All of these make it an excellent candidate for several infrared applications such as photodetection, optical modulation, and optical sensing. However, a standalone monolayer graphene still suffers from a weak infrared absorption, which is ≅2.3%. In this work, a novel configuration of graphene metamaterial embedded inside Bundt optical-antenna (optenna) is demonstrated. It can leverage the graphene absorption up to 57.7% over an ultra-wide wavelength range from 1.26 to 1.68 µm . This range covers the entire optical communication bands of O, E, S, C, L, and U. The configuration mainly consists of a Bundt-shaped plasmonic antenna with a graphene metamaterial stack embedded within its nano-wide waveguide that has a 1.5 µm length. The gold average plasmonic loss is ≅25%. This configuration can enhance graphene ultra-broadband absorption through multiple mechanisms. It can nano-focus the infrared radiation down to a 50 nm spot on the graphene metamaterial, thus yielding an 11.5 gain in optical intensity . The metamaterial itself has seven concentric cylindrical graphene layers separated by silicon dioxide thin films, thus each layer contributes to the overall absorption. The focused infrared propagates tangential to the graphene metamaterial layers , and thus maximizes the light–graphene interaction length. In addition, each graphene layer experiences a double-face exposure to the nano-focused propagating spot, which increases each layer’s absorption. This configuration is compact and polarization-insensitive. The estimated maximum absorption enhancement compared to the standalone monolayer graphene was 25.1 times . The estimated maximum absorption coefficient of the graphene stack was 5700 cm Graphene is an attractive material for photodetection, optical modulation, and optical sensing applications because of its broadband optical absorption, high electron mobility, and electrical conductivity . The syn−1 [2 area consisting of a large number of graphene layers and arranged in a grating device backed by a mirror showed an enhanced unpolarized light absorption of 85% over the solar-spectral bandwidth [−1 at a slot gap of ≅15 nm. Critical coupling with guided Bragg-mirror resonance was used to achieve a narrow-band and polarization-sensitive complete absorption of ≅99% in the monolayer graphene [−1 absorption coefficient. A double layer graphene electro-absorption modulator on a silicon-on-insulator waveguide was demonstrated with an optical absorption of 0.13 dB µm−1 [Different techniques have been reported thus far on manipulating the graphene optical absorption ,16,17,18−1 . A 90 nmandwidth , which agraphene . A graphgraphene , which c dB µm−1 . Dart-ty−1. The absorption enhancement compared to standalone monolayer graphene can reach up to 25.1 times . The enhanced absorption has an almost continuous response over all the optical communication bands: O (1260 to 1360 nm), E (1360 to 1460 nm), S (1460 to 1530 nm), C (1530 to 1565 nm), L (1565 to 1625 nm), U (1625 to 1675 nm), with an overall bandwidth of ≅420 nm. This device configuration is promising for free-space infrared optical communications with applications in photodetection, optical modulation, monitoring, and sensing.In this work, a novel configuration of the graphene metamaterial embedded in a plasmonic waveguide  of Bundt1). At the horn input, the inner and outer diameters are 0.05 and 1.4 µm, respectively, whereas, the inner and outer diameters at the horn output are 0.7 µm and 0.8 µm, respectively, resulting in an annular 50 nm-wide gap. The second stage is a straight waveguide that is 50 nm wide and 1.5 µm long. The graphene metamaterial annular stack is embedded to fill the nano waveguide width. The stack consists of seven concentric cylindrical graphene sheets separated by 7 nm silicon dioxide thin films. The first and last graphene layers are in contact with the waveguide gold inner and outer surfaces. Of course, more graphene layers would enhance the metamaterial absorption further, however, seven layers were enough to fill up the 50 nm-wide waveguide, given that the minimum standard width of the separating thin films is 7 nm. The graphene metamaterial embedded Bundt optenna device was designed and simulated using the three-dimensional finite-difference time-domain (FDTD) method . The FDTσ) library, which is built around the well-known Kubo graphene model. The graphene complex refractive indices (n) are obtained using the formula:rε’ is relative permittivity; ‘oε’ is free-space permittivity; ‘ω’ is the infrared angular frequency; ‘Δ’ is the graphene layer thickness, which is assumed here to be 1 nm. The graphene chemical potential was selected to be 0.1 eV. A multi-coefficient model was used to fit the materials’ complex indices.The gold and silicon dioxide material models were selected from the software complex refractive indices library of Palik  whereas 2 = 1.5 µm) was maximized to achieve almost total absorption within the metamaterial. The waveguide acts as a Fabry–Perot due to multiple reflections between its input and output ports. Thus, the waveguide length was also optimized to have almost total destructive interference among the back-reflected waves at its input. In addition, the inner perimeter of the waveguide gap was selected to be equal to the maximum operating wavelength to sustain the mode propagating inside the waveguide. As seen in All of the Bundt optenna and the graphene metamaterial dimensions were optimized through numerical iterations to minimize the infrared back reflections and thus ensure the maximum input power to the device and in turn the maximum graphene absorption. The input coaxial horn dimensions were optimized to match the optical impedance of the free-space incident radiation. Additionally, the plasmonic waveguide dimensions were optimized to match the output optical impedance of the first stage coaxial horn. The length of the plasmonic waveguide  over the volume of the 1 nm thick graphene layer. This was achieved by applying two volumetric monitors, one for the electric field and the other for the refractive index within the absorbing layer. The absorbed power density was then calculated by E2 Imagε  where ‘|2 at the input to 0.11 µm2 at the output . After subtracting the gold losses on the horn gold surface, the gain  in the inferred intensity becomes ≅11.5 . Still, the dip in the curve (3.8%) corresponds to the maximum back reflection and thus yields a minimum graphene absorption. The intensity gain at the waveguide input for the 1476 nm wavelength was almost 11 dB, which yielded a maximum absorption after interaction with the metamaterial. out = Iin e−αL2, where ‘Iin’ is the input intensity to the waveguide, ‘Iout’ is the output intensity of the waveguide, and ‘L2′ is the metamaterial length that equals the plasmonic waveguide length. The maximum absorption coefficient was 5700 cm−1, which corresponds to the maximum graphene absorption. The average absorption coefficient was ≅4500 cm−1, which was considered as one of the record-high reported values of the graphene absorption coefficient. Still, the dip in the curve corresponded to the minimum graphene absorption and maximum back reflection.2) separating thin films , covering the entire optical communication bands . The configuration of the graphene-embedded Bundt optenna is promising for free-space infrared optical communications with applications in photodetection, optical modulation, monitoring, and sensing.A novel configuration to enhance the ultra-broadband infrared absorption coefficient in a graphene metamaterial using a Bundt optical antenna was numerically demonstrated. The graphene metamaterial stack consisted of seven layers of separated cylindrical graphene layers with a length of 1.5 µm. The antenna can nano-focus infrared radiation and propagate it tangential to each graphene layer, thus allowing for a double-face exposure. This polarization-insensitive configuration gives a 10.6 dB intensity gain and enhanced the graphene metamaterial absorption of up to 57.7%. The estimated maximum absorption coefficient of the graphene metamaterial was 5700 cm1 + L2), which constitutes the Bundt central post. The CVD can be used to deposit alternating layers of graphene and silicon dioxide of metamaterial on the rod bottom surface with a length of 1.5 µm. After that, CVD can be used to deposit more gold onto the metamaterial together with the entire rod sidewalls until reaching the full width of a unit cell. Then, the concentric conical horn can be formed inside the gold using focused ion beam milling while controlling the milling area by changing the beam current and etching time.Although this work focused mainly on the numerical simulations of graphene metamaterial embedded within a Bundt optenna, it is worth mentioning a hint on one suggested method for fabrication. A unit cell can be fabricated from the inside out. The chemical vapor deposition (CVD) method can be used to fabricate a cylindrical gold rod with a diameter of 0.7 µm and a total length of 3.5 µm  spectroscopy. The fabricated Bundt optenna samples without embedded graphene metamaterial can be tested with micro-FTIR to measure the optical absorption spectra across different wavelength ranges. Next, other fabricated Bundt optenna samples with the embedded graphene metamaterial can be tested to measure the difference in the optical absorption spectra over the same wavelength bands, and thus estimate the graphene metamaterial absorption by itself. Another method is to use a scattering-type scanning near-field optical microscope (SNOM) that is combined with a pseudo-heterodyne detection module, which can image the scattered near-fields of the micro- and nanostructures at a very small spatial resolution as small as 10 nm. The SNOM can map the scattered electric fields from the fabricated Bundt optenna samples with/without embedded graphene metamaterial, similar to extracting the optical power absorption by the Bundt gold material and then the graphene metamaterial.


Results from studying the effect of an applied electric voltage on the Raman spectrum of graphene deposited on a lithium niobate crystal substrate with a ferroelectric domain structure are presented. The use of the principal component method for data processing in combination with correlation analysis made it possible to reveal the contribution to the change in the spectra associated with the linear deformation of the substrate due to the inverse piezoelectric effect. An effect of the graphene coating peeling was found. Furthermore, bending deformations of the graphene coating associated with the presence of a relief on the substrate were found. An analysis of the change in the spectra of graphene under the application of an electric voltage made it possible to determine the height of this relief. The com devices . The dev devices ,9. Recen devices ,11,12,13Further investigation of the characteristics of graphene/piezoelectric structures will make it possible to expand their application in sensorics, acousto-optics and optoelectronics. An important direction is the development of non-destructive methods for characterizing both the substrate material and the 2D coating itself (graphene). One attractive technique is Raman spectroscopy. The main problem of this method is the noise of the spectra, as a result of which it is very challenging to reveal the influence of any small effects in the structures under study on the Raman spectra. This work presents results from a study on the possibility of using the principal component method in combination with correlation analysis to analyze the effect of piezoelectric substrate deformation on the coating of monolayer graphene. Previously, this approach has been used to probe changes in the composition and piezoelectric properties of crystals ,16.To study the effect of compression/stretching strain on the Raman spectra of monolayer graphene, a sample was fabricated based on a Z-cut substrate of a lithium niobate single crystal with a ferroelectric domain structure. The domain width is 500 µm for a sample thickness of 0.5 mm.3 substrate. An aluminum electrode is deposited on the underside of the substrate. The application of electrical voltage to the top and bottom electrodes causes periodic deformation of the substrate due to the inverse piezoelectric effect. The sign of deformation is determined by the direction of the crystallographic Z axis of the LiNbO3 substrate. A schematic representation of the deformed sample is shown in On the upper face of the substrate, a monolayer graphene coating is formed by the transfer method. This coating serves as the upper electrode. A monolayer CVD graphene on a copper foil manufactured by Rusgrafen was used. The transfer is carried out as follows. A polymethyl methacrylate (PMMA) film is deposited onto a copper foil with grown monolayer graphene by spin coating. After drying the PMMA, the graphene is removed from the backside of the copper foil in oxygen plasma. Then, the foil is etched in a solution of ferric chloride. After that, PMMA with graphene is washed in deionized water and caught on a LiNbOThe deformation of the graphene coating occurs due to the deformation of the substrate and can be studied using Raman spectroscopy. For this purpose, a Bruker Senterra Raman microscope with a 50× objective is used. The laser wavelength is 532 nm, with a power of 10 mW. The laser beam diameter is 2 μm. Electrical voltage is applied in the range from −1500 V to +1500 V with a step of 250 V. Thus, the maximum electric field strength applied to the sample is ±3 kV/mm, which is far from the values at which nonlinear effects appear .β) = 0.9 and a correlation factor |r| ≥0.5, the sample size should be at least N = 29. A total of 73 spectra was obtained, which corresponds to a total of three cycles of changes in the applied electrical voltage. Thus, the analysis of the results should be counted as statistically reliable and will make it possible to establish the presence of a correlation between the changes in the spectra and the applied electrical voltage.−1, and the I(2D)/I(G) ratio is greater than 1 [The spectra contain peaks characteristic of monolayer graphene, since the full width at half the maximum of the 2D and G line peaks is less than 40 cmr than 1 . There ir than 1 ,20, indir than 1 ,22. ThusIt should be noted that a significant spread of the background of the obtained spectra was observed, as well as the noisiness of the peaks. In addition, it is known that the dependence of the position and intensity of the G-peak of graphene, depending on the applied electric field, is nonlinear . The comr on the number of the main component.N scalar observations, then the Pearson correlation coefficient is defined as [Aμ and Aσ are the mean and standard deviation of A, respectively, and Bμ and Bσ are the mean and standard deviation of B.The correlation coefficient of two random variables is a measure of their linear dependence. If each variable has fined as r=1p-values lies between 0 and 1, where values close to 0 correspond to a significant correlation in r and a low probability of observing the null hypothesis. The p-values are calculated from the deviation between the observed value and a chosen reference value, given the probability distribution of the statistic, with a greater difference between the two values corresponding to a lower p-value. Mathematically, the p-value is calculated using integral calculus from the area under the probability distribution curve for all values of statistics that are at least as far from the reference value as the observed value is relative to the total area under the probability distribution curve.The range of p = 6.05 × 10−6.A correlation corresponding to the above parameters of statistical significance is observed for the seventh principal component PC7: r = 0.62, The linear regressions of PC7 for the full data set and for each cycle separately are shown in A comparison of the load vector for the first principal component, which is essentially a spectrum cleared of changes caused by any influences, with the load vector for the seventh principal component, for which a linear dependence on the applied electrical voltage was found, is shown in 2 in A periodical change in the intensity of the peak presumably associated with nitrogen adsorbed N2 in  on the g−1 towards larger wave numbers, which changes the position of the maximum in the range ±5 cm−1, depending on the magnitude and sign of the applied electric field. The characteristic shape of the peak, shifted by 6 cm−1 towards lower wave numbers from the 2D peak, indicates a change in its amplitude and width at half height.Most interesting is the fact that the graphene peaks shifted from the position of the maximum of the main graphene peaks, showing a linear dependence on the magnitude of the applied electrical voltage. Thus, next to the G peak, a satellite is found shifted by 11 cmObviously, the change in the position of the 2E peak is associated with the inverse piezoelectric effect. The combination of changes in the peaks next to G and 2D can be explained by the presence of bending deformations of the graphene coating .δh according to the inverse piezoelectric effect equation for the given experimental conditions:δh—crystal size changing along voltage applying direction; V—applied voltage; d33—piezoelectric strain coefficient of the LiNbO3 crystal. Piezoelectric constants of LiNbO3 can be found in [d33 = 6.2 pC/N. A simple calculation yields the change of crystal size for the applied voltage as V = 1500 V δh = 9.3 nm. The second part of the crystal is stretched by the same amount.Based on the above analysis, a conclusion can be drawn about the structure of the sample under study. First, the domain structure initially had a relief that caused the bending of the graphene coating, which manifested itself in the splitting of the G and 2D peaks. The application of voltage caused a change in the height of the relief. Based on the fact that the change in the position of the peak did not reach the main peak of graphene, it can be concluded that the relief did not disappear during the change in voltage. This means that the initial height of the relief was greater than its maximum change due to the application of an electric field. The height of the initial relief can be estimated according to the following reasoning: as a result of the application of an electric field, one part of the crystal is compressed by found in , such th−1 towards larger wave numbers is observed. The peak shifts towards lower wave numbers when the relief height decreases by the same value. It is shown above that the dependence of the peak position on the applied voltage is linear. Thus, in order for the peak to coincide with the main graphene peak G, it is necessary to apply approximately twice as much voltage, i.e., 3000 V. Consequently, the height of the domain structure relief without the application of an electric field is 37.2 nm.In the case of increasing relief height, a shift of the peak by 5 cmAs a result of this research, a linear dependence of the Raman spectrum of graphene deposited on the domain structure of a lithium niobate crystal on the applied electric voltage was isolated. This part of the contribution to the change in the Raman spectrum is associated with the deformation of the piezoelectric substrate due to the inverse piezoelectric effect. It was found that, during the cyclic application of an electric field, the effect of substrate deformation on the change in the Raman spectrum weakens from cycle to cycle. This may be due to the peeling of the graphene coating. It was also found that the substrate has a relief due to the presence of a ferroelectric domain structure.


Clinically validated, automated arm-cuff blood pressure measuring devices (BPMDs) are recommended for BP measurement. However, most BPMDs available for purchase by consumers globally are not properly validated. This is a problem because non-validated BPMDs are less accurate and precise than validated ones, and therefore if used clinically could lead to misdiagnosis and mismanagement of BP. In response to this problem, several validated device lists have been developed, which can be used by clinicians and consumers to identify devices that have passed clinical validation testing. The purpose of this review is to describe the resources that are available for finding validated BPMDs in different world regions, to identify the differences between validated device lists, and describe current gaps and challenges. How to use validated BPMDs properly is also summarised. It is difficult to measure blood pressure (BP) accurately using the traditional manual auscultatory method. Automated, ‘press-button’ BP measuring devices (BPMDs) have simplified the measurement process greatly. Automated BPMDs eliminate most user-related errors in BP measurement that are common to manual BP , 2. HoweAll clinical validation studies should be conducted independently of the manufacturer to avoid potential conflicts of interest. New clinical validation studies of cuff-based BPMDs should adhere to the recently published ISO standard ISO 81060-2:2018) , also co0-2:2018 Most automated BPMDs available for purchase by consumers globally have not been properly validated for accuracy –9. PotenThis problem has created the need for resources to help clinicians and consumers determine which BPMDs have passed clinical validation testing. The primary resources that have been developed are validated device lists. There are several lists that summarise information from the clinical validation studies of BPMDs and are designed to be accessible to a non-specialist audience . This brhttps://bit.ly/ResourcesBP.Online validated device lists can be used to find validated BPMDs. The lists are developed and maintained by hypertension societies or not-for-profit collaboratives, as well as by one for-profit private organisation Table . HyperteMost BPMDs are validated for use in ‘general populations.’ This refers to subjects aged over 12 years, at least 30% men and 30% women, with a wide range of arm circumferences and BP levels . HoweverAs shown in Table Consensus still needs to be achieved on the definition of equivalent/derivative BPMDs. The levels of evidence currently required from manufacturers for a device to be accepted as equivalent on a validated device lists are varied. These range from acceptance in good faith on the basis of some equivalence information being provided to requiring more stringent notarised affidavits or evidence of adherence to European Union criteria (MEDDEV 2.7/1 rev 4) , as are the two general lists that are designed for global use . There is anecdotal evidence from some low-middle income countries that finding validated BPMDs is challenging . There aWeak and fragmented regulatory frameworks around BPMD validation has been identified by the Pan American Health Organisation/World Health Organisation flagship hypertension control program, HEARTS in the Americas . HEARTS There are some differences in the types of information provided by validated device lists about BPMDs for use in special populations and use of different cuff sizes. Some validated device lists use specific labelling or separate pages for BPMDs that are validated in special populations. This is an important step to ensure that the individuals who require these BPMDs can easily identify and select a suitably validated device. Some validated device lists provide information about the number and type of cuff sizes that are available for each BPMD. Cuff size and arm circumference range are important device characteristics because the accuracy of BP measurement is contingent on using a correctly sized cuff , 28, 29.Validated BPMDs must be used properly to ensure accurate BP measurements are obtained. There are at least five steps required to obtain accurate BP measurements, which are summarised in a video that was developed by the Welch Center for Prevention, Epidemiology and Clinical Research at the Johns Hopkins Bloomberg School of Public Health . The firhttps://bit.ly/ResourcesBP [www.stridebp.org/training).Those who are responsible for measuring BP should be skilled in the aforementioned steps required to obtain accurate readings. After initial training, regular refreshers on the correct measurement technique should be mandated . Any traourcesBP . The STRourcesBP . The e-lIn summary, most automated cuff BPMDs available for purchase by consumers globally have not been clinically validated for accuracy. Validated device lists enable consumers to identify accurate BPMDs. However, there are differences between validated device lists due to the validation protocols that are accepted, procedures for inclusion of equivalent devices and the types of BPMDs listed. Further, the different validated device lists may not be relevant across different regions of the world. Altogether, these differences may create confusion for consumers trying to identify clinically validated BPMDs. Other gaps and challenges to optimal use of validated device lists relate to identification of (1) validated BPMDs available for purchase in low-middle income countries, (2) BPMDs validated in special populations, and (3) cuff sizes available for purchase with each device. While selecting a clinically validated BPMD is essential to accurate BP measurement, these devices must also be used properly so that accurate BP measurements are obtained. Skill achievement and maintenance with training and refreshers to ensure that the five essential measurement steps are followed consistently is recommended.


A key component of the marine sulfur cycle is the climate-active gas dimethylsulfide (DMS), which is synthesized by a range of organisms from phytoplankton to corals, and accounts for up to 80% of global biogenic sulfur emissions. The DMS cycle starts with the intracellular synthesis of the non-gaseous precursor dimethylsulfoniopropionate (DMSP), which is released to the water column by various food web processes such as zooplankton grazing. This dissolved DMSP pool is rapidly turned over by microbially mediated conversion using two known pathways: demethylation (releasing methanethiol) and cleavage (producing DMS). Some of the formed DMS is ventilated to the atmosphere, where it undergoes rapid oxidation and contributes to the formation of sulfate aerosols, with the potential to affect cloud microphysics, and thus the regional climate. The marine phase cycling of DMS is complex, however, as heterotrophs also contribute to the consumption of the newly formed dissolved DMS. Interestingly, due to microbial consumption and other water column sinks such as photolysis, the amount of DMS that enters the atmosphere is currently thought to be a relatively minor fraction of the total amount cycled through the marine food web—less than 10%. These microbial processes are mediated by water column temperature, but the response of marine microbial assemblages to ocean warming is poorly characterized, although bacterial degradation appears to increase with an increase in temperature. This review will focus on the potential impact of climate change on the key microbially mediated processes in the marine cycling of DMS. It is likely that the impact will vary across different biogeographical regions from polar to tropical. For example, in the rapidly warming polar oceans, microbial communities associated with the DMS cycle will likely change dramatically during the 21st century with the decline in sea ice. At lower latitudes, where corals form an important source of DMS (P), shifts in the microbiome composition have been observed during thermal stress with the potential to alter the DMS cycle. In comp−1 , and the−1 . However−1 , with ne−1 .42−) and methanesulfonate (MSA) aerosols, but the efficiency of this process in producing CCN has been questioned [Once ventilated to the atmosphere, DMS is rapidly oxidized to form non-sea-salt sulfate , the precursor compound to DMS. It has been long recognized that different phytoplankton genera synthesize DMSP to varying degrees , with coRecent observational studies have confirmed the importance of marine DMS emissions to atmospheric CCN ,29 and nMarine bacteria were first recognized for their role in the decomposition of organic material and the remineralization of inorganic nutrients, a role that only became fully understood during the 1980s. Azam and colleagues described a “microbial loop” in which dissolved organic matter released by phytoplankton and grazers is consumed by bacteria. Bacteria are consumed by protozoa, which are then consumed by microzooplankton that are part of the traditional grazing chain . It was However, the role of microbial heterotrophs in the DMS (P) cycle was not fully appreciated at the time of the original CLAW hypothesis. Indeed, it was not until two seminal papers by Simo  and Kien2 and warming on the marine microbial loop and the cycling of DMS (P). As noted by Cavicchioli et al. [Algal intracellular DMSP can be released to the water column via a number of processes, namely, zooplankton grazing , exudatii et al. , the rec42−), which is abundant in the ocean. Sea-to-air transfer of S occurs via the ability of phytoplankton to synthesize cellular DMSP, the microbial-mediated transformation to DMS, and its subsequent emission to the atmosphere, where it has a possible involvement in climate regulation. As noted above, DMS provides the main biogenic source of reduced S to the global atmosphere. The annual global production of DMSP by deep ocean phytoplankton  is conservatively estimated as 3.8 Pg C year−1 [−1 [It is now recognized that organosulfur compounds both in the water and the cell play important roles in the marine food web by mediating interactions between phytoplankton and heterotrophic bacteria ,60. SulfC year−1 —this is C year−1 . DMSP isC year−1 ,64 and cC year−1 ,65. FielC year−1 ,67, wherar−1 [−1 .3SH), via the demethiolation pathway, or to DMS via the enzymatic cleavage pathway, and the consumption of both dissolved DMSP and DMS by bacteria. Interestingly, MeSH is also a volatile compound but its sea-to-air flux estimates are scant, although it has recently been estimated to be comparable to, albeit less than, that of DMS [A conceptual model of the key processes in the marine cycle of DMS and its precursor compound DMSP is presented in t of DMS .However, this conceptual model is only partly complete as Li et al.  describeAlgal intracellular DMSP is released into the water column by a variety of processes, e.g., exudation , cell lyPelagibacterales) clade, which is of ancient evolutionary origin and comprises the most abundant and ubiquitous clade of heterotrophic marine bacteria in the oceans, estimated to make up 25% of the plankton community [The uptake and assimilation of dissolved DMSP can satisfy the energy, carbon, and sulfur demands of entire marine bacterial communities . A case ommunity . Tripp eommunity  observe Roseobacter group  can establish mutualistic relationships with phytoplankton that are, in part, maintained by exchanges of DMSP. A similar sulfonate-based mutualistic interdependence between phytoplankton and SAR11 organisms has also been found in the North Pacific [Furthermore, O’Brien et al.  point ou Pacific .From the conceptual model presented in Measurements of DMS yield ,81,82,83Roseobacter group, a ubiquitous group of marine bacteria, are well-known MeSH producers [Members of the roducers , and in roducers  posited roducers , which croducers .2-driven impacts in the coming decades, including ocean acidification (OA), warming, deoxygenation, and loss of sea ice cover [2 increases appear to confound the situation, with decreases in phytoplankton biomass combined with increases in bacterial production reported in the Arctic [The global oceans face multiple COce cover , all of ce cover . Warmingce cover ,90. The ce cover ,92,93. Sce cover . Thus, tce cover . Howeverce cover . Despitece cover . Howevere Arctic .Over the last two decades, numerous studies have explored the effect of climate change on the broad structure and functioning of the marine food web and the possible changes in net primary production (NPP). This has been attempted through both modelling and mesocosm experiments ,103,104.Prognostic DMS models have been under development since the early 1990s . Most ofThe difficulty of applying DMS prognostic models at the global scale has prompted efforts to develop globally applicable diagnostic schemes that predict DMS seawater concentration based on variables such as surface chlorophyll and light, which can be retrieved using satellite remote sensing algorithms ,119,120.Notwithstanding the lack of a globally applicable DMS prediction algorithm , there hBock et al.  examine −1 reduction in ocean carbon uptake by 2100 under the high-emission scenario RCP8.5. The inclusion of more complex ecological parametrizations in the ESM simulates a more modest decline in the ocean carbon sink capacity of ~0.06 PgC year−1 during the 21st century [−1 [As indicated above, it is likely that the simulated variability in future DMS trends is related to the inability of current ESMs to accurately project future changes in marine primary production. Depending on whether the ESM formulation has biological processes that are temperature-dependent or not, simulated NPP can either increase or decrease under projected climate change . Indeed, century , comparetury [−1 .2 level on the DMS (P) cycle by perturbing either one or both variables simultaneously. Avgoustidi et al. [2 (700 ppm) in Emiliania huxleyi and found that DMS production was roughly halved, which they attributed to a change in intracellular DMSP at lower pH values. Spielmeyer and Pohnert [Thalassiosira pseudonana, Phaeodactylum tricornutum) and a prymnesiophyte (Emiliania huxleyi) under the influence of increased temperature, by 6 °C, and elevated CO2 to 790 ppmv. The diatoms and prymnesiophytes revealed opposite trends for DMSP. In diatoms, increased CO2 and temperature led to decreased DMSP concentrations, however elevated levels of this metabolite under the influence of these parameters were observed for Emiliania huxleyi.Over the past decade, several mesocosm and ship-board bioassay experiments have examined the impact of future increased temperature and pCOi et al.  looked a Pohnert  analyzedEmiliania huxleyi. Four different environmental conditions were tested: ambient, elevated CO2 (+CO2), elevated temperature (+T), and elevated temperature and CO2 (+TCO2). In comparison to the ambient treatment, average DMS production was about 50% lower in the +CO2 treatment. Importantly, temperature had a strong effect on DMS production, and the impacts outweighed the effects of a decrease in pH, with a more than doubling of intracellular DMSP.Arnold et al.  also rep2 (160–830 ppm) favored the growth of large diatoms, which outcompeted other phytoplankton species and reduced the growth rate of smaller, DMSP-rich dinoflagellates. This decreased the grazing rate of heterotrophic dinoflagellates, resulting in reduced DMS production via grazing activity, and highlights the influence of community composition changes on future DMS production under warming.Park et al.  conducte2 perturbation experiments in NW European waters and found that the changes induced consistent, marked increases in DMS and decreases in DMSP, in contrast to results from longer-term mesocosm experiments. Bacterially mediated DMS processes appeared to be insensitive to ocean acidification, with no detectable effects on dark rates of DMS consumption and gross production and no consistent response seen in bacterial abundance [Hopkins and Archer  conductebundance .Amphidinium carterae to investigate the effects of elevated CO2 concentration and temperature on the growth and production of DMSP and DMS, however they found no significant effects on the concentrations and cell-normalized concentrations of DMSP or DMS. Saint-Macary et al. [Li et al.  conductey et al.  observed2 resulted in a 15% and 40% decline in average concentrations of DMS compared to the control. Results from S-35-DMSPd uptake assays indicated that neither concentrations nor microbial scavenging efficiency of dissolved DMSP was affected by increased pCO2. However, their results show a reduction of the mean microbial yield of DMS by 34% and 61% in the 2 × pCO2 and 3 × pCO2 treatments, respectively [Significant positive correlations were found between bacterial production and concentrations of DMS in Canadian waters during autumn. The 13-day mesocosm experiments were characterized by blooms of diatoms, with the results pointing to temperature-associated enhancement of bacterial DMSP metabolism and large increases to DMS (>200%), negating any decreases due to acidification . Howeverectively .Emiliania huxleyi, it would seem likely that the adverse effect of increased pH on the growth of this calcifying organism would also result in a negative impact on the overall production of both DMSP and DMS [Clearly, the results of these perturbation experiments are varied and appear to sensitively depend on the phytoplankton groups present, the ocean region examined (polar or temperate), and the perturbation applied. Subtle interactions are also evident, which can lead to counter-intuitive results. For instance, in studies of natural communities that are dominated by the DMSP-rich species  and DMS , but thi and DMS .2 changes on future DMS (P) production. It is apparent that the results are sensitive not only to the phytoplankton functional group present but also to the length and type of experiment (mesocosm versus bioassay) and thus the potential for shifts in the community composition to occur.The range of different results in these experiments makes it difficult to present a synthetic view of the impact of temperature and/or pCOThe Coupled Model Intercomparison Project Phase 6 (CMIP6) provides climate projections for a range of scenarios to understand the past, present, and future climate. For a better understanding of the impact of the projected climate change on SST, mixed layer depth (MLD), and pH, these are examined for both a contemporary (2001–2020) and end of century (2081–2100) climate, as simulated by CMIP6 models under a SSP2-4.5 and SSP5-8.5 Shared Socioeconomic Pathway (SSP). The possible impact of ocean warming and acidification on DMS (P) production and cycling is then discussed below.Model output for monthly mean SST (°C) and MLD (m) was obtained from the Australian Community Climate and Earth-System Simulator-Coupled Model version 2 (ACCESS-CM2)  for the −2) is expected by 2100, assuming a shift towards renewable energy and sustainable development [−2) is expected by 2100, assuming that development will be largely driven by fossil fuels [https://esfg-node.llnl.gov/search/cmip6 (accessed on 19 June 2022)).The historical simulations run to 2014, with solar variability, volcanic aerosols, and anthropogenic-driven changes in atmospheric composition (GHG and aerosols) forced by datasets that are largely based on observations . The conelopment . For SSPil fuels . Data weOcean warming poses a serious threat to many marine ecosystems. Anthropogenic GHG emissions trap solar radiation within the Earth’s atmosphere, leading to an accumulation of excess heat energy. More than 90% of this excess heat is stored in the ocean, leading to a 0.5 °C rise in global mean SST over the past 40 years . By the Temperature impacts the physiology of marine organisms, ocean currents, mixing, and the availability of nutrients in the ocean. Rising SST is predicted to contribute to a stratification of the upper ocean layers and an overall reduction in global mixed layer depth, particularly in the Southern Hemisphere mid–high latitudes and North Atlantic Ocean, where present-day MLD is deepest . Reduced2. Dissolution of CO2 forms carbonic acid, which readily dissociates into bicarbonate ions and protons, thereby reducing pH. Current anthropogenic CO2 emissions are 10.1 ± 0.5 Gt C year−1 [2 is absorbed by the ocean and has led to a decrease in global mean ocean pH of 0.1 units over the past 100 years [2 emissions by the end of this century under an SSP2-4.5 scenario, global mean ocean pH is predicted to decline by −0.18  concentrations and a low carbonate system buffering capacity, mainly due to the increased solubility of COd waters . This mad waters , althougd waters . Althougd waters ,158.In contrast, Hopkins et al.  report fOcean warming and acidification pose serious threats to tropical coral reef ecosystems, with impacts already evident through more frequent and severe coral bleaching events ,162,163,Reef-building Scleractinian corals have relatively narrow temperature tolerance ranges ,166,167,−1 of DMS  [a) in the Great Barrier Reef (GBR), Australia, average approximately 30 ppt in winter and 100 ppt in summer [a concentration reached 1149 ppt when the coral reef flat was thermally and osmotically shocked by rainfall [Coral reef ecosystems are important regional sources of dissolved and atmospheric sulfur, emitting an estimated 0.05–0.08 Tg yearear−1 S) . Reporten summer ,174, andn summer . On one DMSP biosynthesis and cleavage to DMS is upregulated in corals in response to thermal and irradiance stress ,176,177.Shifts in the coral holobiont microbiome can result in a change in DMS (P) production ,185. DMSIf corals can withstand rising ocean temperatures through natural means, such as the recruitment of temperature-tolerant endosymbionts ,184, DMSPorites corals have declined by 0.36% and 1.02%, respectively [Exacerbating the impacts of ocean warming, ocean acidification has already led to a decline in the bioavailability of carbonate ions , limitinectively . AlthougAs for ocean regions, algal and microbial communities play an important role in the production and cycling of DMS (P) in the coral holobiont and in coral reef waters . IncreasFurther, corals and algae compete for light, nutrients, and space in the reef matrix. Predicted declines in coral cover due to ocean warming, acidification, predation, and declining water quality may lead to an increase in algal biomass in coral reefs. Increased algal biomass is often observed after mass coral bleaching and mortality events , impedinEcological interactions between marine bacteria and phytoplankton are now recognized as playing a central role in the ocean’s major biogeochemical cycles. How these interactions may be modified as a result of climate change is the focus of this review, which examined the role of heterotrophic bacterioplankton in the cycling of a suite of organo-sulfur compounds, such as DMS. This volatile compound and its precursor DMSP are ubiquitous in the oceans, being synthesized by a large range of marine organisms from algae to corals. After ventilation, DMS constitutes the largest source of natural sulfur to the atmosphere and is thus also an important contributor to the atmospheric burden of sulfate aerosol with key relevance to the Earth’s radiative balance and climate.Due to its synthesis by numerous marine organisms, DMSP and its related compounds are an important source of DOM for bacterial heterotrophy in the surface ocean, where it has been estimated to contribute up to 100% of the sulfur requirements of some important marine bacteria groups. There is growing evidence that sulfonates serve as an ecologically important currency for nutrient and energy exchange between autotrophs and heterotrophs, highlighting the importance of organo-sulfates in regulating ecosystem function. This suggests that climate change impacts on the synthesis and cycling of DMS (P) could have important future consequences for the structure of the marine food web.2 changes on future DMS (P) production. It is apparent that the results are sensitive not only to the phytoplankton functional group present but also to the length and type of experiment conducted.However, perturbation experiments seeking to understand the impact of warming and OA on the synthesis of DMS have so far yielded equivocal results. The range of different results makes it difficult to provide a synthetic view of the impact of temperature and/or pCOAlthough numerous attempts have been made to numerically model the impact of warming on the DMS (P) cycle, there is no general agreement in the literature with regards to the sign and amplitude of the future trend in DMS concentration and sea-to-air flux. Importantly, these efforts are also constrained  by a lack of an explicit temperature-dependent parameterization of the key bacterial-mediated processes, such as demethylation and enzymatic cleavage. Considering the critical roles DMS and its precursor DMSP appear to play in supplying carbon and sulfur to marine heterotrophs, future efforts should focus on informing the many uncertainties still apparent in the literature regarding the ecological role of these compounds, and especially the nexus between future CC impacts on marine bacteria and the possible resultant changes in the marine DMS (P) cycles.


Intracellular accumulation of abnormal proteins with conformational changes is the defining neuropathological feature of neurodegenerative diseases. The pathogenic proteins that accumulate in patients' brains adopt an amyloid-like fibrous structure and exhibit various ultrastructural features. The biochemical analysis of pathogenic proteins in sarkosyl-insoluble fractions extracted from patients’ brains also shows disease-specific features. Intriguingly, these ultrastructural and biochemical features are common within the same disease group. These differences among the pathogenic proteins extracted from patients’ brains have important implications for definitive diagnosis of the disease, and also suggest the existence of pathogenic protein strains that contribute to the heterogeneity of pathogenesis in neurodegenerative diseases. Recent experimental evidence has shown that prion-like propagation of these pathogenic proteins from host cells to recipient cells underlies the onset and progression of neurodegenerative diseases. The reproduction of the pathological features that characterize each disease in cellular and animal models of prion-like propagation also implies that the structural differences in the pathogenic proteins are inherited in a prion-like manner. In this review, we summarize the ultrastructural and biochemical features of pathogenic proteins extracted from the brains of patients with neurodegenerative diseases that accumulate abnormal forms of tau, α-synuclein, and TDP-43, and we discuss how these disease-specific properties are maintained in the brain, based on recent experimental insights. The pathological hallmark of neurodegenerative diseases is the accumulation of misfolded proteins in neurons and/or glial cells. The accumulation of amyloid-β (Aβ) and tau in the brains of patients with Alzheimer's disease (AD) was reported in the 1980s, and the group of diseases characterized by abnormal tau inclusions is referred to as tauopathies , 315. InC), whereas when converted to the abnormal form (PrPSc), it forms amyloids rich in β-sheet structures. . 286]. TLike tau, insoluble α-syn extracted from the brain of patients with synucleinopathies exhibits prion-like properties and causes seed-dependent α-syn aggregation in vitro and in vivo. Heterogeneity of the prion-like seeding activity has also been reported, depending on the α-syn strain , 314. SiTARDBP gene encoding TDP-43 are associated with the onset of ALS and FTLD-TDP [C9ORF72 gene also cause TDP-43 proteinopathy, suggesting that the interaction of these RNA-binding proteins with TDP-43 and disruption of RNA metabolic homeostasis are involved in the intracytoplasmic accumulation of TDP-43 [TDP-43 is an RNA-binding nuclear protein localized mainly in the nucleus . It consFTLD-TDP . More thFTLD-TDP , 277. Muf TDP-43 , 243. Ref TDP-43 , 81. Undf TDP-43 , 95, 187Immuno-electron microscopic studies of brain sections from cases of ALS and FTLD-with ubiquitin-positive inclusions have shown the presence of TDP-43 and ubiquitin-positive bundles of straight filaments 10–20 nm in diameter in neurons , 188. AmE. coli as substrates [GRN or C9ORF72 gene mutations into Tg mice expressing human TDP-43 in the cytoplasm reproduced TDP-43 pathology associated with the inoculated samples in a time-dependent manner [Patient-derived insoluble TDP-43 exhibits prion-like properties in vitro and in vivo. An RT-QuIC study found that abnormal TDP-43 in brain homogenates and CSF derived from ALS and FTLD cases were amplified using full-length TDP-43 and truncated TDP-43 (residues 263–414) purified from bstrates . Abnormabstrates . Furtherbstrates . Insolubbstrates , 176. Inbstrates . In vivot manner . Inoculat manner .As we have described, abnormal proteins that accumulate in the brains of patients exhibit ultrastructural and biochemical properties that are characteristic of each disease. It is worth emphasizing that these properties are common in the same disease group, and even in different brain regions of one individual. These results suggest that pathogenic tau, α-syn and TDP-43 spread throughout the brain, retaining their disease-specific structural and biochemical properties.To further explore this possibility, we examined whether disease-specific tau aggregation and filament formation were reproduced in cultured cells . InsolubThe requirement of amino acid sequence identity between template and substrate for template-dependent amplification is also clearly demonstrated by the in vitro and in vivo observation of low seeding and propagation efficiency caused by species barriers , 251. SeThe heterogeneity of abnormal proteins accumulated in patients’ brains is a key factor in the onset and progression of neurodegenerative diseases. Structural and biochemical analyses of post-mortem brains have revealed structural polymorphisms (strains) and prion-like properties of pathogenic proteins. Notably, recent cryo-EM studies of tau and α-syn filaments extracted from patients’ brains have provided direct evidence of strain formation in the brain Table . Detaile


The aim of the HEARTS in the Americas initiative is to promote the adoption of global best practices in the prevention and control of cardiovascular diseases, and improve the control of hypertension. HEARTS is being implemented in 21 countries and a diverse set of actions and measures are in progress to improve exclusive access in primary health care facilities to automated blood pressure measuring devices that have been validated for accuracy. The purpose of this manuscript is to illustrate these efforts, mainly in the regulatory and public procurement arena, and to present information on common challenges and solutions identified. Examples from six countries confirm the need for not only a robust regulatory framework to increase availability of validated automated blood pressure measuring devices but also a comprehensive strategic approach that involves relevant stakeholders, includes a multi-pronged approach and is associated with a national program to prevent and control non communicable diseases. High blood pressure (BP) is a leading risk factor for cardiovascular disease, which is a major health burden on the Region of the Americas . HEARTS In work by PAHO and countries implementing HEARTS, regulatory deficiencies have been identified that allow automated BPMDs to be marketed without evidence of accuracy validation , which iSince 2017 the number of countries implementing HEARTS in the Americas has grown, and there are currently 21 countries enrolled in the initiative at different stages of implementation and level of expansion. The efforts to improve access to validated automated BPMDs are different for each country, in line with its priorities, health system maturity including regulatory, economic, and political conditions. Nevertheless, there are common themes between countries for successes, challenges and the steps taken improve access to validated automated BPMDs. The purpose of this manuscript is to provide examples from six selected countries that are trying to address the problem of non-validated automated BPMDs. The information contained in this manuscript may be useful for other countries that are considering changes to regulatory and procurement processes with the goal of achieving exclusive use of automated BPMDs clinically validated for accuracy.In order to assist the transition towards exclusive use of validated automated BPMDs, and in line with the WHO recommendations , the PanAny modifications aiming to improve regulations or procurement mechanisms related to automated BPMDs need to be coordinated, progressive and sustainable and therefore must be integrated into a national health strategy and cardiovascular health programs. Policies should also be flexible enough to account for technological innovations and advancement of research methods.Box 1 Elements of HEARTS in the Americas strategy to ensure exclusive use of validated automated blood pressure measuring devices (BPMDs) in primary health care facilitiesUnderstanding the regulatory context through mapping of regulatory bodies and processes.Creating awareness by bringing the concept and know-how of accuracy validation into the public health agenda.Training on protocols for accuracy validation of automated BPMDs to enable countries to perform studies and educate on the difference between accuracy validation and other mechanisms of quality assurance.Providing information on which automated BPMDs are validated and available in the Region of the Americas for acquisition by the public sector.Developing technical specifications for procurement of automated BPMDs to be used as criteria for procurement and for regulations.Guidance and technical support in the development, implementation and monitoring of regulations.Promotion of a process that counts on the ample participation of key stakeholders and that is implemented gradually.Different approaches to improve access to validated automated BPMDs have been taken by governments of each country, based on their priorities, regulatory systems, political and economic characteristics. Examples of key actions and challenges specific to Brazil, Chile, Cuba, Dominican Republic, Ecuador and Saint Lucia were provided by representatives of governments  of selected HEARTS countries. The narratives provided were checked against other information previously obtained and online records for consistency, condensed and edited for clarity and validated by the coauthor representatives . An overview of the common strengths, challenges, key actions and lessons are summarized in Table Accuracy validation based on ISO 81060-2: 2018 or other validation protocols is currently required for the marketing of automated BPMDs in Brazil. Manufacturers (or importers) must submit a clinical investigation report to the National Institute of Metrology (INMETRO), which analyzes the report content to confirm that all points required by the protocols are met. At INMETRO, investigation reports are reviewed by metrology researchers, generally with a background in engineering and experience in metrology, focusing on healthcare.The accuracy validation study results are provided directly by the manufacturer. However, the results are not required to be included on registries of validated automated BPMDs or published in peer-reviewed scientific journals. This suggests a lack of independence of the manufacturer from the accuracy validation data, which is not recommended as best practice , 16. ForThe implementation of the HEARTS Initiative in 2017, in which Chile was part of the first cohort, has reinforced the need to improve the quality of BP measurement. Since 2012, the purchase of validated automated BPMDs was recommended by the Ministry of Health (MoH). This recommendation was stressed in 2018 by HEARTS implementation with the development of the BP measurement protocol, videos of correct BP measurement and educational materials for patients, all emphazing that automated BPMDs must be validated for accuracy. The MoH’s National Supply Center reported that between 2018 and 2020, automated BPMD purchases increased from 15% to 75% of the total number of devices. Likewise, the proportion of validated automated BPMDs acquired for use in the public sector increased from 34% in 2018 to 64% in 2020. It is important to note that there are other purchasing mechanisms, such as those defined by the different Health Services , which are autonomous to make their own decisions.In 2021, a BP measurement protocol was published on the MoH website stressing the recommendation of only using validated automated BPMDs . In addiChile still has challenges from the regulatory perspective because the measurement protocol and the recommendations for acquisition of automated BPMDs aforementioned are not normative yet and thus are not enforceable. To address this challenge, a group including representatives of government bodies responsible for the purchase and surveillance of medical devices across Chile is currently working on a regulation proposal that includes impact assessment and identification of the automated BPMDs available in all health care facilities across the country.Cuba cannot access validated automated BPMDs available in the global market due to their high cost and other economic and trade restrictions. Therefore, the validated automated BPMDs available as of December 2021 were obtained mainly through international technical cooperation projects. However, a Cuban medical equipment manufacturer has developed automated BPMDs for 24-hour ambulatory monitoring and, as of 2016, an automated BPMD for home and office use. The locally produced automated BPMDs are currently used at all levels of care. In 2018, due to the HEARTS Initiative emphasis on replacing aneroid devices, domestic automated BPMDs were introduced and rapidly expanded to provide at least one device for approximately 70% of the 11,000 PHC teams in the 489 health centers across the country. However, those devices are not yet clinically validated using the ISO 81060-2:2018 standard or any other validation protocol.Catalyzed by the HEARTS in the Americas, in 2019, training on accuracy validation studies was provided by experts from the University of Alberta, Canada. The purpose of the training was to develop the technical expertise and knowledge to conduct validation studies according to the highest international standards and assess the accuracy of the locally produced automated BPMDs. Subsequently, the National Hypertension Commission, an independent technical body, approved the formation of a technical group to conduct an accuracy validation study under the academic coordination of the Institute of Cardiology and Cardiovascular Surgery, with the participation of the State Center for the Control of Medicines, Equipment and Devices, a WHO collaborating center, to verify the accuracy of locally produced automated BPMDs. There was no industry participation in any step of the process.In parallel to the accuracy validation effort, the conditions will be created to modify the regulatory framework to incorporate ISO 81060-2:2018 into Cuban Standards to ensure exclusive use of validated automated BPMDs before 2025. Finally, the availability of automated BPMDs must be improved, including expanding the production of the current model and the development and commercialization of new ones, with more capabilities, such as data transmission features.A challenge in the Dominican Republic is the precariousness of the electrical power supply in many remote health centers and the absence of uninterrupted availability of batteries to operate automated BPMDs. For these reasons, the HEARTS national managing team chose to temporarily maintain the use of aneroid BPMDs in some facilities but also to provide additional training for health personnel focused on the correct use of automated BPMDs. Simultaneously, an exhaustive search was conducted to identify automated or semi-automated BPMDs that would not need batteries to operate. The search led to choosing a validated semi-automatic BPMD with rechargeable batteries that is accurate in pregnancy and meets the WHO criteria for use in a low-resource setting . This deSince this was the first time a digital device would be used in the country, a 15-day study was conducted with a small sample of health personnel to explore how they would respond to this change. This study, which is yet to be published, was conducted by taking measurements alternatively with aneroid devices and the semi-automated BPMDs on the same patient. There was some resistance to change by the medical profession. To overcome this resistance progressively, health care personnel are being trained through local HEARTS workshops and the HEARTS BP measurement course, to educate them on the difficulty of accurately diagnosing hypertension with an aneroid sphygmomanometer.In 2018, 94 validated automated BPMDs were acquired to conduct the Ecuador non-communicable diseases risk factors survey and PHC facilities that had started implementing HEARTS. Unfortunately, budget cuts within the Ecuadorean MoH have since hindered the purchase of new validated automated BPMDs. However, the initial devices were followed by the acquisition of an additional 468 validated automated BPMDs, including 300 devices through liaison with the HEARTS coordinating team and international cooperation agencies. As of December 2021, 352 health centers were implementing HEARTS, which corresponds to 18% of the country’s 1940 health centers. Approximately 85% of these 352 centers have validated automated BPMDs, which means 15% of the total in the country.In addition, the HEARTS in the Americas pillar on education and training has found great receptivity demonstrated by the high number of health professionals taking the HEARTS virtual course on BP measurement . The nurTo ensure exclusive public procurement of validated automated BPMDs for HEARTS implementing centers, technical specifications that include international accuracy validation standards have been developed by the MoH with the support of. In addition, the process to make the standards enforceable for the acquisition of BPMDs for use in any public facility, especially those in PHCs, has been initiated within the MoH and is expected to be approved in the first trimester of 2022.A challenge has been the limited availability of validated automated BPMDs in the national market. This was identified when procuring BPMDs for use in HEARTS implementing centers in 2021, by analysis of the National Agency for Regulation, Control and Sanitary Surveillance (ARCSA) database of BPMDs with pre-market approval for sale. Only one had presented proof of passing accuracy validation testing from the five models registered for sale. An additional challenge is the lack of knowledge of the advantages of using automated BPMDs and preventive maintenance to extend their useful life. Provision of information and advocacy with health care personnel and managers are being conducted to address these issues. However, a key step will be modifying regulations to include accuracy validation as a requirement for registration at ARCSA, which is underway.In Saint Lucia, registration of automated BPMDs for sale in the country is dependent upon approval by the Saint Lucia Bureau of Standards (SLBS), which has responsibility for enforcement of the Metrology Act. The Act is a law which gives the SLBS responsibility for approval and verification of measuring instruments used in the field of public health, including automated BPMDs. However, achieving the goal of enacting legislation that would ensure the exclusive sale of accuracy validated automated BPMDs in the country involves other government sectors, and, to that end, discussions between the stakeholders, such as MoH, Ministry of Commerce, Attorney General’s Chambers, and Customs, have been underway.Meanwhile, in May 2021, accuracy validation became a prerequisite for verification of accuracy, performance, and calibration by the SLBS, as per OIML R149 requirements. A campaign to promote the use of validated BPMDs has been carried out with the use of social media, and two webinar presentations were given by the SLBS to the medical sector and importers recommending that only validated automated BPMDs approved for sale in the country and tested for accuracy against established protocols be used. One large pharmacy chain in Saint Lucia imported a stock of validated automated BPMDs for sale to the public as a result of an SLBS presentation to the medical sector and it is anticipated that competitive forces will play a role in ensuring that other suppliers follow suit. The public service announcement from the SLBS on the verification of automated BPMDs, which first aired in 2017, and is presently on the SLBS’ YouTube channel will be edited to include specific information on validated automated BPMDs.Among the challenges are online purchases of non-validated automated BPMDs at distributors and retail outside Saint Lucia, pressure from suppliers to sell the remaining stock of non-validated automated BPMDs and the variability of information available on online registries.The six countries that were the focus of this manuscript have shown the political will to reach the exclusive availability of validated automated BPMDs. Indeed, most of the facilities implementing HEARTS began to use accuracy-validated automated BPMDs, and this represented an important stimulus to advance this strategic work. The general achievements by these six countries showed in concrete actions are twofold: (a) sectors of governments have been investing politically and administratively in modifications to regulations that do not require a substantive and complex legislative process; and (b) in parallel, improved procurement toward exclusive access of validated automated BPMDs has been at least partially achieved. The improvement of procurement mechanisms has focused on defining technical specifications that include accuracy validation. In addition, lack of access to validated automated BPMDs has been counteracted by local production of devices and cooperative procurement approaches. The lessons shared in Table There are many ongoing challenges confronted by countries implementing HEARTS. The common challenges are related to changing regulations and/or legislation, budgetary limitations and resistance to uptake of automatic BPMDs by health professionals, particularly physicians Table . Steps tThe key next step for countries is to develop, implement and enforce regulations that guarantee that only those automated BPMDs that have passed an accuracy validation study are approved for sale in the country. This step will require the participation of different actors. It may need to start with the education and advocacy actions, providing information on the benefits of using validated automated BPMDs to policymakers, procurement officers, health care providers and managers of health services. In addition, advocacy involving medical and professional societies, patients (or consumers) groups and civil society may create pressure to improve the quality of care. These processes, which are underway to different degrees in each country, may require understanding the audience, timing, and engaging with real-world policy-making .Another next step that will improve access to and knowledge of validated automated BPMDs is the development of country-specific lists or a regional list of validated automated BPMDs relevant to the Region of the Americas. A key feature of this list, in addition to the standard specifications of devices, should be information about the power source of the validated automated BPMDs, because access to reliable power varies greatly across the Americas. There has been a substantial increase of awareness of the importance of using accuracy validated automated BPMDs in countries implementing HEARTS. However, there are still several gaps in knowledge of technical aspects of automated BPMDs, which need to be summarized and disseminated to procurement officers.The challenges that the countries face to reach the goal of exclusive use of validated BPMDs in PHC are enormous and multifactorial. This confirms the need for a robust regulatory framework and comprehensive strategic approach to exclusive use of clinically validated automated BPMDs at regional level. HEARTS in the Americas has adopted a strategy to overcome these challenges over time, concomitantly conducting parallel efforts in several areas. The successful implementation of the initiative depends on a coordinated effort across government and other stakeholders that will contribute to better diagnosis and management of hypertension in the Americas.Blood pressure measuring devices that have been clinically validated have shown to be more accurate than those that have not.Most blood pressure measuring devices found in the global market have not been clinically validated.The regulatory framework pertinent to the marketing of blood pressure measuring devices in the Region of the Americas is weak and fragmented. There is a need to implement regulations and procurement mechanisms to ensure exclusive use of validated measuring devices.There are multiple strategies to reach the goal of exclusive use of validated automated blood pressure measuring devices, and these should be adopted concomitantly to the extent of their feasibility.The diversity of challenges faced by countries are related to their political and economic landscape, health systems and regulatory maturity, and factors such as geography and population size.The different approaches to these challenges describe in the paper could be used as lessons by other countries in their efforts to reach the goal of exclusive use of validated automated blood pressure measuring devices in primary health care.


Past work has focused on the thermal properties of microscale/nanoscale suspended/supported graphene. However, for the thermal design of graphene-based devices, the thermal properties of giant-scale (~mm) graphene, which reflects the effect of grains, must also be investigated and are critical. In this work, the thermal conductivity variation with temperature of giant-scale chemical vapor decomposition (CVD) graphene supported by poly(methyl methacrylate) (PMMA) is characterized using the differential transient electrothermal technique (diff-TET). Compared to the commonly used optothermal Raman technique, diff-TET employs joule heating as the heating source, a situation under which the temperature difference between optical phonons and acoustic phonons is eased. The thermal conductivity of single-layer graphene (SLG) supported by PMMA was measured as 743 ± 167 W/(m·K) and 287 ± 63 W/(m·K) at 296 K and 125 K, respectively. As temperature decreased from 296 K to 275 K, the thermal conductivity of graphene was decreased by 36.5%, which can be partly explained by compressive strain buildup in graphene due to the thermal expansion mismatch. A massive amount of work has focused on the experimental and theoretical calculation of the k of suspended and supported graphene, and great progress has been achieved [k of graphene has been deeply studied. Last but not least, since temperature affects the phonon propagation, the k of graphene shows strong temperature dependence. It has been reported that the k of supported graphene increases with increasing temperature, with the peak k appearing around 300 K [The discovery of graphene created explosive growth in research on the various properties of graphene ,2,3,4. Dk) , ultrahik) , and remk) , graphenk) ,9, photok) , batterik) , and so k) . With thachieved ,15,16,17achieved ,19,20, sachieved ,22, and achieved ,24,25 onnd 300 K . When thnd 300 K .k depends on the absorbed laser power and the temperature coefficient of the Raman shift of the G peak [k of graphene will be overestimated. Wang et al. first detected the lumped temperature difference between optical and acoustic phonons by nanosecond energy transport state-resolved Raman spectroscopy [k of supported graphene. The micro-bridge method uses joule heating as the heating source. In the experiment, the graphene supported by SiO2 acts as the thermal bridge between the heating part and the temperature-sensing part [Thermal property measurement is critical to the application of graphene in thermal management. Since graphene is extremely thin, the commonly used thermal conductivity measurement techniques of graphene are optothermal Raman spectroscopy ,27,28 ane G peak . Li et ae G peak ,30. It ie G peak . Under ttroscopy . Seol eting part . In prining part .k of suspended graphene is size/geometry dependent. The k of graphene has a ~log L (L: sample length) dependence which was confirmed by experiments (up to 9 μm) [k of supported graphene is less sensitive to the length size due to substrate coupling [k of macroscale supported graphene is critical, since the edge-phonon scattering usually leads to a great reduction in k. Furthermore, graphene has important applications in the field of flexible electronics, which calls for the thermal properties of graphene supported by flexible materials. To date, seldom work has been conducted on the temperature dependence of the thermal conductivity of millimeter-scale graphene on soft substrates, yet such knowledge is essential to graphene-based device design and optimization.So far, most thermal conductivity measurements of graphene focus on microscale samples. It is reported that the to 9 μm)  and theoto 9 μm) . Althougcoupling ,35, the k of PMMA is much lower than that of graphene. Choosing extremely thin (~457 nm) PMMA as the substrate can ensure the contribution of graphene to the overall thermal conductivity is comparable to that of PMMA. Thus, it is feasible to measure the k of graphene with high accuracy. The k of supported SLG is reported to be 743 ± 167 W/(m·K) at 296 K, which is 23.8% higher than that of micro-scale SiO2-supported graphene measured using the micro-bridge method [k of supported SLG is reduced to 287 ± 63 W/(m·K) when the temperature is 125 K, partly due to the strain-induced rips in the sample.In this work, the temperature dependence of the thermal conductivity of millimeter-scale SLG supported by poly(methyl methacrylate) (PMMA) is characterized by a differential transient thermoelectrical technique (diff-TET) . The dife method . The k o2 flow rate of 500 sccm. Then, the H2 flow rate and chamber pressure were adjusted to 70 sccm and 108 Torr, respectively. By introducing 0.15 sccm CH4 into the chamber, the graphene starts to grow. The copper was etched off after PMMA was coated on the graphene. Finally, graphene supported by PMMA was transferred to a filter substrate. The layer number of graphene was provided in the product technical data.SLG supported by PMMA characterized in this work was obtained from Jiangsu Xianfeng nanoscale materials company. The samples used in this experiment were fabricated using the chemical vapor deposition (CVD) method. The graphene is grown on a copper (Cu) in a controlled chamber pressure CVD system. At first, a clean Cu foil was annealed at 1077 °C with a Hk of these samples will be measured by diff-TET without any further processing. The thickness of PMMA (pδ) is necessary to determine the k of graphene when subtracting the effect of PMMA. Atomic force microscopy (AFM) was used to determine the thickness of PMMA. The supported graphene was transferred to a silicon substrate; then, the thickness of PMMA was determined with AFM. The as-received graphene was cut into the desired size by scissors. Then, the experimental sample was suspended between two electrodes, as shown in −1) can be observed in the Raman spectra, indicating that the supported graphene has rare D band-related defects. Peaks at 1588.3 cm−1 (G band) and 2681.5 cm−1 (2D band) can be observed. We used a ratio (IG/I2D) of the intensity of the G band to the intensity of 2D band to evaluate the layer number of the as-received sample [Even though the layer number of the as-received sample was given in the technical data sheet, the layer number of the as-received graphene on PMMA was verified with confocal Raman spectroscopy . In total, 30 random spots were tested. In the Raman spectroscopy test, a 532 nm laser with ~0.45 mW was focused on the graphene under 50× objective. The integration time was 10 s. Spectra of the as-received sample are shown in d sample . It was V0 and V1 are the initial voltage and steady-state voltage over the sample, respectively. The environmental temperature was controlled by the temperature controller which ranges from 7 K to 300 K. Since most of the samples were broken at 125 K with a sudden jump resistance to a very high value, we did the experiments from room temperature (RT) down to 125 K in 25 K steps. During the joule heating, the thermal transport in the sample can be regarded as one-dimensional, thus the energy governing equation can be expressed as:ρ, pc, and k are the density, specific heat capacity of the sample, respectively. A and L are the cross-sectional area and length of the sample, respectively. I and sR are the fed-in current and the sample resistance, respectively. Since the two electrodes are much larger than the sample, the temperature of the two electrodes can be regarded as environmental temperature. Thus, the boundary conditions can be depicted as: T = T0 (T0: room temperature). The theoretical normalized temperature rise is defined as: The thermal diffusivity of graphene supported by PMMA was characterized by diff-TET . As showeffα which gives the best fit of the experiment data was taken as the sample’s effective thermal diffusivity. A Matlab program created based on Equation (2) was used to fit the normalized temperature rise obtained by the experiments. The trial value of effα) includes the radiation effect (radα) which can be expressed as:ε, Bk, and δ are emissivity, the Stefan–Boltzmann constant, and thickness of the sample, respectively. The emissivity of the sample is taken from [realα), the effective thermal conductivity (effk) can be obtained as effk = realα·(pρc)p. The volumetric heat capacity of PMMA was used for the whole sample with high accuracy due to the extremely low mass proportion of graphene. In part 2, the Raman spectroscopy study of graphene showed that the graphene is distributed on the PMMA uniformly and all the graphene in samples is found to be a single layer. The relationship between effective thermal conductivity and thermal conductivity of PMMA and graphene can be depicted as:The effective thermal diffusivity  between graphene and PMMA is neglectable in comparison to the thermal resistance (~106 K/W) of PMMA. More details can be found in [Here, ferences ,39. The ectively ,39. The ectively . Additiofound in .R* = R/R0, R0: resistance at RT) variation against the temperatures of S1, S2, S3, and S4 is presented in eρ) of graphene is linearly proportional to T, as temperature is higher than the Bloch–Gruneisen temperature (BGΘ) of graphene and is proportional to T4 in the opposite case (BGT < Θ) [R* of the four samples decreases slightly as temperature decreases, then increases as temperature is decreased from RT to 125 K. The turning point is in the range of 250–275 K. The R* of S2 and S4 is increased by 35% and 23%, while the R* of S1 and S3 is decreased by 0.012% and 0.0075% as temperature changes from RT to 125 K. To obtain more details on the resistance of supported graphene, the temperature dependence of R* of S5 was measured every 10–25 K for three rounds. R* trends of S5 are similar to that of S1 and S3. As temperature continues to decrease from 150 K, the R* of S5_r1 and S5_r2 first decreases and then increases with temperature, while the R* of S5_r3 continues to increase. Hinnefeld et al. studied the resistance of graphene supported by PDMS under strain and it was found that the tensile strain in the supported graphene can lead to rips in the graphene. These rips cause the resistance of the supported graphene to increase significantly with increased strain [The normalized resistance (T < ΘBG) . Howeverd strain . As tempγ are the intrinsic TCR of relaxed graphene and a positive constant, respectively. pβ and gβ are the thermal expansion coefficients (β) of PMMA and graphene, respectively. pβ decreases with decreasing temperature and remains positive when the temperature is above 0 K. gβ remains negative when temperature is lower than RT. In the entire temperature range, pβ is relatively large, which helps maintain a positive TCR in supported graphene. As temperature is decreased, the difference between pβ and gβ becomes smaller in comparison to the effect of The temperature coefficient of resistance (TCR) of graphene supported by PMMA is further discussed based on the data of S5_r3. The TCR of S5_r3 is shown in negative ,43. Whenrealα of S1, S2 and S4 decreases first, then the realα of S2 remains constant while the realα of S1 and S4 increases slightly. The change in the realα of S3 is relatively small when compared to the other three samples. The k of SLG supported by PMMA is presented in k of SLG supported by SiO2 [k of supported SLG is 743 ± 167 W/(m·K), which is smaller than that of SiO2-supported SLG (840 W/(m·K)) [k of supported graphene is measured by a comprehensive Raman optothermal method which eliminated the laser absorption uncertainty [k of supported graphene is overestimated. The k in this work is larger than two literature values (~600 W/(m·K) for SiO2-supported SLG [k of our work and above two differences may be attributed to the different interface coupling strength.The real thermal diffusivity without the effect of radiation of four samples is shown in  by SiO2 ,27 and b by SiO2  are showrted SLG  and 560 rted SLG ). The dik of supported SLG first decreases by 36.5%, which is much larger than the k reduction in [k of graphene supported by a flexible substrate. As such, we turn our attention to the effect on the k of suspended graphene. As reported in the literature, compressive strain in suspended graphene suppresses thermal conductivity [k can be reduced by 26% [k reduction when temperature decreases from RT to 275 K. Thus, Raman spectroscopy is used to investigate the G peak under different temperatures. The graphene sample suspended between two electrodes was placed in a cryogenic cell where the temperature can be controlled between 77 and 300 K. A confocal Raman is used to collect the Raman spectra of graphene under different temperatures.As temperature decreases from RT to 275 K, the ction in ,27. As ductivity . This isuctivity ,44. Withd by 26% . We specGω) of SLG on PMMA as a function of temperature. The G peak blueshifts as temperature goes down from RT. The temperature dependent frequency shift of the G peak is attributed to three parts: thermal expansion of the lattice ΔωGΔωGS(/% at RT . Since tulations  are subtgraphene . Howevere strain . For graany rips ,42. At lR–T relationship is due to the TEC mismatch between graphene and PMMA and rips in graphene appearing at lower temperature. Using the diff-TET technique, the temperature dependence of the thermal conductivity of graphene supported by a flexible substrate is obtained. Through monitoring the blueshift of the Raman peak, compressive strain is confirmed to be built up in the graphene. The large reduction in k as temperature decreases from RT to 275 K is partly due to the compressive strain built up in graphene. This work can provide some guidance on the design of graphene-based electrothermal devices.In summary, we first reported the resistance–temperature relationship for supported graphene since this relationship is critical for explaining the behavior of graphene in thermal characterization. The TCR of our sample reduced from a positive value at RT to a negative value at low temperatures, while the free-standing graphene has a negative TCR throughout the entire temperature range. The abnormal