Recursive partitioning identifies patients at high and low risk for ipsilateral tumor recurrence after breast-conserving surgery and radiation.

PURPOSE: Recursive partitioning analysis (RPA), a method of building decision trees of significant prognostic factors for outcome, was used to determine subgroups at significantly different risk for ipsilateral breast tumor recurrence (IBTR) in early-stage breast cancer. PATIENTS AND METHODS: Nine hundred twelve women underwent breast-conserving surgery, axillary dissection, and radiation. Systemic therapy was chemotherapy with or without tamoxifen in 32%, tamoxifen in 27%, or none in 41%. RPA was used to create a decision tree according to predictive variables that classify patients by IBTR risk, and the Kaplan-Meier method was used to calculate 10-year risks. Median follow-up was 5.9 years. RESULTS: Age was the first split in the partition tree. Patients more than 55 years old had a 4% 10-year IBTR, the only further division being use of tamoxifen or not (2% v 5%, P =.03). For patients

Defining the optimal radiation dose with three-dimensional conformal radiation therapy for patients with nonmetastatic prostate carcinoma by using recursive partitioning techniques.

BACKGROUND: The objective of this study was to determine the effect of dose and its interaction with known prognostic variables, including pretreatment prostate specific antigen (PSA), Gleason score (GS), and T classification, on patients with nonmetastatic prostate carcinoma treated with three-dimensional conformal radiation therapy (3DCRT) alone using recursive partitioning analysis. METHODS: Between November 1987 and November 1997, 939 patients with nonmetastatic prostate carcinoma were treated with 3DCRT alone at Fox Chase Cancer Center. Biochemical no evidence of disease (bNED) control was defined using the American Society of Therapeutic Radiology and Oncology Consensus definition. Recursive partitioning analysis was used to identify subgroups with similar risks of bNED failure. Prognostic factors used in the model included pretreatment PSA, GS, T classification, and radiation dose. The median follow-up was 47 months (range, 2-133 months). RESULTS: Twelve terminal nodes of the decision tree were merged to form four prognostic groups with similar bNED control rates. The 5-year actuarial rates of bNED control rates for Groups I, II, III, and IV were 84%, 41%, 16%, and 67%, respectively (P < 0.0001). Increasing the dose to greater than 7235 centigray (cGy) improved bNED control rates for patients with PSA levels of 10-19.9 ng/mL and T1/2a classification disease. Increasing the dose to greater than 7629 cGy improved bNED control rates for patients with T2b/3 classification disease with PSA levels less than 20 ng/mL. Patients with PSA levels greater than or equal to 20 ng/mL need high-dose 3DCRT. For those patients with GS 2-6 and T1/2a classification disease, treatment with greater than 7400 cGy resulted in 67% bNED control rate versus 16% at 5 years for treatment with less than 7400 cGy. High radiation dose (> 7700 cGy) improved bNED control rate from 16% to 41% for patients with high-risk disease (PSA > or = 20 ng/mL and GS 7-10) at 5 years. CONCLUSIONS: The authors showed that with recursive partitioning techniques radiation dose continues to be an important predictor of bNED control rate and that a radiation dose response for patients with clinically localized prostate carcinoma exists. Patients with one or more prognostic feature (PSA > 10 ng/mL, classification T2b/T3, GS 7-10, or the presence of perineural invasion) achieve similar rates of bNED control compared with those patients with lower volume disease when radiation dose is increased.

Fractionation and outcomes with palliative radiation therapy.

A dose-response relationship can be established for local control of a variety of malignancies treated with radiation, yet palliation of symptoms oftentimes does not have a clear dose-response relationship. It is important that palliation be achieved with as efficient a fractionation schedule as possible in patients with limited life expectancy and with as few side effects as possible. This article reviews the literature addressing optimal schedules of radiation for palliation based on prognostic factors.

Do semiclassical zero temperature black holes exist?

The semiclassical Einstein equations are solved to first order in epsilon = Planck's over 2pi/M2 for the case of a Reissner-Nordström black hole perturbed by the vacuum stress energy of quantized free fields. Massless and massive fields of spin 0, 1/2, and 1 are considered. We show that in all physically realistic cases, macroscopic zero temperature black hole solutions do not exist. Any static zero temperature semiclassical black hole solutions must then be microscopic and isolated in the space of solutions; they do not join smoothly onto the classical extreme Reissner-Nordström solution as epsilon-->0.

Specificity of four serologic assays for Mycobacterium avium ss paratuberculosis in llamas and alpacas: a single herd study.

An investigation was conducted for Mycobacterium avium ss paratuberculosis infections in a research herd of llamas and alpacas. Herd culture-negative status was established over a 23-month period by screening any individuals with any signs compatible with paratuberculosis (n = 1), high serology values (n = 8), or other health and research related reasons (n = 24). There were no M. avium ss paratuberculosis isolates from radiometric cultures of multiple tissue and fecal samples from these individuals and no known sources of exposure. Paratuberculosis is uncommon in North American llamas and alpacas: only 5 cases were identified after an extensive search of the Veterinary Medical Data Base, diagnostic laboratory records, publication databases, and personal communications. Therefore, serum samples from llamas (n = 84) and alpacas (n = 16) in the culture-negative herd were used to obtain preliminary estimates of test specificity for 3 enzyme-linked immunoassays (ELISAs) and an agar gel immunodiffusion (AGID) assay kit for detecting serum antibodies to M. avium ss paratuberculosis in South American camelids. The ELISAs were modifications of established bovine assays for antibody detection. With provisional cutoffs, ELISA-A had 52 false positives (specificity 48%), ELISA-B had 8 false positives (specificity 92%), ELISA-C had two false positives (specificity 98%), and the AGID had 0 false positives (specificity 100%). The range of ELISA values for culture-positive llamas and alpacas (n = 10) from other herds overlapped the range of values for culture-negative llamas and alpacas. The accuracy of the ELISAs may be improved by using age- and sex-specific cutoffs because uninfected male llamas and alpacas that were older than 1 year had higher values for some tests. These tests can be used for either llamas or alpacas; the protein-G conjugate ELISA (ELISA-B) may be useful for multispecies applications. These assays are best used for rapid presumptive diagnoses of llamas and alpacas with diarrhea and weight loss and as a screening tool for herds known to be exposed to infection. All seropositive results should be confirmed with culture.

Outcome and predictive factors for patients with Gleason score 7 prostate carcinoma treated with three-dimensional conformal external beam radiation therapy.

BACKGROUND: The purpose of this study was to determine the biochemical outcome and factors predictive of outcome in prostate carcinoma patients with Gleason score 7 tumors who were treated with three-dimensional conformal radiation therapy (3DCRT). METHODS: Between August 1990 and October 1997, 163 T1-T3NXM0 prostate carcinoma patients with Gleason score 7 were treated with definitive 3DCRT alone. The median follow-up, International Commission on Radiological Units dose, and pretreatment prostate specific antigen (PSA) for the entire group were 50 months, 76 grays (Gy), and 11.4 ng/mL, respectively. Independent predictors based on multivariate results were used to stratify the patients into prognostic groups for which biochemical no evidence of disease (bNED) control was reported. Biochemical NED failure was defined according to the American Society for Therapeutic Radiology and Oncology Consensus Panel definition. RESULTS: The 5-year bNED control for all patients was 66%. Stratified by pretreatment PSA, 5-year bNED control rates were 83%, 65%, and 21% for 0-9.9 ng/mL, 10-19.9 ng/mL, and > or =20 ng/mL, respectively. Dose to the central axis was found to be a significant treatment factor, with patients receiving > or =76 Gy experiencing 76% 5-year bNED control versus 54% when treated with <76 Gy to isocenter. Pretreatment PSA, dose, and palpation stage were significant independent predictors for bNED control upon multivariate analysis. Patients with a PSA <10 ng/mL who received a dose of > or =76 Gy had excellent 5-year bNED control of 100% compared with 50% bNED if patients had PSA >10 ng/mL or received radiation therapy doses of <76 Gy. CONCLUSIONS: Patients with Gleason score 7 adenocarcinoma who had a pretreatment PSA <10 ng/mL and received doses of > or =76 Gy had excellent 5-year bNED control, emphasizing the importance of higher central axis doses in treating Gleason 7 tumors. Patients with intermediate PSA (10-19.9 ng/mL) also required doses > or =76 Gy. Pretreatment PSA > or = 20 ng/mL portends a very poor bNED outcome for Gleason 7 patients treated with radiation therapy alone, and thus efforts should be directed toward multimodal or long term hormonal treatment strategies.

Optimum beam angles for the conformal treatment of lung cancer: a CT simulation study.

Treatment of lung cancer is often performed with cone-down oblique beams to spare spinal cord and normal structures. However, there is no optimum technique to determine oblique beam angles when a CT simulation is not available. Impact of oblique beam angle was investigated in this study. Fifteen patients with centrally located lung tumors were immobilized and scanned using a CT simulator. The target volumes, left and right lungs, and spinal cord were delineated on each slice. Patients were simulated starting with anterior-posterior treatment beams and subsequently an oblique opposed pair beam from 0 degrees up to 60 degrees at an interval of 5 degrees to optimize the projection of target-to-cord distance and minimize the lung volume in the treatment fields. Analysis was performed with a dose volume histogram (DVH) in each beam orientation. The distance between the target volume and spinal cord was linearly related to the angle of the beam. A larger angle facilitated further sparing of the spinal cord; however, progressively more lung volume was exposed. The 50% DVH data for lung volume was used as an indicator of lung volume. Although, the minimum lung volume was irradiated with an angle of 30 degrees, the additional lung treated increased by only 8 +/- 7% of the total lung volume for 30-60 degrees beam angles and cord distance increased by 18.5 mm. A 30 degrees oblique parallel-opposed beam for the cone-down treatment of lung provided minimum lung volume in the irradiated field; however, the spinal cord distance increased linearly with beam angle. A CT simulator is ideally suited for simulation of lung cancer to maximize the clearance from the spinal cord and minimize the additional lung volume irradiated. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 359-365 (2000).

Sparing effect of leptin on liver glycogen stores in rats during the fed-to-fasted transition.

The effect of moderate hyperleptinemia ( approximately 20 ng/ml) on liver and skeletal muscle glycogen metabolism was examined in Wistar rats. Animals were studied approximately 90 h after receiving recombinant adenoviruses encoding rat leptin (AdCMV-leptin) or beta-galactosidase (AdCMV-betaGal). Liver and skeletal muscle glycogen levels in the fed and fasted (18 h) states were similar in AdCMV-leptin- and AdCMV-betaGal-treated rats. However, after delivery of a glucose bolus, liver glycogen levels were significantly greater in AdCMV-leptin compared with AdCMV-betaGal rats (P < 0.05). To investigate the mechanism(s) of these differences, glycogen levels were measured immediately after the cessation of a 3- or 6-h glucose infusion or 3, 6, and 9 h after the cessation of a 6-h glucose infusion. Similar increases in liver and skeletal muscle glycogen occurred in hyperleptinemic and control rats in response to glucose infusions. However, 3 and 6 h after the cessation of a glucose infusion, liver glycogen levels were approximately twofold greater (P < 0.05) in AdCMV-leptin-treated compared with AdCMV-betaGal-treated animals. Skeletal muscle glycogen levels were similar in AdCMV-leptin-treated and AdCMV-betaGal-treated animals at the same time points. Glycogen phosphorylase, phosphodiesterase 3B, and glycogen synthase activities were unaltered by hyperleptinemia. We conclude that moderate increases in plasma leptin levels decrease liver glycogen degradation during the fed-to-fasted transition.

Perineural invasion and Gleason 7-10 tumors predict increased failure in prostate cancer patients with pretreatment PSA <10 ng/ml treated with conformal external beam radiation therapy.

PURPOSE: It has been well established that prostate cancer patients with pretreatment PSA <10 ng/ml enjoy excellent bNED control when treated with definitive external beam radiation therapy. This report identifies predictors of failure for patients with pretreatment PSA <10 ng/ml. These predictors are then used to define favorable and unfavorable prognostic subgroups of patients for which bNED control is compared. METHODS AND MATERIALS: Between 3/87 and 11/94, 266 patients with T1-T3NXM0 prostate cancer and pretreatment PSA values <10 ng/ml were treated with definitive external beam radiation therapy. Median central axis dose and median follow-up for the entire group was 72 Gy (63-79 Gy) and 48 months (2-120 months). Predictors of bNED control were evaluated univariately using Kaplan-Meier methodology and the log-rank test and multivariately using Cox proportional hazards modeling. Covariates considered were pretreatment PSA, palpation stage, Gleason score, presence of perineual invasion (PNI) and central axis dose. Independent predictors based on multivariate results were then used to stratify the patients into two prognostic groups for which bNED control was compared. bNED failure is defined as PSA > or = 1.5 ng/ml and rising on two consecutive determinations. RESULTS: Univariate analysis according to pretreatment and treatment factors for bNED control demonstrates a statistically significant improvement in 5-year bNED control for patients with Gleason score 2-6 vs. 7-10, patients without evidence of perineural invasion (PNI) vs. those with PNI, and patients with palpation stage T1/T2AB vs. T2C/T3. Multivariate analysis demonstrates that Gleason score (p = 0.0496), PNI (p = 0.0008) and palpation stage (p = 0.0153) are significant independent predictors of bNED control. Based on these factors, patients are stratified into a more favorable prognosis group (Gleason 2-6, no PNI, and stage T1/T2AB, n = 172) and a less favorable prognosis group (Gleason 7-10 or PNI or T2C/T3, n = 94). A comparison of the two groups reveals that bNED control is significantly lower in the less favorable prognosis group (74% vs. 91% at 5 years, p = 0.0024). CONCLUSIONS: (1) This report identifies Gleason 7-10 and the presence of PNI as well as palpation stage T2C/T3 as factors that predict worse bNED outcome for patients with pretreatment PSA <10 ng/ml who are treated with radiation therapy alone. (2) Patients with these pretreatment prognostic factors may benefit from adjuvant therapies or altered treatment programs. (3) In order to make fair comparisons between radiation therapy and prostatectomy series, the distribution of perineual invasion and Gleason 7-10 must be taken into account.

Prostate cancer patient subsets showing improved bNED control with adjuvant androgen deprivation.

PURPOSE: Cooperative groups have investigated the outcome of androgen deprivation therapy combined with radiation therapy in prostate cancer patients with variable pretreatment prognostic indicators. This report describes an objective means of selecting patients for adjuvant hormonal therapy by a retrospective matched case/control comparison of outcome between patients with specific pretreatment characteristics who receive adjuvant hormones (RT+H) vs. patients with identical pretreatment characteristics treated with radiation therapy alone (RT). In addition, this report shows the 5-year bNED control for patients selected by this method for RT+H vs. RT alone. METHODS AND MATERIALS: From 10/88 to 12/93, 517 T1-T3 NXM0 patients with known pretreatment PSA level were treated at Fox Chase Cancer Center. Four hundred fifty-nine of those patients were treated with RT alone while 58 were treated with RT+H. The patients were categorized according to putative prognostic factors indicative of bNED control, which include the palpation stage, Gleason score, and pretreatment PSA. We compared actuarial bNED control rates according to treatment group within each of the prognostic groups. In addition, we devised a retrospective matched case/control selection of RT patients for comparison with the RT+H group. Five-year bNED control was compared for the two treatment groups, excluding the best prognosis group, using 56 RT+H patients and 56 matched (by stage, grade, and pretreatment PSA level) controls randomly selected from the RT alone group. bNED control for the entire group of 517 patients was then analyzed multivariately using step-wise Cox regression to determine independent predictors of outcome. Covariates considered for entry into the model included stage (T1/T2AB vs. T2C/T3), grade (2-6 vs. 7-10), pretreatment PSA (0-15 vs. > 15), treatment (RT vs. RT+H), and center of prostate dose. bNED failure is defined as PSA > or = 1.5 ngm/ml and rising on two consecutive determinations. The median follow-up for the 112 matched case/control patients was 41 months. The median follow-up was 46 months for the RT (range 11-102 months) and 37 months for the RT+H group (range 6-82 months). RESULTS: Univariate analysis according to treatment for the prognostic factors of palpation stage, Gleason score, and pretreatment PSA demonstrates a significant improvement in 3-year bNED control with the addition of hormones for patients with T2C/T3, Gleason score 7-10, or pretreatment PSA > 15 ngm/ml. A comparison of bNED control according to treatment demonstrates improvement in 5-year bNED control of 55% for patients treated with RT+H vs. 31% for those patients treated with RT alone (p = 0.0088), although there is not a survival advantage. Multivariate analysis demonstrates that hormonal treatment is a highly significant independent predictor of bNED control (p = 0.0006) along with pretreatment PSA (p = 0.0001), palpation stage (p = 0.0001), grade (p = 0.0030), and dose (p = 0.0001). CONCLUSIONS: (1) Patients with specific adverse pretreatment prognostic factors (i.e., T2C/T3, Gleason score 7-10, pretreatment PSA > 15) benefit from adjuvant hormonal therapy. (2) Upon multivariate analysis, hormonal therapy is determined to be a highly significant predictor of bNED control, after adjusting for all other covariates. (3) The 5-year bNED control rates of 55% for RT+H vs. 31% for RT alone represents the magnitude of benefit from adjuvant hormone therapy. (4) The bNED control curves are separated by about 20 months, representing a delay in disease progression with adjuvant hormonal therapy, as there is no overall survival difference.

The effect of outdoor fungal spore concentrations on daily asthma severity.

The relationship between day-to-day changes in asthma severity and combined exposures to community air pollutants and aeroallergens remains to be clearly defined. We examined the effects of outdoor air pollutants, fungi, and pollen on asthma. Twenty-two asthmatics ages 9-46 years were followed for 8 weeks (9 May-3 July 1994) in a semirural Southern California community around the air inversion base elevation (1,200 ft). Daily diary responses included asthma symptom severity (6 levels), morning and evening peak expiratory flow rates (PEFR), and as-needed beta-agonist inhaler use. Exposures included 24-hr outdoor concentrations of fungi, pollen, and particulate matter with a diameter < 10 microns (PM10; maximum = 51 micrograms/m3) and 12-hour day-time personal ozone (O3) measurements (90th percentile = 38 ppb). Random effects longitudinal regression models controlled for autocorrelation and weather. Higher temperatures were strongly protective, probably due to air conditioning use and diminished indoor allergens during hot, dry periods. Controlling for weather, total fungal spore concentrations were associated with all outcomes: per minimum to 90th percentile increase of nearly 4,000 spores/m3, asthma symptom scores increased 0.36 (95% CI, 0.16-0.56), inhaler use increased 0.33 puffs (95% CI, -0.02-0.69), and evening PEFR decreased 12.1 l/min (95% CI, -1.8-22.3). These associations were greatly enhanced by examining certain fungal types (e.g., Alternaria, basidiospores, and hyphal fragments) and stratifying on 16 asthmatics allergic to tested deuteromycete fungi. There were no significant associations to low levels of pollen or O3, but inhaler use was associated with PM10 (0.15 inhaler puffs/10 micrograms/m3; p < 0.02). These findings suggest that exposure to fungal spores can adversely effect the daily respiratory status of some asthmatics.

Community-based educational programs for cancer nursing.

A United Way grant allowed the Department of Nursing Research and Education to make available its expertise in cancer nursing and establish itself as a resource for oncology. Community educational needs were assessed by a questionnaire sent to outside agencies prior to designing an oncology educational program. In a 9-month period, 57 classes at 21 different facilities representing 417 hours of instruction were provided. Nurses attending the classes totaled 1,175. Results showed an increase in scores from pre-test to post-test, indicating that participants demonstrated increased knowledge as a result of class participation. This funding provided the catalyst to prepare a large number of community hospital nurses in the complex care of oncology patients.

Health quality of life and colorectal cancer.

BACKGROUND: Quality of life associated with cancer and radiation treatment includes the dimensions of psychologic and physical well-being, nutrition concerns/side effects, and radiation treatment-related anxiety/adjustment. An understanding of the impact of colorectal cancer and radiation treatment on these aspects of health quality of life can be reached by comparing this diagnostic group to others undergoing similar treatment. METHODS: Thirty-six patients with colorectal cancers, 41 with uterocervical cancers, 43 with genitourinary tumors, 13 with leukemia or bone metastasis, and 129 with head and neck cancers undergoing radiation therapy provided complete health quality of life index (QLI-RT) data during weeks 1 and 3 of treatment and at the first follow-up visit after treatment completion. The QLI-RT was found to be reliable and valid. RESULTS: Those with colorectal cancer had similar QLI-RT summary scores as the other groups at the beginning of treatment and during the follow-up period. QLI-RT scores tended to range from 62 to 84 for the summary score and individual-item scores; this was a narrow span considering the QLI-RT uses a 0-100-mm linear analog-response scale. The exceptions were strength, which elicited scores in the 46-68 range and a couple of responses to worrying about radiation therapy. The largest change in QLI-RT score in relation to the treatment trajectory was 11 mm. CONCLUSIONS: These findings tend to support the notion that patients with cancer try to maintain health quality of life at an acceptable level despite the occurrence of stressful negative events. Future research should explore the stable versus dynamic attributes of health quality of life to learn more about the factors that contribute to the adaptive process that maintains such quality of life at an acceptable level.

Effects of microbial floras on the distributions of five domestic Drosophila species across fruit resources.

The distributions of five Drosophila species and four components of the microflora have been compared across a total of 48 traps baited with four different fruit and vegetable substrates in two domestic compost heaps in Canberra (Australia). Large and consistent differences are found, both among the Drosophila and among the microbial classes, in their distributions across traps baited with different substrates. Moreover the distribution of each Drosophila species shows a unique set of strong associations with the microbial distributions. Thus the distributions of both D. simulans and D. melanogaster are found to be strongly negatively correlated with the abundance of bacteria while D. simulans is also strongly positively correlated with the titre of fermenter yeasts. D. immigrans is strongly positively correlated both with bacteria and with non-fermenter yeasts. D. hydei is positively correlated with nonfermentery yeasts and D. busckii is negatively correlated with fermenter yeasts. Moulds are the only microbial class not consistently associated with the distribution of any of the Drosophila species. The correlations with the other microbial classes are sufficient to explain the majority of the abundance differences of the Drosophila species among the trap types. It is therefore proposed that the clear partitioning of the fruit resources by the Drosophila is due to their differing primary interactions with the microflora.

Observations on the extent and temporal stability of latitudinal clines for alcohol dehydrogenase allozymes and four chromosome inversions in Drosophila melanogaster.

Previously we have presented evidence of large-scale latitudinal clines in the frequencies of four chromosome inversions and alleles at six enzyme loci in populations of D. melanogaster in Australasia, Asia and North America. Subsequent sampling by others in Japan and western U.S.A. has failed to repeat this observation for the steepest of the clines (alcohol dehydrogenase and the four chromosome inversions). We argue that this failure reflects the few populations and small latitudinal range sampled in these later studies. From extensive sampling over a long latitudinal transect in Australasia we here document Adh and inversion clines which are virtually identical to those originally obtained in different Australian populations four years earlier. We also repeat our observation that the Adh cline is largely independent of the cline in the linked inversion In(2L)t. We therefore retain our original conclusion that these polymorphisms are subject to natural selection. However the new Australasian data do not indicate an association between Adh and maximum rainfall which had been evident in the earlier data for Australasia, Asia and North America. We therefore retract our claim that the selective agent on Adh is related to rainfall.

HTLV-III serology in hemophilia: relationship with immunologic abnormalities.

We investigated the relationship of the presence of antibodies to HTLV-III and immunologic abnormalities in patients with hemophilia. Serum antibodies to HTLV-III were analyzed by ELISA assay, immunoprecipitation of labeled cell extracts, and immunoprecipitation of purified HTLV-III p24. Thirty-four (61%) of the total group (n = 56) had antibody to HTLV-III; 34 (76%) of 45 patients given commercial factor VIII preparations were seropositive, compared with none of 11 patients treated exclusively with cryoprecipitate obtained from volunteer blood donors. Of patients who were seropositive for HTLV-III antibody, 94% had abnormal T4/T8 ratios, and 33% of those whose serum was antibody negative had abnormal T4/T8 ratios; five patients, each antibody positive, have lymphadenopathy syndrome. Sequential studies in a subset of patients indicate that there is a changing pattern of antibody production to HTLV-III antigens after seroconversion.

Postoperative respiratory complications in non-idiopathic scoliosis.

The medical records of 303 patients undergoing fusions for scoliosis correction were retrospectively reviewed. The frequency and type of postoperative respiratory complications were compared in idiopathic versus non-idiopathic scoliosis patients in relation to age, type of spinal fusion procedure, pulmonary function test (PFT) results and preoperative diagnoses. The following factors were found to increase the incidence of problems in the postoperative period: a non-idiopathic type of scoliosis, mental retardation, anterior spinal fusion procedures, age of 20 or more years, a relative arterial hypoxemia and an obstructive component to the PFT's. Topics for further investigation are suggested.