Larynx Preservation in Pyriform Sinus Cancer: Preliminary Results of a European Organization for Research and Treatment of Cancer Phase III Trial

Size: px
Start display at page:

Download "Larynx Preservation in Pyriform Sinus Cancer: Preliminary Results of a European Organization for Research and Treatment of Cancer Phase III Trial"

Transcription

1 Larynx Preservaton n Pyrform Snus Cancer: Prelmnary Results of a European Organzaton for Research and Treatment of Cancer Phase Tral JeanLous Lefebvre, Domnque Chevaler, Bernard Lubonsk, Anne Krkpatrck, Laurence Collette, Tarek Sahmoud* For the EORTC Head and Neck Cancer Cooperatve Group Background: As a general rule, surgery whenever possble, followed by rradaton s consdered to be the standard treatment for cancer of the hypopharynx, thus sacrfcng natural speech. n most patents, surgery ncludes removal of the larynx. Purpose: A prospectve, randomzed phase study was conducted by the European Organzaton for Research and Treatment of Cancer (EORTC) startng n 99 to compare a larynxpreservng treatment (nducton chemotherapy plus defntve, radaton therapy n patents who showed a complete response or surgery n those who dd not respond) wth conventonal treatment (total laryngectomy wth partal pharyngectomy, radcal neck dssecton, and postoperatve rradaton) n prevously untreated and operable patents wth hstologcally proven squamous cell carcnomas of the pyrform snus or aryepglottc fold, but free of other cancers. Methods: Patents were randomly assgned to one of two treatment arms: ) mmedate surgery wth postoperatve radotherapy (7 Gy) or ) nducton chemotherapy (csplatn [ mg/m ] gven as a bolus ntravenous njecton on day, followed by nfuson of fluorouracl [ mg/m per day] on days ). An endoscopc evaluaton was performed after each cycle of chemotherapy. After two cycles, only partal and complete responders receved a thrd cycle. Patents wth a complete response after two or three cycles of chemotherapy were treated thereafter by rradaton (7 Gy); nonrespondng patents underwent conventonal surgery wth postoperatve radaton (7 Gy). Salvage surgery was also performed when patents relapsed after chemotherapy and rradaton. The tral was desgned to test the equvalence of the two treatment arms;.e., the nducton chemotherapy treatment would be judged equvalent to mmedate surgery f the relatve rsk of death for nducton chemotherapy compared wth mmedate surgery was sgnfcantly less than.4 usng a onesded hypothess test at the. level of sgnfcance. Results: Two hundred two patents entered the tral and were randomly assgned; only 94 were elgble for treatment (94 n the mmedatesurgery arm and n the nductonchemotherapy arm). n the nductonchemotherapy arm, complete response was seen n (4%) of 97 patents wth local dsease (prmary tumor) and n (%) of patents wth regonal dsease (nvolvement of the neck). Treatment falures at local, regonal, and second prmary stes occurred at approxmately the same frequences n the mmedatesurgery arm (%, 9%, and %, respectvely) and n the nductonchemotherapy arm (7%, %, and %, respectvely). n contrast, there were fewer falures at dstant stes n the nductonchemotherapy arm than n the mmedatesurgery arm (% versus %, respectvely; P =.4). The medan duraton of survval was months n the mmedatesurgery arm and 44 months n the nductonchemotherapy arm and, snce the observed hazard rato was.8 (logrank test, P.), whch was sgnfcantly less than.4, the two treatments were judged to be equvalent. The and year estmates of retanng a functonal larynx n patents treated n the nductonchemotherapy arm were 4% (9% confdence nterval = %%) and % (9% confdence nterval = %48%), respectvely. Conclusons and mplcatons: Larynx preservaton wthout jeopardzng survval appears feasble n patents wth cancer of the hypopharynx. On the bass of these observatons, the EORTC has now accepted the use of nducton chemotherapy followed by radaton as the new standard treatment n ts future phase larynx preservaton trals. [J Natl Cancer nst 99;88:899] Squamous cell carcnoma of the hypopharynx s dagnosed n most patents at an advanced stage that requres combned therapes. For a long tme, surgery followed by postoperatve rradaton has been the most common treatment, because salvage surgery followng rradaton falure n patents wth hypopharynx cancer was known to produce hgher morbdty than n "Afflatons of authors. J.L. Lefebvre, Centre Oscar Lambret, Llle, France; D. Chevaler, Hoptal Claude Hurez, Llle; B. Lubonsk, nsttut GustaveRoussy, Vllejuf, France; A. Krkpatrck, L. Collette, T. Sahmoud. EORTC Data Centre, Brussels, Belgum. Correspondence to: JeanLous Lefebvre, M.D., Centre Oscar LambretBP 7, 9 Llle (Cedex), France. See "Notes" secton followng "References." 89 ARTCLES Journal of the Natonal Cancer nsttute, Vol. 88, No., July, 99 Downloaded from on 8 January 8

2 patents wth other head and neck cancer. The avalablty of actve chemotherapy regmens has opened a new area of research n head and neck cancer, n partcular wth the goal of organ preservaton. At present, there s enough evdence to support the vew that larynx preservaton s feasble (7). However, larynxconservng approaches have been assessed manly n patents wth larynx cancer. Because of the generally poor overall condton of patents wth hypopharynx cancer and the rsks nvolved n salvage surgery, head and neck specalsts have been, n most nstances, qute reluctant to explore such approaches n patents wth hypopharyngeal cancer. n the early 98s n the Unted States, the Department of Veterans Affars Laryngeal Cancer Study Group ntated a randomzed tral (/) for patents wth larynx cancer to determne whether nducton chemotherapy followed by defntve radaton n responders, wth surgery n reserve for salvage, could be a better approach than the standard treatment consstng of surgery and postoperatve radaton. A smlar trend exsted at the same tme n Europe; n partcular, a comparable randomzed tral nvolvng patents wth hypopharynx cancer (EORTC 489) was extensvely dscussed wthn the European Organzaton for Research and Treatment of Cancer Head and Neck Cancer Cooperatve Group (EORTCHNCCG). Because of some reluctance, n 98 t was decded to start ths tral n only two nsttutons workng together (the Northern France Comprehensve Cancer Center and Unversty Hosptal). n 99, after checkng the feasblty of ths approach n the frst patents, the tral was opened to other nsttutons wthn the EORTCHNCCG. Materals and Methods Patent Elgblty The followng crtera had to be satsfed for the patents to be consdered elgble for entrance n the study: hstologcally proven squamous cell carcnoma of the pyrform snus or of the hypopharyngeal aspect of the aryepglottc fold (whch are hardly dstngushable from true pyrform snus tumors when they are advanced) classfed [Amercan Jont Commttee on Cancer/nternatonal Unon Aganst Cancer jont classfcaton, 987 (9,)] as T (excludng exophytc T lesons of the membranous porton of the pyrform snus or of the aryepglottc fold), T, or T4 wth NO, Nl, Na, or Nb stages of neck nvolvement. At the begnnng of the tral, patents wth Nc dsease were accepted for entry; however, n 99, n the second phase of the tral, we decded that these patents were nelgble, and therefore they were excluded. Because these patents wth blateral node nvolvement had a partcularly poor prognoss, we consdered t to be unethcal to propose to them radcal treatment to retan the functonal larynx. (The treatment of these patents was left to the dscreton of nvestgators at each nsttuton.) The three patents who entered the tral before ths protocol modfcaton have snce been consdered nelgble. Patents wth stage N (operable lymph nodes slghtly exceedng cm n dameter that were rcsectable wthout any need of carotd or skn resecton) were also accepted n the tral for random assgnment. Hypopharynx tumors had to be operable at the frst attempt of treatment and only elgble for a classc total laryngectomy wth partal pharyngectomy. Patents wth a possblty of ether surgery for preservng functonal larynx or extended surgery requrng a plastc procedure for pharyngeal closure were not elgble for the tral to avod jeopardzng ther chances to be properly operated on n case of progresson durng chemotherapy. t was requred that patents had not receved any prevous treatment and were free of other cancers (except n stu carcnoma of the cervx and adequately treated basal or squamous cell carcnoma of the skn) as well as of dstant metastases. Patents had to be between 8 and 7 years of age and had to have had a medcal condton that could be treated wth surgery under general anesthesa or wth chemotherapy (.e., a World Health Organzaton performance status of, a good nutrtonal status or poor nutrtonal status that could be restored to far wthn weeks, a serum creatnne level < umol/l [. mg/dl] and/or a creatnne clearance level > ml/mnute. a whte blood cell count >4 x lo'/l. and a platelet count > x v /L). The dsease had to be measurable or evaluable and had to be documented as precsely as possble before treatment by endoscopy and, f possble, by computed tomography (CT) scan. nformed consent had to be obtaned before enterng the study. Elgble patents were randomly assgned to receve one of two treatment arms and were stratfed accordng to the followng: nsttuton, T classfcaton (T versus TT4), N classfcaton (NN versus NN), and ste (pyrform snus versus aryepglottc fold). A random assgnment of patents n dfferent arms was carred out centrally at the EORTC Data Center usng the mnmzaton technque (//) (.e., tendng to balance the margnal dstrbuton of each prognostc factor n the dfferent treatment arms). Chemotherapy nducton chemotherapy conssted of csplatn ( mg/m ) gven ntravenously as a sngle njecton after an ntravenous bolus of. g of manntol and followed by a 4hour nfuson of g of manntol n L of % dextrose n.4% NaCl wth meq of KQ. The fluorouracl nfuson was then started wth mg/m per day n L of % dextrose n.4% NaCl nfuson over days. Response to chemotherapy was clncally evaluated by endoscopy performed before each cycle and weeks after the prevous cycle (a CT scan was recommended but was not mandatory). After the frst cycle, patents wth progressve dsease were surgcally treated whle the other patents receved a second cycle of chemotherapy. After the second cycle, patents wth ether progressve dsease or no change were surgcally treated, whle patents wth a partal response (PR) receved a thrd cycle of chemotherapy. Patents wth a complete response (CR) were treated wth rradaton (7 Gy). After the thrd cycle, patents wth CR were treated wth rradaton (7 Gy), and the other patents were treated wth surgery. n the case of a CR at the prmary ste of the tumor wthout a CR n the palpable lymph nodes n the neck, the decson as to whether to perform a neck dssecton pror to radaton therapy was left to the dscreton of the respectve nsttuton's protocols. A CR at the prmary ste was defned as the complete dsappearance of all macroscopc dsease wth, mandatorly, a complete recovery of larynx moblty, and a PR was defned as a decrease n the pnmary tumor area (product of the largest dameter by ts perpendcular dameter) that was greater than or equaj to % of the ntal area. Progressve dsease was defned as an ncrease of greater than or equal to % of the ntal area of the pnmary tumor. Patents who dd not meet the crtera for CR, PR, or progressve dsease were consdered to have no change. The regresson volume of palpable lymph node(s) was assessed separately by clncal examnaton and palpaton. Radaton Therapy All patents were ntended to receve external radotherapy ether postoperatvely or mmedately after chemotherapy n the case of CR. n both cases, the rradated volumes ncluded the prmary ste and both sdes of the neck. Patents were rradated n a supne poston wth megavoltage radaton usng a conventonal fractonaton ( fracton of Gy per day, days per week). n the case of defntve rradaton after chemotherapy, a dose of Gy was gven, followed by a booster dose of Gy on the tumor ste and on palpable lymph node(s), f present. When delvered postoperatvely, a dose of Gy was ntended to be gven to the entre remanng pharynx, both sdes of the neck, and the tracheostomy; n addton, a booster dose of 4 Gy was gven to stes of postve margns and/or of extracapsular spread and/or of three or more postve lymph nodes, f any. n all nstances, the spnal cord had to be shelded at 4 Gy, and electrons were used to complete the rradaton of the posteror part of the neck. The nterval between surgery and the last cycle of chemotherapy had to be at least weeks. Patents randomly allocated to receve mmedate surgery and patents who dd not respond to chemotherapy had to undergo a total laryngectomy wth partal pharyngectomy allowng a prmary closure wthout any knd of flap. The hyod bone and the strap muscles, whenever nvolved, were also surgcally removed. A thyrod lobectomy was consdered f thyrod nvolvement was suspected. The margns of excson were determned by the extent of the tumor before chemotherapy as documented at the ntal examnaton conducted under general anesthesa; the margns as altered by response to chemotherapy Journal of the Natonal Cancer nsttute, Vol. 88, No., July, 99 ARTCLES 89 Downloaded from on 8 January 8

3 were not consdered. The type of neck dssecton was determned by the clncal nodal status: for patents wth stage NO, a modfed neck dssecton sparng the stemocledomastod muscle, the nternal jugular ven, and the accessory nerve was proposed; for patents wth stage Nl or N, only the nerve removal was optonal: and for patents wth stage N. a classc radcal neck dssecton was mandatory. Qualty Control Data receved from the nvestgators were keypunched twce to mnmze typng errors. The data manager checked for any dscrepances n the patent's dala prevously entered n tre database before acceptng the new data. Computer programs for crosscheckng were run afterwards, and any suspcous or mssng data were handled by further contacts wth the nvestgator. The study coordnator checked the fles every months, on average, for further evaluaton. Statstcs Assumng a 47% (99fc confdence nterval = 44%l%) survval rate at years n the mmedatesurgery arm (correspondng to the data of the study coordnator's experence and consdered to be classc data n France for hypopharynx cancer treated by total laryngectomy wth partal pharyngectomy wth radcal neck dssecton and postoperatve rradaton), we consdered that a decrease n survval of more than % below the lower lmt of the confdence nterval would be unacceptable no matter what the percentage of patents wth preserved larynges was. The tral was desgned to test the equvalence of the two treatment arms, where the nductonchemotherapy treatment would be judged essentally equvalent to the mmedatesurgery arm f the relatve rsk of death n the chemotherapy arm compared wth the surgery arm was sgnfcantly less than 4 usng a onesded hypothess test at the. level of sgnfcance. t was estmated that 7 patents who were followed untl death would be enough to test the equvalence of the two treatment regmens wth a power of 9% (). Survval curves were estmated usng the KaplanMeer technque (). Dfferences n duraton of survval were compared usng a onesded logrank test for equvalence (.4). When other comparsons were made, both the 9% confdence ntervals and the corrected 9% confdence nterval (9% corrected confdence nterval: based on an O'BrenFlemng procedure wth an alphaspendng functon, whch corresponds to the 99.% confdence nterval) were presented (). Results Patent Populaton As of December 99, patents were enrolled n ths study (99 n the surgery arm and n the chemotherapy arm). Because of the dffcultes of gettng the patents' acceptance to enter the surgery arm, there was an mpressve decrease n the rate of accrual. Despte not havng reached the expected number of patents, t was decded to carry out an nterm analyss to assess whether the tral could be closed to patent entry. The nterm analyss was revewed by a Data Montorng Commttee that ncluded an ndependent nternatonal expert. The Data Montorng Commttee concluded, after ths nterm analyss, that the tral could be closed to patent entry. Among the patents enrolled, sx were found to be nelgble (one had dstant metastases, one had a tumor of the anteror eplarynx, one had had a prevous cancer, and three had Nc stage of nodal nvolvement n the neck). For two more patents, no nformaton had been receved after randomzaton; therefore, 94 patents were ncluded n the analyss (94 n the surgery arm and n the chemotherapy arm). The medan followup was months (range, months), whch s a suffcent duraton of tme for the evaluaton of outcome n patents wth cancer of the hypopharynx. There was no sgnfcant dfference between the dstrbuton of patents n the two arms wth respect to sex, age, World Health Organzaton performance status, presence of assocated dseases, prmary ste and hstology, T classfcaton, N classfcaton, or stage groupng (Tables and ). Ths was a classc populaton of patents wth hypopharynx cancer: 8 (9%) men and eght women, wth a medan age of years (range, 7 years). The fact that (7%) patents had stage dsease and 7 (7%) had stage V dsease was consstent wth the ndcaton of a total laryngectomy wth partal pharyngectomy. Protocol Complance Among the 94 elgble patents n the surgery arm (Fg. ), two dd not undergo the planned surgery. (One had a severe lung nfecton the day before surgery and was no longer operable, and one was found to be noperable n the neck durng the surgcal procedure, whch as a result, was stopped.) Nnetytwo patents had surgery. Three patents who had had surgery receved no postoperatve radotherapy. (One had local complcatons, one had persstent dsease wth local complcaton, both cases contrandcatng rradaton, and one refused.) n other words, 89 (9%) patents had the planned treatment. All of the 94 elgble patents were nevertheless ncluded n ths analyss. Among the elgble patents n the chemotherapy arm (Fg. ), three dd not start the chemotherapy. One patent refused chemotherapy, and one was not gven chemotherapy because of an unstable angor pectors after treatment randomzaton. Both patents were treated wth rradaton alone, and one presented wth dyspnea. To avod a tracheotomy that could have had a deleterous effect on local tumor control, we mmedately Table. Characterstcs of patents wth cancer of (he hypopharynx at the tme of random assgnment to treatment groups Chemotherapy Total Characterstc No. of patents (n = 94) % No. of patents (n= ) No. of patents (n= 94) % Ste Pyrform snus Aryepglottc fold Stage V ARTCLES Journal of the Natonal Cancer nsttute. Vol. 88. No.. July, 99 Downloaded from on 8 January 8

4 Table. Clncal stagng of the patenls wth cancer of the hypopharynx at the tme of random assgnment remanng patents had the planned three cycles. Doselmtng toxc effects were cardovascular n sx patents, renal n three, hematologc n three, and mparment of general condton n one. n all patents except three, the toxc effects were reversble. n addton, one patent had cardovascular falure wthn week after the thrd cycle. T classfcaton T N classfcaton T T4 4 8 mmedatesurgery arm NO Nl Na Nb N 4 Response to Chemotherapy Q nductonchemotherapy arm NO 7 N Na S Nb N * treated the latter patent wth surgery and postoperatve radaton therapy. Nnetyseven patents had chemotherapy as planned. Three of these 97 patents had no subsequent treatment (two refused and one ded of toxc effects of chemotherapy). Sxty of these patents were rradated (four after a neck dssecton wthout surgcal removal of the prmary tumor), and 4 had surgery that was followed by rradaton n (the 4th patent ded after surgery). n ths arm, 9 (9%) patents underwent the planned treatment. Nevertheless, all of the elgble patents were ncluded n the analyss accordng to the ntenttotreat polcy. Among the 97 patents who started the chemotherapy, eght had only one cycle (seven stopped because of toxc effects, and one stopped because of dsease progresson), had two cycles (sx stopped because of toxc effects of chemotherapy, one refused further treatment, and had no change), and the 7 Among the 97 patents who started ther treatment, (4%) had a clncal CR of the prmary tumor after the last completed cycle, (%) had a PR, (%) had no change, and one (%) had progressve dsease (treated by total laryngectomy wth partal pharyngectomy). CRs were more frequently observed (P =.) among patents wth stage T dsease (8 of patents, 8%) than among patents wth T dsease (4 of 7, 48%) and T4 dsease (none of four). n contrast, there was no dfference n the CR rates wth respect to prmary ste (P =.7): 44 (8%) of 7 patents for pyrform snus and eght (8%) of patents for aryepglottc fold. Only patents were assessable for response n the neck, snce the remanng patents had no palpable lymph nodes. n the assessable patents, (%) had a CR, 9 (48%) had a PR or no change, and one had progressve dsease. Fnally, one patent wth a PR had developed dstant metastases durng chemotherapy and was treated wth rradaton to the prmary tumor alone. After completon of chemotherapy, 4 patents (4% of the 97 patents who receved chemotherapy) had no evdence of any dsease above the clavcles. n contrast, patents had a CR at the prmary ste wthout a CR for the nodes n the neck. Four patents underwent a radcal neck dssecton before rradaton; none of these patents had a relapse n the neck. Sx patents had rradaton wthout neck dssecton; two had a relapse n the Randomzed, no data XRT 89 mmedate 99 Chemotherapy M Elgble nelgble nelgble 4 no data Elgble 9 no no Chemo XRT Chemo 97 XRT (nd. 4 RNO) 4 no XRT XRT! no XRT Salvage surgery 8 no no XRT _L no Salvage surgery Fg.. Actual number of patents and ther treatments. XRT = radaton therapy, Chemo = chemotherapy, RND = radcal neck dssecton. Journal of the Natonal Cancer nsttute, Vol. 88, No., July, 99 Downloaded from on 8 January 8 ARTCLES 89

5 neck that occurred smultaneously wth the appearance of dstant metastases, and these two patents ded. Radotherapy n the chemotherapy arm, patents receved rradaton mmedately after chemotherapy: accordng to the protocol and despte no CR (three patents had toxcty that contrandcated surgery, sx patents refused the proposed surgery, and one patent developed dstant metastases durng chemotherapy). These patents receved a medan dose of 7 Gy (range, 4 7 Gy) to the prmary tumor and of Gy (range, 47 Gy) to the neck area. The rradaton was temporarly nterrupted for two patents (one because of mucosts and one because of lung nfecton), whle for the thrd patent the rradaton was defntvely stopped because of patent refusal after recevng 4 Gy. n the same treatment arm, patents receved rradaton postoperatvely. The medan dose was Gy (range, 8 Gy) delvered to the pharynx and Gy (range, 447 Gy) delvered to the neck. None of these patents had ther treatment nterrupted. n the surgery arm, 89 patents had postoperatve rradaton. The same dose was delvered to both the pharynx and the neck, wth a medan dose of Gy (range, 47 Gy). n ths arm, there was one temporary nterrupton (because of wound dehscence or wound breakdown), and three patents stopped prematurely (one because of progresson n the neck, one because of vascular dsease, and one because of a depressve llness). Whatever the therapeutc sequence, radaton therapy was equally well tolerated. n the surgery arm, 9 patents had surgery, wth a medan tme to wound healng of days (range, 98 days), but two patents never healed. Surgcal margns were postve n fve (%) patents. Seventeen (8%) patents were free of nodal nvolvement, 8 (%) had nodal nvolvement wthout capsular rupture, and 47 (%) had nodal nvolvement wth capsular rupture. n the chemotherapy arm, 4 patents had surgery after chemotherapy, wth a medan tme to wound healng of days (range, 89 days), but one patent ded postoperatvely. Surgcal margns were postve n one patent. Sx (8%) patents were free of postve lymph nodes, (%) had postve node(s) wthout capsular rupture, and (47%) had postve node(s) wth capsular rupture. n addton, n ths arm, eght patents had salvage surgery after radotherapy, wth no postoperatve death. The surgery data dd not dffer markedly accordng to the therapeutc sequence. Survval At the tme of analyss, patents had ded, 7 (%) of 94 n the surgery arm and 9 (9%) of n the chemotherapy arm. Causes of death were as follows: hypopharynx cancer n 4 patents n the surgery arm and n n the chemotherapy arm, second prmary cancers n eght patents n the surgery arm and n seven patents n the chemotherapy arm, treatmentrelated causes n two patents n the chemotherapy arm, noncancerrelated causes n sx patents n the surgery arm and n eght patents n the chemotherapy arm, and unknown causes n three Survval, * " 9 " N O 7 9 mmedate surgery nducton chemotherapy 7 " " " 4 " " " u. _ LLL. RR = 8 (9% CC:..48) "u L,_ L _. j Fg.. Survval by treatment arm. arm: medan survval = months. year survval = 4%. nductonchemotherapy arm: medan survval = 44 months, year survval = 7%. N = number of patents. O = observed number of events, RR = relatve rsk, and CC = corrected confdence nterval. 4 Years 7 8 t 9 Number of patents at rsk : mmedate surgery nducton chemotherapy 894 ARTCLES Journal of the Natonal Cancer nsttute, Vol. 88, No., July, 99 Downloaded from on 8 January 8

6 patents n the surgery arm and n seven patents n the chemotherapy arm. At years, the survval rate (Fg. ) seemed superor for the chemotherapyarm patents (7%, 9% corrected confdence nterval = 4%7%) than for patents entered n the surgery arm (4%, 9% corrected confdence nterval = 7%9%). n contrast, at years there was no dfference between the two treatment arms. The year estmate was, however, based on a small number of patents at rsk (% n the chemotherapy arm, patents at rsk versus % n the surgery arm, patents at rsk). The medan duraton of survval was months n the mmedatesurgery arm and 44 months n the nductonchemotherapy arm, wth an observed death hazard rato of.8. Because the upper lmt of the 99.% confdence nterval (9% corrected confdence nterval) of the death hazard rato was barely touchng.4 (logrank test, P =.), the two treatments were judged to be equvalent. n other words, the drecton of the dfference was opposte to what was antcpated n 98, when the tral was ntated. The trend for dseasefree survval (Fg. ) was smlar to that for overall survval: the and year dseasefree survval rates were 4% (9% corrected confdence nterval = 8%8%) and % ( patents at rsk) for the chemotherapy arm versus % (9% corrected confdence nterval = 7%47%) and 7% (eght patents at rsk) for the surgery arm, respectvely. Further detals are provded n Table. Pattern of Relapse As of December 994, there were no notable dfferences between the two arms wth respect to local or locoregonal falures nor wth respect to occurrence of second prmares. n contrast, % n the surgery arm developed dstant metastases compared wth % n the chemotherapy arm, wth borderlne statstcal sgnfcance (P =.4; Fg. 4). Table provdes further detals. Larynx Preservaton n the surgery arm, all patents except two had radcal surgery: one patent had radaton therapy for a deteroraton of hs general condton and ded months later wth tracheotomy. The other patent had radaton therapy because of unresectablty of nodes and ded year later of nodal evoluton assocated wth dstant metastases and second prmary cancers but wthout tracheotomy or feedng tube. Ths was the only patent wth a functonal larynx n place at the last evaluaton of the patents who had entered the surgery arm. n the chemotherapy arm, one patent had surgery because of dyspnea, 4 had not acheved a CR, and eght requred salvage surgery, for a total of 4 radcal surgery procedures. n addton, among the other patents, seven had a tracheotomy durng the followup perod that was assocated n fve patents wth a feedng tube or a gastrostomy. Wth ths strategy of nducton chemotherapy for larynx preservaton, t was antcpated at the start that n the chemotherapy arm about % of the patents would not acheve a CR. n other words, only half of the patents could theoretcally beneft from a conservatve approach. Ths makes the evaluaton of larynx preservaton somewhat confusng. The strctest way would be to assess the survval wth a functonal larynx (.e., wthout local dsease, tracheotomy, feedng tube, or gastros Dseasefree survval, % 9 ~ 8 " N 94 mmedate surgery 9 nducton chemotherapy 7 " " " 4 " " " " \ \ RR =.87 (9% CC:..4) Fg.. Dseasefree survval by treatment arm. arm: medan = months, year estmates = %. nductonchemotherapy arm: medan survval = months, year estmates = 4%. N = number of patents, O = observed number of events, RR = relatve rsk, and CC = corrected confdence ntervaj. 4 Years Number of patents t rsk : mmedate surgery nducton chemotherapy Journal of the Natonal Cancer nsttute, Vol. 88, No., July, 99 ARTCLES 89 Downloaded from on 8 January 8

7 Table. Patterns of falure among patents wth cancer of the hypopharynx accordng to treatment groups End pont O/N* % Medan duraton, mo Relatve rsk estmate 9% Ct 9% cat Duraton of survval mmedate surgery nducton chemotherapy Tme to local progresson mmedate surgery nducton chemotherapy Tme to nodal progresson mmedate surgery nducton chemotherapy 7/94 9/ /94 7/ 8/94 / JO Tme to locoregonal progresson mmedate surgery nducton chemotherapy /94 9/ Tme to dstant metastases mmedate surgery nducton chemotherapy Dseasefree survval mmedate surgery nducton chemotherapy Tme to second prmary tumor mmedate surgery nducton chemotherapy 4/94 / /94 9/ /94 / *O/N = observed number of events/number of patents. tc = confdence nterval. $CC = corrected confdence nterval (correspondng to the 99.% confdence nterval). Reference category. Metattasefree, % \ \ \ N 94 4 mmedate Sugey nducton Chemotherapy 4 L_ L RR = 9 (9* CC:.7.7) Fg. 4. Tme to dstant metastases by treatment arm. year metastassfree estmates: surgery arm = %; nductonchemotherapy arm = 7%. N = number of patents, O = observed number of events. RR = relatve rsk, and CC = corrected confdence nterval. 4 Years Number of patents at rsk : mmedate nducton Chemotherapy 89 ARTCLES Journal of the Natonal Cancer nsttute, Vol. 88. No., July. 99 Downloaded from on 8 January 8

8 tomy) n place for the entre group of patents. n ths arm. the and year estmates were: 8% (9% confdence nterval = 7%7%) and 7% (9% confdence nterval = 8%%), respectvely (Fg. ). However, t s necessary to take nto account that larynx preservaton was acheved n patents who ded of causes other than local dsease progresson and wth a functonal larynx n place. Thus, only deaths from local dsease progresson are consdered (n addton to any local dsease, tracheotomy, feedng tube, or gastrostomy); the and year estmates are 4% (9% confdence nterval =!%%) and % (9% confdence nterval = %48%), respectvely (Fg. ). n fact, n the chemotherapy arm, there are three dfferent groups of patents who rase specfc and dfferent questons. The frst group s those who acheved a CR and, at least n the frst nstance, could avod radcal surgery. For them, the queston s the duraton of the larynx functon preservaton. The second group s those who dd not acheve such a CR and who subsequently had surgery. One must ask two questons of ths group: ) Do these patents really have a poor prognoss, and were they dentfed as such because of chemotherapy? ) Has an nducton chemotherapy jeopardzed ther chances for survval? The thrd group s those who dd not acheve a CR but, nevertheless, were treated by rradaton because of patent refusal or toxc effects of chemotherapy. For these patents, there was a real concern about ther outcome. An attempt to answer these dfferent questons follows. For the patents wth a CR n the frst group, the and year estmates of havng a functonal larynx, as defned above (death was consdered as a falure of the strategy only f due to falure of the local dsease), were 4% (9% confdence nterval = 48%8%) and 8% (9% confdence nterval = 4O%7%), respectvely. For the 4 patents n the second group who dd not show a CR. survval estmates at and years were 9% (9% confdence nterval = %8%) and 8% (9% confdence nterval = 8%8%). respectvely. Despte the relatvely small number of patents, these survval rates are exceptonally good and cannot be consdered to be less than what was acheved n the surgcal arm, although a formal statstcal comparson was not justfed n ths case. For the patents n the last group who dd not show a CR and refused surgery, three were alve wth a functonal larynx n place when last assessed: after years and months (no evdence of dsease [NED]), years (wth dstant metastases), and years and months (NED). The seven other patents ded at 7 months (pulmonary nfecton, NED), months (cerebrovascular accdent, NED), 4 months (dstant metastases), months (nodal progresson after local recurrence treated by total laryngectomy months after randomzaton), months (unknown cause, NED), 8 months (severe hyponatrema, NED but wth postradaton edema of the larynx), and months (dstant metastases). Fve of these seven patents had retaned a functonal larynx untl death. Because of the very small number of patents, t s dffcult to reach a clear concluson, but globally, the outcome dd not seem partcularly poor. Thus, the answer to the man queston of the tral "s larynx preservaton wth nducton chemotherapy safe n hypopharynx cancer?" s "yes," snce nether the entre group nor the dfferent subgroups have been penalzed by ths approach. Survval wth functonal ; rynx, % 9 " 8 " N O 77 (A) (B) 7 " " " 4 " " " _, ^ J L_ J Fg.. Survval wth functonal larynx n the nductonchemotherapy arm. A = death from any cause s consdered as falure; B = only death from local dsease s consdered as falure: N = number of patents; O = observed number of events. " Yean 4 7 Number of patenu at rsk : (A) Journal of the Natonal Cancer nsttute, Vol. 88, No., July, 99 ARTCLES 897 Downloaded from on 8 January 8

9 Dscusson Snce the end of the 97s, numerous studes have been publshed on nducton chemotherapy n patents wth head and neck cancer. Most nvestgators have concluded that nducton chemotherapy was qute dsappontng, snce no mprovement n survval or n dsease control had been demonstrated; however, some studes reported control of dstant dsease. Nevertheless, the use of nducton chemotherapy has shown that larynx preservaton s feasble. The largest studes [n partcular the randomzed study of the Veterans Group (/)] have provded convergng and convncng conclusons. n general, the overall survval s not mpared by the nductonchemotherapy strategy, and year dseasefree survval wth a functonal larynx s observed n about one thrd of the cases. n general, two thrds of those who were stll alve at years had retaned functonal larynges, and there was an advantage wth respect to dstant falures. Classc crtcsms of ths approach have been made. nducton chemotherapy has been used manly as a prognostc test (.e., chemosenstvty s supposed to antcpate radosenstvty) and has been gven at suboptmal dosages that could not have had a durable effect on control of dstant dsease. Although n responders, the actve treatment has begun on the frst day, t could be hypotheszed that t could have been delayed n nonresponders untl the end of chemotherapy, when only the standard treatment could begn (.e., months later, assumng that patents receved three cycles of nducton chemotherapy). Nonmutlatng approaches have been proposed only for patents wth CR n most studes; fnally, after nducton chemotherapy, some patents could refuse to follow the physcan's advce. Our study s consstent wth what has been reported n the lterature. The survval n the chemotherapy arm has not been jeopardzed, and about half the patents who were stll alve at years had retaned functonal larynges. There were fewer dstant metastases but, consderng the duraton of tme requred to progress to dstant metastases (Fg. 4), t seemed that these falures had been delayed rather than avoded. n addton, ths study provdes an overall evaluaton of the larynxconservng approach, and even wth a close descrpton of the dfferent subgroups of patents n the chemotherapy arm, none of these subgroups has been penalzed. Ths leads one to consder that the upfront surgery s no longer the standard treatment. Ths study was closed to entry before reachng ts complete accrual because of the decrease n ts accrual rate and because of smlar survval rates at the nterm analyss (). n ths way, another tral could be set up wth the goal of mprovng control of local dsease (and, subsequently, of larynx preservaton) and/or preventng falures from dstant dsease. One can antcpate that delverng more than three cycles of nducton chemotherapy could have a more mportant and durable mpact on dstant metastases, but t would delay for a longer perod of tme the standard treatment n nonresponders. t could be proposed to avod surgery not only n the case of CR but also n the case of PR, but the evaluaton of a PR s more debatable than that of a CR and could lead to an heterogenety of outcomes n a multcenter study. Adjuvant chemotherapy could be added after treatment of local dsease to prevent falures n treatng dstant dsease. However, there are no convncng data supportng ths hypothess. n addton, ths type of patent could hardly undergo any addtonal therapy after havng already receved ntense treatment. t would be logcal to assess the value of bfractonated or accelerated rradaton after nducton chemotherapy, but t could only have an mpact on control of local dsease and not on dstant metastases. Fnally, there s no comparson wth defntve radaton therapy, but t s qute dffcult to neglect the effect on dstant metastases that can be attrbuted only to nducton chemotherapy, even f ths effect s not durable. Wth ths n mnd, there s now a consensus wthn the EORTCHNCCG to consder the chemotherapy arm as the reference arm and to begn, jontly wth the EORTC Radotherapy Group, a randomzed study comparng ths approach wth a combned chemoradotherapy arm n larynx and hypopharynx squamous cell carcnoma (EORTC 494) parallel to another randomzed tral comparng defntve rradaton wth combned chemoradotherapy (EORTC 94). References (/) nducton chemotherapy plus radaton compared wth surgery plus radaton n patents wth advanced laryngeal cancer. The Department of Veterans Affars LaryngeaJ Cancer Study Group [see comment ctaton n Medlne]. N Engl J Med 99:4:89. () Pfster DG, Strong EW, Harrson L, Hanes E, Pfster DA, Sessons R, et al. Larynx preservaton wth combned chemotherapy and radaton therapy n advanced but resectable head and neck cancer. J Cln Oncol 99;9:8 9. (J) Karp DD, Vaughan CW, Carter R, Wllett B, Heeren T, Calarese P, et al. Larynx preservaton usng nducton chemotherapy plus radaton therapy as an alternatve to laryngectomy n advanced head and neck cancer. A longterm followup report. Am J Cln Oncol 99; 4:79. (4) Depondt J, Gehanno P, Martn M, Lelevre G, Guerrer B, Peytral C, et al. Neoadjuvant chemotherapy wth carboplatn/fluorouracl n head and neck cancer. Oncology 99: Suppl :7. () Fu KK. ntegraton of chemotherapy and radotherapy for organ preservaton n head and neck cancer. n: Johnson JT, Ddolkar MS, edtors. Head and neck cancer. Vol.. Amsterdam: Excerpta Medca, 99:7. () Demard F, Chauvel P, Schneder M, Dassonvlle O, Ramaol A. nducton chemotherapy for larynx preservaton n laryngeal and hypopharyngeal cancers. n: Johnson JT, Ddolkar MS, edtors. Head and neck cancer. Vol.. Amsterdam: Excerpta Medca, 99:. (7) Urba SG, Forastere AA, Wolf GT, Esclamado RM, McLaughln PW, Thornton AF. ntensve nducton chemotherapy and radaton for organ preservaton n patents wth advanced resectable head and neck carcnoma. J Cln Oncol 994::94. (8) Shrnan MH, Weber RS. Lppman SM. Dmery W. Earley CL, Garden AS, et al. Laryngeal preservaton by nducton chemotherapy plus radotherapy n locally advanced head and neck cancer: the M. D. Anderson Cancer Center experence. Head Neck 994; :944. (9) nternatonal Unon Aganst Cancer. TNM, classfcaton of malgnant tumors. New York: SprngerVerlag, 987. (7) Amercan Jont Commttee on Cancer. TNM, manual for stagng of cancer. Phladelpha: Lppncott, 988. (//) Pocock SJ, Smon R. Sequental treatment assgnment wth balancng for prognostc factors n the controlled clncal tral. Bometrcs 97;:. () ComNougue C, Rodary C, Pane C. How to establsh equvalence when data are censored: a randomzed tral of treatments for B non Hodgkn lymphoma. Stat Med 99::4. () Kaplan EL, Meer P. Nonparametrc estmaton from ncomplete observatons. J Am Stat Assoc 98;:478. (4) Mantel N. Evaluaton of survval data and two new rank order statstcs arsng n ts consderaton. Cancer Chemother Rep 9::7. () O'Bren PC, Flemng TR. A multple testng procedure for clncal trals. Bometrcs 979::49. () Lefebvre JL, Sahmoud T for the EORTC Head and Neck Cancer Cooperatve Group. Larynx preservaton n hypopharynx squamous cell carcnoma: prelmnary results of a randomzed study (EORTC 489). Proc ASCO 994:: ARTCLES Journal of the Natonal Cancer nsttute, Vol. 88, No.. July, 99 Downloaded from on 8 January 8

10 Notes The followng prncpal nvestgators and nsttutons, lsted accordng to accrual of patents, partcpated n ths EORTC Head and Neck Cancer Cooperatve Group study: J.L. Lefebvre (Centre Oscar Lambret, Llle, France): D. Chevaler (Hdptal Claude Hurez. Llle); B. Lubonsk (nsttut GustaveRoussy, Vllejuf, France): L. Trassac (Hptal Pellegrn, Bordeaux, France): G. Andry (nsttut Jules Bordet, Brussels, Belgum); J.P. Rame (Centre Francos Baclesse. Caen. France): S. Crspno (Ospedale San Gerardo. Monza. taly); C. Chament (Ospedale Verona, taly): J. M. H. van den Beek (Unversty Hosptal, Maastrcht, The Netherlands); J.M. Davd (Centre Claudus Regaud, Toulouse. France): and J. Bemer (Ospedale San Govann. Bellnzona, Swtzerland). Medcal supervsor for the study: D. Lacombe (Brussels): scentfc coordnator: R. Sylvester (Brussels): and scentfc expert for the nterm analyss (December 99): M. K. B. Parmar (statstcan, Medcal Research Councl Cancer Tral Offce, Cambrdge, U. K.). Supported by Publc Health Servce grants CA488 through CA488 from the Natonal Cancer nsttute. Natonal nsttutes of Health, Department of Health and Human Servces. Manuscrpt receved September, 99: revsed February 9, 99; accepted Aprl. 99. Wheat Bran and Psylum Dets: Effects on AfMethylntrosoureanduced Mammary Tumorgeness n F44 Rats Leonard A. Cohen, Zhongln Zhao, Edth A. Zang, Tn T. Wynn, Barbara Sm, Abraham Rvenson* Background: Expermental and epdemologc evdence suggests that ncreased detary fber s assocated wth decreased breast cancer rsk. Lttle s known about the role played by dfferent types of Tber and, partcularly, mxtures of soluble and nsoluble fbers smlar to those consumed by human populatons n reducng breast cancer rsk. Hgh ntake of fber may suppress bacteral hydrolyss of blary estrogen conjugates to free (absorbable) estrogens n the colon and thus may decrease the avalablty of crculatng estrogens necessary for the development and growth of breast cancers. Purpose: The purpose of ths study was to evaluate the effect of wheat bran (an nsoluble fber) and psyllum (a soluble fber) alone and n combnaton on overall estrogen status, on fecal bacteral fjdglucurondase (a key detresponsve estrogendeconjugatng enzyme) actvty, and on the nducton of mammary tumors n rats treated wth yvmethylntrosourea (MNU). Methods: One hundred ffty vrgn female F44 rats were fed the NH7 det from 8 days of age untl days of age; they were then gven a sngle dose (4 mg/kg of body weght) of MNU by tal ven njecton. Three days later, they were randomly assgned to one of fve expermental detary groups ( anmals per group). Soft, whte wheat bran (4% detary fber content) and psyllum (8% detary fber content) were added to a modfed (hghfat) Amercan nsttute of Nutrton (AN) 7A det at the followng percents, respectvely: % + % (group ), 8% + % (group ), % + % (group ), 4% + 4% (group 4), and % + % (group ). Blood, urne, and feces were collected and analyzed by radommunoassay technques for estrogens. Cecal contents were analyzed for bacteral [Dglucurondase actvty. After 9 weeks on the expermental dets, the rats were klled, and mammary tumors were counted and classfed by hstologc type. Cumulatve tumor ncdence was evaluated by the Kaplan Meer lfetable method and the logrank test. Tumor number was evaluated by the chsquared test of assocaton, and tumor multplcty was evaluated by the MantelHaenszel chsquared test. All statstcal tests were twotaled. Results: As the level of psyllum relatve to that of wheat bran ncreased, the total tumor number and multplcty of mammary adenocarcnomas n rats decreased as a statstcally sgnfcant lnear trend across groups (f <.O). Compared wth the group gven wheat bran alone, the group gven the : (wheat bran:psyllum) combnaton had maxmum protecton aganst mammary tumorgeness, whle the groups gven the 4: or : (wheat bran:psyllum) combnaton or psyllum alone had ntermedate protecton. No statstcally sgnfcant dfferences n crculatng estrogens or urnary estrogen excreton patterns were observed among the fve expermental groups. Fecal estrogen excreton, however, decreased wth ncreasng levels of psyllum (P<.), and cecal fdglucurondase actvty exhbted a decreasng trend wth respect to the ncreasng psyllum content of the det across groups (P<.l). Conclusons: The addton of a 4%:4% mxture of an nsoluble (wheat bran) fber and a soluble (psyllum) fber to a hghfat det provded the maxmum tumornhbtng effects n ths mammary tumor model. Although ncreasng levels of detary psyllum were assocated wth decreased cecal bacteral pdglucurondase actvty, these changes were not reflected n decreased crculatng levels of tumorpromotng estrogens. Therefore, the mechansm(s) by whch mxtures of soluble and nsoluble detary fbers protect aganst mammary tumorgeness remans to be clarfed. [J Natl Cancer nst 99;88:89997] *Afflatons of authors: L. A. Cohen, Z. Zhao, T. T. Wynn, B. Sm (Dvson of Nutrton and Endocrnology), E. A. Zang (Dvson of Epdemology), A. Rvenson (Research Anmal Faclty), Amercan Health Foundaton, Valhalla, NY. Correspondence to: Leonard A. Cohen, Ph.D., Dvson of Nutrton and Endocrnology, Amercan Health Foundaton, Dana Rd., Valhalla, NY 9. See "Notes" secton followng "'References." Journal of the Natonal Cancer nsttute, Vol. 88, No., July, 99 ARTCLES 899 Downloaded from on 8 January 8

THE NATURAL HISTORY AND THE EFFECT OF PIVMECILLINAM IN LOWER URINARY TRACT INFECTION.

THE NATURAL HISTORY AND THE EFFECT OF PIVMECILLINAM IN LOWER URINARY TRACT INFECTION. MET9401 SE 10May 2000 Page 13 of 154 2 SYNOPSS MET9401 SE THE NATURAL HSTORY AND THE EFFECT OF PVMECLLNAM N LOWER URNARY TRACT NFECTON. L A study of the natural hstory and the treatment effect wth pvmecllnam

More information

National Polyp Study data: evidence for regression of adenomas

National Polyp Study data: evidence for regression of adenomas 5 Natonal Polyp Study data: evdence for regresson of adenomas 78 Chapter 5 Abstract Objectves The data of the Natonal Polyp Study, a large longtudnal study on survellance of adenoma patents, s used for

More information

Parameter Estimates of a Random Regression Test Day Model for First Three Lactation Somatic Cell Scores

Parameter Estimates of a Random Regression Test Day Model for First Three Lactation Somatic Cell Scores Parameter Estmates of a Random Regresson Test Day Model for Frst Three actaton Somatc Cell Scores Z. u, F. Renhardt and R. Reents Unted Datasystems for Anmal Producton (VIT), Hedeweg 1, D-27280 Verden,

More information

RENAL FUNCTION AND ACE INHIBITORS IN RENAL ARTERY STENOSISA/adbon et al. 651

RENAL FUNCTION AND ACE INHIBITORS IN RENAL ARTERY STENOSISA/adbon et al. 651 Downloaded from http://ahajournals.org by on January, 209 RENAL FUNCTION AND INHIBITORS IN RENAL ARTERY STENOSISA/adbon et al. 65 Downloaded from http://ahajournals.org by on January, 209 Patents and Methods

More information

Concentration of teicoplanin in the serum of adults with end stage chronic renal failure undergoing treatment for infection

Concentration of teicoplanin in the serum of adults with end stage chronic renal failure undergoing treatment for infection Journal of Antmcrobal Chemotherapy (1996) 37, 117-121 Concentraton of tecoplann n the serum of adults wth end stage chronc renal falure undergong treatment for nfecton A. MercateUo'*, K. Jaber*, D. Hfflare-Buys*,

More information

ARTICLES. Patients and Methods

ARTICLES. Patients and Methods ARTICLES Radotherapy Alone Versus Combned Chemotherapy and Radotherapy n Nonresectable Non-Small-Cell Lung Cancer: Frst Analyss of a Randomzed Tral n Patents Therry Le Chevaler* Rodrgo Arragada, Elzabeth

More information

Recent Trends in U.S. Breast Cancer Incidence, Survival, and Mortality Rates

Recent Trends in U.S. Breast Cancer Incidence, Survival, and Mortality Rates Recent Trends n U.S. Breast Cancer Incdence, Survval, and Mortalty Rates Kenneth C. Chu, Robert E. Tarone, Larry G. Kessler, Lynn A. G. Res, Benjamn F. Hankey, Banj A. Mller, Brenda K. Edwards* Background:

More information

Giuseppe Cartel, Francesco Cartel, Aldo Cantone, Domenico Causarano, Giuseppe Genco, Arnaldo Tobaldin, Gaetano Interlandi, Tullio Giraldi*

Giuseppe Cartel, Francesco Cartel, Aldo Cantone, Domenico Causarano, Giuseppe Genco, Arnaldo Tobaldin, Gaetano Interlandi, Tullio Giraldi* CsplatnCyclophosphamdeMtomycn Combnaton Chemotherapy Wth Supportve Care Versus Supportve Care Alone for Treatment of Metastatc NonSmallCell Lung Cancer Guseppe Cartel, Francesco Cartel, Aldo Cantone, Domenco

More information

310 Int'l Conf. Par. and Dist. Proc. Tech. and Appl. PDPTA'16

310 Int'l Conf. Par. and Dist. Proc. Tech. and Appl. PDPTA'16 310 Int'l Conf. Par. and Dst. Proc. Tech. and Appl. PDPTA'16 Akra Sasatan and Hrosh Ish Graduate School of Informaton and Telecommuncaton Engneerng, Toka Unversty, Mnato, Tokyo, Japan Abstract The end-to-end

More information

Cancer morbidity in ulcerative colitis

Cancer morbidity in ulcerative colitis Gut, 982, 2, 49-497 Cancer morbdty n ulceratve colts P PRIOR, S N GYDE, J C ACARNEY, H HOPSON, J A H WAERHOUSE, and R N ALLAN rom the Gastroenterology Unt, General Hosptal, Brmngham, and Cancer Epdemology

More information

Alma Mater Studiorum Università di Bologna DOTTORATO DI RICERCA IN METODOLOGIA STATISTICA PER LA RICERCA SCIENTIFICA

Alma Mater Studiorum Università di Bologna DOTTORATO DI RICERCA IN METODOLOGIA STATISTICA PER LA RICERCA SCIENTIFICA Alma Mater Studorum Unverstà d Bologna DOTTORATO DI RICERCA IN METODOLOGIA STATISTICA PER LA RICERCA SCIENTIFICA Cclo XXVII Settore Concorsuale d afferenza: 13/D1 Settore Scentfco dscplnare: SECS-S/02

More information

Economic crisis and follow-up of the conditions that define metabolic syndrome in a cohort of Catalonia,

Economic crisis and follow-up of the conditions that define metabolic syndrome in a cohort of Catalonia, Economc crss and follow-up of the condtons that defne metabolc syndrome n a cohort of Catalona, 2005-2012 Laa Maynou 1,2,3, Joan Gl 4, Gabrel Coll-de-Tuero 5,2, Ton Mora 6, Carme Saurna 1,2, Anton Scras

More information

THIS IS AN OFFICIAL NH DHHS HEALTH ALERT

THIS IS AN OFFICIAL NH DHHS HEALTH ALERT THIS IS AN OFFICIAL NH DHHS HEALTH ALERT Dstrbuted by the NH Health Alert Network Health.Alert@dhhs.nh.gov August 26, 2016 1430 EDT (2:30 PM EDT) NH-HAN 20160826 Recommendatons for Accurate Dagnoss of

More information

International Journal of Emerging Technologies in Computational and Applied Sciences (IJETCAS)

International Journal of Emerging Technologies in Computational and Applied Sciences (IJETCAS) Internatonal Assocaton of Scentfc Innovaton and Research (IASIR (An Assocaton Unfyng the Scences, Engneerng, and Appled Research Internatonal Journal of Emergng Technologes n Computatonal and Appled Scences

More information

Joint Modelling Approaches in diabetes research. Francisco Gude Clinical Epidemiology Unit, Hospital Clínico Universitario de Santiago

Joint Modelling Approaches in diabetes research. Francisco Gude Clinical Epidemiology Unit, Hospital Clínico Universitario de Santiago Jont Modellng Approaches n dabetes research Clncal Epdemology Unt, Hosptal Clínco Unverstaro de Santago Outlne 1 Dabetes 2 Our research 3 Some applcatons Dabetes melltus Is a serous lfe-long health condton

More information

Using the Perpendicular Distance to the Nearest Fracture as a Proxy for Conventional Fracture Spacing Measures

Using the Perpendicular Distance to the Nearest Fracture as a Proxy for Conventional Fracture Spacing Measures Usng the Perpendcular Dstance to the Nearest Fracture as a Proxy for Conventonal Fracture Spacng Measures Erc B. Nven and Clayton V. Deutsch Dscrete fracture network smulaton ams to reproduce dstrbutons

More information

Appendix for. Institutions and Behavior: Experimental Evidence on the Effects of Democracy

Appendix for. Institutions and Behavior: Experimental Evidence on the Effects of Democracy Appendx for Insttutons and Behavor: Expermental Evdence on the Effects of Democrac 1. Instructons 1.1 Orgnal sessons Welcome You are about to partcpate n a stud on decson-makng, and ou wll be pad for our

More information

Leukemia in Polycythemia Vera. Relationship to Splenic Myeloid Metaplasia and Therapeutic Radiation Dose

Leukemia in Polycythemia Vera. Relationship to Splenic Myeloid Metaplasia and Therapeutic Radiation Dose Leukema n Polycythema Vera Relatonshp to Splenc Myelod Metaplasa and Therapeutc Radaton Dose JOHN H. LAWRENCE, M.D., D.SC, F.A.C.P., H. S. WINCHELL, M.D., PH.D., F.A.CP., and W. G. DONALD, M.D., F.A.C.P.

More information

Physical Model for the Evolution of the Genetic Code

Physical Model for the Evolution of the Genetic Code Physcal Model for the Evoluton of the Genetc Code Tatsuro Yamashta Osamu Narkyo Department of Physcs, Kyushu Unversty, Fukuoka 8-856, Japan Abstract We propose a physcal model to descrbe the mechansms

More information

PDF hosted at the Radboud Repository of the Radboud University Nijmegen

PDF hosted at the Radboud Repository of the Radboud University Nijmegen PDF hosted at the Radboud Repostory of the Radboud Unversty Njmegen The followng full text s a publsher's verson. For addtonal nformaton about ths publcaton clck ths lnk. http://hdl.handle.net/2066/23963

More information

NHS Outcomes Framework

NHS Outcomes Framework NHS Outcomes Framework Doman 1 Preventng people from dyng prematurely Indcator Specfcatons Verson: 1.21 Date: May 2018 Author: Clncal Indcators Team NHS Outcomes Framework: Doman 1 Preventng people from

More information

DECREASING SYMPTOMS IN INTERSTITIAL CYSTITIS PATIENTS: PENTOSAN POLYSULFATE VS. SACRAL NEUROMODULATION. A Research Project by. Katy D.

DECREASING SYMPTOMS IN INTERSTITIAL CYSTITIS PATIENTS: PENTOSAN POLYSULFATE VS. SACRAL NEUROMODULATION. A Research Project by. Katy D. DECREASING SYMPTOMS IN INTERSTITIAL CYSTITIS PATIENTS: PENTOSAN POLYSULFATE VS. SACRAL NEUROMODULATION. A Research Project by Katy D. Prce Bachelor of General Studes, Unversty of Kansas, 2005 Submtted

More information

The effect of salvage therapy on survival in a longitudinal study with treatment by indication

The effect of salvage therapy on survival in a longitudinal study with treatment by indication Research Artcle Receved 28 October 2009, Accepted 8 June 2010 Publshed onlne 30 August 2010 n Wley Onlne Lbrary (wleyonlnelbrary.com) DOI: 10.1002/sm.4017 The effect of salvage therapy on survval n a longtudnal

More information

Saeed Ghanbari, Seyyed Mohammad Taghi Ayatollahi*, Najaf Zare

Saeed Ghanbari, Seyyed Mohammad Taghi Ayatollahi*, Najaf Zare DOI:http://dx.do.org/10.7314/APJCP.2015.16.14.5655 and Anthracyclne- Breast Cancer Treatment and Survval n the Eastern Medterranean and Asa: a Meta-analyss RESEARCH ARTICLE Comparng Role of Two Chemotherapy

More information

(From the Gastroenterology Division, Cornell University Medical College, New York 10021)

(From the Gastroenterology Division, Cornell University Medical College, New York 10021) ROLE OF HEPATIC ANION-BINDING PROTEIN IN BROMSULPHTHALEIN CONJUGATION* BY N. KAPLOWITZ, I. W. PERC -ROBB,~ ANn N. B. JAVITT (From the Gastroenterology Dvson, Cornell Unversty Medcal College, New York 10021)

More information

PANCREATIC CANCER. - Exocrine: the production of enzymes that help digesting fats and proteins.

PANCREATIC CANCER. - Exocrine: the production of enzymes that help digesting fats and proteins. PANCREATIC CANCER 1. The pancreas It s a 15 cm gland located between the stomach and the spne, ntmately related to the vascular structures. It s dvded nto 3 parts: the wder end s called head, the mddle

More information

Sequential meta-analysis to determine whether or not to start another trial: the high frequency versus conventional mechanical ventilation example

Sequential meta-analysis to determine whether or not to start another trial: the high frequency versus conventional mechanical ventilation example . Sequental meta-analyss to determne whether or not to start another tral: the hgh frequency versus conventonal mechancal ventlaton example Sequental analyss shows value of new trals Casper W. Bollen,

More information

ALMALAUREA WORKING PAPERS no. 9

ALMALAUREA WORKING PAPERS no. 9 Snce 1994 Inter-Unversty Consortum Connectng Unverstes, the Labour Market and Professonals AlmaLaurea Workng Papers ISSN 2239-9453 ALMALAUREA WORKING PAPERS no. 9 September 211 Propensty Score Methods

More information

Lateral Transfer Data Report. Principal Investigator: Andrea Baptiste, MA, OT, CIE Co-Investigator: Kay Steadman, MA, OTR, CHSP. Executive Summary:

Lateral Transfer Data Report. Principal Investigator: Andrea Baptiste, MA, OT, CIE Co-Investigator: Kay Steadman, MA, OTR, CHSP. Executive Summary: Samar tmed c ali ndus t r esi nc 55Fl em ngdr ve, Un t#9 Cambr dge, ON. N1T2A9 T el. 18886582206 Ema l. nf o@s amar t r ol l boar d. c om www. s amar t r ol l boar d. c om Lateral Transfer Data Report

More information

DS May 31,2012 Commissioner, Development. Services Department SPA June 7,2012

DS May 31,2012 Commissioner, Development. Services Department SPA June 7,2012 . h,oshawa o Report To: From: Subject: Development Servces Commttee Item: Date of Report: DS-12-189 May 31,2012 Commssoner, Development Fle: Date of Meetng: Servces Department SPA-2010-09 June 7,2012 Applcaton

More information

Length of Hospital Stay After Acute Myocardial Infarction in the Myocardial Infarction Triage and Intervention (MITI) Project Registry

Length of Hospital Stay After Acute Myocardial Infarction in the Myocardial Infarction Triage and Intervention (MITI) Project Registry JACC Vol. 28, No. 2 287 CLINICAL STUDIES MYOCARDIAL INFARCTION Length of Hosptal Stay After Acute Myocardal Infarcton n the Myocardal Infarcton Trage and Interventon (MITI) Project Regstry NATHAN R. EVERY,

More information

The Influence of the Isomerization Reactions on the Soybean Oil Hydrogenation Process

The Influence of the Isomerization Reactions on the Soybean Oil Hydrogenation Process Unversty of Belgrade From the SelectedWorks of Zeljko D Cupc 2000 The Influence of the Isomerzaton Reactons on the Soybean Ol Hydrogenaton Process Zeljko D Cupc, Insttute of Chemstry, Technology and Metallurgy

More information

Survival Comparisons for Breast Conserving Surgery and Mastectomy Revisited: Community Experience and the Role of Radiation Therapy

Survival Comparisons for Breast Conserving Surgery and Mastectomy Revisited: Community Experience and the Role of Radiation Therapy Clncal Medcne & Research Volume 13, Number 2: 65-73 2015 Marshfeld Clnc Health System clnmedres.org Orgnal Research Survval Comparsons for Breast Conservng Surgery and Mastectomy Revsted: Communty Experence

More information

Studies In Blood Preservation

Studies In Blood Preservation Howard Unversty Dgtal Howard @ Howard Unversty Faculty Reprnts 12-1-1939 Studes In Blood Preservaton Charles R. Drew Follow ths and addtonal works at: http://dh.howard.edu/reprnts Part of the Medcne and

More information

What Determines Attitude Improvements? Does Religiosity Help?

What Determines Attitude Improvements? Does Religiosity Help? Internatonal Journal of Busness and Socal Scence Vol. 4 No. 9; August 2013 What Determnes Atttude Improvements? Does Relgosty Help? Madhu S. Mohanty Calforna State Unversty-Los Angeles Los Angeles, 5151

More information

Evaluation of the generalized gamma as a tool for treatment planning optimization

Evaluation of the generalized gamma as a tool for treatment planning optimization Internatonal Journal of Cancer Therapy and Oncology www.jcto.org Evaluaton of the generalzed gamma as a tool for treatment plannng optmzaton Emmanoul I Petrou 1,, Ganesh Narayanasamy 3, Eleftheros Lavdas

More information

Price linkages in value chains: methodology

Price linkages in value chains: methodology Prce lnkages n value chans: methodology Prof. Trond Bjorndal, CEMARE. Unversty of Portsmouth, UK. and Prof. José Fernández-Polanco Unversty of Cantabra, Span. FAO INFOSAMAK Tangers, Morocco 14 March 2012

More information

INITIAL ANALYSIS OF AWS-OBSERVED TEMPERATURE

INITIAL ANALYSIS OF AWS-OBSERVED TEMPERATURE INITIAL ANALYSIS OF AWS-OBSERVED TEMPERATURE Wang Yng, Lu Xaonng, Ren Zhhua, Natonal Meteorologcal Informaton Center, Bejng, Chna Tel.:+86 684755, E-mal:cdcsjk@cma.gov.cn Abstract From, n Chna meteorologcal

More information

Modeling the Survival of Retrospective Clinical Data from Prostate Cancer Patients in Komfo Anokye Teaching Hospital, Ghana

Modeling the Survival of Retrospective Clinical Data from Prostate Cancer Patients in Komfo Anokye Teaching Hospital, Ghana Internatonal Journal of Appled Scence and Technology Vol. 5, No. 6; December 2015 Modelng the Survval of Retrospectve Clncal Data from Prostate Cancer Patents n Komfo Anokye Teachng Hosptal, Ghana Asedu-Addo,

More information

Decreased Nailfold Capillary Density in Limited Scleroderma with Pulmonary Hypertension. and a longer disease duration. 3,4

Decreased Nailfold Capillary Density in Limited Scleroderma with Pulmonary Hypertension. and a longer disease duration. 3,4 j :1.1 4 1, t j f ASAN PACFC JOURNAL OF ALLERGY AND MMUNOLOGY (1998) 16: 81-86 Decreased Nalfold Capllary Densty n Lmted Scleroderma wth Pulmonary Hypertenson t r Yang Y. Ong, Tony Nkoloutsopoulos, Coln

More information

Copy Number Variation Methods and Data

Copy Number Variation Methods and Data Copy Number Varaton Methods and Data Copy number varaton (CNV) Reference Sequence ACCTGCAATGAT TAAGCCCGGG TTGCAACGTTAGGCA Populaton ACCTGCAATGAT TAAGCCCGGG TTGCAACGTTAGGCA ACCTGCAATGAT TTGCAACGTTAGGCA

More information

NUMERICAL COMPARISONS OF BIOASSAY METHODS IN ESTIMATING LC50 TIANHONG ZHOU

NUMERICAL COMPARISONS OF BIOASSAY METHODS IN ESTIMATING LC50 TIANHONG ZHOU NUMERICAL COMPARISONS OF BIOASSAY METHODS IN ESTIMATING LC50 by TIANHONG ZHOU B.S., Chna Agrcultural Unversty, 2003 M.S., Chna Agrcultural Unversty, 2006 A THESIS submtted n partal fulfllment of the requrements

More information

WHO S ASSESSMENT OF HEALTH CARE INDUSTRY PERFORMANCE: RATING THE RANKINGS

WHO S ASSESSMENT OF HEALTH CARE INDUSTRY PERFORMANCE: RATING THE RANKINGS WHO S ASSESSMENT OF HEALTH CARE INDUSTRY PERFORMANCE: RATING THE RANKINGS ELLIOTT PARKER and JEANNE WENDEL * Department of Economcs, Unversty of Nevada, Reno, NV, USA SUMMARY Ths paper examnes the econometrc

More information

Modeling Multi Layer Feed-forward Neural. Network Model on the Influence of Hypertension. and Diabetes Mellitus on Family History of

Modeling Multi Layer Feed-forward Neural. Network Model on the Influence of Hypertension. and Diabetes Mellitus on Family History of Appled Mathematcal Scences, Vol. 7, 2013, no. 41, 2047-2053 HIKARI Ltd, www.m-hkar.com Modelng Mult Layer Feed-forward Neural Network Model on the Influence of Hypertenson and Dabetes Melltus on Famly

More information

The impact of asthma self-management education programs on the health outcomes: A meta-analysis (systemic review) of randomized controlled trials

The impact of asthma self-management education programs on the health outcomes: A meta-analysis (systemic review) of randomized controlled trials Calforna State Unversty, San Bernardno CSUSB ScholarWorks Theses Dgtzaton Project John M. Pfau Lbrary 2003 The mpact of asthma self-management educaton programs on the health outcomes: A meta-analyss (systemc

More information

THE IMPACT OF IMPLANTABLE CARDIOVERTER- DEFIBRILLATORS ON MORTALITY AMONG PATIENTS ON THE WAITING LIST FOR HEART TRANSPLANTATION

THE IMPACT OF IMPLANTABLE CARDIOVERTER- DEFIBRILLATORS ON MORTALITY AMONG PATIENTS ON THE WAITING LIST FOR HEART TRANSPLANTATION THE IMPACT OF IMPLANTABLE CARDIOVERTER- DEFIBRILLATORS ON MORTALITY AMONG PATIENTS ON THE WAITING LIST FOR HEART TRANSPLANTATION Implantable cardoverter-defbrllators were nvestgated for ther mpact on mortalty

More information

Myocardial Mural Thickness During the Cardiac Cycle

Myocardial Mural Thickness During the Cardiac Cycle Myocardal Mural Thckness Durng the Cardac Cycle By Erc O. Fegl, M.D., and Donald L. Fry, M.D. An understandng of the relatonshp between forces and veloctes of contracton n muscle fbers to the pressures

More information

Journal of Engineering Science and Technology Review 11 (2) (2018) Research Article

Journal of Engineering Science and Technology Review 11 (2) (2018) Research Article Jestr Journal of Engneerng Scence and Technology Revew () (08) 5 - Research Artcle Prognoss Evaluaton of Ovaran Granulosa Cell Tumor Based on Co-forest ntellgence Model Xn Lao Xn Zheng Juan Zou Mn Feng

More information

Using Past Queries for Resource Selection in Distributed Information Retrieval

Using Past Queries for Resource Selection in Distributed Information Retrieval Purdue Unversty Purdue e-pubs Department of Computer Scence Techncal Reports Department of Computer Scence 2011 Usng Past Queres for Resource Selecton n Dstrbuted Informaton Retreval Sulleyman Cetntas

More information

A comparison of statistical methods in interrupted time series analysis to estimate an intervention effect

A comparison of statistical methods in interrupted time series analysis to estimate an intervention effect Peer revew stream A comparson of statstcal methods n nterrupted tme seres analyss to estmate an nterventon effect a,b, J.J.J., Walter c, S., Grzebeta a, R. & Olver b, J. a Transport and Road Safety, Unversty

More information

The Effect of Fish Farmers Association on Technical Efficiency: An Application of Propensity Score Matching Analysis

The Effect of Fish Farmers Association on Technical Efficiency: An Application of Propensity Score Matching Analysis The Effect of Fsh Farmers Assocaton on Techncal Effcency: An Applcaton of Propensty Score Matchng Analyss Onumah E. E, Esslfe F. L, and Asumng-Brempong, S 15 th July, 2016 Background and Motvaton Outlne

More information

Effect of Acute-Phase Retinopathy of Prematurity on Grating Acuity Development in the Very Low Birth Weight Infant

Effect of Acute-Phase Retinopathy of Prematurity on Grating Acuity Development in the Very Low Birth Weight Infant Effect of Acute-Phase Retnopathy of Prematurty on Gratng Acuty Development n the Very Low Brth Weght Infant Velma Dobson* Graham E. Qurng C. Gal Summers,X Rchard A. Saunders,\ Dale L. Phelps,\\ Betty Tung,^

More information

ARTICLE IN PRESS Neuropsychologia xxx (2010) xxx xxx

ARTICLE IN PRESS Neuropsychologia xxx (2010) xxx xxx Neuropsychologa xxx (200) xxx xxx Contents lsts avalable at ScenceDrect Neuropsychologa journal homepage: www.elsever.com/locate/neuropsychologa Storage and bndng of object features n vsual workng memory

More information

A MIXTURE OF EXPERTS FOR CATARACT DIAGNOSIS IN HOSPITAL SCREENING DATA

A MIXTURE OF EXPERTS FOR CATARACT DIAGNOSIS IN HOSPITAL SCREENING DATA Journal of Theoretcal and Appled Informaton Technology 2005 ongong JATIT & LLS ISSN: 1992-8645 www.jatt.org E-ISSN: 1817-3195 A MIXTURE OF EXPERTS FOR CATARACT DIAGNOSIS IN HOSPITAL SCREENING DATA 1 SUNGMIN

More information

Statistical models for predicting number of involved nodes in breast cancer patients

Statistical models for predicting number of involved nodes in breast cancer patients Vol.2, No.7, 641-651 (2010) do:10.4236/health.2010.27098 Health Statstcal models for predctng number of nvolved nodes n breast cancer patents Alok Kumar Dwved 1 *, Sada Nand Dwved 2, Suryanarayana Deo

More information

RECENT STUDIES in this department

RECENT STUDIES in this department Preventon of Coronary Atheroscleross by -Androgen Admnstraton n the Cholesterol-Fed Chck By JEREMAH STAMLER, M.D., RUTH PCK, M.D., AND LOUS X. KATZ, M.D. s are hghly effectve both prophylacteally and therapeutcally

More information

Disconnection of the Amygdala from Visual Association Cortex Impairs Visual Reward-Association Learning in Monkeys

Disconnection of the Amygdala from Visual Association Cortex Impairs Visual Reward-Association Learning in Monkeys The Journal of Neuroscence, September 1988, 8(9): 31443150 Dsconnecton of the Amygdala from Vsual Assocaton Cortex mpars Vsual Reward-Assocaton Learnng n Monkeys E. A. Gaffan, Davd Gaffan, and Susan Harrson

More information

Estimation of Relative Survival Based on Cancer Registry Data

Estimation of Relative Survival Based on Cancer Registry Data Revew of Bonformatcs and Bometrcs (RBB) Volume 2 Issue 4, December 203 www.sepub.org/rbb Estmaton of Relatve Based on Cancer Regstry Data Olaf Schoffer *, Ante Nedostate 2, Stefane J. Klug,2 Cancer Epdemology,

More information

Prediction of Total Pressure Drop in Stenotic Coronary Arteries with Their Geometric Parameters

Prediction of Total Pressure Drop in Stenotic Coronary Arteries with Their Geometric Parameters Tenth Internatonal Conference on Computatonal Flud Dynamcs (ICCFD10), Barcelona, Span, July 9-13, 2018 ICCFD10-227 Predcton of Total Pressure Drop n Stenotc Coronary Arteres wth Ther Geometrc Parameters

More information

Incorrect Beliefs. Overconfidence. Types of Overconfidence. Outline. Overprecision 4/22/2015. Econ 1820: Behavioral Economics Mark Dean Spring 2015

Incorrect Beliefs. Overconfidence. Types of Overconfidence. Outline. Overprecision 4/22/2015. Econ 1820: Behavioral Economics Mark Dean Spring 2015 Incorrect Belefs Overconfdence Econ 1820: Behavoral Economcs Mark Dean Sprng 2015 In objectve EU we assumed that everyone agreed on what the probabltes of dfferent events were In subjectve expected utlty

More information

HIV/AIDS-related Expectations and Risky Sexual Behavior in Malawi

HIV/AIDS-related Expectations and Risky Sexual Behavior in Malawi HIV/AIDS-related Expectatons and Rsky Sexual Behavor n Malaw Adelne Delavande Unversty of Essex and RAND Corporaton Hans-Peter Kohler Unversty of Pennsylvanna January 202 Abstract We use probablstc expectatons

More information

EXAMINATION OF THE DENSITY OF SEMEN AND ANALYSIS OF SPERM CELL MOVEMENT. 1. INTRODUCTION

EXAMINATION OF THE DENSITY OF SEMEN AND ANALYSIS OF SPERM CELL MOVEMENT. 1. INTRODUCTION JOURNAL OF MEDICAL INFORMATICS & TECHNOLOGIES Vol.3/00, ISSN 64-6037 Łukasz WITKOWSKI * mage enhancement, mage analyss, semen, sperm cell, cell moblty EXAMINATION OF THE DENSITY OF SEMEN AND ANALYSIS OF

More information

Journal of Economic Behavior & Organization

Journal of Economic Behavior & Organization Journal of Economc Behavor & Organzaton 133 (2017) 52 73 Contents lsts avalable at ScenceDrect Journal of Economc Behavor & Organzaton j ourna l ho me pa g e: www.elsever.com/locate/jebo Perceptons, ntentons,

More information

ARTICLES. Epidemiologic Evidence Showing That Human Papillomavirus Infection Causes Most Cervical Intraepithelial Neoplasia

ARTICLES. Epidemiologic Evidence Showing That Human Papillomavirus Infection Causes Most Cervical Intraepithelial Neoplasia ARTICLES Epdemologc Evdence Showng That Human Papllomavrus Infecton Causes Most Cervcal Intraepthelal Neoplasa Mark H. Schffman, Hed M. Bauer, Robert N. Hoover, Andrew G. Glass, Dane M. Cadell, Brenda

More information

Rainbow trout survival and capture probabilities in the upper Rangitikei River, New Zealand

Rainbow trout survival and capture probabilities in the upper Rangitikei River, New Zealand Ranbow trout survval and capture probabltes n the upper Rangtke Rver, New Zealand Rchard J Barker Department of Mathematcs and Statstcs Unversty of Otago P.O. Box 56 Dunedn, New Zealand Peter H Taylor

More information

Kim M Iburg Joshua A Salomon Ajay Tandon Christopher JL Murray. Global Programme on Evidence for Health Policy Discussion Paper No.

Kim M Iburg Joshua A Salomon Ajay Tandon Christopher JL Murray. Global Programme on Evidence for Health Policy Discussion Paper No. Cross-populaton comparablty of self-reported and physcan-assessed moblty levels: Evdence from the Thrd Natonal Health and Nutrton Examnaton Survey Km M Iburg Joshua A Salomon Ajay Tandon Chrstopher JL

More information

TIME RESPONSE OF JEJUNAL SUCRASE AND MALTASE ACTIVITY TO A HIGH SUCROSE DIET IN NORMAL MAN

TIME RESPONSE OF JEJUNAL SUCRASE AND MALTASE ACTIVITY TO A HIGH SUCROSE DIET IN NORMAL MAN GASTROEKTEROLOGY Copyrght 1969 by The Wllams & Wlkns Co. Vol. 56, No.3 Prnted n U.S.A. TIME RESPONSE OF JEJUNAL SUCRASE AND MALTASE ACTIVITY TO A HIGH SUCROSE DIET IN NORMAL MAN NORTON S. RoSENSWEIG, M.D.,

More information

Normal variation in the length of the luteal phase of the menstrual cycle: identification of the short luteal phase

Normal variation in the length of the luteal phase of the menstrual cycle: identification of the short luteal phase Brtsh Journal of Obstetrcs and Gvnaecologjl July 1984, Vol. 9 1, pp. 685-689 Normal varaton n the length of the luteal phase of the menstrual cycle: dentfcaton of the short luteal phase ELIZABETH A. LENTON,

More information

SMALL AREA CLUSTERING OF CASES OF PNEUMOCOCCAL BACTEREMIA.

SMALL AREA CLUSTERING OF CASES OF PNEUMOCOCCAL BACTEREMIA. SMALL AREA CLUSTERING OF CASES OF PNEUMOCOCCAL BACTEREMIA. JP Metlay, MD, PhD T Smth, PhD N Kozum, PhD C Branas, PhD E Lautenbach, MD NO Fshman, MD PH Edelsten, MD Center for Health Equty Research and

More information

Encoding processes, in memory scanning tasks

Encoding processes, in memory scanning tasks vlemory & Cognton 1976,4 (5), 501 506 Encodng processes, n memory scannng tasks JEFFREY O. MILLER and ROBERT G. PACHELLA Unversty of Mchgan, Ann Arbor, Mchgan 48101, Three experments are presented that

More information

Intergenerational Use of and Attitudes Toward Food Labels in Louisiana

Intergenerational Use of and Attitudes Toward Food Labels in Louisiana Intergeneratonal Use of and Atttudes Toward Food Labels n Lousana Patrca E. McLean-Meynsse and Jock J. Summers esults from a random sample of,300 households n Lousana suggest that senors are the most frequent

More information

Leberco*Celsis Testing

Leberco*Celsis Testing n km Leberco*Celss Testng 23 Hawthorne Street Roselle Park, NJ 724-26 98.245.933 / 8.523.LABS Fax 98.245.6253 Nov. 5, 996 SUBMTTED TO: ACTS Testng Labs Buffalo, NY Patty Dck ASSAY NUMBER: 96234 DATE RECEVED:

More information

Statistical Analysis on Infectious Diseases in Dubai, UAE

Statistical Analysis on Infectious Diseases in Dubai, UAE Internatonal Journal of Preventve Medcne Research Vol. 1, No. 4, 015, pp. 60-66 http://www.ascence.org/journal/jpmr Statstcal Analyss on Infectous Dseases 1995-013 n Duba, UAE Khams F. G. 1, Hussan H.

More information

Strategies for the Early Diagnosis of Acute Myocardial Infarction Using Biochemical Markers

Strategies for the Early Diagnosis of Acute Myocardial Infarction Using Biochemical Markers Clncal Chemstry / EARLY DIAGNOSIS OF ACUTE MYOCARDIAL INFARCTION USING IOCHEMICAL MARKERS Strateges for the Early Dagnoss of Acute Myocardal Infarcton Usng ochemcal Markers Martna Zannotto, Leopoldo Celegon,

More information

HIV/AIDS-related Expectations and Risky Sexual Behavior in Malawi

HIV/AIDS-related Expectations and Risky Sexual Behavior in Malawi Unversty of Pennsylvana ScholarlyCommons PSC Workng Paper Seres 7-29-20 HIV/AIDS-related Expectatons and Rsky Sexual Behavor n Malaw Adelne Delavande RAND Corporaton, Nova School of Busness and Economcs

More information

Carcinoembryonic antigen in patients with intraeranial tumors

Carcinoembryonic antigen in patients with intraeranial tumors J Neurosurg 53:355-360, 980 Carcnoembryonc antgen n patents wth ntraeranal tumors YASUO SUZUKI, M.D., AND RvuIfm TANAKA, M.D. Department of Neurosurgery, Bran Research Insttute, Ngata Unversty, Ngata,

More information

A REVIEW OF DIABETES COST OF ILLNESS STUDIES

A REVIEW OF DIABETES COST OF ILLNESS STUDIES A REVIEW OF DIABETES COST OF ILLNESS STUDIES George Szava-Kovats 2, Jeffrey A. Johnson 1,2 Workng Paper 97-3 1 2 Faculty of Pharmacy and Pharmaceutcal Scences, Unversty of Alberta, Edmonton, Canada Insttute

More information

Gurprit Grover and Dulumoni Das* Department of Statistics, Faculty of Mathematical Sciences, University of Delhi, Delhi, India.

Gurprit Grover and Dulumoni Das* Department of Statistics, Faculty of Mathematical Sciences, University of Delhi, Delhi, India. Journal of AIDS and HIV Research Vol. 3(), pp. -9, January 20 Avalable onlne http:// academcjournals.org/jahr ISSN 24-2359 20 Academc Journals Full Length Research Paper Decrement table and the estmaton

More information

The Limits of Individual Identification from Sample Allele Frequencies: Theory and Statistical Analysis

The Limits of Individual Identification from Sample Allele Frequencies: Theory and Statistical Analysis The Lmts of Indvdual Identfcaton from Sample Allele Frequences: Theory and Statstcal Analyss Peter M. Vsscher 1 *, Wllam G. Hll 2 1 Queensland Insttute of Medcal Research, Brsbane, Australa, 2 Insttute

More information

KOUJI KAJINAMI, MD,*t HIROYASU SEKI, MD,t NOBORU TAKEKOSHI, MD,t HIROSHI MABUCHI, MD* Kanazawa, Japan

KOUJI KAJINAMI, MD,*t HIROYASU SEKI, MD,t NOBORU TAKEKOSHI, MD,t HIROSHI MABUCHI, MD* Kanazawa, Japan JACC Vol. 26, No. 5 209 November I, 995:209-2 Nonnvasve Predcton of Coronary Atheroscleross by Quantfcaton of Coronary Artery Calcfcaton Usng Electron Beam Computed Tomography: Comparson Wth Electrocardographc

More information

We analyze the effect of tumor repopulation on optimal dose delivery in radiation therapy. We are primarily

We analyze the effect of tumor repopulation on optimal dose delivery in radiation therapy. We are primarily INFORMS Journal on Computng Vol. 27, No. 4, Fall 215, pp. 788 83 ISSN 191-9856 (prnt) ó ISSN 1526-5528 (onlne) http://dx.do.org/1.1287/joc.215.659 215 INFORMS Optmzaton of Radaton Therapy Fractonaton Schedules

More information

Natural History of Bronchopleural Fistula After Pneumonectomy: A Review of 96 Cases

Natural History of Bronchopleural Fistula After Pneumonectomy: A Review of 96 Cases Natural Hstory of Bronchopleural Fstula After Pneumonectomy: A Revew of 96 Cases Peter H. Hollaus, MD, Franz Lax, MD, PhD, Basem B. EI-Nashef, MD, Herwg H. Hauck, MD, Paolo Luccarn, MD, and Nestor S. Prdun,

More information

THE ASSOCIATION OF PNEUMOCOCCI, HEMOPHILUS INFLUENZAE, AND STREPTOCOCCUS HEMOLYTICUS WITH CORYZA, PHARYNGITIS, AND SINUSITIS

THE ASSOCIATION OF PNEUMOCOCCI, HEMOPHILUS INFLUENZAE, AND STREPTOCOCCUS HEMOLYTICUS WITH CORYZA, PHARYNGITIS, AND SINUSITIS THE ASSOCIATION OF PNEUMOCOCCI, HEMOPHILUS INFLUENZAE, AND STREPTOCOCCUS HEMOLYTICUS WITH CORYZA, PHARYNGITIS, AND SINUSITIS IN MAN B~ L. T. WEBSTER, M.D., AND A. D. CLOW (From the Laboratores of The Rockefeller

More information

Appendix F: The Grant Impact for SBIR Mills

Appendix F: The Grant Impact for SBIR Mills Appendx F: The Grant Impact for SBIR Mlls Asmallsubsetofthefrmsnmydataapplymorethanonce.Ofthe7,436applcant frms, 71% appled only once, and a further 14% appled twce. Wthn my data, seven companes each submtted

More information

Optimal Planning of Charging Station for Phased Electric Vehicle *

Optimal Planning of Charging Station for Phased Electric Vehicle * Energy and Power Engneerng, 2013, 5, 1393-1397 do:10.4236/epe.2013.54b264 Publshed Onlne July 2013 (http://www.scrp.org/ournal/epe) Optmal Plannng of Chargng Staton for Phased Electrc Vehcle * Yang Gao,

More information

Willingness to Pay for Health Risk Reductions: Differences by Type of Illness

Willingness to Pay for Health Risk Reductions: Differences by Type of Illness Wllngness to Pay for Health Rsk Reductons: Dfferences by Type of Illness Workng Paper: Prelmnary and Incomplete Trudy nn Cameron Department of Economcs Unversty of Oregon J.R. DeShazo UCL Lews Center for

More information

1 0 1 Neither A nor B I Both Anti-A and Anti-B 1 0, A, B, AB I 0 1. Simulated ABO 6; Rh Bood vping Lab Activity Student Study Guide BACKGROUND

1 0 1 Neither A nor B I Both Anti-A and Anti-B 1 0, A, B, AB I 0 1. Simulated ABO 6; Rh Bood vping Lab Activity Student Study Guide BACKGROUND Smulated ABO 6; Rh Bood vpng Lab Actvty Student Study Gude BACKGROUND nces Around 900, Karl Landstener dscovered that there are at least four dfferent knds of human blood, determned by the presence or

More information

Thallium Redistribution in Dogs with Severe Coronary Artery Stenosis of Fixed Caliber

Thallium Redistribution in Dogs with Severe Coronary Artery Stenosis of Fixed Caliber Thallum Redstrbuton n Dogs wth Severe Coronary Artery Stenoss of Fxed Calber 439 GERALD M. POHOST, ROBERT D. OKADA, DENNIS D. O'KEEFE, HENRY GEWIRTZ, GEORGE BELLER, H. WILLIAM STRAUSS, JOHN S. CHAFFIN,

More information

Association between cholesterol and cardiac parameters.

Association between cholesterol and cardiac parameters. Short communcaton http://www.alledacademes.org/cholesterol-and-heart-dsease/ Assocaton between cholesterol and cardac parameters. Rabndra Nath Das* Department of Statstcs, The Unversty of Burdwan, Burdwan,

More information

Desperation or Desire? The Role of Risk Aversion in Marriage. Christy Spivey, Ph.D. * forthcoming, Economic Inquiry. Abstract

Desperation or Desire? The Role of Risk Aversion in Marriage. Christy Spivey, Ph.D. * forthcoming, Economic Inquiry. Abstract Desperaton or Desre? The Role of Rsk Averson n Marrage Chrsty Spvey, Ph.D. * forthcomng, Economc Inury Abstract Because of the uncertanty nherent n searchng for a spouse and the uncertanty of the future

More information

This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and

This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and Ths artcle appeared n a journal publshed by Elsever. The attached copy s furnshed to the author for nternal non-commercal research and educaton use, ncludng for nstructon at the authors nsttuton and sharng

More information

Estimation for Pavement Performance Curve based on Kyoto Model : A Case Study for Highway in the State of Sao Paulo

Estimation for Pavement Performance Curve based on Kyoto Model : A Case Study for Highway in the State of Sao Paulo Estmaton for Pavement Performance Curve based on Kyoto Model : A Case Study for Kazuya AOKI, PASCO CORPORATION, Yokohama, JAPAN, Emal : kakzo603@pasco.co.jp Octávo de Souza Campos, Publc Servces Regulatory

More information

Maize Varieties Combination Model of Multi-factor. and Implement

Maize Varieties Combination Model of Multi-factor. and Implement Maze Varetes Combnaton Model of Mult-factor and Implement LIN YANG,XIAODONG ZHANG,SHAOMING LI Department of Geographc Informaton Scence Chna Agrcultural Unversty No. 17 Tsnghua East Road, Bejng 100083

More information

Non-linear Multiple-Cue Judgment Tasks

Non-linear Multiple-Cue Judgment Tasks Non-lnear Multple-Cue Tasks Anna-Carn Olsson (anna-carn.olsson@psy.umu.se) Department of Psychology, Umeå Unversty SE-09 87, Umeå, Sweden Tommy Enqvst (tommy.enqvst@psyk.uu.se) Department of Psychology,

More information

Drug Prescription Behavior and Decision Support Systems

Drug Prescription Behavior and Decision Support Systems Drug Prescrpton Behavor and Decson Support Systems ABSTRACT Adverse drug events plague the outcomes of health care servces. In ths research, we propose a clncal learnng model that ncorporates the use of

More information

A GEOGRAPHICAL AND STATISTICAL ANALYSIS OF LEUKEMIA DEATHS RELATING TO NUCLEAR POWER PLANTS. Whitney Thompson, Sarah McGinnis, Darius McDaniel,

A GEOGRAPHICAL AND STATISTICAL ANALYSIS OF LEUKEMIA DEATHS RELATING TO NUCLEAR POWER PLANTS. Whitney Thompson, Sarah McGinnis, Darius McDaniel, A GEOGRAPHICAL AD STATISTICAL AALYSIS OF LEUKEMIA DEATHS RELATIG TO UCLEAR POWER PLATS Whtney Thompson, Sarah McGnns, Darus McDanel, Jean Sexton, Rebecca Pettt, Sarah Anderson, Monca Jackson ABSTRACT:

More information

Single-Case Designs and Clinical Biofeedback Experimentation

Single-Case Designs and Clinical Biofeedback Experimentation Bofeedback and Self-Regulaton, VoL 2, No. 3, 1977 Sngle-Case Desgns and Clncal Bofeedback Expermentaton Davd H. Barow: Brown Unversty and Butler Hosptal Edward B. Blanchard Unversty of Tennessee Medcal

More information

Working Paper Asymmetric Price Responses of Gasoline Stations: Evidence for Heterogeneity of Retailers

Working Paper Asymmetric Price Responses of Gasoline Stations: Evidence for Heterogeneity of Retailers econstor www.econstor.eu Der Open-Access-Publkatonsserver der ZBW Lebnz-Informatonszentrum Wrtschaft The Open Access Publcaton Server of the ZBW Lebnz Informaton Centre for Economcs Faber, Remer P. Workng

More information

Implications of Intraindividual Variability in Bioavailability Studies of Furosemide

Implications of Intraindividual Variability in Bioavailability Studies of Furosemide Eur J Cln Pharmacol (1984) 27:595-602 European Journal of Clncal Pharmacology Sprnger-Verlag 1984 Implcatons of Intrandvdual Varablty n Boavalablty Studes of Furosemde A. Grahnrn 1, M. Hammaflund 2, and

More information

Introduction ORIGINAL RESEARCH

Introduction ORIGINAL RESEARCH ORIGINAL RESEARCH Assessng the Statstcal Sgnfcance of the Acheved Classfcaton Error of Classfers Constructed usng Serum Peptde Profles, and a Prescrpton for Random Samplng Repeated Studes for Massve Hgh-Throughput

More information