Nitrous oxide

Structural formula
Mesomeric boundary structures of the nitrous oxide molecule
General
Surname	Nitrous oxide ( INN )
other names	Laughing gas Nitrous oxide Nitric oxide Azo oxide E  942 NITROUS OXIDE ( INCI )
Molecular formula	N 2 O
Brief description	colorless gas with a sweet smell
External identifiers / databases
CAS number 10024-97-2 EC number 233-032-0 ECHA InfoCard 100.030.017 PubChem 948 ChemSpider 923 DrugBank DB06690 Wikidata Q905750
Drug information
ATC code	N01 AX13
Drug class	analgesic
properties
Molar mass	44.01 g mol −1
Physical state	gaseous
density	1.848 kg m −3 (15 ° C, 1 bar)
Melting point	−90.8 ° C
boiling point	−88.5 ° C
Vapor pressure	50.8 bar (20 ° C) 57.2 bar (25 ° C) 63.2 bar (30 ° C)
solubility	only slightly soluble in water (1.5 g l −1 at 20 ° C) soluble in ethanol and diethyl ether
Dipole moment	0.16083 D (5.365 · 10 -31  C  ·  m )
Refractive index	1,000516 (0 ° C, 101.325 kPa)
safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed GHS labeling of hazardous substances danger H and P phrases H: 270-280-336 P: 220-244-260-370 + 376-304 + 340 + 315-403
MAK	DFG : 100 ml · m -3 or 180 mg · m -3 Switzerland: 100 ml · m -3 or 182 mg · m -3
Global warming potential	298 (based on 100 years)
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions . Refractive index: Na-D line , 20 ° C

Nitrous oxide , commonly known by the common name of laughing gas , is a colorless gas from the group of nitrogen oxides . The chemical sum formula for the gas is N ₂ O . In older literature, nitrous oxide is also referred to as nitrogen oxide or nitrogen oxide . The English name Nitrous Oxide is used in international literature .

history

Nitrous oxide was first represented and described in pure form in 1772 by the English chemist and physicist Joseph Priestley (1733–1804). The discovery of the psychoactive and, in particular, narcotic and analgesic effects goes back to the English pharmacist and later chemist Humphry Davy (1778–1829), who began around 1797 to test the effects of laughing gas, which he also used to treat toothache, with self-experiments to research, which he published in 1800 and also suggested for anesthesia during surgical operations.

The first dentist to use nitrous oxide as an anesthetic was Horace Wells of Hartford, Connecticut. He started using it for tooth extractions and dental treatments from 1844 after he happened to observe its analgesic effect in a pleasure application on December 10, 1844, as was common at fairs in his day, and the following day he himself had a tooth under nitrous anesthesia had let go. Since 1868, nitrous oxide has been used in combination with oxygen as an anesthetic to carry out clinical operations in order to achieve an effective, sufficiently high concentration. This was first practiced in this way by the Chicago surgery professor Edmund Andrews (1824–1904) who also carried out statistical studies on the safety of ether and chloroform anesthesia in around 100,000 cases each. Andrews also developed a method of liquefying nitrous oxide.

Origin of name

The German term “laughing gas” is a translation of the English word laughing gas .

There are different assumptions about the origin of the name; one is that the name comes from the euphoria that can arise when breathing in nitrous oxide, making the consumer laugh . Gardner Quincy Colton, for example, who in 1863 reintroduced nitrous oxide, which was initially out of use as an anesthetic after the death of Horace Wells, wrote in 1866: “The laughing gas […] acts as an exhilarant, as by supplying an extra supply of oxygen to the lungs, the pulse is increased fifteen to twenty beats to the minute. The former agents carry the patients down towards the point of death: the latter up into increased life. ”The nitrous oxide, which was on public display in Hartford on December 10, 1844, was referred to as“ Exhilarating or Laughing Gas ”and to the audience to be entertained as gas , which, depending on the character of the intoxicated test persons, could cause laughing, singing, dancing, talking or beating when inhaled.

Manufacturing

It is produced in an intramolecular redox reaction through the controlled thermal decomposition of chloride-free ammonium nitrate

${\displaystyle \mathrm {NH_{4}NO_{3}\longrightarrow N_{2}O+2\ H_{2}O} }$

or in a redox reaction by heating a mixture of ammonium sulfate and sodium nitrate . However, the temperature must not rise above 300 ° C for either method of presentation, as otherwise ammonium nitrate may break down explosively.

release

Laughing gas is primarily formed as a by-product of natural processes, for example in the course of bacterial nitrification , and released into the atmosphere. As a by-product of man-made processes, nitrous oxide is not only released from combustion processes, but also from intensive agriculture . Compared to conventional farming , organic farming produces around 40% less nitrous oxide per hectare.

Sources of nitrous oxide	global emissions [10 6 t / a]
natural sources	6.6-12.2
• Oceans / lakes	2.0-4.0
• natural soils	4.6-8.2
anthropogenic sources	1.4-6.5
• Burning biomass	0.2-2.4
• Use of artificial fertilizers (soil and groundwater)	1.0-3.6
all sources 1	8.9-18.7

¹ Other possible sources are photochemical reactions in the stratosphere and troposphere and the formation of nitrous oxide by catalysts.

Nitrogen fertilizer is converted into nitrous oxide under certain conditions. Normally, N ₂ O is enzymatically broken down in the soil. The copper-containing enzyme nitrous oxide reductase plays an important role in the ongoing biochemical process , as it converts N ₂ O into N ₂ . However, this enzyme is extremely sensitive to oxygen and often fails in the reaction chain. This is the reason that large amounts of N ₂ O are released from fertilized arable land. When growing energy crops such as rapeseed, greater amounts of nitrous oxide are released due to increased fertilization, especially in winter. The N ₂ O emissions from rapeseed cultivation correspond to those from other fields. Nevertheless, in terms of N ₂ O emissions, the climate balance of rapeseed is more negative than that of gasoline.

Nitrous oxide concentration in the earth's atmosphere since year 1 ( ice core analyzes , measurements at Cape Grim (Australia), NOAA , March 2017)

Recent studies have shown that measures to reduce nitrogen oxide emissions from combustion processes also lead to a sometimes considerable increase in nitrous oxide emissions. For example, in power plants with circulating fluidized bed combustion , which have low nitrogen oxide emissions due to the process, very large nitrous oxide emissions are found. The same applies to motor vehicles with a regulated three-way catalytic converter , the effects of which on the global N ₂ O budget are still uncertain. Since the proportion of catalytic converters is currently increasing worldwide, a significant increase in vehicle-related N ₂ O emissions can be expected in the next few years when using today's three-way catalytic converters . N ₂ O is also produced during exhaust gas aftertreatment in diesel engines by means of selective catalytic reduction .

In the chemical industry, the synthesis of adipic acid ( polyamide precursor) is a nitrous oxide-releasing process that is listed in the greenhouse budget of companies and is also a target of reduction efforts.

Under certain conditions, nitrous oxide can also form on solid surfaces under normal conditions. This was first observed in a salt lake in the Antarctic.

In contrast to these sources, as a sink, the photochemical degradation in the stratosphere with around 20.5 · 10 ⁶ t / a.

${\displaystyle \mathrm {N_{2}O+h\nu \longrightarrow N_{2}+O} }$

${\displaystyle \mathrm {N_{2}O+O\longrightarrow N_{2}+O_{2}} }$

${\displaystyle \mathrm {N_{2}O+O\longrightarrow 2\ NO} }$

The quantities that are also broken down through uptake in soil and by aquatic microorganisms are not known.

properties

Laughing gas is readily soluble in cold water: at 0 ° C the gas dissolves in a volume ratio of 1: 1.305 in liquid water, at 25 ° C it dissolves in a ratio of 1: 0.596. A crystalline gas hydrate can be separated from neutral aqueous solutions at low temperatures in which there are 5.75 water molecules for each N ₂ O molecule. Under increased pressure, nitrous oxide shows very good solubility in fats.

Laughing gas is not flammable, but it can oxidize other substances. Therefore it has an oxidizing effect. Coal, sulfur and phosphorus burn in nitrous oxide as in oxygen. In this way, the formation of nitrous oxide in a sample can be demonstrated with the glow chip sample . In order to also oxidize other substances, it requires a significantly higher temperature than oxygen for the corresponding reactions. Since N ₂ O is a metastable compound, it breaks down into its elements at approx. 600 ° C:

${\displaystyle \mathrm {2\ N_{2}O\longrightarrow 2\ N_{2}+O_{2}+164{,}20\ kJ} }$.

Under the designation E 942 , laughing gas is approved as a food additive for use as a propellant , for example for whipped cream ; it is very similar to isoelectronic carbon dioxide , which is almost equally heavy , in its physical properties, such as the density of the condensed liquid or the melting and boiling point .

Contribution to the greenhouse effect and damage to the ozone layer

Global, anthropogenic nitrous oxide emissions (in billion tonnes of CO ₂ equivalent , May 2010, according to FAO figures )

Due to the location of its IR absorption in an atmospheric window and its long atmospheric dwell time of around 120 years, N ₂ O has a high global warming potential . As the third most important long-lived greenhouse gas, it makes a significant contribution to global warming . Its contribution to global warming via the greenhouse effect is just under 10%. Its emissions from the cultivation of oilseeds for biofuels completely negates their contribution to climate protection.

Due to its breakdown in the stratosphere, nitrous oxide increases the concentration of NO _{x there} , which catalytically breaks down ozone . Among the anthropogenic ozone-damaging emissions, laughing gas is now more important than all chlorofluorocarbons (CFCs) combined.

thermodynamics

• Δ _f H ⁰ _g : + 82.10 kJ / mol ( metastable )
• S ⁰ _{g, 1 bar} : 219.96 J / (mol K)

use

Mobile system for the application of an N ₂ O-oxygen mixture

Nitrous oxide propellant vials left behind in the countryside (probably after the nitrous oxide rush was induced)

Nitrous oxide cylinder on a motorcycle

• In the medicine nitrous oxide is used as an analgesic acting (the pain) gas for anesthesia purposes used or in a fixed combination of 50% nitrous oxide and 50% oxygen ( nitrous oxide and oxygen ) for the treatment of pain for a short, moderately painful surgical procedures. It has also become widely used in dentistry as a so-called titratable nitrous oxide sedation . It is an anesthetic that has been used regularly since 1844 and has relatively few side effects. The use of N ₂ O can impair the effect of vitamin B12 and folic acid and thus lead to pernicious anemia . When used in patients with severe disorders of the myocardial function, there is also a risk of undesirable effects on the cardiovascular system. In addition, nitrous oxide can increase pulmonary vascular resistance. In order to achieve an effective concentration of 70% it must (as Andrews first recognized in 1868) be given with pure oxygen . It is considered a relatively weak anesthetic and is mainly used as support. In modern anesthesia , the effect of nitrous oxide is by adding other anesthetic supplements. It is advantageous that the gas flows in and out quickly (low blood / gas distribution coefficient), so that the anesthesia can be easily controlled and there is little or no respiratory depression . The gas is mainly excreted again via the lungs, with a small part diffusing through the skin. Diffusion of nitrous oxide into air-filled cavities in the body can be problematic; this can lead to diffusion hypoxia in the lungs. In the process, nitrous oxide displaces the oxygen from the alveoli . This can be avoided by inhaling oxygen. The medical use of nitrous oxide as an anesthetic has been on the decline for a long time. It is recommended for self-application for mild and moderate pain. Today it is used again in obstetrics to reduce pain in labor . In addition, laughing gas is used as a liquid coolant (nitrogen oxide, laughing gas) during cryoablation and fed into the cryoballoon catheter. There it evaporates and removes heat from the surrounding tissue. The affected heart muscle cells are destroyed by the formation of ice.
• In dentistry , nitrous oxide has been a tried and tested agent for decades, which is used primarily in children and anxious patients, but also in the case of strong gag reflex. When administered correctly, side effects are rare.
• In food technology , nitrous oxide is used as an approved food additive ( E 942 ) due to its good fat solubility under pressure as a propellant, preferably for dairy products, e.g. for frothing (instead of whipping) whipped cream.
• In the drug scene , nitrous oxide is used because of its dissociative effect and its easy availability. The high lasts for about 30 seconds to 3 minutes. There are dissociative effects, strong changes in sound perception (echo, distortion), tingling in the limbs, relaxation of the muscles and a strong sense of well-being, sometimes euphoria. With frequent consumption there is a risk of vitamin B12 deficiency . Repeated fatalities occurred during this application (see section Hazards ).
• In drive technology , for example in cars , nitrous oxide is used to increase the engine performance of gasoline engines, as it contains more oxygen than air . This so-called nitrous oxide injection requires only relatively minor structural changes to the engine and can increase its output by around 20 to 50% in the short term. The nitrous oxide is blown into the intake tract from pressure vessels. This tuning is especially widespread in the USA , but its use on public roads is prohibited both there and in Germany (with the exception of a system with ABE ) and is only permitted to a limited extent in most other countries. The best known manufacturers of nitrous oxide injections are NOS , NX and Venom as well as ZEX. In the Second World War, aircraft engines were also increased in their performance in this way ( see also GM-1 ).
• In rocket technology , nitrous oxide is used as an oxidizer in hybrid rockets such as the SpaceShipOne . The advantage is that it can be liquefied by pressure without cooling . For this reason, only a throttle valve is required for use in such engines , but no fuel pump or complex cryogenics .
• In atomic absorption spectrometry (AAS), nitrous oxide is used in flame AAS instead of air in an acetylene flame to generate higher temperatures (2800 ° C).
• In catalysis research , nitrous oxide is used in reactive frontal chromatography to determine the catalytically active copper surface.

pharmacology

The gas is colorless, odorless, and tasteless; sometimes a slightly sweet taste is reported when inhaled. It has an analgesic and weakly narcotic effect. Analgesic (pain relieving) effects occur from a concentration of about 20 percent nitrous oxide in the breath. Laughing gas oxidizes vitamin B12 in the body , which is then no longer available as a coenzyme for the enzyme methionine synthase . If laughing gas is used for more than six hours, the function of methionine synthase, which is important for the production of many important protein building blocks, is reduced. The effect of laughing gas is only brief, after about 15 minutes the effects are no longer noticeable. Due to its pain-relieving effect in anesthesia, nitrous oxide can be added to the gas mixture when performing general anesthesia, where it greatly reduces the consumption of inhaled anesthetics.

Against the background of alternative anesthetic methods, improved equipment technology (e.g. low-flow anesthesia) and increased vigilance with regard to possible environmental pollution ( greenhouse gas ), less nitrous oxide has been used in anesthesia since the late 1990s. Many hospitals have meanwhile stopped using nitrous oxide and only use compressed air and oxygen in their central gas supply. From a medical point of view, however, there is still little to be said against the use of nitrous oxide for anesthesia.

hazards

There is a risk of suffocation when using large gas cylinders in closed rooms. Laughing gas is fire-promoting (compare: glow chip test ). There are special dangers when used as a drug: If you inhale nitrous oxide pure - e.g. B. from filled balloons - the consequences can be dysphoria , confusion, nausea, headache, hiccups and a drop in blood pressure. With high amounts, the blood is insufficiently supplied with oxygen ( hypoxemia ), which can lead to cardiac arrest , brain damage and death. If laughing gas is inhaled directly from the gas container, symptoms of frostbite can occur on the lips, larynx and bronchi due to the evaporation cold of the gas liquefied under pressure. There is an increased risk of injury from falling if you lose consciousness.

literature

• Albert Faulconer, Thomas Edward Keys: Nitrous Oxide. In: Foundations of Anesthesiology. Charles C Thomas, Springfield (Illinois) 1965, pp. 372-441, and pp. 605 f. ( Gas Mixtures ).

Web links

Commons : Nitrous Oxide  - Collection of Pictures, Videos and Audio Files

• Laughing gas . In: Erowid . (English)
• Nitrous oxide textbook online freely accessible textbook on the medical use of nitrous oxide

Individual evidence

1. ↑ Entry on E 942: Nitrous oxide in the European database for food additives, accessed on June 27, 2020.
2. ↑ Entry on NITROUS OXIDE in the CosIng database of the EU Commission, accessed on June 27, 2020.
3. ↑ ^{a b c d e f g h i j k} Entry on nitrous oxide, condensed in the GESTIS substance database of the IFA , accessed on June 10, 2020 (JavaScript required)
4. ↑ ^{a b c d} Entry on nitrogen oxide. In: Römpp Online . Georg Thieme Verlag, accessed on 2015-09-25.
5. ↑ David R. Lide (Ed.): CRC Handbook of Chemistry and Physics . 90th edition. (Internet version: 2010), CRC Press / Taylor and Francis, Boca Raton, FL, Dipole Moments, pp. 9-51.
6. ↑ David R. Lide (Ed.): CRC Handbook of Chemistry and Physics . 90th edition. (Internet version: 2010), CRC Press / Taylor and Francis, Boca Raton, FL, Index of Refraction of Gases, pp. 10-254.
7. ↑ Swiss Accident Insurance Fund (Suva): Limit values ​​- current MAK and BAT values (search for 10024-97-2 or nitrous oxide ), accessed on June 10, 2020.
8. ↑ P. Forster, P., V. Ramaswamy et al .: Changes in Atmospheric Constituents and in Radiative Forcing. In: Climate Change 2007: The Physical Science Basis. Contribution of Working Group I to the Fourth Assessment Report of the Intergovernmental Panel on Climate Change. Cambridge University Press, Cambridge / New York 2007, p. 212, (PDF)
9. ↑ Threatened ozone layer: nitrous oxide is a bigger problem than CFCs. In: Spiegel Online . August 28, 2009, accessed April 13, 2015 . 
10. ^ Rudolf Frey , Otto Mayrhofer , with the support of Thomas E. Keys and John S. Lundy: Important data from the history of anesthesia. In: R. Frey, Werner Hügin , O. Mayrhofer (Ed.): Textbook of anesthesiology and resuscitation. Springer, Heidelberg / Basel / Vienna 1955; 2nd, revised and expanded edition. With the collaboration of H. Benzer. Springer-Verlag, Berlin / Heidelberg / New York 1971. ISBN 3-540-05196-1 , pp. 13–16, here: p. 14.
11. ↑ Christoph Weißer: Laughing gas. In: Werner E. Gerabek et al. (Ed.): Enzyklopädie Medizingeschichte. De Gruyter, Berlin / New York 2005, ISBN 3-11-015714-4 , p. 820 f.
12. ^ Edmund Andrews: The oxygen mixture, a new anaesthetic combination. In: Chicago Medical Examiner. Volume 9, (November) 1868, pp. 656-661.
13. ^ History in the laughing gas lexicon
14. ^ Albert Faulconer, Thomas Edward Keys: Nitrous Oxide. 1965, pp. 373 and 430-437.
15. ↑ Edmund Andrews: Liquid Nitrous Oxide as an Anesthetic. In: Medical Examiner. Volume 13, 1872, pp. 34-36.
16. ↑ from exhilarant : "cheering, invigorating, amusing, exhilarating". See www.dict.cc.
17. ^ Albert Faulconer, Thomas Edward Keys: Nitrous Oxide. 1965, pp. 372-441, cited here: p. 373.
18. ^ Werner Hügin : Anaesthesia. Discovery, progress, breakthroughs. Editiones ‹Roche›, Basel 1989, ISBN 3-88878-060-8 , p. 11 f.
19. ↑ G. Brauer (Ed.): Handbook of Preparative Inorganic Chemistry. 2nd Edition. vol. 1, Academic Press, 1963, pp. 484-485.
20. ↑ N. Wrage: grassland as source and sink for N ₂ O . Göttingen 2009, accessed (via the Bavarian State Institute for Agriculture) on April 8, 2019.
21. ↑ Pamela Dörhöfer: The laughing gas problem is bigger than expected. In: Klimareporter. November 27, 2019, accessed on November 27, 2019 (German). 
22. ↑ Colin Skinner, Andreas Gattinger, Maike Krauss, Hans-Martin Krause, Jochen Mayer, Marcel GA van der Heijden, Paul Mäder: The impact of long-term organic farming on soil-derived greenhouse gas emissions. In: Scientific Reports. nature.com , February 8, 2019, accessed April 9, 2019 . 
23. ↑ Rudolf-Werner Dreier: Sulfur atoms in the enzyme. Albert-Ludwigs-Universität Freiburg im Breisgau, press release from August 15, 2011 from the Science Information Service (idw-online.de), accessed on April 13, 2015.
24. ↑ O. HeinemeyerI, M. Kücke, K. Kohrs, E. Schnug, JC Munch, EA Kaiser: nitrous oxide emissions in rapeseed cultivation. In: thuenen.de. Retrieved June 1, 2018 . 
25. ↑ Silke Schmidt-Thrö: Laughing gas: How can rapeseed cultivation become more sustainable? In: BR.de. June 3, 2015, accessed June 1, 2018 . 
26. ↑ Biofuel: Sobering carbon footprint. In: Zeit Online. Retrieved June 1, 2018 . 
27. ↑ German Bundestag Printed Matter 18/12691, June 8, 2017. Accessed July 26, 2017 . 
28. ↑ Antarctica: nitrous oxide discovery at salt lake amazes researchers. In: Spiegel Online . April 26, 2010, accessed April 13, 2015 . 
29. ^ AF Holleman , E. Wiberg , N. Wiberg : Textbook of Inorganic Chemistry . 101st edition. Walter de Gruyter, Berlin 1995, ISBN 3-11-012641-9 , p. 689.
30. ↑ Additive Admissions Ordinance : Annex 3 (to Section 5, Paragraph 1 and Section 7) Generally permitted additives .
31. ↑ ^{a b} R. L. Thompson, L. Lassaletta, PK Patra et al. : Acceleration of global N2O emissions seen from two decades of atmospheric inversion. In: Nat. Clim. Chang. 2019. doi: 10.1038 / s41558-019-0613-7
32. ^ Paul J. Crutzen et al .: N ₂ O Release from Agro-biofuel Production Negates Global Warming Reduction by Replacing Fossil Fuels. Atmos. Chem. Phys. 8, 2008, doi: 10.5194 / acp-8-389-2008 .
33. ^ AR Ravishankara et al.: Nitrous Oxide (N ₂ O): The Dominant Ozone-Depleting Substance Emitted in the 21st Century. In: Science . 2009, PMID 19713491 .
34. ↑ Reinhard Larsen: Anesthesia and intensive medicine in cardiac, thoracic and vascular surgery. (1st edition 1986) 5th edition. Springer, Berlin / Heidelberg / New York et al. 1999, ISBN 3-540-65024-5 , pp. 14-16 and 516.
35. ↑ Gottfried Alber in: Diseases of the cat. Section 24.5 - Inhalation Anesthesia, Subsection 24.5.2.2 - Nitrous Oxide, p. 631.
36. ^ Opinion on the introduction of Livopan in Germany by the anesthesia specialist associations
37. ↑ 'Laughing gas' teenager dies after party in Bexley. In: BBC News. July 26, 2015, accessed July 26, 2015 . 
38. ^ RD Sanders, J. Weimann, M. Maze: Biologic effects of nitrous oxide: a mechanistic and toxicologic review. In: Anesthesiology. Volume 109, Number 4, October 2008, pp. 707-722, doi: 10.1097 / ALN.0b013e3181870a17 . PMID 18813051 (Review).
39. ^ J. Weimann: Toxicity of nitrous oxide. In: Best practice & research. Clinical Anaesthesiology. Volume 17, Number 1, March 2003, pp. 47-61. PMID 12751548 (Review).
40. ^ J. Schulte Am Esch, J. Scholz: [Nitrous Oxide - End of an Era - a Specific German Discussion]. In: Anaesthesiology, intensive care medicine, emergency medicine, pain therapy: AINS. Volume 36, Number 10, October 2001, pp. 597-598, doi: 10.1055 / s-2001-17680 . PMID 11592018 .
41. ↑ European Society of Anesthesiology task force on the use of nitrous oxide in clinical anaesthetic practice: The current place of nitrous oxide in clinical practice: An expert opinion-based task force consensus statement of the European Society of Anesthesiology. In: European Journal of Anaesthesiology. Volume 32, Number 8, August 2015, pp. 517-520. PMID 26244467 .
42. ^ PS Myles, K. Leslie, MT Chan, A. Forbes, PJ Peyton, MJ Paech, WS Beattie, DI Sessler, PJ Devereaux, B. Silbert, T. Schricker, S. Wallace; ANZCA Trials Group for the ENIGMA-II investigators: The safety of addition of nitrous oxide to general anesthesia in at-risk patients having major non-cardiac surgery (ENIGMA-II): a randomized, single-blind trial. In: The Lancet. Volume 384, Number 9952, October 2014, pp. 1446-1454. PMID 25142708 .
43. ^ Carola Gessner: Party drug laughing gas. In: medical-tribune.de. February 28, 2015, accessed January 11, 2016 . 

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