Adding optical protection from water and high humidity reduces these values by ~10%. We describe tradeoffs between peak efficacy and cost.Light-emitting diodes (LEDs) have enabled a historic increase in the conversion of electric energy to photons, but this is approaching a physical limit. The theoretical maximum efficiency occurs when all input energy is converted to energy in photosynthetic photons. Blue LEDs can be 93% efficient, phosphor-converted “whites” 76% efficient, and red LEDs 81% efficient. These improvements open new opportunities for horticultural lighting. Here we review (1) fundamental physics and efficiency of LEDs, (2) the current efficacy of LEDs, (3) the effect of spectral quality on crop yield, and (4) the potential efficacy of horticultural fixtures. Advances in the conversion of photons to yield can be achieved by optimization of spectral effects on plant morphology, which vary among species. Conversely, spectral effects on photosynthesis are remarkably similar across species, but the conventional definition of photosynthetic photons (400–700 nm) may need to be modified. The upper limit of LED fixture efficacy is determined by the LED package efficacy multiplied by four factors inherent to all fixtures: current droop, thermal droop, driver (power supply) inefficiencies, and optical losses. With current LED technology, the calculations indicate efficacy limits of 3.4 µmol JThe term efficiency applies to ratios with the same units in the numerator and denominator, which can be expressed as a percentage. LED efficiency describes the optical power output divided by the electrical power input (watt/watt or %). The term efficacy applies to ratios with different units. In horticultural lighting, efficacy refers to micromoles of photon output per second, per watt of input power. Since a watt is a joule per second, this simplifies to µmol per joule. The relationship between photon energy and wavelength is expressed in the Planck–Einstein relation, often just called Planck’s equation. This equation states that energy is inversely proportional to wavelength . LED performance specifications are for LED packages. An LED fixture refers to LED packages integrated into a fixture.]By converting LED efficiency into efficacy, we get the appropriate units for determining the impact of photons on plants per input electrical power. This follows another physical law called the Stark–Einstein Law, which states that for every photon absorbed, only one molecule can react. This Law can be restated to say that one photon excites one electron. In this paper, photon efficacy is limited to photons between 400 and 700 nm, except in the case of far-red LEDs, where photons from up to 800 nm are included. LED package manufacturers often report efficacy in lumens per watt, because this is a meaningful metric for human lighting, but it is not applicable for horticultural lighting because it is a measure of photons weighted for human vision based on the human eye response to different colors.photon/Vf), affected by internal electrical resistance of the LED.Electrical efficiency: the ratio of the emitted photon energy expressed in electron volts to the applied voltage : the conversion of electrons to photons, affected by non-radiative recombination pathways, including impurities and microphysical defects.Photon extraction efficiency: the ratio of photons that exit the LED semiconductor material to total generated photons, affected by internal reflection and reabsorption. Losses in extracting photons out of an LED package are termed “package losses” within the LED industry. These can vary greatly among LED package types.The fundamental efficiency of LEDs (LED packages) is the product of the following three sub-efficiencies:1. Incremental improvements have been made to each of the three factors above resulting in a substantial improvement of LED packages over the past 10 years. Now, far-red, red, white, and blue LEDs, respectively, can be 77, 81, 76, and 93% efficient  that absorbs blue photons and luminesces at longer wavelengths. Phosphor-converted white LEDs are designed to transmit some blue photons, with the remainder converted to longer wavelengths. Types and amounts of phosphor are varied to create multiple hues and color qualities. Figure 2). Both CRI and the TM-30 metric of Rf use a scale of 0–100 to describe color fidelity. A high color fidelity facilitates observing subtle color differences. This is important to human observers for visual identification of tiny insects, nutritional disorders, and diseases. Suitable color fidelity is also necessary for machine vision.White LEDs consist of blue LEDs with a luminescent material coating , neutral white (3500–4500 K), cool white (4500–5500 K), and daylight (5500–7500 K). A lower CCT (2700–4000 K) and higher CRI (greater than 80) are often preferred for indoor lighting to provide incandescent-like light qualities for humansIncreased density of phosphor coatings and increased use of red phosphor materials decreases efficiency. A 6500 K LED (daylight) with about 30% blue photons can have 95% of the photon output of its non-phosphor-converted blue LED counterpart, but this value decreases to 80–85% for a warm white LED with 10% blue photons. In addition, as the optical output of white LEDs increases, the phosphor efficiency will decrease. This is due to conversion, energy, and optical losses within the phosphor conversion process.LEDs are designed for performance at specific current ranges. Moderate LED drive current density enables higher efficiency, but at very low drive currents, efficiency decreases. LED loss mechanisms are typically a function of current density. So at a given current, increasing the size of an LED chip can increase the efficacy of an LED by reducing the current density. Unfortunately, chip area is often confidential, and LED manufacturers only report LED specifications at the total LED drive current, not drive current density.4, Osram 7, and Samsung 8. These companies provide LED efficacy data in µmol J−1. Additional LED manufacturers include Nichia 9, Cree 10, Epistar 11, and many others. As technology improves, see the companies’ websites to find the latest LED package efficacy information, and apply the principles described below to determine potential fixture efficacy. Figure 13. For a white LED, which has a blue LED and a phosphor conversion layer, the droop is caused by Auger in the blue LED and reduction in phosphor conversion efficiency at higher optical flux concentrations14. For red and far-red LEDs, the current droop is caused by carrier leakage due to poor confinement of electrons in the active regions15. In general, decreasing the drive current increases the efficacy, but eventually Shockley–Read–Hall defect losses will dominate at very low drive current16. LED manufacturers continue to both increase LED peak efficiency and reduce current droop. The theoretical maximum lines for red (centered at 660 nm) and blue (centered at 450 nm) LEDs are based on the assumption of 100% power efficiency of the LED or hypothetical photon generating device (1 W electricity input = 1 W photon output) followed by a conversion to number of photons using Planck’s equation. White LEDs would be as efficient as blue LEDs if phosphor conversion was 100% efficient. However, phosphor conversion efficiencies range from 80 to 95%, depending on amount of phosphor, phosphor material, temperature, and photon flux density. A color-mixed “white” fixture using direct-emitting (not phosphor converted) green LEDs (550 nm) as well as red and blue LEDs would have a theoretical maximum of ~4.6 µmol J−1, but direct-emitting green LEDs currently have low efficiency (referred to as the green gap17) resulting in low efficacy (about 1.9 µmol J−1)18.Figures Junction temperature refers to the operating temperature at the actual diode. There are two temperature standards for reporting the efficacy of LEDs: 25 and 85 °C. Efficacy decreases ~10%, as the temperature increases from 25 to 85 °C . Thermal droop is typically worse in red compared with blue LEDs.19).A timeline of the historic and projected increases in LED efficacy is presented in Fig. Figure Horticultural LED fixtures typically contain combinations of red (peak ≈ 660 nm), blue (peak ≈ 450 nm), white, and/or far-red (peak ≈ 730 nm) emitting LEDs. Other peak wavelengths are available, but they have lower efficiencies and efficacies and are less common. Fixture manufacturers choose the ratios of these LEDs for specific applications and based on their perception of best practices and market demands.20. The first LED-produced photons used to grow plants were red21, which was shortly followed by the development of high output blue LEDs22. For a review of the historical significance of this Nobel prize-winning discovery, see ref. 23. Before widespread adoption of blue LEDs, early studies demonstrated the value of blue photons for plant growth using blue fluorescent fixtures to supplement red photons from LEDs25.Morrow discussed the significance of LEDs for horticultural lighting and reviewed the early adoption of the technology27. Due to widespread use in lighting applications for human vision, white LED packages are now ~20% of the cost of red LEDs. This has contributed to the increase in the fraction of white LEDs to more than 60% in some horticultural fixtures.The first commercial horticultural LED fixtures were blue + red combinations. These fixtures, which produced a spectrum that appeared magenta, had a higher efficacy than white or white + red fixtures. Many people thought that these blue + red fixtures would enhance photosynthesis compared with full spectrum fixtures due to their close match to the chlorophyll absorption spectrum, which shows peak absorption in the blue and red regions of the photosynthetically active radiation  spectrum. This thinking was advanced by early LED manufacturers, even though green photons have long been known to be effective for photosynthesisPhotons excite electrons and photobiology is thus driven by the number of photons, not energy or lumens. Biologically active photons must have sufficiently high energy to excite pigment photoreceptors, and there are multiple photoreceptors with weighting functions for wavelengths, which are biophysically or empirically derived. Lumens are an example of a weighting function applied to a photon flux and spectral distribution for human visual function.28, and may vary over the plant life cycle. Some principles, however, apply across all species. The impacts of spectrum on plant growth and development are much greater in sole-source lighting than in greenhouse supplemental lighting where electric lighting makes up only a small portion of the plant lighting diet.The effect of spectral quality on plant shape is synergistic among wavelengths, interacts with intensity, varies among speciesIn plant biology, spectra are traditionally separated into the following coarse categories.Ultra-violet photons are further separated into three broad categories: UV-C (100–280 nm), UV-B (280–315/320 nm), and UV-A (315/320–400 nm). The wavelength at which UV-C and UV-B are separated (280 nm) is determined by the shortest wavelength of solar radiation that reaches the surface of Earth. The wavelength at which UV-B and UV-A are separated (315 or 320 nm) is generally determined by the effect of sun on human skin sunburn (315 nm) or skin cancer (320 nm). There is no universal agreement on the wavelength transition between UV-B and UV-A, both are equally used. Fortunately, UV-C photons are completely blocked by our atmosphere because they are highly damaging to biological organisms. UV-B photons are also damaging, but can have beneficial effects including increased production of secondary metabolites29. UV-A photons are less damaging than UV-B, and can have either stimulatory or inhibitory effects on plant growth, depending on species and interacting environmental factors30.31, but these photons can have large biological effects in small quantities. At 25 °C and 700 mA, the efficiency of UV-A LEDs increases from 50 to 60% as the wavelength increases from 370 to 395 nm32. A violet LED with a peak between 402 and 408 nm is ~65% efficient, and has 15–30% of its photons below 400 nm. Efficiency will increase as current density decreases.At 25 °C and 350 mA, UV-B and UV-C LEDs are only ~3% efficient27, PAR only includes photons with wavelengths between 400 and 700 nm. However, McCree’s studies show significant differences in the photosynthetic efficiency of species at wavelengths below ~425 nm. Some species, like radish, have equal photosynthesis between 375 and 500 nm. Photons between 350 to 400 nm can be photosynthetic, but a high fraction are typically absorbed by non-photosynthetic pigments.Based on studies by McCreeBlue photons (400–500 nm) reduce plant height and leaf expansion in nearly all species35. Because of absorption by inactive pigments , blue photons are ~20% less photosynthetically efficient than photons from the most common red LED (660 nm)27. However, the blue-induced decreases in leaf area (reducing photon capture) may have a larger effect on overall plant growth than the blue-induced reduction in photosynthetic rate28. A range of 5–30% blue is typically used in horticultural LED fixtures to inhibit excessive stem extension and reduce plant height, which is typically beneficial for controlled environment growth.Green photons (500–600 nm) improve human perception of color. Unfortunately, monochromatic direct emitting (non-phosphor converted) green LEDs have low efficacy. White (phosphor-converted blue) LEDs are thus used to provide the green photons that are important to human vision; and they have the added benefit of providing blue and red photons. Green photons are up to 10% less photosynthetically efficient than photons from the most common red LED (660 nm)27, but they penetrate deeper into plant canopies than blue or red photons36.Arabidopsis suggest that green photons can reverse blue photon effects 38 or induce shade avoidance 40. Some studies suggest that green-induced shade avoidance also occurs in food crops and other economically valuable plants41, but several other studies have shown minimal effects45.The effect of green photons on plant shape is generally much less than the effects of blue or far-red photons. Studies in Red photons (600–700 nm) are well absorbed by leaves, are photosynthetically efficient, and are efficiently generated by LEDs so they are widely used in horticultural fixtures. The classical paradigm has been that red and far-red act antagonistically to inhibit or induce shade avoidance symptoms, such as stem elongation, hyponastic leaf orientation, and/or reduced branching47. However, the high absorbance of red photons by chlorophyll means that the impact of red on shade responses may be overestimated48. Replacing green photons with red photons has minimal effects on plant shape45, but plants grown in the complete absence of red and green photons (sole-source blue LEDs) can rapidly elongate49.Far-red photons (700–800 nm) can have powerful effects on plant shape, and are efficiently generated by LEDs so they are a promising addition to horticultural lighting. Along with several other laboratories, we are working to quantify the effects of far-red photons on plant morphology. In some species , far-red photons beneficially increase leaf expansion, but they also significantly increase stem elongation in many other species50, which may not be beneficial.52. These photons are thus being reconsidered for their role in photosynthesis. Far-red photons must be used with caution, particularly in sole-source environments, because they can induce stem elongation associated with shade avoidance.Despite the classic definition of PAR, recent studies indicate that far-red photons (700–750 nm) are photosynthetically synergistic with shorter wavelength photons53:LED drive currentLED junction temperatureDriver efficiencyOptical losses in the fixtureThe upper limit of fixture efficacy is determined by the choice of LEDs and operating conditions. Different colors of LEDs have different efficacies, but the quality of LEDs within and among manufacturers also varies. In addition to the efficacy of the selected LEDs, fixture efficacy is determined by four additional factors1. Drive currentThe effect of drive current on LED efficacy has been discussed above. Due to different types of efficiency reductions at high and low drive currents, efficiency can be maximized at some relatively low drive current (less than 100 mA). Fixture manufacturers seek to co-optimize fixture size, cost, output, and efficacy for specific applications. While low drive currents will increase the efficacy of the fixture, the output of each LED would be relatively low. This increases the cost and complexity of the fixture.2. LED junction temperature53. Better thermal management may increase fixture cost, but it also increases efficacy and longevity of the LEDs . A typical L70 for LED fixtures is 50,000 h. As the LEDs and fixture age, the efficacy will decline; a problem that is exacerbated by high junction temperatures. Rates of fixture aging can vary greatly among manufacturers. Most manufacturers characterize their fixture lifetime  in terms of LED output depreciation based on a standard LED package test—IES LM-80, which can be interpolated into luminaire lumen maintenance. Projections of luminaire lumen maintenance based on LED depreciation cannot exceed six times of the duration that the LEDs were tested, so for a depreciation lifetime claim of 60,000 h the LEDs must have been tested for 10,000 h. Many fixtures that claim extended lifetimes are exceeding the allowable six times interpolation based on LED testing. Fixture lifetimes based on LED depreciation also do not include optical loss mechanisms in the fixture and accelerated aging of the LEDs due to higher temperatures. Also, typical lifetime claims do not consider catastrophic failure of the LED driver, which often fails before the LEDs have reached the L70.]The junction temperature of LEDs in fixtures depends on the drive current, ambient temperature, and the heat dissipation  of the fixture, but is typically around 85 °C3. LED drivers  are necessary to convert AC to DC power and provide regulated voltage and current. The efficiency of LED drivers ranges from 85 to 95%. LED drivers can be less efficient when they provide dimming, color control and/or communication functionality.4. Optical losses occur when LEDs are mounted in fixtures. The sides of the fixture can obstruct low-angle photons. Protective transparent covers  transmit up to 92% of the photons and thus reduce the output by 8%, but this protection can significantly improve the lifetime of a fixture. Fixtures with unprotected LEDs can have 99% optical efficiency, but may have shorter lifetimes in harsh growing environments .56.Optical covers can also diffuse the photons, which reduces efficiency, but can result in more uniform mixing of colors and improved photon penetration into plant canopies57.Photons must impact leaves to be absorbed, and this is an important consideration in fixture design. Early LED fixtures had focused photon output over a small area. This facilitated precise photon placement, but caused nonuniform distribution. LED package and fixture design has transitioned to a less-focused photon distribution, but as long as the photons exit the fixture this does not affect our analysis of optical efficacy−2 to 50 mA mm−2).Drive current minimized to achieve 104% of the reported LED efficacy  to achieve 95% of the reported LED efficacy (at 25 °C).The LED driver is 95% efficient.Unprotected LEDs in the fixture to achieve 99% optical efficiency.Using the following near-maximum parameters, we now calculate an achievable fixture efficacy using presently-available technology:−2 and 25 °C here). Reducing drive current is much easier than reducing temperature.The resulting fixture efficacy would be 1.04 × 0.95 × 0.95 × 0.99 = 93% of the reported efficacy of the LED. The first two factors can be above 100%, if the LEDs are operated at lower drive current and lower temperature than the reported specification  could potentially achieve an efficacy of 4.1 µmol J−1 .The LED driver is 90% efficient.Protected LEDs in the fixture achieve 92% optical efficiency.Using more typical parameters:The resulting fixture efficacy would be 0.90 × 0.90 × 0.90 × 0.90 = 67% of the reported efficacy of the LEDs.−1 (ref. 57).In 2014, the best LED fixtures had an efficacy of 1.7 µmol J−1 for white + red fixtures and 3 µmol J−1 for blue + red fixtures have been achieved  maintains a list of horticultural lighting products that meet their listing requirements−1 of output capacity. HPS fixtures (1 kW) range from $200 to $350 USD per kW (5–9 µmol s−1 per $). LED fixtures range from $1000 to $3000 USD per kW (0.5–1.5 µmol s−1 per $). On a photon flux basis, the initial cost is therefore, 3–18 times higher for LED vs. HPS fixtures. The cost of both technologies has decreased, but the cost of LED fixtures are expected to decrease faster than HPS fixtures. While initial cost is higher, LED fixtures reduce energy cost compared with HPS. Depending on usage periods and price of energy, the electric savings can equal the difference in initial cost after of 3–5 years for sole- source applications and 5–8 years for supplemental applications57.Initial fixture cost per photon s59.Spectral quality for plant morphology and photon capture60.Adequate green photons to create “white” light to facilitate human comfort and visual identification of insects, diseases, and nutritional disordersFixture reliability, including environmental protection of the LEDs.Fixture operating temperatures, which affect LED and system longevity.Uniformity and distribution of photon output. Many early LED fixtures had narrow beam angles, but more recent fixtures have a broader distribution of photons. High wattage HPS fixtures need to be mounted higher above the canopy than LED fixtures to achieve uniform distribution of photons.Fixture size for shading in a greenhouse application.In addition to efficacy, several other factors affect fixture choice, including:62. However, some recent evidence indicates that longer-term cycling of LEDs (minute to hours) can alter plant shape (hypocotyl length) and color (anthocyanin synthesis)63.Because LEDs can be cycled on and off over short intervals, there has been interest in rapid cycling of LED fixtures to improve plant growth. Unfortunately, high frequency flickering (10–10000 Hz) has been well-studied, and there is neither empirical nor theoretical evidence that this can be used to increase the quantum yield of photosynthesis. Plants appear to integrate light intensity for photosynthesis−2 and a junction temperature of 25 °C.Blue LEDs are now 93% efficient, phosphor-converted “whites” are 76% efficient, and reds are 81% efficient when run at the near-optimal conditions of 100 mA mmBoth junction temperature and drive current density will affect the photon efficacy of LEDs, and in general, the most efficient LED fixture will run their LEDs at low drive currents. However, a lower drive current results in a lower photon output per LED, and the resulting fixture will require many LEDs to achieve a high photon output and thus will be more expensive.Broad spectrum distribution of photons is useful for diagnosis of plant disorders. Broad spectrum lighting is not necessarily beneficial for photosynthesis or plant growth. Unique spectra, selectively applied during specific stages of the life cycle, can, however, have a beneficial effect on plant shape and development.−1 for white + red fixtures, and 4.1 µmol J−1 for blue + red fixtures. These values are significantly higher than current typical values of 2–3 µmol J−1.The calculations in this paper show current possible performance levels of LED fixtures of 3.4 µmol Jhttps://cubes.space/; https://www.hortlamp.org/index.html.Although fixture efficacy is paramount, timing and angular delivery of photons to photosynthetic tissues, spectrum, and intensity also determine the effectiveness of the photon delivery system. Efficient lighting is then coupled with optimal temperature, humidity, nutrition, plant water potential, atmospheric carbon dioxide concentration, delivery of oxygen to root surfaces, and genetics. Both NASA and the USDA are funding research at universities to optimize these factors and improve the economic potential of electric lighting in in controlled environments:


This article includes an updated review of the classification, uses and side effects of surfactants for their application in the cosmetic, personal care and pharmaceutical industries. Based on their origin and composition, surfactants can be divided into three different categories: (i) synthetic surfactants; (ii) bio-based surfactants; and (iii) microbial biosurfactants. The first group is the most widespread and cost-effective. It is composed of surfactants, which are synthetically produced, using non-renewable sources, with a final structure that is different from the natural components of living cells. The second category comprises surfactants of intermediate biocompatibility, usually produced by chemical synthesis but integrating fats, sugars or amino acids obtained from renewable sources into their structure. Finally, the third group of surfactants, designated as microbial biosurfactants, are considered the most biocompatible and eco-friendly, as they are produced by living cells, mostly bacteria and yeasts, without the intermediation of organic synthesis. Based on the information included in this review it would be interesting for cosmetic, personal care and pharmaceutical industries to consider microbial biosurfactants as a group apart from surfactants, needing specific regulations, as they are less toxic and more biocompatible than chemical surfactants having formulations that are more biocompatible and greener. Surfactants are amphiphilic compounds that contain a tail, which is insoluble in water, presenting hydrophobic groups and a water-soluble head with hydrophilic groups ,2. Due tThe synthesis of surfactants usually involves chemical reactions to combine a hydrophobic chain with a hydrophilic group. Surfactants can be classified from different points of view , as therOther classifications divide surfactants into synthetic surfactants and bio-based surfactants, including also as bio-based surfactants produced by living cells, called microbial biosurfactants. Bio-based surfactants are usually produced by chemical synthesis but integrating fats, sugars or amino acids obtained from renewable sources, whereas microbial surfactants are obtained from living cells, typically bacteria and yeasts, without the intermediation of organic synthesis. However, the synthesis and composition of bio-based surfactants produced by organic synthesis differ from the surfactants directly produced from living cells and, therefore, they should be classified separately ,23.Microbial biosurfactants are secondary metabolites produced by different microorganisms, including bacteria, fungus and yeast . They caAnother group of substances with surfactant capacity that can be considered biosurfactants, as they are extracted from vegetable or animal cells, are phospholipids . HoweverSynthetic surfactants are usually classified on the basis of their ionic charge as cationic, anionic, non-ionic and zwitterionic or amphoteric surfactants . The mosN,N-(dimethylammonio)-butyrate and lauryl-N,N-(dimethyl)-glycinebetaine -1-propanesulfonate (CHAPS). A slightly modified version is 3-[(3-cholamidopropyl)dimethylammonio]-2-hydroxy-1-propanesulfonate, which is slightly more hydrophilic than CHAPS. There are also several aromatic quaternary ammonium surfactants which possess zwitterionic properties, as is the case of 3-(4-tert-butyl-1-pyridinio)-1-propanesulfonate, 3-(1-pyridinio)-1-propanesulfonate, and 3-(benzyl-dimethylammonio)propanesulfonate .N-oxide [Additionally, zwitterionic surfactants can be obtained by reaction of phosphoric acid and quaternary ammonium ions, as is the case of the other acids mentioned above. Another group of zwitterionic surfactants is obtained from quaternary ammonium ions with an attached hydroxy group. A typical example of this class of surfactants is lauryldimethylamine N-oxide .N, N′, N″- dodecyl diethylene triamine pentaacetic acid (DDTPA) with three dodecyls, five carboxylic acid groups and three quaternary ammoniums. The above-mentioned betaine synthetized possesses better surface-active properties than the conventional betaine derivatives.Finally, this group of surfactants includes betaines, which can exist in two ionic forms, zwitterionic and cationic . Zhou etBio-based surfactants can also be classified as anionic, non-ionic, cationic and amphoteric surfactants. Below, different examples of each group are presented .Fatty acid methyl ester sulfonates (MES) are oleochemical-based anionic surfactants, derived mainly from palm or coconut oil, obtained by a sulfonation reaction followed by acid digestion. MES, linear alkylbenzene sulfonates (LASs), alkyl sulfonates (ASs), and alpha olefin sulfonates (AOSs), are used as detergent surfactants . MES comLASs are fossil fuel-derived surfactants that can possess good bio-degradability and low ecotoxicity. However, due to the interest of detergent companies in natural fat- and oil-based surfactants, rather than those that are petroleum-based like LAS, MES are considered as a main laundry detergent ingredient with good surface-active properties as well as good biodegradability ,41,42,43This type of bio-based surfactant has been defined by some authors as a high-performance surfactant, capable of reducing builders dosage in detergents, presenting a superior soil removal index and detergency, in comparison to alkyl benzene sulfonates . MoreoveThis group includes C10–C18 alcohol sulfates containing, for instance, coconut fatty alcohol sulfates or from ethylene via Ziegler C12/14 alcohol. Depending on the length of the fatty acid chain, detergents with different properties can be obtained. Those containing short fatty acids (C12–C14) are used in a wide range of personal care products like shampoos, bubble bath products, toothpaste, dishwashing liquids and products for delicate laundry washing .In addition, ammonia or amine salts of lauryl alcohol sulfates are also used in shampoos and bubble products, whereas sodium salts of C16–C18 alcohol sulfates are used in the formulation of heavy-duty laundry products for hand and machine washing, with a detergency power higher than ammonium lauryl sulfate (ALS) .In general, alcohol ether sulfates (AES) are considered the most efficient in terms of detergency, good tolerance to hard water and mildness; however, they are very unstable at high temperatures . This grSLS is a purified version of the SCS. In this case, most of the non-carbon 12 fatty acids in coconut oil are removed. The starting material is then 80% carbon 12 fatty acids (mainly lauric acid) subjected to the same sulfation process as in the previous case.Both products, SCS and SLS, are mainly sodium lauryl sulfate , with SLS being more efficient, and SCS a highly diluted, and therefore milder form .Detergents companies use SLS in some products and SLES in others, depending on the purpose of the product. However, for example, SLS can be irritating to the skin so many manufacturers use SLES instead. SLES is prepared similarly to SLS, but by going through a process of ethoxylation of dodecyl alcohol  and then sulfated. The addition of ethylene oxide to the fatty alcohols in the formula makes them more soluble in water, which reduces the level of irritation. Thus, SLES turns out to be a detergent with high skin compatibility, and great moisturizing and emulsifying capacity . HoweverThese bio-based surfactants can be synthesized using cocoyl chloride, derived from fatty acid, and phosphorus trichloride. Recently, some authors have proposed the use of coconut oil in combination with amino acids in order to obtain more eco-friendly bio-based glycinate surfactants . ExampleBeta vulgaris) and is obtained after extraction of saccharose. This compound reacts with electrophilic reagents such as alkyl halides and their tosylate counterparts to obtain the ester-type surfactant. Conversely, glycine betaine reacts with n-alcohol and fatty amines such as lauric, stearic and oleic amines, in order to obtain the amides [This group includes a specific type of cationic surfactant based on natural glycine betaines and vegetable oils, produced from renewable raw materials. Glycine betaine is a natural low-expense substance, which possesses a quaternary trimethylalkylammonium moiety and a carboxylate function. It constitutes the main raw material for the preparation of biodegradable and biocompatible cationic surfactants such as glycine betaine esters and amides. It accounts for 27% of the weight of molasses of sugar beet  being the most important group. These surfactants are composed of a fatty acid tail, which contains from 8 to 14 carbon atoms, and a sugar moiety composed of glucose, sucrose, galactose, mannose and other sugars. They are composed of sugars derived from plants, which makes them biodegradable [N-methylglucamides or sorbitan esters, with alkyl polyglucosides (APGs) being the most important group. These surfactants are composed of a fatty acid tail, which contains from 8 to 14 carbon atoms, and a sugar moiety composed of glucose, sucrose, galactose, mannose and other sugars. When the fatty acids of APGs are derived from coconut oil, they are called coco glucosides, and are typically included in many cosmetic formulations.There are several types of sugar surfactants such as sucrose esters, methyl glycoside esters, ethyl glycoside esters, gradable . When thgradable ,55. TherGaudin et al.  describeThe sugar molecule constitutes the hydrophilic head and the fatty acid residue is considered the hydrophobic tail of the molecule. It is possible to obtain both components from renewable sources and secondary raw materials.Another group of non-ionic bio-based surfactants is the polysorbates formed by the ethoxylation of sorbitan esters. For instance, Polysorbate 20 is a non-ionic surfactant, formed by the ethoxylation of sorbitan before the addition of lauric acid. Its stability and relative non-toxicity allow it to be used as a detergent and emulsifier in a number of domestic, scientific and pharmacological applications. As the name implies, the ethoxylation process leaves the molecule with 20 repeated units of polyethylene glycol; these are distributed across four different chains, leading to a commercial product containing a range of chemical species ,58.Conversely, polysaccharide biomass is used to synthesize sorbitan esters such as the non-ionic surfactants Tween and Span (through the single dehydration of sorbitol) and to produce isosorbide, which can be obtained from the starch industry . IsosorbIn this regard, native cyclodextrins are oligosaccharides composed of six or more D-glucopyranose residues attached by β-1,4-linkages in a cyclic array. The most common cyclodextrins contain six, seven or eight glucose residues and are named α-cyclodextrin, β-cyclodextrin and γ-cyclodextrin, depending on the number of glucose residues, respectively. Machut et al.  have alsRecently, Cho et al.  have pro® isosorbide, which is a cycloaliphatic monomer obtained from sorbitol dehydration that can be used for the synthesis of bio-based isosorbide surfactants.Other authors have proposed the synthesis of derived isosorbide surfactants (dodecylamino diglycidyl ether of isosorbide) by the condensation of isosorbide and epichlorhydrin yielding a low molar mass prepolymer and subsequent condensation to a fatty amine . For insCocoamidopropyl is an example of an amphoteric betaine bio-based surfactant produced by the reaction of dimethylaminopropylamine with fatty acids (lauric acid or its methyl ester) from different sources such as coconut or palm kernel oil. In this sense, despite the name, cocamidopropyl betaine is not synthesized from betaine. Moreover, it is considered a mild surfactant, although it can produce some allergic reactions ,66,67.On the other hand, the BASF company has started to commercialize an algal betaine surfactant made from renewable microalgae oil as an alternative to cocoamidopropyl.Contrarily to chemically synthesized and bio-based surfactants, which are classified according to the nature of their polar group, microbial biosurfactants can be classified based on the chemical nature, on the ionic charge and on the producer microorganism , althougGlycolipids are the most common and popular microbial biosurfactants  with theOn the other hand, Candida bombicola and Starmerella bombicola. Concerning the use of sophorolipids contemplated in the CosIng, they can exert cleansing, antimicrobial, emulsifier, deodorant, anti-seborrheic, antioxidant, skin conditioning and skin-protecting capacities.From these two types of microbial biosurfactants, sophorolipids are only included in the CosIng database as surfactants, whereas rhamnolipids are included because of their emollient, emulsifier and skin conditioning properties. The sophorolipids included in the CosIng database are mostly produced by Mucor circinelloides, which is able to reduce the surface tension of water to 26 mN/m. Moreover, it presents a huge emulsifying capacity for synthetic oils, such as engine oils. Nevertheless, this capacity is lowered in water emulsions systems containing natural oils like olive oil, although it is still higher than the emulsifying activity of Tween 80. Conversely, Kaur et al. [As an example, Hasani-Zadeh et al.  have detr et al.  have repRegarding their surfactant properties, they are able to reduce the surface tension of water by more than 30 mN/m and possess a CMC below 100 mg/L .Pseudozyma [Other types of glycolipid microbial biosurfactants used in the cosmetic field are the mannosylerythritol lipids (MELs), which are extensively produced by different basidiomycetous yeasts like eudozyma . Cosmetieudozyma .Bacillus subtilis. Depending on the length of the fatty acid chain, their molecular weight can vary from 879 to 1620 Da, although most lipopeptide microbial biosurfactants possess a molecular weight of around 1000 Da [These microbial biosurfactants, together with glycolipids, are the most studied in the literature ,73. They 1000 Da ,75,76,77B. subtilis [Pseudomonas libanensis produces a lipopeptide microbial biosurfactant named viscosin [The most studied lipopeptide is surfactin produced by subtilis . This misubtilis . Other mviscosin .From the above-mentioned microbial biosurfactants, only surfactin (as sodium surfactin) is included in the CosIng database as a cosmetic ingredient.Lipopeptide microbial biosurfactants are widely used in cosmetics due to their anti-wrinkle and moisturizing properties and cleansing activity. Furthermore, they could be a potentially topical dermatological product, because of their good skin compatibility with low irritation .Lactobacillus pentosus [These are the least known microbial biosurfactants, mainly produced by lactic acid bacteria ,87,88. Tpentosus .As can be observed, lipopeptides and glycolipids are more yellowish and viscous than glycolipopeptides, possessing poor solubility in water. This appearance is observed for microbial lipopeptide and glycolipopeptide biosurfactants from corn steep liquor stream and lactic acid bacteria, respectively under specific extraction conditions ; but theLactobacillus agilis [Lactobacillus plantarum [Lactobacillus paracasei [L. pentosus [L. paracasei produces a glycolipopeptide, whereas when lactose is used as a carbon source the same strain produces glycopeptides or glycoproteins; showing that the nature of the carbon source plays an important role in the polymeric composition of microbial biosurfactants. The same fact was observed by other authors with microbial biosurfactants of different types like rhamnolipids produced by Pseudomonas aeruginosa [Bacillus strains [The most studied glycolipopeptide and glycopeptide microbial biosurfactants are those produced by lactic acid bacteria such as s agilis , Lactobalantarum , Lactobaaracasei ,95,96 anpentosus ,96,97,98pentosus . For insruginosa  or lipop strains .Lactobacillus and can be extracted using saline buffer phosphate or just buffer phosphate [Cyclopeptide and glycopeptide microbial biosurfactants are linked to the cell membrane of hosphate ,97,101.L. pentosus showed an important antimicrobial activity against P. aeruginosa, Streptococcus agalactiae, Staphylococcus aureus, Escherichia coli, Streptococcus pyogenes and Candida albicans similar to the antimicrobial activity shown by L. paracasei. Additionally, microbial biosurfactants produced by both microorganisms also showed significant anti-adhesive properties against all the microorganisms named above, except for E. coli and C. albicans [Lactobacillus strains could be introduced in the cosmetic and personal care industry not only as a detergent but also as prebiotic ingredients as they are produced by probiotic bacteria and inhibit the growth of harmful skin microorganisms [Some glycopeptide and glycolipopeptide microbial biosurfactants have shown antimicrobial activity against skin pathogens . Therefoalbicans . Based organisms ,96.These substances are included in this classification owing to their origin as they can be obtained from vegetable or animal cells. Phospholipids are mostly classified as zwitterionic substances and are polar lipids. The phospholipids can be classified into two groups: glycerophospholipids and sphingolipids. Glycerophospholipids are composed of a glycerol base structure with two fatty acids esterified at the sn-1 and sn-2 positions, and a phosphorylated alcohol , obtaining phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol and phosphatidylserine derivates. Otherwise, sphingolipids are formed by the aliphatic amino alcohol sphingosine base structure, fatty acids and sugars or alcohols or phosphoric acid; and they can include sphingomyelin, gangliosides and cerebrosides ,103.The CosIng ingredient list includes various substances within the phospholipids category such as some glycine soy lipids or an alcohol soluble extract consisting predominantly of phospholipids. Other examples are sterols and triglycerides and hydrolysed phospholipids, obtained from different vegetable sources and hydrolysed with acids or enzymes .It is interesting to remark that although phospholipids possess surfactant capacity, they are not included in the CosIng database as surfactants. They are used in hair and skin conditioning formulations , whereasAcinetobacter calcoaceticus [Candida lipolytica, composed of 83% carbohydrates and 17% proteins. It has been applied in the food and cosmetic industries as an emulsifier [The most studied polymeric microbial biosurfactants are polymeric emulsifiers with surfactant capacity produced by microorganisms. Of these, in turn, the most studied is emulsan, which is a polyanionic amphipathic heteropolysaccharide produced by aceticus . The capaceticus . Other baceticus . In thisulsifier .Acinetobacter spp. [The most studied particulate microbial biosurfactants are articulated vesicles, which are composed of proteins, phospholipids and polysaccharides . These pter spp. . Despiteter spp. .Bacillus strain with the capacity to generate both extracellular and cell-bound microbial biosurfactants. On the other hand, this microbial biosurfactant has already been tested in hair care [Due to the huge operational costs to obtain microbial biosurfactants compared to synthetic or bio-based surfactants , their uair care ,114,115 air care ,118,119 Microbial biosurfactants were applied to cosmetic, personal care and pharmaceutical formulations, achieving interesting results with fewer side effects than those produced by synthetic surfactants. Among all microbial biosurfactants used in the cosmetic industry, lipopeptides and glycolipids are the ones selected due to their multifunctional profile, especially based on their physiochemical properties and biological activities ,140.A notable example for the cosmetic industry is the development of new formulations with sunscreen properties. Rincón-Fontán et al.  designedL. paracasei as a stabilizing agent in oil-in-water (O/W) emulsions containing essential oils and a natural antioxidant extract from grape seeds. These formulations were evaluated using the sulforhodamine B (SRB) assay (with mouse fibroblast cell line 3T3) and compared with SDS. The results showed that O/W emulsions containing 10 g/L of microbial biosurfactant and 5 g/L of the antioxidant extract showed EV values about 100% after 7 days of emulsion formation. On the other hand, formulations containing 5 g/L of microbial biosurfactant presented cell proliferation values of 97%, whereas 0.5 g/L of SDS showed a strong inhibitory effect.Ferreira et al.  used a gNocardiopsis VITSISB, in a toothpaste formulation, replacing SLS, which is normally used in commercial toothpaste as a surfactant. The results indicated that microbial biosurfactant is more efficient and less toxic than chemical surfactant. Farias et al. [Mentha piperita) essential oil. Additionally, three microbial biosurfactants obtained from Pseudomonas aeruginosa UCP 0992 (PB), Bacillus cereus UCP 1615 (BB) and Candida bombicola URM 3718 (CB) were examined. The antimicrobial action against oral microorganisms and toxicity using the MTT -2,5-diphenyltetrazolium bromide)) method for the L929 (mouse fibroblast) and RAW264.7 (mouse macrophage) cell lines of the mouthwashes were evaluated. The results showed that the mouthwashes, containing the microbial biosurfactant and other natural products, represented lower toxicity than the commercial ones.Other interesting applications related to personal care applications were found. Das et al.  used a ms et al.  formulat1/2 of this microbial biosurfactant (time to achieve 50% of biodegradation) was no lower than 35 days at pH 5.Nevertheless, these studies did not take into account the biodegradation of these surface-active compounds in cosmetic formulations. This is a challenge, since immediate microbial biosurfactant biodegradation would not be desirable before realizing their role in the cosmetic formulation. For that reason, Rodríguez-López et al.  recentlyConversely, there are several works that have demonstrated the toxicity of surfactants and bio-based surfactants, which can reach animals through feeding or through the skin. When the surfactant concentration in water is too high, surfactants can enter the gills, blood, kidney, pancreas, gallbladder and liver and produce an aquatic toxicity effect . SurfactThe side effects of surfactants can be avoided by using bio-based surfactants or microbial biosurfactants. However, the challenge to incorporate ingredients of natural origin or microbial biosurfactants in cosmetic products is the safety assessment according to the Scientific Committee on Consumer Safety . For thaCandida sp. SY16 in mouse fibroblast L929 cells after 48 h of exposure using a Neutral Red (NR) assay. The midpoint toxicity value (NR50) of MEL was higher (5 g/L) in comparison with synthetic surfactants such as SDS and LAS , which had NR50 values of 0.05 g/L and 0.01 g/L, respectively. The data clearly suggest that MEL-SY16 is not harmful to human skin and eyes when compared to synthetic surfactants.Kim et al.  tested tMorita et al.  assessedSphingobacterium detergens  in 3T3 fibroblast and HaCaT keratinocyte cell lines after 24 h of exposure using the Neutral Red Uptake (NRU) and MTT assays. It was observed that both fractions showed similar cytotoxicity in fibroblasts and keratinocytes cell lines; however, it was worth noting that fraction B showed lower cytotoxicity than those obtained using SDS, indicating low skin irritability.Burgos-Díaz and collaborators  evaluateL. pentosus or by the microbial biosurfactant extract composed of lipopeptides obtained from a residual stream of the corn milling industry (corn steep liquor), spontaneously fermented by Bacillus strains.Rodríguez-López et al.  have stuOn the other hand, it is important to remark that although chemical surfactants possess a low CMC, they are used in high concentrations to be effective in cosmetic and pharmaceutical formulations. Some of these formulations contain up to 30% of surfactants. 50) and effective concentration (EC50) of microbial biosurfactants in comparison to synthetic surfactants [According to factants .The increasing demand for surfactants by the cosmetic and personal care and pharmaceutical industries has generated huge consumption of petroleum-based synthetic surfactants, which are often toxic, irritant and non-biodegradable. Bio-based surfactants have come along as an alternative to synthetic surfactants, obtained from the petrochemical industry. Bio-based surfactants are compounds obtained using renewable sources and biomass. Hence, these kinds of surface-active compounds prevent the use of petrochemical sources; however, although vegetable and animal oils are used in their production, they are obtained through a chemical reaction that involves the consumption also of non-renewable sources. Nevertheless, microbial biosurfactants, which are produced by microorganisms, using biological reactions, as secondary metabolites, could represent a promising alternative since they are composed of lipids, carbohydrates or proteins, which makes them more biocompatible and biodegradable than their synthetic and bio-based counterparts. Additionally, they present low toxicity, stability in extreme conditions and several bioactivities.Therefore, if microbial biosurfactants are less toxic and more biodegradable than chemical surfactants, what is wrong with microbial biosurfactants? Why are they not being included in cosmetic, personal care and pharmaceutical formulations? The main problem is related to the biotechnological production of microbial biosurfactants, which means a higher production cost, as they are secondary metabolites. Moreover, the biotechnological production of microbial biosurfactants involves an important cost regarding not only the nutritional medium but also the extraction and purification steps. Therefore, it is necessary to seek an increase in the overall productivity of microbial biosurfactants by obtaining higher producer microorganisms and by exploring the use of cost-competitive nutritional media, including the use of fermented residual streams (like corn steep liquor) where microbial biosurfactants can be produced spontaneously. Lastly, due to the current trend towards green consumption, it is expected there will be a significant effort to develop cosmetic, personal care and pharmaceutical formulations in which synthetic surfactants are replaced by renewable and environmentally friendly microbial biosurfactants. Therefore, international cosmetic regulations are required to incorporate microbial biosurfactants as a separate group of surfactants in order to obtain more biocompatible and greener formulations.


The properties investigated were the mass attenuation coefficient (mµ), linear attenuation coefficient (µ), and half value layer (HVL) of the composites, determined at varying photon energies of 0.001–5 MeV and varying filler contents of 0–1000 parts per hundred parts of rubber by weight (phr). The simulated results, which were in good agreement with previously reported experimental values (average difference was 5.3%), indicated that overall shielding properties increased with increasing filler contents but decreased with increasing incident photon energies. The results implied the potential of bismuth compounds, especially Bi2O3, to replace effective but highly toxic Pb as a safer high-energy-photon protective filler, evidenced by just a slight reduction in mµ values compared with Pb fillers at the same filler content and photon energy. Furthermore, the results suggested that the addition of 20 phr wood particles, primarily aimed to enhance the rigidity and dimensional stability of Pb/NR, Bi2O3/NR, and Bi2S3/NR composites, did not greatly reduce shielding abilities; hence, they could be used as dimensional reinforcers for NR composites. Lastly, this work also reported the optimum Pb, Bi2O3, or Bi2S3 contents in NR and wood/NR composites at photon energies of 0.1, 0.5, 1, and 5 MeV, with 316–624 phr of filler being the recommended contents, of which the values depended on filler type and photon energy of interest.This work aimed to theoretically determine the high-energy-photon-shielding properties of flexible wood/natural rubber (NR) and NR composites containing photon protective fillers, namely Pb, Bi High-energy photons, especially X-rays and gamma rays, are presently used in various applications, for instance, X-ray and gamma imaging for medical and industrial purposes ,2,3, rad2O3)/poly(vinyl) alcohol (PVA) [2O3-filled concrete [One of the three ALARA principles is the use of effective and appropriate radiation-shielding equipment that could sufficiently reduce radiation exposure on users to within occupational dose limits recommended by the International Commission on Radiological Protection (ICRP) . Howeverol (PVA) , flexiblol (PVA) ,14, biocol (PVA) , and envconcrete .Z) and densities (ρ), which could increase interactions between materials and incident photons through the mechanisms of the photoelectric absorption, Compton scattering, and pair production that consequently result in better radiation attenuation [2O3 and Bi2S3, which are considered safer for producers and users than Pb, has gained much attention from researchers [2O3 had a linear attenuation coefficient (µ) of 24.3 ± 2.2 m−1 at a gamma energy of 1.25 MeV [µ value of 26.0 m−1 [2O3 and Bi2S3 to replace Pb as effective and safe protective fillers.Among these materials used for the production of radiation-shielding equipment, NR has presented itself as one of the most interesting materials due to excellent tensile properties, high tear resistance, lower odor than synthetic rubber (SR), and waterproofing ability . Howeverenuation ,19. In aenuation . Howeverenuation . Therefoearchers ,14. For 1.25 MeV , which w26.0 m−1 . This co2O3 and Bi2S3 in NR composites generally resulted in enhanced shielding properties, the overall mechanical properties of the composites could be inversely reduced, mostly due to their poor interfacial compatibility and the different contraction/expansion behaviors during curing and cooling processes between NR and Bi2O3 (Bi2S3), which possibly created voids between the surfaces of the two substances. Furthermore, high filler contents could also lead to agglomerations of particles from filler-filler interactions. Consequently, these effects lowered the overall strength and flexibility of the materials. Examples of the effects from high filler contents are a decrease in the tensile strength of Bi2O3/NR composites from ~13 MPa in a sample with 100-phr Bi2O3 to ~8 MPa and ~6 MPa for samples with 300-phr and 500-phr Bi2O3, respectively [Although high contents of Bi2O3/NR composites, which were developed as flexible neutron shielding materials, increased by 44% after normal usage at room temperature for 150 days. Subsequently, this unfortunate behavior led to a significant reduction in the shielding abilities of the material (approximately 36%) due to the decrease in material thickness by 31% that resulted in lower photon interactions with the materials [2O3/NR composites increased by just 14% after 150 days of usage, resulting in a decrease in the shielding abilities by 13% compared to the 36% drop in those without the addition of wood particles [2O3/NR and Bi2S3/NR composites, especially in the case of high filler contents.In addition to the filler contents that could affect the shielding and mechanical properties of NR composites, the self-solid-lubricant properties of most metal compounds added to NR could result in decreased crosslink densities, shortened lifetimes, and unpleasantly expanded dimensions of the NR composites after some periods of usage . For insaterials . To enhaarticles . Clearlymµ), linear attenuation coefficient (µ), and half value layer (HVL) of Pb/NR, Bi2O3/NR, and Bi2S3/NR composites with or without the addition of wood particles using XCOM provided by the National Institute of Standards and Technology (NIST) [2O3 contents as well as the photon energy used in the simulation were varied in the ranges 0–1,000 phr and 0.001–5 MeV, respectively, and the obtained results were compared with previously reported experimental values with similar material preparations and testing procedures to ensure the correctness and the reliability of the simulated results. Furthermore, the investigation reported and discussed the recommended filler contents of Pb, Bi2O3, and Bi2S3 in wood/NR and NR composites at various gamma energies , which were selected based on the determination of the least filler content that increased the µ value of the composites by less than 5% after the addition of 40 phr of the filler. This content optimization was carried out to minimize the negative effects on the mechanical properties of the composites from high filler contents while still offering relatively high shielding ability.Consequently, the current work aimed to theoretically determine the high-energy photon shielding properties, based on the mass attenuation coefficient (y (NIST) . To fullmµ in the wood/NR and NR composites containing Bi2O3, Bi2S3, or Pb particles (mµ represent the fraction of attenuated incident photons in a monoenergetic beam per unit mass) [mµ reported in this work were calculated from the total attenuation with the inclusion of coherent scattering [The web-based XCOM software provided by the National Institute of Standards and Technology (NIST), Gaithersburg, MD, USA, was used to determine the values of it mass) . Originaattering .µ and HVL, which represent the fraction of attenuated incident photons in a monoenergetic beam per unit thickness and the thickness of the materials required to attenuate 50% of incident photons, respectively, of the wood/NR and NR composites containing Bi2O3, Bi2S3, or Pb particles with contents varying from 0 to 1000 phr at photon energies of 0.001–5 MeV were determined from the obtained values of mµ (XCOM) using Equations (1) and (2), respectively:ρ is the density of the composites theoretically estimated using Equation (3):i is the thi chemical in iρ is the density of the thi chemical in ic is the content of the thi chemical in The values of 2O3, Bi2S3, and Pb contents at photon energies of 0.1, 0.5, 1, and 5 MeV were determined by considering the percentage change in mµ (%change) after the addition of 40 phr of fillers and was calculated using Equation (4):mµ,1 is the initial mµ of the composites and m,µ2 is the resulting mµ of the composites after the additional 40-phr Bi2O3, Bi2S3, or Pb.The recommended Bichange for all contents (0–1000 phr) were determined and the least contents that had %change less than 5% were selected as the recommended contents . Furthermore, in order to determine recommended contents at any photon energies besides the reported values at 0.1, 0.5, 1, and 5 MeV, trendlines were also developed using equations in the form:f(x) is the threshold of %change, x is the recommended filler content, and A and B are mathematical constants determined using a trendline function available in Microsoft Excel. It should be noted that the objective of this determination was to minimize the effects of too-high filler contents on lowering the mechanical properties of the composites.To obtain the recommended contents for each filler type and photon energy, %mµ values at photon energies of 0.001–5 MeV for Bi2O3/NR, Bi2S3/NR, Pb/NR, Bi2O3/wood/NR, Bi2S3/wood/NR, and Pb/wood/NR composites with varying filler contents of 0, 400, and 800 phr are shown in 2O3, Bi2S3, or Pb had noticeably higher mµ values than the pristine NR and wood/NR composites at all investigated photon energies , which contained Bi atoms, and the Pb particles greatly enhanced the interaction probabilities between the incident photons and the composites through photoelectric absorption, Compton scattering, and pair production (pair production could occur only at photon energies greater than 1.022 MeV) due to their high Z and ρ values, with the relationships between the cross sections for each mechanism and its photon/material characteristics being shown as Equations (6)–(8):pe is the photoelectric cross section, σcomp is the Compton scattering cross section, σpp is the pair production cross section, Z is the atomic number of the element, h is Planck’s constant, ν is the frequency of the photon, and en is the electron density, which is related to density and Z of the material [The energies , with thcontents . This comaterial .2O3 and Pb and their contents on enhancing high-energy photon attenuation are graphically illustrated in The effects of Bimµ values tended to decrease with increasing photon energies and the effects of fillers on mµ were more pronounced at lower energies. These behaviors were observed because higher-energy photons were less likely to interact with materials they encountered than lower-energy photons due to the inverse relationship between linear energy transfer (LET) and photon energies [mµ values. Interestingly, there were sharp increases in the values of mµ in NR composites containing Bi2O3, Bi2S3, and Pb at photon energies of:2O3/NR, Bi2S3/NR, Bi2O3/wood/NR, and Bi2S3/wood/NR composites , resulting in substantially enhanced probabilities of photon interaction through photoelectric absorption at these particular energies [mµ in pristine NR were higher than those in Bi2O3/NR, Bi2S3, and Pb/NR at the photon energies of 1–2 MeV. These behaviors were due to the rapid drops in photoelectric absorption and Compton scattering probabilities of Bi2O3, Bi2S3, and Pb particles at these mid-ranged photon energies. These behaviors were in contrast with the decreases in interaction probabilities of C and H that were much less pronounced . However, pair- production probability of Bi2O3, Bi2S3, and Pb sharply increases at photon energies greater than 2 MeV, resulting in much enhanced interaction probabilities of composites containing Bi2O3, Bi2S3, and Pb that consequently led to higher mµ in Bi2O3/NR, Bi2S3/NR, and Pb/NR composites (pair production cross sections (probabilities) of light elements were relatively smaller than those of heavy elements).And in all composites at the photon energy of 9.6 keV a,c due tenergies . It is nmµ values than the Bi2O3/NR and Bi2S3/NR composites for the same filler content and photon energy , resulting in higher attenuation abilities and consequently, higher mµ values in the Bi2O3/NR composites. In addition, comparing mµ values of NR and wood/NR composites with the addition of Bi2O3 and Bi2S3 at the same filler content and photon energy, 2O3 exhibited slightly higher µm than those with Bi2S3. This could be due to higher mass fraction of Bi in a molecule of Bi2O3 (0.89) than Bi2S3 (0.81), which resulted in higher numbers of Bi atoms in Bi2O3 than Bi2S3 at the same filler content.n energy a,b,d. Thed to Bi  and the m,XCOMµ is the µm value from the simulated result, m,reportµ is the µm value from the previously reported experimental value.To validate the simulated results from XCOM in this work, previously reported experimental values were used to compare their agreements. The comparisons of the two values for the NR composites containing different filler types/contents at various photon energies are shown in µ, HVL, and the recommended filler contents in this work. It should be pointed out that the differences in the two values could have been due to several factors, including experimental setup and equipment that caused an imperfectly monoenergetic and narrow photon beam, agglomerations of fillers, voids at the interfacial surfaces of the NR matrix and filler particles, and build-up factors that lowered the experimental mµ values to be generally less than the theoretical ones [As shown in cal ones ,32.µ and HVL values of the Bi2O3/NR, Bi2S3/NR, Pb/NR, Bi2O3/wood/NR, Bi2S3/wood/NR, and Pb/wood/NR composites, the densities for each filler content must be estimated. The results of the density calculations using Equation 3 are shown in 2O3 and Bi2S3 due to the higher density of Pb (11.35 g/cm3) compared to Bi2O3 (8.90 g/cm3) and Bi2S3 (6.78 g/cm3). Furthermore, 3) compared to NR (0.92 g/cm3), Bi2O3, Bi2S3, and Pb. It should be noted that the densities of actual NR and wood/NR composites might differ from the theoretical densities shown in To determine the µ and HVL of the Bi2O3/NR, Bi2S3/NR, Pb/NR, Bi2O3/wood/NR, Bi2S3/wood/NR, and Pb/wood/NR composites with varying filler contents and photon energies. The results indicated that µ tended to increase but HVL tended to decrease with increasing filler contents. These results agreed with the trends found in mµ (µ), and consequently, less material thickness being required to attenuate 50% of the incident photon intensity (HVL). Additionally, µ values than the Bi2O3/NR composites for the same filler content and photon energy, mainly due to the former having greater density and mµ than the latter (Equation (1)). Similarly, the NR composites with the addition of wood particles had lower µ but higher HVL values than those without wood particles. This behavior was observed due to the low density of the wood particles  were reduced by as much as 16% (33%) at a photon energy of 0.1 MeV and by 5% (24%) at a photon energy of 5 MeV , the potential of using bismuth compounds, especially Bi2O3, as an alternative but safer protective filler was promising. In addition, the µ (HVL) values at lower energies were generally higher (lower) than those at higher energies and the effects of additional filler contents on enhancing shielding abilities were more pronounced at lower energies than at higher energies (determined for the same type of composites). This could have been due to the higher-energy photons being less likely to interact with the materials they encountered (Equations (6)–(8)), leading to less attenuation and therefore, smaller (larger) µ (HVL) values.nd in µm  due to tarticles  that genarticles  as well 2O3/NR, Bi2S3/NR, Pb/NR, Bi2O3/wood/NR, Bi2S3/wood/NR, and Pb/wood/NR composites at different photon energies, the values of %change in µ were calculated using Equation 4 and the results are shown in 2O3, Bi2S3, and Pb were in the ranges 358–594 phr, 316–557 phr, and 398–624 phr, respectively, depending on photon energies and the present of wood particles. Furthermore, it is noteworthy that values of %change were initially much higher at low filler contents due to the more pronounced effects of Bi and Pb in enhancing shielding properties from their relatively higher cross sections for photoelectric absorption and Compton scattering than C, H, and O in the pristine NR and wood/NR composites. This effect led to a significant enhancement in photon attenuation of the NR composites at low photon energies. However, as more fillers were added to the composites, the effects of fillers on %change were less pronounced and essentially became less than 5% (a threshold set in this work for the determination of recommended filler contents).To determine the recommended filler contents for the Bi%change with the form shown in Equation (5) were developed and mathematical constants (A and B) were obtained using a trendline function available in Microsoft Excel. The values of A and B as well as recommended filler contents for photon energies of 0.1 MeV, 0.5 MeV, 1 MeV, and 5 MeV (based on the threshold of 5%) determined from the fitted curves are shown in %change than those at higher photon energies (1 MeV and 5 MeV). This behavior was observed because Bi2O3, Bi2S3, and Pb could better interact with photons at lower energies, leading to greater shielding enhancement after adding more fillers to the composites.To obtain the recommended filler contents for all photon energies, fitted curves of 2O3 or Bi2S3 by considering the percentage difference in µ values of Pb and Bi2O3 (Bi2S3) at the determined recommended contents. The results indicated that the differences were in the range 8.3–16.3% for those with Bi2O3 and 19.6–28.4% for those with Bi2S3, of which NR and wood/NR composites containing Pb had higher µ values than those with Bi2O3 and Bi2S3. Nonetheless, as a considerably safer chemical than Pb, bismuth compounds, especially Bi2O3, showed their potential to replace the former as effective radiation-protective fillers.mµ values for all filler contents were not greatly different (0.068–0.071 cm2/g), resulting in lower filler contents being required to obtain <5% of %change. On the other hand, the results pointed out that higher filler contents were required to achieve the same %change at the 5 MeV photon energy, mostly due to the initiation of pair production, which again enhanced the effects of added Bi2O3, Bi2S3, and Pb in photon attenuation, as seen by larger changes in mµ when the filler contents increased from 0 to 1000 phr (mµ increased from 0.029 to 0.040 cm2/g). It should be noted that the recommended filler contents given in this work were not intended for the highest µ of the composites but rather the least amount of filler that produced a %change of an additional 40 phr filler to be less than 5% in order to minimize the effects of having too much filler in the NR matrix and its impact on lowering mechanical properties [Interestingly, operties ,20,24,31mµ, µ, and HVL as well as the recommended filler contents for Bi2O3/NR, Bi2S3/NR, Pb/NR, Bi2O3/wood/NR, Bi2S3/wood/NR, and Pb/wood/NR composites with the filler contents in the range 0–1000 phr and photon energies in the range 0.001–5 MeV for the development of X-ray and gamma-shielding equipment with flexibility and enhanced dimensional stability. The XCOM simulation software was used in this work and was provided by NIST, USA. The results showed that values of mµ and µ (HVL) increased (decreased) with increasing filler contents but decreased (increased) with increasing photon energies. Furthermore, the addition of wood particles in the wood/NR composites did not greatly affect the overall shielding properties compared with the NR composites, implying the possibility of applying wood fillers as a dimensional reinforcer for composites with high filler contents. In addition, Bi2O3 and Bi2S3 also showed great potential to replace Pb as a high-energy-photon protective filler due to its relatively high attenuation efficiency and being considerably less hazardous than Pb. Lastly, the determination of the recommended filler contents based on calculation of the %change in µ indicated that the optimum Pb, Bi2O3, or Bi2S3 contents at photon energies of 0.1, 0.5, 1, and 5 MeV were in the range 316–624 phr, depending on the filler type and the intended photon energy.This work determined the theoretical high-energy photon shielding properties consisting of


Attention deficit hyperactivity disorder (ADHD) is the commonest disorder presenting to Child and Adolescent Mental Health Services in Ireland. This article considers the impact of the Covid-19 pandemic on the provision of mental health services for young people with ADHD with specific reference to the difficulties that have been experienced in ADMiRE, a specialist ADHD service in Dublin, since the outbreak of Covid-19 in Ireland. Current guidelines and alternative ways of ensuring adequate service provision are discussed. Restrictions to mitigate the spread of Covid-19 are likely to continue for many months, and child and adolescent mental health services need to find new ways to provide a sustainable service to young people in Ireland. There is a growing evidence base for the use of telepsychiatry in the assessment and management of ADHD. Factors that should be considered when developing a telepsychiatry service for children and adolescents with ADHD are highlighted. CADDRA n = 131) or Lisdexamphetamine (n = 20)], 12% are on Atomoxetine and 5% are on Guanfacine (both as monotherapy and stimulant augmentation). 37% are also prescribed Melatonin. NICE guidelines recommend that for young people on ADHD medication, blood pressure and heart rate are monitored before and after each dose change and every 6 months, height is monitored every 6 months and weight every 3 months (for <10 years) or 6 months (>10 years)  are prescribed ADHD medication. The majority (85%) are on a psychostimulant [Methylphenidate  Scheme. Under this scheme, the GP is required to transcribe the prescription onto a GMS script, which is then brought to the pharmacy by the family. There were two difficulties with this process especially in the early days of the Covid-19 pandemic. Firstly, it involved an excessive number of journeys for families between the mental health service, GP and pharmacy, which exposed them to unnecessary risk. Secondly, GP services were overwhelmed and many families reported that they were unable to access their GMS prescription. At this time, many pharmacists adopted a flexible approach, whereby they dispensed non-GMS prescriptions at no charge in order to assist patients who were unable to get the GMS prescription from their GP. However for controlled drug prescriptions for stimulants, pharmacists were unwilling to dispense without the GMS script leaving many patients from ADMiRE without medication. By early April 2020, GPs were accepting email prescriptions from ADMiRE clinicians for GMS patients and were emailing the GMS scripts directly to the patient’s pharmacy necessitating only one journey for the parent to collect medication.Initial HSE guidelines for use of PPE in ADMiRE and community CAMHS appeared to differ from the practice that was being followed by GPs and by clinicians in paediatric Emergency Departments. These initial guidelines recommended a phone risk assessment, with face-to-face appointments only to be offered to young people if the family were asymptomatic. For those who were asymptomatic, it was suggested that no PPE was required, that clinicians and families should wash their hands at the start and end of review, sit 2 metres or more from each other and that face-to-face appointments could last for 15 minutes, followed by a short break before continuing for a further 15 minutes.et al.et al.Clinicians in ADMiRE became increasingly uncomfortable about face-to-face contact using these guidelines as emerging epidemiological data from March and early April 2020 suggested that the majority of children with Covid 19 infection may be asymptomatic  and the American Telemedicine Association (ATA) have published a guide on best practices in clinical videoconferencing in mental health  if technical difficulties cause a disruption of the videoconferencing session.During a telepsychiatry session, both locations are considered the patient examination room, and it is important to consider the therapeutic space and level of privacy that is available for a young person and their caregiver in their home as this will vary significantly from family to family. In the case where the videoconferencing is taking place in professionally unsupervised settings such as the patient’s home, the parent/caregiver needs to be able to set up the videoconferencing system and select a suitable and private space.The ability of the parent/caregiver to engage in the videoconference should be considered. It may be particularly difficult for them to encourage a young person with ADHD to attend a videoconference in their home environment. For adolescents, a quiet room with minimal distractions may be most appropriate, but for younger children, a room with some toys and activities may increase interest in the session and facilitate engagement with the parent and clinician. Engagement with adolescents may be increased through exploration of relevant and appropriate material on YouTube or other sites. Younger children may enjoy using online drawing apps and can be encouraged to tell stories while drawing.As discussed above, physical examination including blood pressure, heart rate, weight and height is routinely required during pharmacotherapy for ADHD  (contact of fingertip with built-in camera) or non-contact PPG, whereby the camera is used to measure changes in the volume of the surface of the body (e.g. Li et al.et al.In relation to blood pressure monitoring, there are a multitude of smartphone apps that claim to accurately record blood pressure; however, many require external equipment, and the accuracy of these has been low (Jamaladin If the young person with ADHD has a Long-Term Illness book or if the family are paying directly for their medication, the prescription can be emailed directly to the pharmacy using a secure email address, and if the young person has a Medical Card, the prescription can be emailed to the GP practice where it is transcribed to a GMS script and emailed on to the pharmacy. These processes minimise face-to-face contact for both healthcare workers and families.The Covid-19 pandemic has had a significant impact on the provision of mental health services for children and adolescents with ADHD in Ireland. With ongoing Covid-19 restrictions anticipated over the coming months, there is an urgent need to find effective new ways of working. There is a growing evidence base for telepsychiatry in assessing and treating young people with ADHD; this is a practical approach that could be considered by CAMHS nationally.


Previous studies of attention-deficit hyperactivity disorder (ADHD) have suggested that structural variants (SVs) play an important role but these were mainly studied in subjects of European ancestry and focused on coding regions. In this study, we sought to address the role of SVs in non-European populations and outside of coding regions. To that end, we generated whole genome sequence (WGS) data on 875 individuals, including 205 ADHD cases and 670 non-ADHD controls. The ADHD cases included 116 African Americans (AA) and 89 of European Ancestry (EA) with SVs in comparison with 408 AA and 262 controls, respectively. Multiple SVs and target genes that associated with ADHD from previous studies were identified or replicated, and novel recurrent ADHD-associated SV loci were discovered. We identified clustering of non-coding SVs around neuroactive ligand-receptor interaction pathways, which are involved in neuronal brain function, and highly relevant to ADHD pathogenesis and regulation of gene expression related to specific ADHD phenotypes. There was little overlap (around 6%) in the genes impacted by SVs between AA and EA. These results suggest that SVs within non-coding regions may play an important role in ADHD development and that WGS could be a powerful discovery tool for studying the molecular mechanisms of ADHD Symptoms persist into adulthood in over two thirds of cases, causing significant life-long impairments3. In the last decade, multiple studies have attempted to investigate the genetic susceptibility of ADHD, most notably by assessing the enrichment of copy number variations (CNVs)4 and single nucleotide variants (SNVs) from genome-wide association studies (GWAS)5. However, the current understanding of this complex trait is incomplete and attempts to replicate previous studies have been inconsistent, due in part to the highly heterogenous phenotype of ADHD, as well as other factors, such as complicated molecular mechanisms underlying ADHD networks and limitations of genotyping arrays to study structural variations (SV)6. Previous studies also show that the susceptibility of ADHD is more likely to be impacted by biological pathways instead of a particular gene8, and by structural variations (SVs), such as copy number variations (CNVs), inversions, translocations that may play important roles in the regulation of ADHD gene networks10. Most of previously published studies have focused on coding regions and have been carried out primarily in patients of European ancestry while intronic and intergenic regions were often omitted from analyses. However, non-coding genomic structural variations and non-coding DNA sequences have been shown to play important roles in many human diseases, including neurodevelopmental diseases such as autism and intellectual disability12. In this regard, the most recent large GWAS studies on 55,374 individuals, including 20,183 ADHD patients, highlighted that variants in non-coding regions, such as non-coding RNA and intergenic region were significantly associated with ADHD susceptibility13. In addition, previous studies have largely focused on European Caucasian populations leaving out studies in African populations and other populations.Attention-deficit hyperactivity disorder (ADHD) has a prevalence of ~ 6–8% in children with male patients outnumbering females by almost doubleTo address the limitations of the previous studies of ADHD, in this study we have generated deep whole genome sequencing (WGS) data on 875 individuals, including 205 ADHD patients and 670 non-ADHD controls, in order to explore the impact of SVs, especially SVs within non-coding regions, on the pathogenesis of ADHD. We have also included a significant number of African Americans in the study, including 116 cases and 408 controls, to expand the analysis into another population other than Europeans. The results suggest that SVs within non-coding regions play critical roles in the molecular mechanisms underlying ADHD and that population-specific SVs are present. This information would be useful for future studies of ADHD genetic network regulation and drug development.LOC100288254.Approximately 160,000 structural variations (SVs) were identified in ADHD patients Fig. a and 38214, there are no known exonic/splicing SV-genes from previous studies passed the statistic threshold. However, a novel exonic deletion in IQSEC3 passed the ethnicity meta-analysis  is the most common neurobiological disorder in children, with a prevalence of 6–8%CHRNA3, GRM5, HTR1F, GRIN2A which were supported by previous literature25. All the identified structural variations related to this pathway are either intronic or intergenic. Similar situations were found in other neurodevelopmental pathways, such as MAPK signaling pathway and Axon guidance. Functional role of SVs in non-coding regions in ADHD therefore warrant further investigation. We also show that there is only a small portion of overlap between the two ethnicities of SV impacted genes, and the result was further replicated as we limited the SV-genes to known ADHD genes based on the ADHD gene database14. 25 ADHD-associated SV-genes have been previously studied and reported in the literature  or have a trend towards significance , 10 of them belong to neuroactive ligand-receptor interaction pathway and five genes are AA SV-genes and the left are EA specific SV-genes Table . The res28, the same ADHD-associated pathways though different genes were involved in the adaption to the environmental selection for survival in the two major human populations. On the other hand, we admit that the current study is limited by the sample size because of the significant expense of WGS. The SVs highlighted by our study warrant further study and confirmation.In summary, we have conducted a genomic-level study in ADHD patients using whole genome sequencing that takes non-coding genes/regions and ethnicity factors into consideration. The results show that non-coding region SVs and non-coding genes may play a role in the development and progression of ADHD, and WGS may be a powerful tool to explore ADHD molecular mechanisms. Additionally, our study highlights that genomic-level population differences exist between Caucasian and African American patients, especially for non-coding SVs in neuronal genes and that these variants may influence response to specific medications. For the potential evolutional advantages of ADHD in human history29. The diagnosis of ADHD was based on the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV) originally, and later confirmed by DSM-V. There were 205 ADHD cases, including 116 African Americans (AA) and 89 European Americans (EA), and 670 controls, including 408 AA and 262 EA , archived in the biobank of the Center for Applied Genomics (CAG) at the Children's Hospital of Philadelphia (CHOP), with full electronic medical record (EMR). Psychopathology of the cohort was assessed using a computerized, structured interview (GOASSESS)30. For quality control, we only included SVs that passed MANTA’s default filters, which required the length of corresponding SVs to be at least 50 bp and rated “PASS” based on MANTA threshold. Passing SVs were stratified into different classes based on their sequence content. Using the hg19 GENCODE reference sequence, if the start and end points of a SV mapped within an exon, it was annotated as “exonic’; if the start and end points of a SV were located within an intronic region and the SV does not spanned an exon, it was annotated as “intronic”; if the SV was located across exon/intron border sites, it was annotated as “splicing”; and the remaining SVs were annotated as “intergenic”.The average coverage for WGS data is 30 ×. The structural variations (SVs), including insertions, deletions, duplications, inversions and translocations, were detected by MANTA Structural Variant Caller developed by IlluminaExonic, intronic and splicing SVs were annotated with the impacted gene, and intergenic SVs were annotated with their closet gene based on genomic locus. The corresponding annotated gene, either the SVs impacted gene or the closet gene, was named as “SV-gene”. Association of SV-genes in ADHD were calculated for AA and EA independently using Chi-square tests and Fisher’s exact tests. Bonferroni correction was used for correction of multiple testing by the number of tested variations or genes. Significance was set at 0.05 after Bonferroni correction. We only included risk variants in downstream analyses, i.e. SVs that had odd ratios greater than 1. Meta-analysis (combined Chi-square test) was applied when combing two ethnicities together. Pathway analysis is based on DAVID bioinformatics platforms.We confirm that all methods were carried out in accordance with relevant guidelines and regulations and all experimental protocols were approved by the Children’s Hospital of Philadelphia (CHOP). Informed consent was obtained from all subjects or, if subjects are under 18, from a parent and/or legal guardian.Supplementary Information.Supplementary Table 1.Supplementary Table 2.Supplementary Table 3.Supplementary Table 4.Supplementary Table 5.Supplementary Table 6.