It has been suggested that air pollution may increase the risk of type 2 diabetes but data on particulate matter with diameter <2.5μm (PM2.5) are inconsistent. We examined the association between ...long-term exposure to PM2.5 and diabetes incidence.
We used the Danish Nurse Cohort with 28,731 female nurses who at recruitment in 1993 or 1999 reported information on diabetes prevalence and risk factors, and obtained data on incidence of diabetes from National Diabetes Register until 2013. We estimated annual mean concentrations of PM2.5, particulate matter with diameter <10μm (PM10), nitrogen oxides (NOx) and nitrogen dioxide (NO2) at their residence since 1990 using a dispersion model and examined the association between the 5-year running mean of pollutants and diabetes incidence using a time-varying Cox regression.
Of 24,174 nurses 1137 (4.7%) developed diabetes. We detected a significant positive association between PM2.5 and diabetes incidence (hazard ratio; 95% confidence interval: 1.11; 1.02–1.22 per interquartile range of 3.1μg/m3), and weaker associations for PM10 (1.06; 0.98–1.14 per 2.8μg/m3), NO2 (1.05; 0.99–1.12 per 7.5μg/m3), and NOx (1.01; 0.98–1.05 per 10.2μg/m3) in fully adjusted models. Associations with PM2.5 persisted in two-pollutant models. Associations with PM2.5 were significantly enhanced in never smokers (1.24; 1.09–1.42), and augmented in obese (1.25; 1.06–1.47) and subjects with myocardial infarction (1.32; 0.86–2.02), but without significant interaction.
Fine particulate matter may the most relevant pollutant for diabetes development among women, and non-smokers, obese women, and heart disease patients may be most susceptible.
•Evidence on association of PM2.5 with diabetes is inconsistent.•We linked residential PM2.5 to diabetes incidence in Danish Nurse Cohort.•We found 39% (4–86%) increased risk of diabetes per 10μg/m3 increase in PM2.5.•PM2.5 may be the most relevant pollutant for diabetes development.•Non-smokers, obese, and heart disease patients may be most susceptible.
This qualitative-phenomenological study aimed to assess the stakeholders’ perspectives on the conservation and urbanization of Lucban, Quezon, as a historic town. The researchers deployed focus group ...discussion and documentary analysis to collect significant information from the key informants (n = 8). A repertory grid and thematic network analysis were used to evaluate and assess the collected information. Based on the findings, Habhab Framework on Stakeholders’ View on Heritage Conservation and Urbanization was conceptualized to provide an in-depth assessment of the town’s current situation. The framework identifies the significance of the historic town’s culture and heritage resources, primary and secondary stakeholders, current programmes, related issues and constraints, tangible and intangible resources needed for conservation, proposed programmes and perceived positive impacts. It will serve as a basis for stakeholders, especially local authorities, to develop sustainable programmes and projects to conserve and safeguard their rich culture and heritage resources.
Water is an essential participant in the stability, structure, dynamics, and function of proteins and other biomolecules. Thermodynamically, changes in the aqueous environment affect the stability of ...biomolecules. Structurally, water participates chemically in the catalytic function of proteins and nucleic acids and physically in the collapse of the protein chain during folding through hydrophobic collapse and mediates binding through the hydrogen bond in complex formation. Water is a partner that slaves the dynamics of proteins, and water interaction with proteins affect their dynamics. Here we provide a review of the experimental and computational advances over the past decade in understanding the role of water in the dynamics, structure, and function of proteins. We focus on the combination of X-ray and neutron crystallography, NMR, terahertz spectroscopy, mass spectroscopy, thermodynamics, and computer simulations to reveal how water assist proteins in their function. The recent advances in computer simulations and the enhanced sensitivity of experimental tools promise major advances in the understanding of protein dynamics, and water surely will be a protagonist.
The modern field of optical angular momentum began with the realisation by Allen et al in 1992 that, in addition to the spin associated with polarisation, light beams with helical phase fronts carry ...orbital angular momentum. There has been much confusion and debate, however, surrounding the intricacies of the field and, in particular, the separation of the angular momentum into its spin and orbital parts. Here we take the opportunity to state the current position as we understand it, which we present as six perspectives: (i) we start with a reprise of the 1992 paper in which it was pointed out that the Laguerre-Gaussian modes, familiar from laser physics, carry orbital angular momentum. (ii) The total angular momentum may be separated into spin and orbital parts, but neither alone is a true angular momentum. (iii) The spin and orbital parts, although not themselves true angular momenta, are distinct and physically meaningful, as has been demonstrated clearly in a range of experiments. (iv) The orbital part of the angular momentum in the direction of propagation of a beam is not simply the azimuthal component of the linear momentum. (v) The component of spin in the direction of propagation is not the helicity, although these are related quantities. (vi) Finally, the spin and orbital parts of the angular momentum correspond to distinct symmetries of the free electromagnetic field and hence are separately conserved quantities.
Mid-infrared quantum cascade lasers are semiconductor injection lasers whose active core implements a multiple-quantum-well structure. Relying on a designed staircase of intersubband transitions ...allows free choice of emission wavelength and, in contrast with diode lasers, a low transparency point that is similar to a classical, atomic four-level laser system. In recent years, this design flexibility has expanded the achievable wavelength range of quantum cascade lasers to ∼3-25 μm and the terahertz regime, and provided exemplary improvements in overall performance. Quantum cascade lasers are rapidly becoming practical mid-infrared sources for a variety of applications such as trace-chemical sensing, health monitoring and infrared countermeasures. In this Review we focus on the two major areas of recent improvement: power and power efficiency, and spectral performance.
The optimal treatment for complex fractures and large bone defects is an important unsolved issue in orthopedics and related specialties. Approximately 5-10% of fractures fail to heal and develop ...non-unions. Bone healing can be characterized by three partially overlapping phases: the inflammatory phase, the repair phase, and the remodeling phase. Eventual healing is highly dependent on the initial inflammatory phase, which is affected by both the local and systemic responses to the injurious stimulus. Furthermore, immune cells and mesenchymal stromal cells (MSCs) participate in critical inter-cellular communication or crosstalk to modulate bone healing. Deficiencies in this inter-cellular exchange, inhibition of the natural processes of acute inflammation, and its resolution, or chronic inflammation due to a persistent adverse stimulus can lead to impaired fracture healing. Thus, an initial and optimal transient stage of acute inflammation is one of the key factors for successful, robust bone healing. Recent studies demonstrated the therapeutic potential of immunomodulation for bone healing by the preconditioning of MSCs to empower their immunosuppressive properties. Preconditioned MSCs (also known as "primed/ licensed/ activated" MSCs) are cultured first with pro-inflammatory cytokines (e.g., TNFα and IL17A) or exposed to hypoxic conditions to mimic the inflammatory environment prior to their intended application. Another approach of immunomodulation for bone healing is the resolution of inflammation with anti-inflammatory cytokines such as IL4, IL10, and IL13. In this review, we summarize the principles of inflammation and bone healing and provide an update on cellular interactions and immunomodulation for optimal bone healing.
Superhydrophobic self-cleaning surfaces are based on the surface micro/nanomorphologies; however, such surfaces are mechanically weak and stop functioning when exposed to oil. We have created an ...ethanolic suspension of perfluorosilane-coated titanium dioxide nanoparticles that forms a paint that can be sprayed, dipped, or extruded onto both hard and soft materials to create a self-cleaning surface that functions even upon emersion in oil. Commercial adhesives were used to bond the paint to various substrates and promote robustness. These surfaces maintained their water repellency after finger-wipe, knife-scratch, and even 40 abrasion cycles with sandpaper. The formulations developed can be used on clothes, paper, glass, and steel for a myriad of self-cleaning applications.
Superhydrophobic pillar arrays, which can generate the droplet pancake bouncing phenomenon with reduced liquid–solid contact time, have huge application prospects in anti-icing of aircraft wings from ...freezing rain. However, the previously reported pillar arrays, suitable for obtaining pancake bouncing, have a diameter ≤100 μm and height–diameter ratio >10, which are difficult to fabricate over a large area. Here, we have systematically studied the influence of the dimension of the superhydrophobic pillar arrays on the bouncing dynamics of water droplets. We show that the typical pancake bouncing with 57.8% reduction in contact time with the surface was observed on the superhydrophobic pillar arrays with 1.05 mm diameter, 0.8 mm height, and 0.25 mm space. Such pillar arrays with millimeter diameter and <1 height–diameter ratio can be easily fabricated over large areas. Further, a simple replication-spraying method was developed for the large-area fabrication of the superhydrophobic pillar arrays to induce pancake bouncing. No sacrificial layer was needed to reduce the adhesion in the replication processes. Since the bouncing dynamics were rather sensitive to the space between the pillars, a method to control the contact time, bouncing shape, horizontal bouncing direction, and reversible switch between pancake bouncing and conventional bouncing was realized by adjusting the inclination angle of the shape memory polymer pillars.
Long Covid is a public health concern that needs defining, quantifying, and describing. We aimed to explore the initial and ongoing symptoms of Long Covid following SARS-CoV-2 infection and describe ...its impact on daily life.
We collected self-reported data through an online survey using convenience non-probability sampling. The survey enrolled adults who reported lab-confirmed (PCR or antibody) or suspected COVID-19 who were not hospitalised in the first two weeks of illness. This analysis was restricted to those with self-reported Long Covid. Univariate comparisons between those with and without confirmed COVID-19 infection were carried out and agglomerative hierarchical clustering was used to identify specific symptom clusters, and their demographic and functional correlates.
We analysed data from 2550 participants with a median duration of illness of 7.6 months (interquartile range (IQR) 7.1-7.9). 26.5% reported lab-confirmation of infection. The mean age was 46.5 years (standard deviation 11 years) with 82.8% females and 79.9% of participants based in the UK. 89.5% described their health as good, very good or excellent before COVID-19. The most common initial symptoms that persisted were exhaustion, chest pressure/tightness, shortness of breath and headache. Cognitive dysfunction and palpitations became more prevalent later in the illness. Most participants described fluctuating (57.7%) or relapsing symptoms (17.6%). Physical activity, stress, and sleep disturbance commonly triggered symptoms. A third (32%) reported they were unable to live alone without any assistance at six weeks from start of illness. 16.9% reported being unable to work solely due to COVID-19 illness. 37.0% reported loss of income due to illness, and 64.4% said they were unable to perform usual activities/duties. Acute systems clustered broadly into two groups: a majority cluster (n = 2235, 88%) with cardiopulmonary predominant symptoms, and a minority cluster (n = 305, 12%) with multisystem symptoms. Similarly, ongoing symptoms broadly clustered in two groups; a majority cluster (n = 2243, 88.8%) exhibiting mainly cardiopulmonary, cognitive symptoms and exhaustion, and a minority cluster (n = 283, 11.2%) exhibiting more multisystem symptoms. Belonging to the more severe multisystem cluster was associated with more severe functional impact, lower income, younger age, being female, worse baseline health, and inadequate rest in the first two weeks of the illness, with no major differences in the cluster patterns when restricting analysis to the lab-confirmed subgroup.
This is an exploratory survey of Long Covid characteristics. Whilst this is a non-representative population sample, it highlights the heterogeneity of persistent symptoms, and the significant functional impact of prolonged illness following confirmed or suspected SARS-CoV-2 infection. To study prevalence, predictors and prognosis, research is needed in a representative population sample using standardised case definitions.
Use of heterologous prime-boost COVID-19 vaccine schedules could facilitate mass COVID-19 immunisation. However, we have previously reported that heterologous schedules incorporating an adenoviral ...vectored vaccine (ChAdOx1 nCoV-19, AstraZeneca; hereafter referred to as ChAd) and an mRNA vaccine (BNT162b2, Pfizer–BioNTech; hereafter referred to as BNT) at a 4-week interval are more reactogenic than homologous schedules. Here, we report the safety and immunogenicity of heterologous schedules with the ChAd and BNT vaccines.
Com-COV is a participant-blinded, randomised, non-inferiority trial evaluating vaccine safety, reactogenicity, and immunogenicity. Adults aged 50 years and older with no or well controlled comorbidities and no previous SARS-CoV-2 infection by laboratory confirmation were eligible and were recruited at eight sites across the UK. The majority of eligible participants were enrolled into the general cohort (28-day or 84-day prime-boost intervals), who were randomly assigned (1:1:1:1:1:1:1:1) to receive ChAd/ChAd, ChAd/BNT, BNT/BNT, or BNT/ChAd, administered at either 28-day or 84-day prime-boost intervals. A small subset of eligible participants (n=100) were enrolled into an immunology cohort, who had additional blood tests to evaluate immune responses; these participants were randomly assigned (1:1:1:1) to the four schedules (28-day interval only). Participants were masked to the vaccine received but not to the prime-boost interval. The primary endpoint was the geometric mean ratio (GMR) of serum SARS-CoV-2 anti-spike IgG concentration (measured by ELISA) at 28 days after boost, when comparing ChAd/BNT with ChAd/ChAd, and BNT/ChAd with BNT/BNT. The heterologous schedules were considered non-inferior to the approved homologous schedules if the lower limit of the one-sided 97·5% CI of the GMR of these comparisons was greater than 0·63. The primary analysis was done in the per-protocol population, who were seronegative at baseline. Safety analyses were done among participants receiving at least one dose of a study vaccine. The trial is registered with ISRCTN, 69254139.
Between Feb 11 and Feb 26, 2021, 830 participants were enrolled and randomised, including 463 participants with a 28-day prime-boost interval, for whom results are reported here. The mean age of participants was 57·8 years (SD 4·7), with 212 (46%) female participants and 117 (25%) from ethnic minorities. At day 28 post boost, the geometric mean concentration of SARS-CoV-2 anti-spike IgG in ChAd/BNT recipients (12 906 ELU/mL) was non-inferior to that in ChAd/ChAd recipients (1392 ELU/mL), with a GMR of 9·2 (one-sided 97·5% CI 7·5 to ∞). In participants primed with BNT, we did not show non-inferiority of the heterologous schedule (BNT/ChAd, 7133 ELU/mL) against the homologous schedule (BNT/BNT, 14 080 ELU/mL), with a GMR of 0·51 (one-sided 97·5% CI 0·43 to ∞). Four serious adverse events occurred across all groups, none of which were considered to be related to immunisation.
Despite the BNT/ChAd regimen not meeting non-inferiority criteria, the SARS-CoV-2 anti-spike IgG concentrations of both heterologous schedules were higher than that of a licensed vaccine schedule (ChAd/ChAd) with proven efficacy against COVID-19 disease and hospitalisation. Along with the higher immunogenicity of ChAd/BNT compared with ChAD/ChAd, these data support flexibility in the use of heterologous prime-boost vaccination using ChAd and BNT COVID-19 vaccines.
UK Vaccine Task Force and National Institute for Health Research.
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