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Vol. 322 No. IK TKKATMKNT OK MAI.AOAPTATION TO NICII I* WOKK — O/.KISI.KR ET Al

during ihis limc aitil jul)j(tiiv*c Kuruninils «*f ulrriinJt »ihI moml cvr*y 20 mi notes. Tlicy wcrr (rtherireK frrr t«»do (Wir own wmt mihI wcrc givc.ii (luiiirr and a siwcŁ during riidi laS^lit shift. Im all Imk Itkii irials, lin* 5iilijccu (one io tłu* eon troi study :ohI nur iii llw ircalnicnl slwly) OmihhmiiI ilicir mols at limes of ilicir owii dm«rt-inj*. A icclmiciau monitorcrl ifw sut>jitls ilimuKlMmi cadi iiigln sliifl ui cnsiirc that tlicy rritiuincd awatr.

Al t er catli »«ij^l*« silili. llic mrn leli ilu: l:iLtrali«rv aml irawfcd Ihhiic. Tlicy «'cfc llms r.\|niMtl lomtuliNir earli OHimiiM; dur* iog linii trawi limc. I Im: m«*ii ni the in aniK iii suiitiri wcrr insinici* C<i In rcinain iii llic dark fmni 09:0(1 In 17:00 Ihmiis each day, in l»citronm.\ in which liic Windows wcrc covcrcd with i»|M<jur materiał lo cxcludc sunlighl. Im coulrasi, (lic men in tliccoutrol simlics wcrc not schcdułcd co rcntaiii in llic dafk al any particular limc each day, alilioujli most diet nsc ilicir cxistiiig wimlnw sh.uics of curtaiiis whiic liicy slcpt, at limes of ilicir own clioosiug. No other restric-Itons wcrc pl.iCcd on ll»c actmitics of llic subjcets in cillięr group during their “nouwork" hours. Ali wcrc prov»dcd witli a brcakfasl and a lunch lo uke łiomc and cal at will.

Asscssmonl of Endogenous Circadian Phasc

Previous ancmpts to cvaluatc the calcnt of circadian adaptaiion to night worlt havc bccn complicatcd by llic masking ćfTccls of aciiwiiy on ihc physiologic variabłes monitored. In this study, ihc constant-roulinc mcihod was uscd io rcvcal ihc endogenous cornpo-ncni of the body-tcmpcrature rhyihm, an established marker of the endogenous circadian paccmakcr.^,,'^M During the constant-roulinc procedurę, we delermined ihc endogenous circadian phasc (il»c par-ticular point at which a regularly recurring eveni oecurs in an in-trinsic oscillaiory proecss) ai which llic nadir of ihc daily body-tcmpcrature cyc lc oocurred. Our mcihod invo!vcd an extcnsion and rcfincmenl of a tcchniquc first proposcd by Mills et a!.,*⁴ according to which the subjcct* arc siudicil under oonstant environmental and bchaviorat conditions in order lo climinatc (or distributc across ihc circadian cydc) the physiologic responses evokcd by cnvirontncnial or bchayioral stimuli, such as sleeping, eating, changing posturę, and changing light lcvcU. During all ihe coastant-routinc studia, the men wcrc rcstrictcd lo absolutc, semireeumbent bedrest in a room with oonsUni indoor lighting (approximatcly ISO lux) and rcquircd to rcmain awakc. Wakefulness was moniiored by a rc-scarch t ech nicią n and v>crificd by coniinuous polysomnographic rc-cording.*⁰ During the oonstant routine, ihe men*s daily nutritional and electrolyte nccds wcrc met by identical hourly snacks, witlfN. approximately 150 mmol of sodium and approaimaiclyJOO mmoly' of potassium cvcnly disiributcd ovcr the 24-hour period. Th ccilo*--' ric rcquircmcnu for wcight maintcnancc wcrc calculatcd wiih usc of the Wilmore nomogram⁵ⁱ to determinc «hc basal metabolit ratę; they wcrc then adjusted upward by a 10 pcrcent aaivity factor. Since ihc constant-roulinc procedurę rcquircd that the subjcets losc al least one night of slccp, ii was carried out concurrcntly with the first and sixth night shift*. Each cousfam routine was begun just after the subjcct awakened on the day of the shift, and ii cominued for as long as was ncccssary (at least 21 hours) to determinc accu-rately the endogenous circadian temperaturę nadir. Im iwo subjects (one in ihe control study and one in the treatment study), an addi-tional 24 hours was required lor this dcicrminatioM during the finał constani routine.

Physiologic and Behavioral Measures

Throughout each constam routine, tliecore body temperaturę of the subjcct was rccorded ai one-minutc intcrvals from a disposablc thermistor (Yellow Spring? Insiruincnt Company, Yclłow Spring*. Ohio) inserted 10 Cin into tlie rccium. In addilion, blond samplcs wcrc collectcd in syringes and transferred to ltC|>arin-coaicd tuiies evcry 15 to 25 mimitcs on a randomized samptiug schcdnle from an iudwclling intravcn<Mis caiłictcc with sidc ImHcs (Descrei Medieał, Samly, Utah) (hal was placcd in a for ca rm vcin^w; ihe sani pirs wcrc chilloei iniKicdiaiely and cciUrifugcd within iwo hours, aml the pląs* ma was frozen at — 20°C. 'l lic plastna cnriisol conccinraiimis wcrc measiirctl within livc miMilhs of satnplc colIcctitMi hy an ^l' ^,ł*coalrtl lulic radioiniiiiuiHMSsay proecilurc (l)iagimstic Products, (x»s An

geles) in llic (awc l-aUtraliu-y of Itrighain aml \ViMiicn‘» I loN|iital (ioiftal Cl u lica I Rcseardi (eiitrr (intraassay eorflicicm of vari-ati<Mi )= |0|, 0.2 jtrreeni at a incan «!’ .VI niemi |>cr liter aml .t.fl Iktccmi at a niraii nf 4iH unml |K:r liier; inlcnissay cocllicicnt uf cariafMin |n = I5<1|, 13.2 per ceni at a ntran ol’ 4 7 nmol |»cr liier and 7.3 |M:rccnt at a mon «if Vtt imml jk*r liter). The minary volmne was Micasuretl at tlirec-liour »nlcrvals.

SulijmiyralcriiKsl was a.<M*s%*’d lince limes |*cr Ihmit i«iih nsc of a lincar. l•l>nnnnlcri^., l(KI-mm hi|Milar dsuat-aiiahigne scalę.^ Coj*-niiivc iłcrfmniaitcc was mcasnreil iHmrły hy a test involwing e-dcul.i-limi tliat incliMlnJ 125 nnnlnmly generalni pairs «»f |w«/Hligil nmn-Itcrs.¹'' ‘Hic men wcrc givcn fmir minutę* io sum as many pairs as (Kissihlc, and ilicir icsts wcrc senred accoriling tu ihc number uf ealculations Cnmpktcd in tlić limc allowcd.

Ex po surę to Brighl Light

The subjcets parlicipating in tlić treatment siudics wcrc scated at a desk and exposcd lo hright ligtu (7000 lo 12,000 lux) from one of Iwo sourccs: eiilicr a wall-mountcd bank of 80 2.4-m (8-fl), 90-wail “ion-gard" K9CTHI2 Viialitc wide-speetrum fluorcsccnt lamps (Duro-test, Nonh Bergen, N.J.), separated from the subjcct by floor-io-ceiling panels madę of iwo sheets of elear glass 3il75 mm thick, separated by a layer of polyvinylbulyl pląs lic (taminated safciy glass);ora ponable bank of 16 1.2-m (4-ft) '‘cool-wliitc" 40-wati lainjn (Norih American Pliitips Lighting, Bloomficld, N.J.), separated from the subjcct by a wirt-mesh icrecn.- Each subjeeKs daily caposure to ultraviolct light during the trials was well within Ihc guidclincs for safeiy of such cxposurc established by the American Confcrcnce of Covernmcn«l Industrial Hygienists and the U.S. Army and recommended by the National Insiitutc for Oceupa-tional Safciy and HeaUh.^,,’^w The men participating in ihc last four bright-light trials wore elear, uhraviolet-exduding polycarbonatc Ultra-Spcc 2000 safety glasscs with 4C coating (Uvex Winter Opti-cal, Smith field, R_i.) throughout the exposurc to bright light. Ulu-minancc was mcasured at fitre-minuie inicrvals with rcscarch photometers (International Light, Newburyport, Mass.), each cquippod with a detecior with a photopic spectra! bias and a cosinc angular r es po nsc; the deteetors were placcd at the subjcets* forc-heads and dirccted ioward the linę of gaże. Fiftccn minutes of transitional illumination peeceded and followcd each exposurc to bright light.

Statistical Analysis

The endogenous circadian phasc was asscssed by non lincar least-squarcs analysis to fit a iwo-harmonie regression model to the data on corc body temperaturę oollccted during che constam routines.*⁰ Temperaturę data gatłicrcd during the first fivc hours of the eon-sunt routine, whai the thcrmoregulatory system was not yet in a sicady State, were czdudcd from the analysis. The endogenous circadian temperaturę nadir was dchncd as the avcragc of-the ftttcd minimums from the singlc-harmonic and composilę wave forms of the model and was uscd as a refercncc marker Tor the phasc of ihe endogenous circadian temperaturę cyclc. In the two siudics in which the finał constani routine was cx(cndcd an additional 24 hours, the temperaturę data uscd in the analyses were those from llic sccond half of llic cousiant routine, sińce the estimates of phasc derived from the first and sccond half of the temperaturę data during sitnilariy estendcd constani routines wcrc tiighly corre-latcd (1'earson’s correlation cocfficicm = 0.908; l*<0.001) (unpub-lishcd data).

Kaired comparisrms betwcen the ialues obtaiucd for llic phasc and amplitudę of endogenous circadian temperaturę initially (dur-iug the first night sliifl) and at the cud of the study (during thr sixtli night shift) wcrc maile fur IkiiIi the cnutrol and the trcatinciit stud-irs l»y tlić paircrl Slntlcnl l-lcst ((Mrametric analysis)/¹ with om-firinaiinn of significant rcsults hy the Wilemmi signed-rank trsl (mm|Ktrauictric analysis). Onujwrisons liclwccn the Contrnl aml treatment siudics willi rcsjico tn the inilial rmlogcimus cirotlian phasc, llic finał endogenous circadian phasc. lh< shift in phasc lic-iwccn the first aml sistli niglils, the calues for alertness and per-fnrnianec ohtaincd during ihrsc niglils. aml the ainplilude of rari-