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The point is that the Gentle Giant track uses a general narrative pattern sending signals of musical erudition that work as follows mens health 5 day workout cheap 250 mg eulexin mastercard. The initial V V I I section (0:11-1:02) forms a large episode (A1) that repeats (1:02 to 1:51) as V V I I I (A2) and is recapitulated (4:42-5:30) prostate cancer freezing treatment 250mg eulexin sale, after the intervening quodlibet and guitar solo (B) prostate cancer warning signs purchase generic eulexin canada, as V V I I I (A3) mens health garcinia cambogia cheap eulexin 250 mg amex. Quodlibet: a piece combining several different snippets of popular tunes in counter point androgen hormone juice generic eulexin 250mg with amex. Aleatoric techniques were practised by avant-garde composers like Boulez and Stockhausen prostate cancer 09 order eulexin on line. The question is what, if anything, the narrative forms and actual durations of these long pieces can communicate apart from themselves. Therefore, if the piece under analysis is an intrinsic part of a more extensive musical work that your listeners hear as a whole. Listener interest in both pieces is partly guaranteed by consistently engaging lyrics. Analysis of all parameters in Faroeste caboclo would in fact reveal complex diataxis even though its 159 lines are all in simple (poetical) ballad metre (8. If so, its identity as a piece is partly determined by the pattern created by how the constituent episodes are managed in terms of order, relative duration, etc. Still, 4:33 is much shorter than movements in a Mahler sym phony or than prog rock and jazz fusion tracks. The music consists of whatever listeners hear during 4:33; see sheet music cover at Gtagg. In short, the duration of a piece is more likely to be a partial style indicator if it lasts much longer than five minutes or less than around two (Table 11-1). Very rough and incomplete guide to average durations of recordings in different types of music47a < 1 min. J 3 Schubert Lieder, most country songs, Billboard #1s in 1947 and 1970, trad and mins. J 5-8 tracks by Oscar Peterson, Iron Maiden, Metallica, Pink Floyd; jazz funk and mins. J 8-10 Ornette Coleman tracks, Liszt piano pieces; first movements in symphonies mins. J 10-20 fusion jazz tracks, Liszt tone poems, Wagner overtures, movements in Bruck mins. It goes without saying that you?re more likely to find extensional dia taxis in pieces of music that are themselves extended. As Table 11-1 shows, durations of over five minutes are rare for pieces (songs, tracks, etc. Diataxis We hear very few purely instrumental pieces lasting more than five min utes, unless free? jazz, fusion jazz or some other form of instrumental art music (including noubas and ragas as well as euroclassical sympho nies, concertos and chamber music pieces) are on our musical daily diet. Unless such music is used as background to other activities, listeners need to pay close attention in order to draw maxi mum benefit from whatever they?re hearing. Charles Mingus certainly believed this to be so when he threatened to walk out of a New York venue if, during his performance, anyone in the audience started talk ing, or if he heard the kching of a cash register or ice cubes clinking in a drinks glass. Rosen (1976: 155) explains the di ataxis of that music from the late eighteenth century as follows. The files represent my own musical interests and music I?ve used in teach ing and research. Online searches for +music + "average duration" typical style and+musik +durchschnittsdauer typisch Gattung Stil Lange were quite unproductive and +music "list of durations" generated references to topics like computer analysis of microdurations in avant-garde art music. Without a reliable guide to average durations for different types of music I was in March 2012 unable to do better than offer the unsatisfactory approximations shown in Table 11-1. Except of course for when, for example, the music co-occurs with lyrics or dramatic action that carry their own relatively extensive narrative, as in the Dylan and Legiao Urbana cases mentioned on page 404. See also timings for almost any recording of Arab, Indian, Cambodian, classical instrumental music. The symphony was forced to become a dra matic performance, and it accordingly developed not only something like a plot, with a climax and a denouement, but also a unity of tone, character and action it had only partially reached before. Its dynamic is worth understanding, at least as a general principle, partly because it so clearly illustrates the extensional pole of the distinction drawn by Chester in Second Thoughts on a Rock Aesthetic (1970) between intensional and extensional music aesthetics (p. The first movements of their symphonies, concertos, quartets and sonatas are usually constructed using some variant of an overall sonata form scheme (see Figure 11-10, p. Everything in the home key is shown on the bottom line of the diagram, the dominant neighbouring key on the upper line. Expositions conclude with a final cadence in that other key (just before 2:07 and 4:22). In fact the irregular shape of harmonic process in the development section of Figure 11-10 does not represent actual key changes: it just serves to indicate that development sections can move the music out of the tonal comfort zone of the exposition and re capitulation. Modulation is a process involving at least one intermediate chord (a pivot?) com mon to the tonal vocabulary of both departure and destination keys. The home key or tonic of the Mozart movement is G minor and the dominant neigh bouring key B$ major, the relative major? key of G minor. If the piece had been in G major the dominant neighbouring key would have been D major. In euroclassical music theory D is even called the dominant? of G, G the dominant of C, etc. The B theme is also stated in the home key and the movement is rounded off with an extended final cadence plus coda, all in the home key. However, this rewarding learning process has tended to over shadow other aspects of analysis and appreciation in conventional studies of Western music in two unfortunate ways. First, the teaching of sonata form, once institutionalised, fell into a rut of key and theme-spotting exercises that were easier to correct and quantify in exams than were insights into emotional, kinetic and other semiotic aspects of the narrative. Secondly, the extensional aspect of so nata form and the canonisation of euroclassical masterworks? con ceived in that mould fell prey to the syntax fixation discussed in Chapter 4, tendencies that trivialised intensional aesthetics and that put tonality, especially its harmonic aspects, on top in a hierarchy distin guishing primary? from secondary? parameters of expression. Common variations on this overall scheme include: [1] adding an introduction or overture? section of a different character before the exposition; [2] expanding the coda (a favourite Beethoven trick) so that it almost becomes another development section; [3] modulating to and from a different neighbouring key in the recapitula tion (often the subdominant as counterbalance to the dominant in the exposition; see ftnt. Both introductions and codas can introduce material not heard elsewhere in the movement. Diataxis Other types of euroclassical diataxis Although sonata form may take pride of place in conventional studies of euroclassical music, it is by no means the only type of diataxis in that tradition. This sort of dia taxis is rare in contemporary Western popular music but is often heard in Indian raga-based music where the recurring theme is called bandish (vocal, refrain) or gat (instrumental, ritornello). It comprises a main theme that is first stated as is?, then subjected to a series of modifications (the variations) before it rounds off the entire piece in either its original guise or as an easily recognisable version of it. Variations are sometimes used to dis play virtuosity involving lots of fast notes or elaborate melodic orna mentation. In euroclassical music, variations can be harmonic as well as melodic, but in jazz performance of 32-bar standards, as well as in blues or rock renderings of eight or twelve-bar matrices, the chord changes are constant and attention is focused on the solo improvisation of me lodic lines that diverge more radically from the original tune than do those of euroclassical variations in relation to their theme. Euroclassical examples of theme and variations: Loth To Depart (Farnabye, 1612); Jhon Come Kisse Me Nowe (Byrd, 1612); the Harmonious Blacksmith (Handel, 1720); Goldberg Variations (Bach, 1741); 7th Symphony, 2nd movement (Beethoven, 1812). Diataxis 413 Many patterns of extensional diataxis in euroclassical music, such as the fugue and classical concerto form, have, like sonata form itself, fallen out of common use since the nineteenth century. The same goes for other euroclassical forms? that are really compositional devices rather than types of diataxis. The twelve-bar blues matrix, for example, repeats the same underlying sin gle-key chord sequence, while others distinguish between sections by introducing different melodic or rhythmic ideas, different instrumenta tion, different chord sequences and so on. However, key changes can also mark episodic difference in other types of popular music, one ob vious example being the 32-bar jazz standard, whose B section (the bridge? or middle eight?) almost always features material in a different 59. This allows the musician enough time to display his/her technical skills and improvisa tory imagination in a longer process. The relevant bass notes in the Bach piece (not a ground bass) are d c# b a g which, transposed to the Procol Harum key of C, gives c b a g f. The complete repeated eight-bar chord sequence and ground bass in A Whiter Shade Of Pale runs [{r hC hC/b |Am C/g |F F/e |Dm F/c |G G/f |C/e G7/d |C F |hG lF/alG/b}]. Similarly, different tunes played in uninterrupted sequence by ceilidh bands as part of the same set are often heard in dif ferent but closely related keys. Diataxis 415 Conclusions and questions Diataxis is semiotically important in two main ways: 1. Which parameters of expression instrumentation, timbre, vocal persona, groove, metre, periodicity, harmony, etc. Is there any sort of build-up or clear run-in to one episode (see Episodic markers?, p. Does the piece go round in circles or proceed more linearly (see Cyclical processes?, p. If the piece is cyclical, does it return to the same basic mood as it started in (centripetal)? Do they in any way contribute to the identification of ep isodes in your analysis piece or of its stylistic and generic habitat? Like composition? in the visual arts, syncrisis involves the si multaneous combination of elements and can also be considered in terms of the shape, form, size and texture of a scene or situation. This chapter is long because it has to confront aspects of form and its meaning that are rarely examined in conventional music studies. To simplify matters, syncrisis can, I think, be understood in two main in terrelated ways. The other important perspective is distinctly social in the sense that scenes? represented in music consist of simultaneous strands of sound (voices, instruments, tracks, etc. These patterns of musical organisation, I argue, vary signifi cantly in time and place because they connect with patterns of social interaction specific to the culture in which they are produced. These connec tions between musical and social organisation may seem pretty obvi ous but they are sometimes, I regret, difficult to explain and even harder to prove. Syncrisis Overview the rest of this chapter starts with an introduction to scenes? as meta phors of musical syncrisis. This dualism, at the basis of much European music over the last 250 years, includes a comparison with contrapuntal po lyphony of the Renaissance (p. Particular attention is paid to the cross-rhythmic syncrisis of Sub-Saharan musics (p. The final part of this chapter is devoted to a dis cussion of other ways in which musical figure[s]/individual[s]? and ground/environment? are put into music (p. A young woman in a long dress strolls through the long grass of a sunlit summer meadow. The reptile invaders? gigantic flying saucer casts its threatening shadow over the whole city. The dark waters of a misty, moonlit lake lie still, deep in a Northern European forest, some time in the dark ages. All ten are either mentioned elsewhere in this book or have been set to mu sic in well-known audiovisual productions or programmatic composi tions. Some contain a variety or unity of quick movement, while others are slower, or even static. Some movement is towards a goal, while other scenes contain veritable hives of non-directional activity. Some are gen tle, others violent; some hot, others cold; some dark, others light; some pleasant and relaxing, others unpleasant and disturbing. Syncrisis also involves texture with its interrelated bipolar scales of musical density/sparsity and singularity/multiplicity. Try also [11] the Kojak theme (Goldenberg, 1973) for heroics in a busy, sunlit New York and [12] Night on a Bare Mountain (Mussorgsky, 1863) for the nocturnal swarming of evil spirits. Diachronic density is horizon tal? and involves notes coming fast and furious with little or no let-up (as in fig. Synchronic density can be close notes bunched together in one register, as in close har mony? or capacious lots of notes in all registers at the same time, as in the Respighi sample. Sparse synchronic texture, if it covers a wide pitch range, will contain ample registral distance between instru ments, voices or parts. Loudness can also be im portant in determining how dense or sparse the music sounds. Sparse texture is more likely to derive from distinct dif ferences in loudness and timbre or, as just implied, from the presence of more windows of silence?, more sonic open space, both vertically and horizontally. Both composers form musical impressions of such vast ness in much the same terms of sparse but continuous and expansive texture: high, quiet, held notes or slowly repeated ones, big registral spaces, not much tonal change. Gradually introduced, melodic ideas are quite simple, moving slowly with plenty of breathing space be tween phrases. The lark in this popular piece rises on solo violin out of that quiet but richly grounded orchestral generality into light but rapid bursts of stylised pentatonic birdsong, ending up, like a real skylark, high above its (and our) home base/bass. More importantly, the sounds of their gross motoric movement would bulldoze the stillness of the scene to an inau dible rubble in terms of loudness and register overlap. Larks nest on the ground and perform their song displays (for territorial reasons) in ascent and at great height in the early morning. Syncrisis Singularity and multiplicity Of course, a single lark, horse, buffalo or motocross bike does not sound the same as several. One reason why we can pick out the cuckoo is that its call re sembles more closely than other birdsong the vocal utterance of a single human in terms of register, pitch profile, surface rate, rhythmic profile and duration. That is not so with the song of a lark ascending in the still of the early morning. A multiplicity of similar sounds that start and end at different points in time but which overlap to form an overall continuum is, at least in modern Western ears, more likely to come across as an acoustic backdrop or musical accompaniment. Single-strand sequences of sound stated in phrases no longer than the extended present, and whose timbre, pitch range, surface rate or tempo differs from that/those of any eventual sonic backcloth, are more likely to be heard as musical figures. The more such single-strand lines tally with what the human voice can produce in terms of register, pitch range and profile, of surface rate, and duration of phrases, the more likely they are to be heard as musical foreground, i. Distinction between sonic foreground and background can, in Western traditions of music, be understood as homologous to the distinction be tween melody (singularity, individual, foreground figure) and ac companiment (generality, environment, background etc.

As a guideline the curve should have the following criteria: Efficiency >80% Slope between 3 mens health protein powder buy eulexin 250 mg mastercard. Greater deviations from the predeter mined Ct value suggest that mens health 15 minute meals purchase 250 mg eulexin visa,??The M gene positive control may have degraded (if Ct greater than pre determined value) prostate health vitamins purchase eulexin now. Detection of Avian Influenza A Matrix Gene 81??Software settings on the instrument are inaccurate/inappropriate and the fluorescence cut-off level excessively high/low and is affecting the Ct value of the predetermined M gene positive control androgen hormone pills order 250mg eulexin mastercard. It may be possible to reset the software after the experiment to restore the expected Ct value provided the other con trols are in order prostate knowledge buy eulexin with a visa. These plots may represent spurious probe degradation or non specific fluorescence mens health 7 day meal buy eulexin 250mg cheap. Probe and primers should be aliquoted once re-suspended to avoid repeated freeze thawing. If the new reagents are fit for purpose both sets of reagents should give equivalent results. Detection utilises a H7 specific hydrolysis (?TaqMan?) probe with fluorescence emission in RealTime. This includes an awareness of risks relat ing to eg dangerous or toxic chemicals, potentially hazardous procedures etc. Here local safety rules in your laboratory should be understood by all relevant members of staff. Higher titre extraction controls may also risk contami nating neighbouring reaction wells. Enter as unknown? (or equivalent) during experi mental set-up using the software on the RealTime instrument. It is advised to cover strips loosely which have not yet been filled with caps (strip covers) to further minimise the risk of cross contamination. If the machine is not booked for immediate use by another colleague upon completion of the run, select the option (if available) to turn off the lamp at the end of the run. There is no need to electrophorese this H7 amplicon through an agarose gel prior to purification. Although such observa tions may not invalidate the experiment, it is advised to discard the ali quot and thaw-out a fresh aliquot of the relevant H7 probe for subsequent experiments and note result. It is also possible that such very late Ct signals may occasionally occur spuriously. Detection and Pathotyping of Eurasian H7 Avian Influenza Isolates 91??It is also possible that the H7 positive control may have degraded if stored incorrectly. These criteria are similar in principle to those listed in the above four paragraphs of Section 5. Revi sion of H7 primer/probe sequences may be necessary and this will be reflected in any future updated versions of this protocol. Detection of H5 & H7 Avian Influenza and Cleavage Site Sequencing 95 3 Procedure/Method 3. However, some non-H5 clinical samples can produce a band(s) of similar mobility, where amplicon sequencing is the only means of establishing whether these are derived from H5 or other microbes. These are the most sensitive primer pair which can amplify from H7 clinical specimens. J3/B2a cycling conditions 30 min at 50?C 95?C for 15 min 35 cycles of 94?C for 45 s 50?C for 45 s and 72?C for 2 min and a final extension at 72?C for 10 min. The common cleavage site nucleotide sequences (and amino acid motifs), and points for their interpreta tion are listed in Appendix 1. The top chromatogram represents a single sequencing run (ie in one orientation) where in places the quality of the data is poor (ie super imposed peaks of more than one signal, a general background pattern of red (ie T) signals), as seen from the character of the plot. This results in clearly one ambigu ous nucleotide call at the cleavage site, and likely errors among neighbouring nu cleotides which upon translation results in poor aminoacid sequence data at the cleavage site. Such a result would be considered unfit for purpose? unless there was a complementary sequencing run available (ie in the opposite orientation) of clearly superior quality. Detection of H5 & H7 Avian Influenza and Cleavage Site Sequencing 99 the next example (below) consists of two complementary sequencing runs in opposite orientations. Compare the quality of the two below chromatograms with the above, ie clear and discrete peaks which agree in both orientations. This illustrates that single nucleotide changes within the cleavage site can result in a pathogenicity change for a particular virus isolate. For the method described in this protocol, haemaglutinnin gene sequences from Eurasian H5 isolates (mainly 1996?2004) were aligned. Here lo cal safety rules in your laboratory should be understood by all relevant members of staff. Enter as unknown? (or equivalent) during experimental set-up using the software on the RealTime in strument. It is important that the caps are fitted firmly and correctly onto the wells before insertion into the RealTime instrument. If the machine is not booked for immediate use by another colleague upon completion of the run, select the option (if avail able) to turn off the lamp at the end of the run. Although such observations may not invalidate the experiment, it is advised to discard the aliquot and thaw-out a fresh aliquot of H5 probe for subse quent experiments and note result. Greater deviations from the predetermined Ct value suggest that:??The H5 positive control may have degraded (if Ct greater than predeter mined value). It may be possible to reset the software after the experiment to restore the expected Ct value provided the other controls are in order. It may be possible to reset the software after the experi ment to restore the expected Ct value provided the other controls are in order. Samples with Ct >33 but with a clear logarithmic/sigmoidal character giving clear final fluorescence greater than that observed during early cycles. Samples with Ct >33 but with a linear character giving final fluorescence which is approximately the same as that observed during early cycles. However, there is some evidence that certain American lineage H5s may be detected by this procedure. Revision of primer/probe sequences will be necessary and this will be re flected in any future updated versions of this protocol. Vali dated H5 Eurasian real-time reverse transcriptase?polymerase chain reaction and its applica tion in H5N1 outbreaks in 2005?2006. Two or three primer pairs are used to amplify the template which gives a long stem loop product under isothermal conditions. For more information about the assay development and validation see Blomstrom et al. The master mix should not be left sitting for long as this can increase background. For more information about the assay de velopment and evaluation with clinical samples see McKillen et al. The reaction was incubated for 5 min at 22 C, followed by 90 min at 37 C, and the enzyme was finally inactivated by heating for 5 min at 95 C. Filter set for RotorGene is 470nm/610hp (emission/detection) # Fluorescence data are collected in the annealing phase and during the probe melting profile 4. As there exist no platform with built in capability to analyze any data generated using an Invader based protocol it has to be extracted and analyzed manually. This can be based on either reaction slopes (from real-time data) or end point measure ments. This protocol describes the calculations/manipulations necessary to get a quanti fied and statistically verified analysis of any sample. This template contains an analysis matrix for duplicate samples and ten known standards. This set-up enables melting curve analysis on completion of the amplification, which provides a convenient and reliable way for confirming its specificity. The assay is capable of rapidly detecting a broad range of influenza A and Newcastle disease viruses. Standard Deviation Quantifies the dispersion of the data point values around the mean, and is used to set limits for acceptable performance ranges. It is permissible to exclude statistical outliers prior to proceeding to next steps, however additional data to allow a minimum of 10 data points for analysis are required. For assays with previously determined acceptable performance ranges (de fined as mean 2 standard deviations) and target performance range (de fined as mean 1. With continued assay use and additional data points, the acceptable performance range should progressively show less variability (smaller standard deviation) before becom ing stabile. The magnitude of assay variability is heavily dependent on original assay design. Detection of Influenza Virus Matrix Gene 151 availability of that specific source material. Selection of medically useful Quality Control procedures for indi vidual tests done in a multitest analytical system. Primer and probe are typically obtained in lyophilized form from commercial suppliers. Amber-colored microtubes or foil wrapped microtubes to protect probe fluo rescent dyes from light-associated decay. Use the total nmoles? value supplied by the manufacturer and multiply by 10 to determine the volume of diluent in microliters required, example, total nmoles? To make more than one aliquot, dilute in one tube and then aliquot to the re maining tubes. Example, To make 6, 50 L tubes of a 10 M working solution (300 L total volume). Label each tube with the concentration and date prepared for Quality Assurance and inventory tracking purposes. New lots and working solution of primers and probes must be tested three times side-by-side with the previous lot for Quality Assurance purposes. The Ct results are documented; and performance limits must be verified as within the performance range previously established for each probe and/or primer sets (Mean Ct standard deviations). Aliquots associated with documented assay failure that is tracked to lot number, stock concentration aliquots, or working con centration aliquots are destroyed. The Influenza matrix as say is not species-specific, and may be used with avian, swine, equine specimens. Foil sealed microtiter plates with mastermix can be stored for up to 7 days at 70?C. Calculations for the volume of each reagent and enzyme needed are performed using a pre-programmed spreadsheet or manually-calculated worksheet. Remove reagents and enzymes needed from 20 storage, quickly thaw, vor tex to mix, pulse spin to remove any liquid adherent to the cap, and place the tubes on ice. Place reaction tubes in the chilled tube rack, handling the tubes by the neck or lid rather than the sides to avoid contact with the reading windows. Label the cap on the individual tubes to insure they are kept in the correct sequence. Remove reagents and enzymes needed from 20?C storage, quickly thaw, vor tex to mix, pulse spin to remove any liquid adherent to the cap, and place the tubes on ice. Using a Matrix pipet tor, load 250 L mastermix and dispense the assay-specific L volume into each well. Cover plates with foil plate sealers to protect from light and evaporation; sealed plates with mastermix can be stored for up to 7 days at 70 C. For Quality Control purposes, it is critical that the extraction controls be handled and extracted at the same time and using the same reagents as the clinical specimens. Working with 1 row (12 specimens) at a time, uncap and place tubes in a sepa rate rack dedicated to the extraction process. Transfer 50 L of each row of specimens to the corresponding row of the 96-well plate. Cap the tubes and transfer to the storage box before moving to the next row of samples. Because multiple specimens are handled in sequence, it is good lab prac tice to check gloved fingertips for any evidence that fluid from the caps or tubes has not contaminated your gloves. If any moisture is dedicated, decon taminate with 10% bleach and dispose of gloves. Wipe the tubes, rack, and immediate work area with 10% bleach and again with ethanol before continu ing. Quality Control specimens are located in wells interspersed with diagnostic specimens to appropriately control for cross-contamination during extraction and amplification steps. If samples have been pre-plated and the 96-well plate frozen, thaw in a bio safety cabinet with the plate covers off to prevent condensation from running onto plate surface. Double check the 96-well plate for loading errors (empty wells, excessive vol ume in wells), and for missing plate numbers/missing bar codes. Add 20 L beads/binding mix in each well of a U-bottom plate, and shake for 4 min. Beads should be suspended, otherwise use a manual 200 L pipettor to re-suspend the beads by pipetting up and down. Transfer the supernatant into a clean plate (25 L per well), cover with an adhesive plate sealer, wrap with aluminum foil and freeze the plate at 70 C. Manual 12 and 8 channel pipettors are not as efficient for the extraction based on slower and less forcefuldispensing of fluid, which is needed to help disperse the magnetic beads. Load the reaction plates into the thermocycler; start the run using 48 C for 30 min 95 C for 2 min 3-step cycling for a total of 45 cycles 94 C for 15 s 60 C for 30 s 72 C for 15 s 4. Load the reaction plates into the thermocycler; start the run using 48 C for 30 min 95 C for 2 min 3-step cycling for a total of 45 cycles 94 C for 15 s 60 C for 30 s 72 C for 15 s 3.

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Hodgson concluded Madame Blavatsky was a phony "one of the most accomplished mens health tv buy eulexin now, ingenious androgen hormone imbalance cheap eulexin 250 mg without a prescription, and interesting imposters of history mens health getting abs pdf buy eulexin no prescription. Most of the evidence was of a circumstantial nature as the original shrine had been destroyed by the time Hodgson had arrived at Adyar prostate cancer 5k cincinnati buy 250 mg eulexin otc. More recently prostate in spanish eulexin 250 mg sale, Theosophical apologist Victor Endersby has written a book challenging the Hodgson report point for point mens health 9 week plan generic eulexin 250mg online. Endersby cites independent testimony from handwriting experts who clearly disagree with those hired by Hodgson. The teachings of the Theosophists continue to have an enormous impact on the esoteric folklore of western culture and for that reason are quoted several times in this book. A Course in Miracles Since the original publication of the Roots of Consciousness, there have emerged numerous examples of ostensible contact with higher intelligence. One of the foremost among these is A Course in Miracles, which is a system of spiritual transformation. Hundreds of thousands of individuals have used this material; and its emphasis on love, foregiveness and freedom from guilt have had an influence on a new generation of spiritual seekers comparable to that of the Theosophical Society in previous years. A Course in Miracles suggests that a miracle is really a shift in perception to see the spirit that lies behind all forms. Judith Skutch Whitson, is the president of the Foundation for Inner Peace, the organization which published A Course in Miracles. Judith Skutch Whitson (courtesy Thinking Allowed Productions) In the following excerpt from a Thinking Allowed interview, she describes the origins of this material: In 1975, I met William Thetford and Helen Suchman, two medical psychologists at Columbia Presbyterian School of Physicians and Surgeons, who served as scribes for the material. They had had a very long period together, teaching, researching, writing grant proposals; yet their life together and among their faculty was not very harmonious. They described it as one of the most stress-filled domains in the world academia, medical academia. One day the quieter of the two of them, Bill Thetford, who was a very gentle man, a very thorough scientist, a very solid person he just blew up. He said in a very meaningful way to her, so that she heard him, that he was sick and tired of the attitudes that that stress seemed to have promoted between the two of them, and that they just were not getting along, that there had to be a better way to live in the world. Instead of laughing at him because she was quite an acerbic woman, very sharp, the older of the two of them by fourteen years she actually took his hand, and she said, "You know, Bill, I think you are right. Not too long after, Helen started to experience what she called heightened visual imagery which gave her the feeling that there was something within her catching her attention and very gently taking her along the way, through experience, to an opening up. After many of these visions, she started to become very familiar with an inner voice which spoke with a gentleness and yet an authority she could not avoid listening to . She called up Bill on the phone, and she said, "You know that voice I told you about? Before the staff came in, they locked the door and pulled down the shades so no one should catch them at this. She actually read from her notebook to him what she had taken down, and he typed it up. Free will does not mean you can establish the curriculum, only the time in which you need to take it. It also said the course could be summed up very simply this way: "Nothing real can be threatened, and nothing unreal exists. At that time she called herself a militant atheist, and he was an agnostic, and here was something that mentioned G-O-D, and it just was not in her vocabulary. So he convinced her that it was beautifully written, and whatever it was, if it should happen again, to keep on doing it. Any time she wished, when she was ready, she could pick up her shorthand notebook and her pen, and literally start from where she left off before, without even checking what the book said. With Bill typing what she had taken down every day, A Course in Miracles came into being. I could not have predicted, in 1975, that there would be three hundred thousand copies of A Course in Miracles in circulation. I have no idea how many people study one copy, so I am guessing over a half a million folk are students of A Course in Miracles. I think we are probably laying the foundation, along with many others, who share basically the same point of view but go about it in different ways a foundation for a tremendous change of mind, which I call the great transformation. Shafica Karagula, director of the Higher Sense Perception Research Foundation in Los Angeles. Karagula specialized in clinical studies of individuals who are gifted with unusual perceptive talents. One of her subjects, whom she called Vicky described a series of experiences she had in her sleep where she seemed to be visiting a college and attending classes in many different subjects. Her vision was quite lucid, recalling the architecture of the buildings, and the subject matter of her lectures. The lectures follow an orderly sequence and Karagula claimed to have carefully recorded a number of them from Vicky. On one occasion, Vicky remembered that a friend of hers, who lived across the United States was in the classroom with her. After some cautious questioning on the telephone, this person verified that he also remembered being present although he did not recall the details of the lecture as clearly as she did. Although similar experiences have been reported by many people, and are known to dream-researchers, they have yet to be more systematically probed. The notion of the Invisible College, of course, stems from the Rosicrucian writings of Francis Bacon. Peter Dawkins, a Francis Bacon scholar, tells a story of his own involvement with this work that falls very much in the Invisible College tradition. Peter Dawkins (courtesy Thinking Allowed Productions) 153 the following excerpt is from my Thinking Allowed interview with him: One day we went on a retreat, my wife and I, and on that retreat was a lady who was the secretary of the Francis Bacon Society in England. There was a certain gentleman making a certain gesture that was important in the dream, with a very short message to send to this lady. I wrote, and I got a letter back from her by return post saying, "Thank you very much. That experience took place in 1972 at a time when I was still a graduate student in criminology at the University of California. However, I was feeling very uncomfortable studying only negative forms of deviance. One evening I felt inspired to tell myself, and to accept without doubt, that I would have a dream which would provide an answer to my career dilemma. Knowing where they hid their housekey, I took the key and let myself into their apartment. I walked into the living room where I found a `agazine sitting in the middle of the floor. I awoke early in the morning and, like Dawkins, felt drawn to act on the inspiration of the dream. Immediately I dressed and ran four miles across Berkeley to the apartment I had dreamt of. To my delight, there was a single magazine in the middle of their living room floor. As I sat there paging through Focus magazine, I was struck with the idea that I would redirect my career through involvement with public broadcast media. Every Tuesday and Thursday I had the oportunity to hold intimate, hour-long, uninterrupted discussions with leaders of the human potential movement, yogis, scientists, psychics, psychologists, visionaries, humorists, etc. It was this experience that gave me the confidence to pursue a unique doctoral diploma in parapsychology at the University of California, Berkeley, and to write the first edition of the Roots of Consciousness. The 154 inspiration of that dream still motivates my life twenty-eight years later as I produce the Thinking Allowed television series and prepare this internet edition. My own dream experience certainly does not reflect a contact with higher intelligence in the romanticized or stereotyped manner characteristic of theosophical and rosicrucian legend. It does suggests a synchronistic connection (which implies some higher intelligence) that has been integrated into the movements and actions of my life pattern. The accurate recording of the event referred to is quite veiled as the only preserved records come from Syncellus in Greek and Eusebius in Latin, both quoting the Greek chronicler Alexander Polyhistor, who is quoting from Berosus, who is in turn quoting from more ancient texts. This article tracing the esoteric symbology of the winged gods appears in an anthology by the editors of the Journal for the Study of Consciousness. Actually Home is quoting directly from Augustine, but neglected to acknowledge the specific source. Hundreds of these delightful Sufi tales have been recorded and translated by Shah, who is considered a spiritual father to story lovers throughout the world. It is said that one can develop inwardly by merely listening to these "teaching stories. Katy Butler, "Events Are the Teacher: A Buddhist Community Asks Its Leader to Stop," Co-Evolution Quarterly, Winter 1983, pp. Heart-Master Da Love-Ananda, the Basket of Tolerance: A Guide to Perfect Understanding of the One and Great Tradition of Mankind. Formerly the chief psychologist at a mental hospital in California, Van Dusen began to treat the hallucinations of his patients as if they were spirits. In fact, he hypothesized that he was encountering the very same world of spirits as described in the encyclopediac writings of Swedenborg. Later, in an anonymously published manifesto, Kant essentially retracted his support of the claims for Swedenborg. Broad, an eminent philosopher of this century, demonstrated that Kant, undoubtedly a great thinker, was nevertheless, a careless psychical researcher. An innovative American psychologist, Hall studied with many of the German pioneers, such as Fechner, about whom he writes. Delightfully written with a consistent sense of humor, this book is now difficult to obtain. However, her book lacks the detail and precision necessary for a scientific evaluation. Myers (author of Human Personality and Its Survival of Bodily Death), who have attempted to catalog the range of psychic experiences, maintain that there is a continuous spectrum of experiences leading from common dream states to heightened creativity to ostensibly spiritualistic and supernatural manifestations of a bizarre nature. Such a spectrum inevitably suggests a relationship between ostensible psychic contact with higher forms of intelligence and ostensible contact with intelligences from other planets or other dimensions of time and space. In fact, it is extremely difficult, if not impossible, to determine if any of the purported contactee claims in these areas are anything other than folklore. Even in those rare cases which seem to produce some independent physical suggestion of extraterrestrial visitations via spacecraft the mythological and archetypal process is also very active. Swedenborg Emmanual Swedenborg For example, the Swedish seer, Emmanual Swedenborg, whose descriptions of angels have been previously quoted, also claimed to have engaged in extensive psychic communication with inhabitants of other planets. His descriptions certainly imply some sort of direct experience: the inhabitants of the Moon are small, like children of six or seven years old; at the same time, they have the strength of men like ourselves. Their voices roll like thunder, and the sound proceeds from the belly, because the Moon is in quite a different atmosphere from the other planets. Swedenborg himself was a very convincing individual and a great scientist in his own day. Self-discipline demands that such yearnings be subjected to and augmented by rational analysis. It is a human dilemma caught as we are between the alienation of existential separation and the promise of spiritual unity. From India to the Planet Mars In 1899, Professor Theodore Flournoy, a psychologist at the University of Geneva, published a book called From India to the Planet Mars which detailed the trance communications of Mlle. In this book he documented striking incidents of telepathy and even a good deal of evidence for a past reincarnation in India complete with historical accuracy and a knowledge of Sanskrit. The medium actually furnished the investigators with a Martian language, complete with its own unique written characters. A number of other investigators defended the extra-terrestrial origin of the language. Muller might have been credited as the first human being to have established intelligent communication with Mars. A more recent analysis of the speech produced by "channeled entities" was conducted by Sara Grey Thomason, professor of linguistics at the University of Pittsburgh. The typical patterns are very inconsistent, suggesting that these verbalizations are, at least partially, the result of conscious or unconscious personification. Three young children, Lucia dos Santos, Francisco Marto and his sister Jacinta, figure in this series of extraordinary events. According to their testimony, they were first visited by an angel who asked them to pray. In May, 1917, they were visited by the figure of a lady who spoke to them and told them to return to the same field on the thirteenth of each month for more messages. Many witnesses noted strange lights and sounds, but only the children reported actual contact with the radiant Lady. The children claimed to receive much information that was passed on to Roman Catholic Church officials, with instructions it be released to the public in 1960. In October, so many people were aware of the phenomena that over 50,000 had gathered at the Cova da Iria to witness the event. Some spectators saw a column of blue smoke in the vicinity of the children that appeared and disappeared three times. Then suddenly the rain ceased and through the clouds was seen a radiant disk, not the sun, spinning, and throwing off fantastic streamers of light-a constantly changing montage of red, violet, blue, yellow, and white. The disk is shown after it had descended, near the horizon (courtesy Association for the Understanding of Man. Taken from the book Fatima Prophecy: Days of Darkness Promise of Light) Then the disk advanced toward the earth until it was just over the crowd.

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These programs prostate cancer bone metastasis generic eulexin 250mg with mastercard, at least in the Old World prostate cancer 5 year survival rates order eulexin 250 mg otc, were characterized by the intro duction of artificial systems of exchange called money prostate oncology nursing buy discount eulexin 250 mg online, and accompanying programs of taxation man health report garcinia purchase 250mg eulexin with amex. These systems were adopted to a greater or lesser degree by all the Old World societies prostate function discount 250 mg eulexin free shipping. In this we find the root of the slogan prostate 95 cheap 250 mg eulexin with visa, "time is money," where money is the artificial medium to negotiate artificial time. The word "calendar" itself is derived from a Latin word meaning "account book," the first day of every month being calendsor the date of payment of debts. Now, let us return to a consideration of the two principal and resultant 12:60 instruments dominating the end of historical time: the Gregorian calendar and the mechanical clock. Within the entire thirteenth baktun cycle, 1618-2012, the coincidence of these three factors-clock, calendar, and European global circumnavigation-induced what amounts to a 12:60 frequency capture of planetary time in the biosphere. What are the implications of this takeover of time by an irregular and irrationally measured Gregorian calendar and its accompanying micro-organizing device, the mechanical clock? Plotting the growth curves of human population, machine, and money, we see that the complete infusion of the 12:60 artificial timing frequency creates an unprec edented acceleration, the exponential peak of which occurs at the moment of the Inevitable Event. The Law of Time in Human Affairs comprehend even more deeply the nature of calendars and their effect, especially with regard to the current global standard. Because the calendar is a macro-organizing principle, when accepted over time it establishes in the mind, individually and collectively, a set of perceptions that are automatically taken for granted as being "real" and "indisputable. The Gregorian calendar, the current global civil standard, is the paradigmatic macro-organizing principle in which are embedded all the laws, cus toms, institutions, and scientific principles governing the present global civilization not to mention all the holidays of the Vatican-ordained Catholic Church. According to the Law of Time, the current calendar is an irregular standard of measure; its units of measure do not correspond. This calendar represents, therefore, the institu tionalization of disorder and entropy. All current beliefs-economic, political, and scientific, from democratic neo-liberalism to the special theory of relativity-are actually products of the underlying percep tions promoted by this calendar, and have no reality apart from the beliefs about time that the calendar engenders. As such, it furthers and maintains all linear time concepts, thereby establishing a host of entropic, disordered value concepts such as the violent universe, the degradation of matter, quantum physics, the arrow oflinear time, the doctrine of techno-economic inexorability, and an attendant host of unresolvable problems-crime, drug abuse, terrorism, environmental deterioration, and so forth. Because as an irregular standard of measure, the Gregorian cal endar is incapable of producing harmony. Condition the mind to an irregular standard and the mind will adjust to disorder and chaos as normal conditions of existence. Without a unifying harmonic standard humanity is incapable of finding long term resolutions for any of its problems. All conflict can only be resolved by the appli cation and within the context of a harmonic timing standard. Now, following the attack on the Twin Towers and the Pentagon, we can say that the Gregorian calendar is bringing history to an end. The Inevitable Event was pro grammed into the Gregorian calendar, and the Gregorian calendar usurped the power of all calendars in the thirteenth and final baktun cycle of history. When the third millennium officially opened at the dawn of the year 2001, the pride of industrial man was at an all-time high. If the last century of the second millennium was the century of total war, was the third millennium going to do anything but inherit the unfinished programs of the old millennium? The Gregorian calendar marks its inception with the birth of Christ, a date and moment that was never historically noted, and so is shrouded in speculation and conjecture. Now the twisted civilization of Gregorian time is locked in mortal combat against a terroristic specter that it alone could have projected into manifestation. Soon, by biospheric standards, the world of artificial time will be over and gone. The very word millennium conjures possibilities of Earth-shattering events and cosmic prospects. It was the termination of more than 5,000 years of the irreversible motion of artificial time. Such symmetry-eleven years after the beginning and eleven years before the end of history-is the hallmark of the synchronic order. For 5,100 years the count of days has numbered the long and increasingly perilous saga of human civilization. The Law of Time in Human Affairs There at the beginning of the cycle was the "first city," Uruk. There at the end of the cycle, the fallen Twin Towers of Babel of the "last city," New York (= New Uruk), the ultimate monument to history itself and the final event to initiate the actual closing of the cycle of history. Urshunnabi, climb up on that wall, the outer all shining with the brilliance of burnished copper. One third of the city is buildings, cunningly executed, one third of the city is garden with rose and bird, and one third of the city isfield with the temple of Ishtar within. Fifty-one centuries later, the gardens are all but gone, the fields themselves mechanized and chemicalized by the technosphere. Five weeks after the Inevitable Event, now known simply as 9-11, the end of history still smolders. It was only in the thirteenth and final baktun that humans became organized by a single timing standard. However, it was not a timing standard in accord with the synchronic order of the Law of Time, but the artificial 12:60 timing frequency as represented by its two organizing instruments, the Gregorian calendar and the mechanical clock. The seeds of this moment had already been planted in the noosphere at the beginning of history. From both Sumeria and Babylonia the taint of the 12:60 fre quency then spread through the noosphere and, by means of historical dissemina tion and conquest, throughout the Old World. By the time the historic moment arrived to ripen the 12:60 frequency into its full fruition-A. The civiliza tions and peoples of the New World were now under the subjugation of the prevail ing world order of European global imperialism. The stage was set for the brief but final phase of mechanization, of which the technosphere itself is the climax. The Climax of History What the Noospheric Time Map also delineates is that the 13:20 frequency was the unconscious organizing factor of prehistory, and that, undoubtedly, a key timing system intuitively evolved among many prehistoric peoples independently of one another. This was the universal, harmonic solar-lunar standard of the Thir teen Moon/2 8-Day calendar. The defining point of history arrives with the estab lishment of a 12:60 timing standard within the noospheric unconscious. This fre quency predominates in the development of twelve-month pseudosolar calendars, as well as the twelve-month synodicallunation calendars that are not the measure of a solar year. These two commingled systems are entwined throughout the an cient history of the Old World as the central thread of development shaping the conception of time and resulting in what were to become the two dominant instru ments of human time reckoning, the Julian/Gregorian calendar and the mechani cal clock. Julius Caesar himself instituted the famous "calendar reform" that created the 446-day year of confusion in 45-44 B. The Essene movement, founded by someone known simply as the Teacher of Righteousness and of which Christ was supposedly a member, began as a revolt against the Hebrew lunar calendar. The issue was the need for fixed holidays within the solar cycle, something that is virtually impossible in a lunar calendar that retrocedes eleven days every solar year. There is strong reason to believe that among other calendars, the Essenes favored the Thirteen Moon/2 8-Day calendar. This even leads to the question: did Christ himself follow a thirteen moon calendar? In any case, it is the 12:60 frequency transmitted through the irrational disorder of the Julian/ Gregorian calendar that captures the mind of the human race and the biosphere during the final years of the cycle of history. And it is precisely for this reason that the pace of human civilization becomes exponentially and entropically accelerated during the last few centuries of its development. Shocked into higher consciousness by its own barbarism masquerading as civili zation, at the end point of history the human has the opportunity to return to the natural 13:20 frequency of synchronization. This return would mark the emergence of humanity from the unconscious mechanistic compulsion of artificial time into the conscious field of post-history. The only possible option to unify humanity-once the yoke of the Gregorian calendar is removed-is the true solar-lunar calendar of Thirteen Moon/28 Days. With the possibility of this positive end in sight, we may turn to a more descriptive and definitive analysis of the technosphere. In this way understanding the modalities of the technosphere as a distinct and entire process, we the Climax of History. The technosphere defines a 56-year cycle, 1945-2001, coordinated by two com plete Gregorian 28-year cycles. For any Gregorian calendar year, the days of the weeks in their irregular monthly succession and in relation to the permutation cycle of leap years repeat precisely every twenty-eight years, during which time there are always exactly seven leap years. This means that Gregorian calendar years 1945, 1973, and 2001 possess the same exact annual arrangement of the days of the week in their monthly succession. In this regard the Law of Time frames the cyclic recurrence of the otherwise irregular 12:60 Gregorian calendar by the intrinsic formulation 28:7. That is, just as the 19:7 factor coordinates the lunar calendars every nineteen years, there being seven intercalations of the thirteenth moon during that cycle, so in the Gregorian calendar every twenty-eight years there are always exactly seven leap days and years. Understanding a calendar as the instrument that locks the conditioned programs of a given culture or people into place, we can now understand how the unconscious metaprogram of the macro-organizing principle of the Gregorian calendar cumula tively recycles all its millennial programs every twenty-eight years. Since its incep tion in 1582, the Gregorian calendar has been dragging forward a host of condi tioned thought forms and perceptions, including those inherited from 1,500 years of the Julian calendar that it had reformed. At points of dramatic break in the continu ity of human consciousness, a new set of cycles is set to recur. The entirety of the mind field conditioned and held in place by the Gregorian calendar then reaches its full frui tion during the two subsequent 28-year cycles, fifty-six years in all-thus bringing forward two millennia of conditionings, conflicts, and unconscious death wishes or apocalyptic programs. The first cycle was initiated in the year 1945, the year in which Vernadsky died, the atomic bomb was tested once and used twice, and the Second World War came to an end. It is most telling that the Second World War was concluded at the beginning of this 56-year cycle of the technosphere, for it was a war concluded not with peace but with instruments of mass destruction and terror. The technosphere has its origins with the full capture of the human mental field by the 12:60 frequency in 1618. From 1618 onward, the noosphere is increasingly obscured by a mental field known as the technospheric sheath. It is important to note that the Julian count, the basis of all modern scientific calculations, is a scale created by Thomas Scaliger in 1583, twenty one years after the 1562 Mayan book burning. This linear time scale, like the Gregorian calendar reform itself, was intended to co-opt the Mayan thirteen baktun Long Count by setting a count of days that begins the first of January, 4713 B. This deliberate historical act, the Julian count, along with the Gregorian calendar and the mechanical clock, established the paradigmatic notion of the linearity of time in the ripening field of scientific thought. Reflected in the noosphere, this linear, irreversible time concept levels and stunts the realization of human mass consciousness. In fact, during the technospheric cycle, especially after 1754, the ceiling of human conscious ness is maintained by a preoccupation with mechanistic third-dimensional operations while becoming increasingly alienated from the organic order of reality. This creates the 12:60 consciousness constant, a mental ceiling that actually diminishes in propor tion to the increasing rates of multiplication, propagation, and intrinsic velocity of the machine. The industrial sheath spreads throughout the biosphere between 1754 and 1901, the official beginning of the twentieth century. During this critical stage of the proto-technosphere, the actions of human behavior interacting with machine technology make the expression of true culture increasingly difficult, if not impos sible. Civilization becomes a set of symbols purveyed through museums, galleries, and theaters, and recorded and reproduced in ever more advanced technological forms. But what of culture, which is not the same as civilization-what becomes of culture? According to the common dictionary definition, which already reflects the mass mind, technology is "the totality of the means employed to provide objects necessary for human suste nance and comfort. In common parlance, therefore, technology refers to the complex apparatus of mechanization. The Climax of History convert human labor into processes carried out purely by machine-oriented or me chanical means. This is also inclusive of the entirety of computer technology, which represents the mechanization of the more purely mental processes of thought and communication. Mechanization, we must remember, originated in the clock, in the mechanization of time. It is the mechanization of time that presupposes the tendency toward mecha nization as a state of mind within the noosphere. Since artificial time is characterized by the illusion of an inexorable and irreversible linearity, the compulsion toward materialism is also experienced in the same way, an inexorable motion spearheaded by the advance of ever more improved machines. The machines themselves are the products and means of industrialization-the technological transformation of raw goods into consumer goods, a process accounting for much of the free energy intro duced into the biogeochemical combustion of the biosphere. Inseparable from mechanized technology, too, are materialism and the con cept of the World Market and, more recently, of globalization. Materialism is im plicit in the dictionary definition of technology as the means employed not only for human sustenance but also for human comfort. This comfort can only be of a material form or nature, hence the pursuit of comfort through mechanized tech nology can only be for the furtherance of a philosophy and exaggerated lifestyle of materialism-the belief that only the material things of this world have any value. Of course, the value of material goods and comforts increases when the value of money is put into the technospheric equation. The first stock market opened early in the eighteenth century, providing a place where money could be used as specu lative capital to promote the advance of commodities and machine products. The entire sphere involving commodity production and its conversion into consumer products eventually came to be known as the World Market. Integral to the suc cess of the World Market was the creation of the modern banking system, based on the institutionalization of interest rates and the principle of lending money to companies for the purpose of furthering the transformation of the biosphere into the technosphere. While the concept of the World Market prevailed for a long time as the defini tion of the system for exploiting and extracting natural resources from the biosphere, and then converting them into industrial goods to be consumed by the human popu lace worldwide, globalization is far more recent.

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Fentanyl is not detected by standard urine tests but can be identified by more specialized proce? dures for several days man health guide discount eulexin online american express. Screening test re? sults for hepatitis A prostate bph buy eulexin in india, B man health advisor purchase eulexin 250 mg otc, and C virus are positive in as many as 80%-90% of injection opioid users androgen hormone jack cheap generic eulexin uk, either for hepatitis antigen (signifying active infection) or for hepatitis antibody (sig? nifying past infection) mens health zma proven 250mg eulexin. Mildly elevated liver function test results are common prostate radiation oncology purchase eulexin online now, either as a result of resolving hepatitis or from toxic injury to the liver due to contaminants that have been mixed with the injected opioid. Sub? tle changes in cortisol secretion patterns and body temperature regulation have been ob? served for up to 6 months following opioid detoxification. Suicide Risk Similar to the risk generally observed for all substance use disorders, opioid use disorder is associated with a heightened risk for suicide attempts and completed suicides. In addition, repeated opioid intoxica? tion or withdrawal may be associated with severe depressions that, although temporary, can be intense enough to lead to suicide attempts and completed suicides. Available data suggest that nonfatal accidental opioid overdose (which is common) and attempted sui? cide are distinct clinically significant problems that should not be mistaken for each other. Functional Consequences of Opioid Use Disorder Opioid use is associated with a lack of mucous membrane secretions, causing dry mouth and nose. Slowing of gastrointestinal activity and a decrease in gut motility can produce severe constipation. Visual acuity may be impaired as a result of pupillary constriction with acute administration. In individuals who inject opioids, sclerosed veins ("tracks") and puncture marks on the lower portions of the upper extremities are common. Veins sometimes become so severely sclerosed that peripheral edema develops, and individuals switch to injecting in veins in the legs, neck, or groin. When these veins become unusable, individuals often inject directly into their subcutaneous tissue ("skin-popping"), resulting in cellulitis, abscesses, and circular-appearing scars from healed skin lesions. Tetanus and Clostridium botulinum infections are relatively rare but extremely serious consequences of injecting opioids, especially with contaminated needles. Hepatitis C infec? tions, for example, may occur in up to 90% of persons who inject opioids. However, the incidence may also be 10% or less in other areas, especially those where access to clean injection material and parapher? nalia is facilitated. Tuberculosis is a particularly serious problem among individuals who use drugs in? travenously, especially those who are dependent on heroin; infection is usually asymptom? atic and evident only by the presence of a positive tuberculin skin test. These individuals often have a newly acquired infection but also are likely to experience reactivation of a prior infection because of impaired immune function. Individuals who sniff heroin or other opioids into the nose ("snorting") often develop irritation of the nasal mucosa, sometimes accompanied by perforation of the nasal septum. Accidents and injuries due to violence that is associated with buy? ing or selling drugs are common. Physiological dependence on opioids may occur in about half of the infants born to females with opioid use disorder; this can produce a se? vere withdrawal syndrome requiring medical treatment. Although low birth weight is also seen in children of mothers with opioid use disorder, it is usually not marked and is generally not associated with serious adverse consequences. Opioid-induced disorders occur frequently in individ? uals with opioid use disorder. Opioids are less likely to produce symptoms of mental disturbance than are most other drugs of abuse. Opioid intoxication and opioid withdrawal are distin? guished from the other opioid-induced disorders. Alcohol intoxication and sedative, hypnotic, or anxiolytic intoxication can cause a clinical picture that resembles that for opioid intoxication. A diag? nosis of alcohol or sedative, hypnotic, or anxiolytic intoxication can usually be made based on the absence of pupillary constriction or the lack of a response to naloxone challenge. In these cases, the naloxone challenge will not reverse all of the sedative effects. The anxiety and restlessness associated with opioid with? drawal resemble symptoms seen in sedative-hypnotic withdrawal. However, opioid withdrawal is also accompanied by rhinorrhea, lacrimation, and pupillary dilation, which are not seen in sedative-type withdrav^al. However, other signs or symptoms of opioid withdrav^al, such as nausea, vomiting, diarrhea, abdominal cramps, rhinorrhea, or lacri? mation, are not present. Comorbidity the most common medical conditions associated v/ith opioid use disorder are viral. These infections are less common in opioid use disorder v^ith prescription opioids. Opioid use disorder is often associated w^ith other substance use disorders, especially those involving tobacco, alcohol, cannabis, stimulants, and benzodiazepines, which are often taken to reduce symptoms of opioid withdrawal or craving for opioids, or to enhance the ef? fects of administered opioids. Individuals with opioid use disorder are at risk for the devel? opment of mild to moderate depression that meets symptomatic and duration criteria for persistent depressive disorder (dysthymia) or, in some cases, for major depressive disorder. These symptoms may represent an opioid-induced depressive disorder or an exacerbation of a preexisting primary depressive disorder. Periods of depression are especially common during chronic intoxication or in association with physical or psychosocial stressors that are related to the opioid use disorder. An? tisocial personality disorder is much more common in individuals with opioid use disorder than in the general population. A history of conduct disorder in childhood or adolescence has been identified as a significant risk factor for substance-related disorders, especially opioid use disorder. Pupillary constriction (or pupillary dilation due to anoxia from severe overdose) and one (or more) of the following signs or symptoms developing during, or shortly after, opioid use: 1. The signs or symptoms are not attributable to another medical condition and are not better explained by another mental disorder, including intoxication with another sub? stance. Specify if: With perceptual disturbances: this specifier may be noted in the rare instance in which hallucinations with intact reality testing or auditory, visual, or tactile illusions oc? cur in the absence of a delirium. Diagnostic Features the essential feature of opioid intoxication is the presence of clinically significant prob? lematic behavioral or psychological changes. Intoxication is accompanied by pupil? lary constriction (unless there has been a severe overdose with consequent anoxia and pupillary dilation) and one or more of the following signs: drowsiness (described as be? ing "on the nod"), slurred speech, and impairment in attention or memory (Criterion C); drowsiness may progress to coma. Individuals with opioid intoxication may demonstrate inattention to the environment, even to the point of ignoring potentially harmful events. The signs or symptoms must not be attributable to another medical condition and are not better explained by another mental disorder (Criterion D). Alcohol intoxication and sedative-hypnotic intoxication can cause a clinical picture that resembles opioid intoxication. A diagnosis of alcohol or sedative-hypnotic intoxication can usually be made based on the absence of pupillary con? striction or the lack of a response to a naloxone challenge. In some cases, intoxication may be due both to opioids and to alcohol or other sedatives. In these cases, the naloxone chal? lenge will not reverse all of the sedative effects. Three (or more) of the following developing within minutes to several days after Criterion A: 1. It is not permissible to code a co? morbid mild opioid use disorder with opioid withdrawal. Diagnostic Features the essential feature of opioid withdrawal is the presence of a characteristic withdrawal syndrome that develops after the cessation of (or reduction in) opioid use that has been heavy and prolonged (Criterion Al). The withdrawal syndrome can also be precipitated by administration of an opioid antagonist. This may also occur after administration of an opioid partial ag? onist such as buprenorphine to a person currently using a full opioid agonist. Opioid withdrawal is characterized by a pattern of signs and symptoms that are oppo? site to the acute agonist effects. The first of these are subjective and consist of complaints of anxiety, restlessness, and an "achy feeling" that is often located in the back and legs, along with irritability and increased sensitivity to pain. Three or more of the following must be present to make a diagnosis of opioid withdrawal: dysphoric mood; nausea or vomiting; muscle aches; lacrimation or rhinorrhea; pupillary dilation, piloerection, or increased sweating; diarrhea; yawning; fever; and insonmia (Criterion B). Piloerection and fever are associated with more severe withdrawal and are not often seen in routine clinical practice because individuals with opioid use disorder usually obtain substances before with? drawal becomes that far advanced. These symptoms of opioid withdrawal must cause clinically significant distress or impairment in social, occupational, or other important ar? eas of functioning (Criterion C). The symptoms must not be attributable to another med? ical condition and are not better explained by another mental disorder (Criterion D). Meeting diagnostic criteria for opioid withdrawal alone is not sufficient for a diagnosis of opioid use disorder, but concurrent symptoms of craving and drug-seeking behavior are suggestive of comorbid opioid use disorder. The speed and severity of withdrawal associated with opioids depend on the half-life of the opioid used. Most individuals who are physiologically dependent on short-acting drugs such as heroin begin to have withdrawal symptoms within 6-12 hours after the last dose. Acute withdrawal symptoms for a short-acting opioid such as heroin usually peak within 1-3 days and gradually subside over a period of 5-7 days. Associated Features Supporting Diagnosis Males with opioid withdrawal may experience piloerection, sweating, and spontaneous ejaculations while awake. Opioid withdrawal is distinct from opioid use disorder and does not necessarily occur in the presence of the drug-seeking behavior associated with opioid use disorder. Opioid withdrawal may occur in any individual after cessation of re? peated use of an opioid, whether in the setting of medical management of pain, during opioid agonist therapy for opioid use disorder, in the context of private recreational use, or following attempts to self-treat symptoms of mental disorders with opioids. Prevaience Among individuals from various clinical settings, opioid withdrawal occurred in 60% of individuals who had used heroin at least once in the prior 12 months. Deveiopment and Course Opioid withdrawal is typical in the course of an opioid use disorder. It can be part of an es? calating pattern in which an opioid is used to reduce withdrawal symptoms, in turn lead? ing to more withdrawal at a later time. For persons with an established opioid use disorder, withdrawal and attempts to relieve withdrawal are typical. However, opioid with? drawal is also accompanied by rhinorrhea, lacrimation, and pupillary dilation, which are not seen in sedative-type withdrawal. Dilated pupils are also seen in hallucinogen intoxication and stimulant intoxication. However, other signs or symptoms of opioid withdrawal, such as nausea, vomiting, diarrhea, abdominal cramps, rhinorrhea, and lacrimation, are not present. Other Opioid-Induced Disorders the following opioid-induced disorders are described in other chapters of the manual with disorders with which they share phenomenology (see the substance/medication-induced mental disorders in these chapters): opioid-induced depressive disorder ("Depressive Dis? orders"); opioid-induced anxiety disorder ("Anxiety Disorders"); opioid-induced sleep disorder ("Sleep-Wake Disorders"); and opioid-induced sexual dysfunction ("Sexual Dys? functions"). For opioid intoxication delirium and opioid withdrawal delirium, see the crite? ria and discussion of delirium in the chapter "Neurocognitive Disorders. Sedative-, Hypnotic-, or Anxiolytic-Related Disorders Sedative, Hypnotic, or Anxiolytic Use Disorder Sedative, Hypnotic, or Anxiolytic Intoxication Sedative, Hypnotic, or Anxiolytic Withdrawal Other Sedative?, Hypnotic-, or Anxiolytic-Induced Disorders Unspecified Sedative-, Hypnotic-, or Anxiolytic-Related Disorder Sedative, Hypnotic, or Anxiolytic Use Disorder Diagnostic Criteria A. A problematic pattern of sedative, hypnotic, or anxiolytic use leading to clinically signif? icant impairment or distress, as manifested by at least two of the following, occurring within a 12-month period: 1. Sedatives, hypnotics, or anxiolytics are often taken in larger amounts or over a lon? ger period than was intended. There is a persistent desire or unsuccessful efforts to cut down or control sedative, hypnotic, or anxiolytic use. A great deal of time is spent in activities necessary to obtain the sedative, hypnotic, or anxiolytic; use the sedative, hypnotic, or anxiolytic; or recover from its effects. Recurrent sedative, hypnotic, or anxiolytic use resulting in a failure to fulfill major role obligations at work, school, or home. Continued sedative, hypnotic, or anxiolytic use despite having persistent or re? current social or interpersonal problems caused or exacerbated by the effects of sedatives, hypnotics, or anxiolytics. Important social, occupational, or recreational activities are given up or reduced be? cause of sedative, hypnotic, or anxiolytic use. Recurrent sedative, hypnotic, or anxiolytic use in situations in which it is physically hazardous. Sedative, hypnotic, or anxiolytic use is continued despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by the sedative, hypnotic, or anxiolytic. A need for markedly increased amounts of the sedative, hypnotic, or anxiolytic to achieve intoxication or desired effect. A markedly diminished effect with continued use of the same amount of the sed? ative, hypnotic, or anxiolytic. Note: this criterion is not considered to be met for individuals taking sedatives, hypnotics, or anxiolytics under medical supervision. The characteristic withdrawal syndrome for sedatives, hypnotics, or anxiolytics (refer to Criteria A and B of the criteria set for sedative, hypnotic, or anxiolytic withdrawal, pp. Sedatives, hypnotics, or anxiolytics (or a closely related substance, such as al? cohol) are taken to relieve or avoid withdrawal symptoms. Specify if: In early remission: After full criteria for sedative, hypnotic, or anxiolytic use disorder were previously met, none of the criteria for sedative, hypnotic, or anxiolytic use disor? der have been met for at least 3 months but for less than 12 months (with the exception that Criterion A4, Craving, or a strong desire or urge to use the sedative, hypnotic, or anxiolytic,? may be met). In sustained remission: After full criteria for sedative, hypnotic, or anxiolytic use dis? order were previously met, none of the criteria for sedative, hypnotic, or anxiolytic use disorder have been met at any time during a period of 12 months or longer (with the exception that Criterion A4, Craving, or a strong desire or urge to use the sedative, hypnotic, or anxiolytic,?may be met). Specify if: In a controlled environment: this additional specifier is used if the individual is in an environment where access to sedatives, hypnotics, or anxiolytics is restricted. Instead the comorbid sedative, hyp? notic, or anxiolytic use disorder is indicated in the 4th character of the sedative-, hypnotic-, or anxiolytic-induced disorder (see the coding note for sedative, hypnotic, or anxiolytic in? toxication; sedative, hypnotic, or anxiolytic withdrawal; or specific sedative-, hypnotic-, or anxiolytic-induced mental disorder). For example, if there is comorbid sedative-, hypnotic-, or anxiolytic-induced depressive disorder and sedative, hypnotic, or anxiolytic use disor? der, only the sedative-, hypnotic-, or anxiolytic-induced depressive disorder code is given with the 4th character indicating whether the comorbid sedative, hypnotic, or anxiolytic use disorder is mild, moderate, or severe: F13. Diagnostic Features Sedative, hypnotic, or anxiolytic substances include benzodiazepines, benzodiazepine? like drugs. This class of substances includes all prescription sleeping medications and almost all prescription antianxiety medications. Like alcohol, these agents are brain depressants and can produce similar substance/ medication-induced and substance use disorders. Sedative, hypnotic, or anxiolytic sub? stances are available both by prescription and illegally. Some individuals who obtain these substances by prescription will develop a sedative, hypnotic, or anxiolytic use disorder, while others who misuse these substances or use them for intoxication will not develop a use disorder.

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