling the results from several tools and public reference datasets and to assess mutational signature contributions in coding and non-coding genomic regions. In conclusion, our study provides a comparative framework to elucidate the impact of distinct computational workflows on mutational signatures.
Topics: Humans; Colorectal Neoplasms; Mutation; Computational Biology; Workflow; Cell Line, Tumor; Exome Sequencing; Female; Algorithms
PubMed: 38783705
DOI: 10.1093/bib/bbae249 -
Scientific Reports May 2024Programmable photonic integrated circuits represent an emerging technology that amalgamates photonics and electronics, paving the way for light-based information...
Programmable photonic integrated circuits represent an emerging technology that amalgamates photonics and electronics, paving the way for light-based information processing at high speeds and low power consumption. Programmable photonics provides a flexible platform that can be reconfigured to perform multiple tasks, thereby holding great promise for revolutionizing future optical networks and quantum computing systems. Over the past decade, there has been constant progress in developing several different architectures for realizing programmable photonic circuits that allow for realizing arbitrary discrete unitary operations with light. Here, we systematically investigate a general family of photonic circuits for realizing arbitrary unitaries based on a simple architecture that interlaces a fixed intervening layer with programmable phase shifter layers. We introduce a criterion for the intervening operator that guarantees the universality of this architecture for representing arbitrary unitary operators with phase layers. We explore this criterion for different photonic components, including photonic waveguide lattices and meshes of directional couplers, which allows the identification of several families of photonic components that can serve as the intervening layers in the interlacing architecture. Our findings pave the way for efficiently designing and realizing novel families of programmable photonic integrated circuits for multipurpose analog information processing.
PubMed: 38740784
DOI: 10.1038/s41598-024-60700-8 -
The Lancet. Rheumatology Jun 2024The humoral and T-cell responses to booster COVID-19 vaccine types in multidisease immunocompromised individuals who do not generate adequate antibody responses to two... (Randomized Controlled Trial)
Randomized Controlled Trial
Immunogenicity of third dose COVID-19 vaccine strategies in patients who are immunocompromised with suboptimal immunity following two doses (OCTAVE-DUO): an open-label, multicentre, randomised, controlled, phase 3 trial.
BACKGROUND
The humoral and T-cell responses to booster COVID-19 vaccine types in multidisease immunocompromised individuals who do not generate adequate antibody responses to two COVID-19 vaccine doses, is not fully understood. The OCTAVE DUO trial aimed to determine the value of third vaccinations in a wide range of patients with primary and secondary immunodeficiencies.
METHODS
OCTAVE-DUO was a prospective, open-label, multicentre, randomised, controlled, phase 3 trial investigating humoral and T-cell responses in patients who are immunocompromised following a third vaccine dose with BNT162b2 or mRNA-1273, and of NVX-CoV2373 for those with lymphoid malignancies. We recruited patients who were immunocompromised from 11 UK hospitals, aged at least 18 years, with previous sub-optimal responses to two doses of SARS-CoV-2 vaccine. Participants were randomly assigned 1:1 (1:1:1 for those with lymphoid malignancies), stratified by disease, previous vaccination type, and anti-spike antibody response following two doses. Individuals with lived experience of immune susceptibility were involved in the study design and implementation. The primary outcome was vaccine-specific immunity defined by anti-SARS-CoV-2 spike antibodies (Roche Diagnostics UK and Ireland, Burgess Hill, UK) and T-cell responses (Oxford Immunotec, Abingdon, UK) before and 21 days after the third vaccine dose analysed by a modified intention-to-treat analysis. The trial is registered with the ISRCTN registry, ISRCTN 15354495, and the EU Clinical Trials Register, EudraCT 2021-003632-87, and is complete.
FINDINGS
Between Aug 4, 2021 and Mar 31, 2022, 804 participants across nine disease cohorts were randomly assigned to receive BNT162b2 (n=377), mRNA-1273 (n=374), or NVX-CoV2373 (n=53). 356 (45%) of 789 participants were women, 433 (55%) were men, and 659 (85%) of 775 were White. Anti-SARS-CoV-2 spike antibodies measured 21 days after the third vaccine dose were significantly higher than baseline pre-third dose titres in the modified intention-to-treat analysis (median 1384 arbitrary units [AU]/mL [IQR 4·3-7990·0] compared with median 11·5 AU/mL [0·4-63·1]; p<0·001). Of participants who were baseline low responders, 380 (90%) of 423 increased their antibody concentrations to more than 400 AU/mL. Conversely, 166 (54%) of 308 baseline non-responders had no response after the third dose. Detectable T-cell responses following the third vaccine dose were seen in 494 (80%) of 616 participants. There were 24 serious adverse events (BNT612b2 eight [33%] of 24, mRNA-1273 12 [50%], NVX-CoV2373 four [17%]), two (8%) of which were categorised as vaccine-related. There were seven deaths (1%) during the trial, none of which were vaccine-related.
INTERPRETATION
A third vaccine dose improved the serological and T-cell response in the majority of patients who are immunocompromised. Individuals with chronic renal disease, lymphoid malignancy, on B-cell targeted therapies, or with no serological response after two vaccine doses are at higher risk of poor response to a third vaccine dose.
FUNDING
Medical Research Council, Blood Cancer UK.
Topics: Humans; Female; Male; COVID-19; Middle Aged; Immunocompromised Host; SARS-CoV-2; COVID-19 Vaccines; Immunogenicity, Vaccine; Aged; BNT162 Vaccine; Antibodies, Viral; Prospective Studies; Immunization, Secondary; 2019-nCoV Vaccine mRNA-1273; Adult; T-Lymphocytes; United Kingdom; ChAdOx1 nCoV-19
PubMed: 38734019
DOI: 10.1016/S2665-9913(24)00065-1 -
Experimental and Clinical... Mar 2024Management of potential organ donors is crucial in the donation process, considering that hemodynamic instability is quite common. (Observational Study)
Observational Study
OBJECTIVES
Management of potential organ donors is crucial in the donation process, considering that hemodynamic instability is quite common.
MATERIALS AND METHODS
In the this single-center retrospective observational study, we analyzed 87 utilized brain death donors consecutively admitted to our intensive care unit from January 1, 2019, to December 31, 2022. We assessed the achievement of donor management goals during the observation period, and we also evaluated whether the achieve-ment of donor goals differed between younger and older donors (arbitrary age cutoff of 65 years).
RESULTS
In our series, mean age of donors was 67 ± 18 y, and organ-per-donor ratio was 2.3. The number of donor goals significantly increased during the 6-hour observation period (P < .001) and all donor goals were achieved in most donors (84/87) at the end of the observation period with no changes in the use and dose of vasoactive drugs. With respect to age, the number of donor goals was significantly higher in older donors at first evaluation, but goals significantly increased in both age subgroups of donors at the end of the 6-hour observation period.
CONCLUSIONS
Our data strongly suggested that a strict hemodynamic monitoring schedule allows the achievement of donor goals both in older and in younger brain death donors. We confirmed our previous findings that hemodynamic management in brain death donors is influenced by age. A strict hemodynamic monitoring schedule of brain death donors is useful to consistently achieve donor goals.
Topics: Humans; Brain Death; Retrospective Studies; Middle Aged; Male; Female; Tissue Donors; Aged; Time Factors; Age Factors; Hemodynamics; Adult; Aged, 80 and over; Donor Selection; Risk Factors
PubMed: 38695586
DOI: 10.6002/ect.2024.0030