<?xml version="1.0" encoding="UTF-8"?><!DOCTYPE article  PUBLIC "-//NLM//DTD Journal Publishing DTD v3.0 20080202//EN" "http://dtd.nlm.nih.gov/publishing/3.0/journalpublishing3.dtd"><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" dtd-version="3.0" xml:lang="en" article-type="research article"><front><journal-meta><journal-id journal-id-type="publisher-id">JCDSA</journal-id><journal-title-group><journal-title>Journal of Cosmetics, Dermatological Sciences and Applications</journal-title></journal-title-group><issn pub-type="epub">2161-4105</issn><publisher><publisher-name>Scientific Research Publishing</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.4236/jcdsa.2019.91002</article-id><article-id pub-id-type="publisher-id">JCDSA-90094</article-id><article-categories><subj-group subj-group-type="heading"><subject>Articles</subject></subj-group><subj-group subj-group-type="Discipline-v2"><subject>Medicine&amp;Healthcare</subject></subj-group></article-categories><title-group><article-title>
 
 
  Clinical Evaluation of a Novel Blended Mode Diode Laser for Hair Removal
 
</article-title></title-group><contrib-group><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Michael</surname><given-names>H. Gold</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Judith</surname><given-names>Hellman</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Serge</surname><given-names>Dahan</given-names></name><xref ref-type="aff" rid="aff3"><sup>3</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>R.</surname><given-names>Stephen Mulholland</given-names></name><xref ref-type="aff" rid="aff4"><sup>4</sup></xref><xref ref-type="corresp" rid="cor1"><sup>*</sup></xref></contrib></contrib-group><aff id="aff2"><addr-line>Mt. Sinai Hospital, New York, USA</addr-line></aff><aff id="aff3"><addr-line>Jean Languedoc Clinic, Toulouse, France</addr-line></aff><aff id="aff4"><addr-line>Private Aesthetic Plastic Surgery Practice, SpaMedica, Toronto, Canada</addr-line></aff><aff id="aff1"><addr-line>Tennessee Clinical Research Center, Nashville, USA</addr-line></aff><pub-date pub-type="epub"><day>15</day><month>01</month><year>2019</year></pub-date><volume>09</volume><issue>01</issue><fpage>19</fpage><lpage>29</lpage><history><date date-type="received"><day>18,</day>	<month>December</month>	<year>2018</year></date><date date-type="rev-recd"><day>20,</day>	<month>January</month>	<year>2019</year>	</date><date date-type="accepted"><day>23,</day>	<month>January</month>	<year>2019</year></date></history><permissions><copyright-statement>&#169; Copyright  2014 by authors and Scientific Research Publishing Inc. </copyright-statement><copyright-year>2014</copyright-year><license><license-p>This work is licensed under the Creative Commons Attribution International License (CC BY). http://creativecommons.org/licenses/by/4.0/</license-p></license></permissions><abstract><p>
 
 
  Introduction
  : Photoepilation by lasers is a popular procedure in aesthetic dermatology for removing unwanted body and facial hair. The use of the most appropriate laser wavelength is crucial as it affects treatment depth and melanin absorption. The three commonly used hair removal lasers are of specific wavelengths: 755
   
  nm, 810
   
  nm, and 1064
   
  nm, each preferred certain types of skin and hair characteristics. The current evaluation reports the safety and efficacy of unique blended modes
   755/810
   
  nm and 810/1064
   
  nm diode lasers for hair removal. 
  <b>Methods</b>
  : 
  Hair removal results from 50 patients treated with the 755/810
   
  nm handpiece and 50 patients treated with the 810/1064
   
  nm handpiece 
  were gathered from a few clinics. 3 treatments on various body areas were conducted 6 weeks apart and patients were followed up with 6 months after the last treatment. Results were evaluated by baseline, follow-up photographs, and hair counts. 
  <b>Results</b>
  : Treatment area photos demonstrated hair reduction in the treated body and facial areas. Average hair count reduction at 6 months follow-up was 84% for the 
  755/810
   
  nm handpiece
   and 81% for the 
  810/1064
   
  nm handpiece
  . No significant or unexpected adverse events were detected in any of the patients. <b>Conclusions</b>: The novel blended mode hair removal diode lasers are proven to be safe and effective for hair removal in facial and body areas for patients of various skin types and hair characteristics.
 
</p></abstract><kwd-group><kwd>Laser Hair Removal</kwd><kwd> 755 nm Diode Laser</kwd><kwd> 810 nm Diode Laser</kwd><kwd>  1064 nm Diode Laser</kwd></kwd-group></article-meta></front><body><sec id="s1"><title>1. Introduction</title><p>Laser hair removal treatment is based on the principle of selective photothermolysis. In this process, the absorbed optical energy is converted into heat, coagulating the hair follicle [<xref ref-type="bibr" rid="scirp.90094-ref1">1</xref>] . There are preferential wavelengths for melanin absorption. At three specific wavelengths (755 nm, 810 nm, and 1064 nm), absorption by melanin is greater than competitive absorption by oxyhemoglobin and water. These wavelengths correspond to three popular hair removal lasers: 755 nm alexandrite, 810 nm diode, and 1064 nm Nd:YAG lasers [<xref ref-type="bibr" rid="scirp.90094-ref2">2</xref>] .</p><p>Numerous published clinical studies have demonstrated the safety and efficacy of different lasers at various wavelengths for hair removal [<xref ref-type="bibr" rid="scirp.90094-ref1">1</xref>] [<xref ref-type="bibr" rid="scirp.90094-ref3">3</xref>] .</p><p>Based on clinical evidence, hair removal diode lasers of 810 nm are considered as the universal hair removal for all skin types, and these lasers are commonly used in the market [<xref ref-type="bibr" rid="scirp.90094-ref1">1</xref>] [<xref ref-type="bibr" rid="scirp.90094-ref2">2</xref>] [<xref ref-type="bibr" rid="scirp.90094-ref3">3</xref>] . Light color or fine hair may be resistant to the treatment due to scarcity of pigmentation in the hair shaft, whereas treatment of dark skin type patients is difficult due to skin melanin absorption [<xref ref-type="bibr" rid="scirp.90094-ref1">1</xref>] . Light color and fine hair respond better to 755 nm, while a wavelength of 1064 nm is more suitable for dark skin [<xref ref-type="bibr" rid="scirp.90094-ref2">2</xref>] .</p><p>Recently new diode lasers of 755 nm and 1064 nm were developed to enable suitable diode laser treatments for a wide variety of skin and hair types [<xref ref-type="bibr" rid="scirp.90094-ref4">4</xref>] [<xref ref-type="bibr" rid="scirp.90094-ref5">5</xref>] [<xref ref-type="bibr" rid="scirp.90094-ref6">6</xref>] .</p><p>This manuscript describes the evaluation of a newly developed device with two different handpieces generating optical energy from diode bars at 755 and 810 nm simultaneously and at 810 and 1064 nm simultaneously. The novel blended wavelength handpieces are applied to the skin for selective hair removal for a variety of hair and skin types.</p><p>This study presents results of a multicenter evaluation of the blended wavelength 755/810 nm and 810/1064 nm lasers for hair removal.</p></sec><sec id="s2"><title>2. Materials and Methods</title><p>The Device</p><p>The InMode Triton/DiolazeXL device (InMode MD Ltd., Israel) is designed to deliver optical energy to the skin via a pre-cooled sapphire block. Good optical contact between the sapphire block and the skin is achieved by using water-based gel. The device provides individual adjustment of light fluence and pulse duration to achieve maximum efficiency and safety for each patient. The handpiece has integrated skin cooling to enhance safety and comfort of the treatment.</p><p>The device is shown in <xref ref-type="fig" rid="fig1">Figure 1</xref>.</p><p>The diode laser handpieces are available in 3 wavelength configurations:</p><p>・ Mix of 755 nm/810 nm and a mix of 810 nm/1064 nm. 810 nm alone is also available as the most commonly used wavelength, but it is not the subject of this study.</p><p>・ Each of the handpieces are comprised of 20 diode laser bars stacked vertically. With the blended modes the corresponding diode bars are alternated and the two wavelengths of 755/810 or 810/1064 are emitted simultaneously through a chilled sapphire light guide.</p><p>A schematic representation of the alternating diode bars is illustrated in <xref ref-type="fig" rid="fig2">Figure 2</xref>.</p><p>The diode laser produces up to 3000 W peak optical power.</p><p>The sapphire light guide is located at the front of the handpiece and delivers the laser beam energy to the treated tissue, while cooling the skin. The sapphire block is surrounded by a chilled gold-plated metal frame. This structure provides increased cooling to a temperature of about 7˚C on the treatment spot and a few millimeters around it. The handpiece cooling flow is demonstrated in <xref ref-type="fig" rid="fig3">Figure 3</xref>. The arrow indicates the tip progress direction on the skin. One part of the metal frame is responsible for pre-cooling, the sapphire light guide is responsible for the cooling stage and the other part of the metal frame is responsible for post-cooling during handpiece progression.</p><p>The dimensions of the sapphire light guide are 11 mm &#215; 27.5 mm.</p><p>A temperature sensor is located on the enclosure of the sapphire cooler and measures the temperature of the tissue cooler to ensure stable sapphire temperature.</p><p>Evaluation Design</p><p>The objectives of this multicenter evaluation were to gather safety and efficacy hair removal data of the newly developed diode laser blended modes 755/810 nm and 810/1064 nm handpieces.</p><p>Results from 50 subjects treated with the 755/810 nm handpiece and 50 subjects who were treated with the 810/1064 nm handpiece were accumulated from a few clinics in the USA, Canada, France, and Israel during 2018.</p><p>Subjects underwent 3 treatment sessions 6 weeks apart and were followed up with 6 months post their last treatment.</p><p>Female and male subjects of Caucasian, Hispanic, Asian, and Afro-American backgrounds were treated on different areas such as the legs, underarms, bikini, chest, back and face.</p><p>The study efficacy was assessed by average hair reduction at the 6 month follow-up visit compared to the baseline count. Hair counts were performed on photographs taken from the subjects’ treatment areas. Subjects consented to use of their photographs.</p><p>Safety of the device was evaluated by assessing the incidence, severity and persistence of adverse events, if any occurred during the study period.</p><p>Photography</p><p>Photos of the treatment areas were taken at baseline and at the 6 month follow-up visit in a reproducible manner. The hair was trimmed to 1 - 3 mm length and the area before trimming as well as the trimmed area was photographed.</p><p>Hair counts were performed by marking visible hairs on photographs of the subjects’ treatment area. <xref ref-type="fig" rid="fig4">Figure 4</xref> demonstrates counting examples.</p></sec><sec id="s3"><title>3. Results</title><p>Hair removal results from 50 subjects treated with the 755/810 nm laser and 50 subjects treated with the 810/1064 nm laser were included in the study. All subjects had completed all treatment and follow-up regimen.</p><p>Results of Hair Removal Using the 755/810 nm Handpiece</p><p>44 female subjects and 6 male subjects, who requested hair removal treatments, were treated with the 755/810 nm handpiece. The mean subject age was 25.4 with minimum and maximum age of 19 and 36, correspondingly. Subjects had the following Fitzpatrick skin types: type II (66%) and type III (34%).</p><p>Subjects were treated on various treatment areas for hair removal with the 755/810 nm blended mode hand piece including underarm, bikini, legs, face, men’s back, and chest.</p><p>Analysis of hair count change from baseline to the 6 month follow-up (<xref ref-type="table" rid="table1">Table 1</xref>) resulted in a weighted average hair count reduction of 84% (range of 75% - 88%).</p><p>Representative photos of various areas treated with the 755/810 nm diode laser handpiece taken at baseline and at 6 month follow-up time points are presented below in Figures 5-7.</p><p>Results of Hair Removal Using the 810/1064 nm Handpiece</p><p>50 female subjects, who were interested in hair removal treatments, were treated with the 810/1064 nm handpiece. The mean subject age was 24 with a range of 19 - 36. Subjects had the following Fitzpatrick skin types: type IV (37.5%), type V (41.5%) and type VI (21%).</p><p>Subjects were treated on various treatment areas for hair removal with the 810/1064 nm blended mode handpiece, including underarm, bikini, legs, and face.</p><p>Analysis of hair count change from baseline to the 6 month follow-up resulted in an average weighted hair count reduction of 81% (range of 70% - 84%). (<xref ref-type="table" rid="table2">Table 2</xref>).</p><table-wrap id="table1" ><label><xref ref-type="table" rid="table1">Table 1</xref></label><caption><title> Weighted average hair count reduction according to different treatment areas</title></caption><table><tbody><thead><tr><th align="center" valign="middle" >Treatment area</th><th align="center" valign="middle" >No.</th><th align="center" valign="middle" >Average % reduction</th></tr></thead><tr><td align="center" valign="middle" >Underarm</td><td align="center" valign="middle" >12</td><td align="center" valign="middle" >88</td></tr><tr><td align="center" valign="middle" >Bikini</td><td align="center" valign="middle" >13</td><td align="center" valign="middle" >86</td></tr><tr><td align="center" valign="middle" >Leg</td><td align="center" valign="middle" >13</td><td align="center" valign="middle" >83</td></tr><tr><td align="center" valign="middle" >Face</td><td align="center" valign="middle" >6</td><td align="center" valign="middle" >75</td></tr><tr><td align="center" valign="middle" >Back</td><td align="center" valign="middle" >3</td><td align="center" valign="middle" >78</td></tr><tr><td align="center" valign="middle" >Chest</td><td align="center" valign="middle" >3</td><td align="center" valign="middle" >77</td></tr><tr><td align="center" valign="middle" >Total</td><td align="center" valign="middle" >50</td><td align="center" valign="middle" >84</td></tr></tbody></table></table-wrap><p>Representative photos of various areas treated with the 810/1064 nm diode laser handpiece taken at baseline and at 6 months follow-up time points are presented below in Figures 8-10.</p><table-wrap id="table2" ><label><xref ref-type="table" rid="table2">Table 2</xref></label><caption><title> Weighted average hair count reduction according to different treatment areas</title></caption><table><tbody><thead><tr><th align="center" valign="middle" >Treatment area</th><th align="center" valign="middle" >No.</th><th align="center" valign="middle" >Average % reduction</th></tr></thead><tr><td align="center" valign="middle" >Underarm</td><td align="center" valign="middle" >14</td><td align="center" valign="middle" >84</td></tr><tr><td align="center" valign="middle" >Bikini</td><td align="center" valign="middle" >15</td><td align="center" valign="middle" >82</td></tr><tr><td align="center" valign="middle" >Leg</td><td align="center" valign="middle" >15</td><td align="center" valign="middle" >81</td></tr><tr><td align="center" valign="middle" >Face</td><td align="center" valign="middle" >6</td><td align="center" valign="middle" >70</td></tr><tr><td align="center" valign="middle" >Total</td><td align="center" valign="middle" >50</td><td align="center" valign="middle" >81</td></tr></tbody></table></table-wrap><p>Safety Analysis</p><p>No unexpected or severe adverse events were reported. Mild erythema and edema that appeared following the treatment subsided shortly.</p></sec><sec id="s4"><title>4. Discussion</title><p>The choice of an optimal laser for the individual patient is critical for treatment success and safety. One should take into consideration the patient’s skin and hair types to match laser wavelength that will reflect melanin absorption and penetration depth.</p><p>The wavelength range of 650 to 1300 nm is considered generally suitable for typical depth of hair from 1 mm to 3 mm. The best penetration depth is around 1060 nm corresponding to the Nd:YAG laser, but this wavelength absorption in hair melanin is relatively low and efficacy of treatment is not very high. The maximal efficacy is around 650 - 700 nm but penetration depth is limited at this wavelength.</p><p>A wavelength of 755 nm is considered very effective for light skin treatment [<xref ref-type="bibr" rid="scirp.90094-ref4">4</xref>] while the 1064 nm Nd:YAG laser became popular for hair removal on dark skin patients [<xref ref-type="bibr" rid="scirp.90094-ref5">5</xref>] [<xref ref-type="bibr" rid="scirp.90094-ref6">6</xref>] .</p><p>One of the compromises between these two ranges is the use of an 810 nm diode [<xref ref-type="bibr" rid="scirp.90094-ref7">7</xref>] [<xref ref-type="bibr" rid="scirp.90094-ref8">8</xref>] [<xref ref-type="bibr" rid="scirp.90094-ref9">9</xref>] [<xref ref-type="bibr" rid="scirp.90094-ref10">10</xref>] [<xref ref-type="bibr" rid="scirp.90094-ref11">11</xref>] which has better penetration depth than 755 nm and much higher absorption coefficient of melanin than the Nd:YAG laser. Sometimes better tuning of the wavelength is optimal, especially for darker skin and non-black hairs.</p><p>For dark skin it would be a logical step to use a wavelength between 810 nm and 1064 nm, but the peak of light absorption by water in this range makes these wavelengths less effective for treatment. In addition, not all wavelengths are available in the market because of technological limitations.</p><p>One of the solutions is to use a combination of two wavelengths, which are already well-known and clinically proven for laser hair removal treatment.</p><p>The use of combination 810 nm and 1064 nm would improve penetration depth and safety for darker skin while maintaining relatively high efficacy of treatment.</p><p>Combination of 755 nm and 810 nm would allow optimization of treatment for different hair colors.</p><p>Because all these wavelengths are recognized as safe and effective for hair removal the combination of the wavelengths does not seem to raise any safety concerns and enables efficacy optimization.</p><p>The novel diode laser Triton/DiolazeXL with the blended mode of wavelengths, 755/810 nm and 810/1064 nm, enables a wide range of penetration depths and hair melanin absorption. <xref ref-type="fig" rid="fig1">Figure 1</xref>1 illustrates the unique penetration of the two blended mode lasers.</p><p>Clinical experience supports the safety and efficacy of both handpieces for hair removal on light and dark skin in various body and facial areas with a range of hair types.</p><p>The current evaluation demonstrated treatment results from female and male subjects who underwent 3 treatment sessions 6 weeks apart and were followed up with 6 months following their last treatment. As expected, due to better absorption in melanin of the lower wavelength, subjects treated with 755/810 nm hand piece displayed slightly better hair reduction results (average reduction of 84%) than those treated with 810/1064 nm handpiece (average reduction of 81%). When comparing different treatment areas, underarms presented the best hair reduction, as expected from relatively lighter skin and coarser, darker hair in these areas. The same applies to bikini areas, but to a slightly lesser degree. The legs usually have finer hair than underarm and bikini, and exhibited less hair reduction, as well as deeper hair on men’s back and chest. The lowest percent of hair reduction was expressed on the face due to its very fine hair with a</p><p>limited amount of melanin. All the above is applicable to both handpieces, 755/810 nm and 810/1064 nm.</p><p>No unexpected adverse events were reported in this study.</p><p>The clinical data presented here demonstrate that the unique blended mode of wavelengths, 755/810 nm and 810/1064 nm, has proven to be safe and effective for hair removal on light and dark skin.</p><p>The novel combination approach enables more accurate and personalized treatment, thus maximizing hair removal results while minimizing treatment risks. More studies are planned to further substantiate the potential clinical contribution of the newly developed blended wavelengths concept.</p></sec><sec id="s5"><title>Conflicts of Interest</title><p>The authors declare no conflicts of interest regarding the publication of this paper.</p></sec><sec id="s6"><title>Cite this paper</title><p>Gold, M.H., Hellman, J., Dahan, S. and Mulholland, R.S. (2019) Clinical Evaluation of a Novel Blended Mode Diode Laser for Hair Removal. Journal of Cosmetics, Dermatological Sciences and Applications, 9, 19-29. https://doi.org/10.4236/jcdsa.2019.91002</p></sec></body><back><ref-list><title>References</title><ref id="scirp.90094-ref1"><label>1</label><mixed-citation publication-type="other" xlink:type="simple">Ibrahimi, O.A., Avram, M.M., Hanke, C.W., Kilmer, S.L. and Anderson, R.R. (2011) Laser Hair Removal. Dermatologic Therapy, 24, 94-107.  
&lt;/br&gt;https://doi.org/10.1111/j.1529-8019.2010.01382.x</mixed-citation></ref><ref id="scirp.90094-ref2"><label>2</label><mixed-citation publication-type="other" xlink:type="simple">Rao, J. and Goldman, M.P. (2005) Prospective, Comparative Evaluation of Three Laser Systems Used Individually and in Combination for Axillary Hair Removal. Dermatologic Surgery, 31, 1671-1676.</mixed-citation></ref><ref id="scirp.90094-ref3"><label>3</label><mixed-citation publication-type="other" xlink:type="simple">Haedersdal, M. and Wulf, H.C. (2006) Evidence-Based Review of Hair Removal Using Lasers and Light Sources. JEADV, 20, 9-20.  
&lt;/br&gt;https://doi.org/10.1111/j.1468-3083.2005.01327.x</mixed-citation></ref><ref id="scirp.90094-ref4"><label>4</label><mixed-citation publication-type="other" xlink:type="simple">Royo, J., Moreno-Moraga, J. and Trelles, M.A. (2017) Clinical Assessment of a New 755 nm Diode Laser for Hair Removal: Efficacy, Safety, and Practicality in 56 Patients. Lasers in Surgery and Medicine, 49, 355-360.</mixed-citation></ref><ref id="scirp.90094-ref5"><label>5</label><mixed-citation publication-type="other" xlink:type="simple">Tahiliani, S.T. and Tahiliani, H.S. (2016) Prospective Evaluation of the Safety and Efficacy of a 1060-nm Large Spot Size, Vacuum-Assisted Hair Removal Diode Laser System in Asian/Pacific Fitzpatrick’s Skin Types IV-V Patients. Journal of drugs in dermatology, 15, 1427-1434.</mixed-citation></ref><ref id="scirp.90094-ref6"><label>6</label><mixed-citation publication-type="other" xlink:type="simple">Passach, U., Wagner, J.A. and Passach, H. (2015) Novel 755-nm Diode Laser vs. Conventional 755-nm Scanned Alexandrite Laser: Side-by-Side Comparison Pilot Study for Thorax and Axillary Hair Removal. Journal Cosmetic and Laser Therapy, 17, 189-193. &lt;/br&gt;https://doi.org/10.3109/14764172.2015.1007062</mixed-citation></ref><ref id="scirp.90094-ref7"><label>7</label><mixed-citation publication-type="other" xlink:type="simple">Courtney, E. and Goldberg, D.J. (2016) Clinical Evaluation of Hair Removal Using an 810 nm Diode Laser with a Novel Scanning Device. Journal of drugs in dermatology, 15, 1330-1333.</mixed-citation></ref><ref id="scirp.90094-ref8"><label>8</label><mixed-citation publication-type="other" xlink:type="simple">Goldberg, D.J. (2018) One-Year Follow-Up Results of Hair Removal Using an 810 nm Diode Laser. Journal of Cosmetic Dermatology, 17, 775-778.   
&lt;/br&gt;https://doi.org/10.1111/jocd.12757</mixed-citation></ref><ref id="scirp.90094-ref9"><label>9</label><mixed-citation publication-type="other" xlink:type="simple">Scilletta, A. and Pompili, G. (2016) Laser Diode 800nm and Hirsutism in Darker Skinned Patients: Our Experience on 552 Women. Journal of Advanced Plastic Surgery Research, 2, 1-4.</mixed-citation></ref><ref id="scirp.90094-ref10"><label>10</label><mixed-citation publication-type="other" xlink:type="simple">Koo, B., Ball, K., Tremaine, A.M. and Zachary, C.B. (2014) A Comparison of Two 810 Diode Lasers for Hair Removal: Low Fluence, Multiple Pass Versus a High Fluence, Single Pass Technique. Lasers in Surgery and Medicine.  
&lt;/br&gt;https://doi.org/10.1002/lsm.22226</mixed-citation></ref><ref id="scirp.90094-ref11"><label>11</label><mixed-citation publication-type="other" xlink:type="simple">Jo, S.J., Kim, J.Y., Ban, J., Lee, Y., Kwon, O. and Koh, W. (2015) Efficacy and Safety of Hair Removal with a Long-Pulsed Diode Laser Depending on the Spot Size: A Randomized, Evaluators-Blinded, Left-Right Study. Annals of Dermatology, 27, 517-522. &lt;/br&gt;https://doi.org/10.5021/ad.2015.27.5.517</mixed-citation></ref></ref-list></back></article>