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Overall molecular descriptors. 3. Overall Zagreb indices.

This paper develops further the concept of overall characterization of molecular topology, which is based on calculation of a given graph-invariant for all subgraphs of molecular graph. The new approach defines a cumulative topological descriptor, and an ordered series of terms (eth-order descriptor), which present the sum of the graph-invariant values for all subgraphs having the same number of edges. Alternatively, the terms in the series may be further partitioned, in the manner of molecular connectivity concept of Randić, Kier, and Hall, into contributions of path, cluster, and path-cluster type of subgraphs. The previous publications on the novel approach were based on the simplest graph-invariants--the sum of entries of the adjacency matrix and the distance matrix. Overall connectivity and overall Wiener index were thus defined, along with their respective series of e-order terms. The present study makes use of two other simple functions of vertex degrees, the first and second Zagreb indices. The overall versions of these two indices, very recently constructed, are analyzed in detail. Their potential applicability is verified by deriving multilinear regression models of ten physicochemical properties of alkanes, and comparing them to the results obtained by molecular connectivity and overall connectivity indices.

Chemical Phenomena↗

An investigation to relate the overall size of the maxillary arch and the area of palatal mucosa in cleft lip and palate cases at birth to the overall size of the upper dental arch at five years of age.

The area of palatal mucosa and the size of the maxillary arches were measured in a group of 30 newborn infants with unilateral clefts of the lip and palate. The overall size of the maxillary arch together with the arch width and arch height were also measured when the children had reached 5 years of age. For comparison purposes, a group of 30 newborn normal children and 30 normal 5-year-old children were similarly measured. The cleft children were found to have a mean deficiency of palatal mucosa of 16.41% at birth, although the overall size of their maxillary arches was 17.08% greater than normal. In the cleft cases there was no significant correlation between the area of palatal mucosa at birth and the overall size of the arch at 5 years of age. A significant correlation did exist between the overall size of the arch at birth and the overall size when the child was 5 years old. The significance of this and other findings is discussed.

Aging↗

Does recombinant factor VIIa, apart from overall hemostasis, regulate TAFI dependent fibrinolysis? In vitro analysis using overall hemostasis potential (OHP) assay.

Using the recently developed overall hemostatic potential (OHP) assay, we investigated the effects of different concentrations of recombinant factor VIIa on overall hemostasis and on thrombin activatable fibrinolysis inhibitor (TAFI) dependent fibrinolysis in different factor deficient plasmas. rFVIIa increased OHP in FV, FVIII and FIX deficient plasmas but not up to the levels in normal pooled plasma (NPP). Maximal levels were found at 2.4 microg/mL of rFVIIa, while higher doses did not further increase OHP. In FXII deficient plasma, OHP is higher than in NPP and addition of rVIIa further increased it. Even very high concentrations of rFVIIa (9.6 microg/mL) did not induce a significant increase of OHP in NPP. Higher concentrations of rVIIa down-regulated fibrinolysis in FVIII, FIX and FXI deficient plasmas to values obtained in NPP. Using potato tuber carboxy-peptidase inhibitor (PTCI), a specific inhibitor of TAFI, it was found that TAFI's influence on fibrinolysis down-regulation in FVIII and FIX deficient plasmas increased after addition of higher concentrations of rFVIIa. From this in vitro study it seems that rFVIIa in a concentration of 2.4 microg/mL improves overall hemostasis in FV, FVIII and FIX deficient plasmas. rFVIIa, even at very high (supra-therapeutic) concentrations, does not induce hypercoagulability either in NPP or in deficient plasmas. Higher concentrations of rVIIa induce, at least partly, TAFI dependent down-regulation of fibrinolysis in FVIII and FIX deficient plasmas. These results, together with some previous ex vivo studies, point to OHP assay as a possible diagnostic tool for evaluating the hemostatic effects of rFVIIa.

Blood Coagulation Tests↗

Is normal or less than normal overall loudness preferred by first-time hearing aid users?

OBJECTIVE: Most prescriptive methods for nonlinear, wide dynamic range compression (WDRC) hearing aids are based on the assumption that a hearing-impaired listener should perceive amplified sounds at the same overall loudness as would a normal-hearing listener without amplification. However, some previous research on linear amplification has indicated that subjects prefer less overall gain than prescribed by the most commonly used prescriptive method for linear hearing aids, NAL-R, a method that gives close to normal overall loudness for a mid-level input. The current study aims at comparing two prescriptive methods for WDRC hearing aids. The methods differ in the overall loudness they aim to give the hearing aid user. One method, called NormLoudn, is based on a generic method that prescribes gain so that the overall loudness is restored to normal. Another method, called LessLoudn, is based on a hearing aid specific prescription, and gives the hearing aid user less than normal overall loudness. Do first-time hearing aid users prefer the method that restores overall loudness to normal or the method that gives less than normal overall loudness? DESIGN: Twenty-one first-time hearing aid users with typical hearing losses for this group of clients participated in a crossover blinded field study where the two fitting methods were compared using a multi-programmable hearing aid, Danalogic 163D. Preference in the field was evaluated using interview, questionnaire, and diary. The field test was accompanied by laboratory tests, which included paired comparison judgments of preference and loudness and a speech recognition test. Loudness calculations were also used when interpreting the results, and a theoretical comparison with other prescriptive methods for WDRC hearing aids was made. RESULTS: After necessary adjustments, the measured gain for the two methods was similar in gain-frequency shape, but NormLoudn gave more overall gain than LessLoudn. Generally, NormLoudn fittings led to calculated overall loudness that was close to normal, whereas LessLoudn fittings, in median, led to 3-7 phon less than normal calculated overall loudness according to the loudness model used. During the interview performed after the field test, 19 out of the 21 subjects stated that they preferred LessLoudn. Also the questionnaire and the diary showed a clear preference for LessLoudn in all types of listening situations. Paired comparisons of preference in the laboratory supported the findings in the field. LessLoudn was preferred to NormLoudn in all tested situations, except for soft speech in very soft noise where there was no significant preference for either method. Speech recognition scores were similar for the two fittings. The difference in calculated loudness was clearly distinguishable to the subjects and seemed to govern their preferences. CONCLUSIONS: LessLoudn, which gave less than normal overall loudness according to the loudness model used, was preferred both in the field and in the laboratory tests. Speech recognition scores were similar for both methods. A comparison between the measured gain for NormLoudn and the gain prescribed by CAMEQ, NAL-NL1, and DSL[i/o], suggests that all three prescriptive procedures (DSL[i/o] in particular) would probably overestimate the required gain for subjects without hearing aid experience and with mild to moderate hearing loss. When providing these clients with hearing aids, it seems important to include a careful adjustment of the overall gain to avoid overamplification if the prescription used aims at restoring overall loudness to normal according to the loudness model used here.

Aged↗

Radiotherapy for T2 and T3 carcinoma of the bladder: the influence of overall treatment time.

The influence of overall treatment time on local control rate was studied on a group of 147 patients with muscle invasive T2 or T3 transitional cell carcinoma of the urinary bladder. All patients received external radiotherapy at the Catharina Hospital, Eindhoven, The Netherlands between January 1974 and December 1984. Patients treated with overall treatment times shorter than 75 days (n = 92) were irradiated during a continuous course; all but one patient, with overall treatment times of 75 days or more (n = 55), received split-course radiotherapy. Actuarial local relapse-free probability at 3 years (LRFP3) was computed from the onset of radiotherapy. LRFP3 proved to be dependent on overall treatment time. For T2 stage, LRFP3 was 80 +/- 18% (n = 5) and 54 +/- 13% (n = 13) for overall times between 15-44 and 45-74 days, respectively, 36 +/- 14% (n = 11) for overall times between 75 and 104 days and 64 +/- 15% (n = 11) for overall times longer than 105 days. For T3 stage, LRFP3 was 33 +/- 19% (n = 6) and 48 +/- 10% (n = 25) for overall times between 15-44 and 45-74 days, respectively, 25 +/- 14% (n = 12) for overall times between 75 and 104 days and 22 +/- 14% (n = 9) for overall times longer than 105 days. The figures between brackets are numbers of patients relapsing within 3 years or at risk of relapse during at least 3 years. Patients who died without local relapse before 3 years were censored. We have reasons to believe that patient selection bias leads to overestimation of LRFP3 for the split-course radiotherapy in retrospective studies where the 'intention to treat' cannot be recalled. This retrospective study suggests that prolonging overall time of radiotherapy has an effect on local control in T2 and T3 transitional cell carcinoma of the urinary bladder. Local control was the worst for patients treated by split-course radiotherapy with a gap of approximately one month. Local control was not further decreased (and seemed even improved) by longer gaps, but this observation is possibly biased as explained in the discussion section. For patients treated by continuous course radiotherapy we could not find a difference in local control rates between patients treated with overall times of 44 days or less and those treated with overall times of 45-74 days.

Adult↗

Estimation of overall pulmonary function after irradiation using dose-effect relations for local functional injury.

PURPOSE: To predict the pulmonary function 3-4 months after irradiation for malignant lymphoma from the three-dimensional (3-D) dose distribution. METHODS: Dose-effect relations for the relative reduction of local perfusion (Q) and local ventilation (V), were calculated in 25 patients, using correlated SPECT (Single Photon Emission Computed Tomography) and CT data. By combining the 3-D dose distribution of an individual patient with the dose-effect relations averaged over all patients, the average reduction of local Q and V (i.e., the overall response parameters) in the whole lung was estimated for each patient. Correlation coefficients were calculated between these overall response parameters and the change in standard lung function tests. In addition, the relation between the overall response parameters and the incidence of radiation pneumonitis was determined. RESULTS: The overall response parameter for perfusion was correlated with the change in standard lung function tests, with correlation coefficients varying between 0.53 (p = 0.007) and 0.71 (p < 0.001) for the change of Vital Capacity and Forced Expiratory Volume at 1 s, respectively. For the overall response parameter for ventilation similar correlations were observed. Four out of the 25 patients developed radiation pneumonitis; in these four patients the overall response parameter for perfusion was on average somewhat higher (13.2 +/- 1.4% (1 standard error of the mean)) than in patients without radiation pneumonitis (10.5 +/- 1.0%), but this difference was not significant. A higher incidence of radiation pneumonitis was observed for larger values of the overall response parameter for perfusion; in patient groups with an overall response parameter for perfusion of 0-5%, 5-10%, 10-15%, and 15-20%, the incidence of radiation pneumonitis was 0 (0/1), 10 (1/10), 13 (1/8) and 33% (2/6), respectively. CONCLUSION: By combining the 3-D dose distribution with the average dose-effect relations for local perfusion or ventilation, an overall response parameter can be calculated prior to irradiation, which is predictive for the radiation-induced change in the overall pulmonary function, and possibly for the incidence of radiation pneumonitis, in this group of patients.

Adolescent↗

Overall fibromyalgia pain is predicted by ratings of local pain and pain-related negative affect--possible role of peripheral tissues.

OBJECTIVES: Despite variable numbers and intensities of local pain areas, fibromyalgia (FM) patients can provide overall clinical pain ratings. We hypothesized that the overall clinical pain is largely determined by the pain intensity of local body areas. Thus, we assessed the role of local body pains as predictors of overall clinical pain in FM patients. METHODS: Ratings of overall clinical pain intensity and pain-related negative affect (PRNA) were obtained from 277 FM patients. In addition, the patients identified painful body areas by shading a body pain diagram and rated the intensity of each pain area using a mechanical visual analogue scale (VAS). Hierarchical regression analyses were used to examine predictors of overall clinical FM pain intensity including PRNA, number of local pain areas, and maximal/average intensity of local pain areas. RESULTS: The average overall clinical pain rating of all FM patients was 4.6 (S.D. 2.3) VAS. The PRNA accounted for 19%, number of painful body areas for 9% and maximal/average local pain for 27% of the variance of overall clinical FM pain (P-values < 0.001). The combination of all factors predicted 55% of the variance in overall clinical pain intensity of FM patients. CONCLUSION: Peripheral factors (maximal/average local pain and number of painful body areas) predicted most of the variance of overall clinical FM pain, suggesting that the input of pain by the peripheral tissues is clinically relevant. About 19% of the pain variance was predicted by PRNA. Thus, peripheral pain and negative affect appear to be particularly relevant for overall FM pain and may represent important targets for future therapies.

Adult↗

The use of "overall accuracy" to evaluate the validity of screening or diagnostic tests.

OBJECTIVE: Evaluations of screening or diagnostic tests sometimes incorporate measures of overall accuracy, diagnostic accuracy, or test efficiency. These terms refer to a single summary measurement calculated from 2 x 2 contingency tables that is the overall probability that a patient will be correctly classified by a screening or diagnostic test. We assessed the value of overall accuracy in studies of test validity, a topic that has not received adequate emphasis in the clinical literature. DESIGN: Guided by previous reports, we summarize the issues concerning the use of overall accuracy. To document its use in contemporary studies, a search was performed for test evaluation studies published in the clinical literature from 2000 to 2002 in which overall accuracy derived from a 2 x 2 contingency table was reported. MEASUREMENTS AND MAIN RESULTS: Overall accuracy is the weighted average of a test's sensitivity and specificity, where sensitivity is weighted by prevalence and specificity is weighted by the complement of prevalence. Overall accuracy becomes particularly problematic as a measure of validity as 1) the difference between sensitivity and specificity increases and/or 2) the prevalence deviates away from 50%. Both situations lead to an increasing deviation between overall accuracy and either sensitivity or specificity. A summary of results from published studies (N = 25) illustrated that the prevalence-dependent nature of overall accuracy has potentially negative consequences that can lead to a distorted impression of the validity of a screening or diagnostic test. CONCLUSIONS: Despite the intuitive appeal of overall accuracy as a single measure of test validity, its dependence on prevalence renders it inferior to the careful and balanced consideration of sensitivity and specificity.

Diagnostic Techniques and Procedures↗

Effect of overall feedback inhibition in unbranched biosynthetic pathways.

We have determined the effects of control by overall feedback inhibition on the systemic behavior of unbranched metabolic pathways with an arbitrary pattern of other feedback inhibitions by using a recently developed numerical generalization of Mathematically Controlled Comparisons, a method for comparing the function of alternative molecular designs. This method allows the rigorous determination of the changes in systemic properties that can be exclusively attributed to overall feedback inhibition. Analytical results show that the unbranched pathway can achieve the same steady-state flux, concentrations, and logarithmic gains with respect to changes in substrate, with or without overall feedback inhibition. The analytical approach also shows that control by overall feedback inhibition amplifies the regulation of flux by the demand for end product while attenuating the sensitivity of the concentrations to the same demand. This approach does not provide a clear answer regarding the effect of overall feedback inhibition on the robustness, stability, and transient time of the pathway. However, the generalized numerical method we have used does clarify the answers to these questions. On average, an unbranched pathway with control by overall feedback inhibition is less sensitive to perturbations in the values of the parameters that define the system. The difference in robustness can range from a few percent to fifty percent or more, depending on the length of the pathway and on the metabolite one considers. On average, overall feedback inhibition decreases the stability margins by a minimal amount (typically less than 5%). Finally, and again on average, stable systems with overall feedback inhibition respond faster to fluctuations in the metabolite concentrations. Taken together, these results show that control by overall feedback inhibition confers several functional advantages upon unbranched pathways. These advantages provide a rationale for the prevalence of this control mechanism in unbranched metabolic pathways in vivo.

Biophysical Phenomena↗

Overall time in telecobalt therapy for T1 glottic carcinoma treated with 2 Gy per day.

BACKGROUND/AIM: We already reported the tumor response during radiotherapy as a prognostic factor for T1 glottic carcinoma. In these reports, we did not evaluate the overall treatment time. There were many reports of correlation between local control and overall treatment time of radiation for head and neck cancer. Our aim was to evaluate the overall treatment time as a prognostic factor of the local control for T1 glottic carcinoma or not. PATIENTS AND METHODS: From 1967 through 1985, 295 patients of T1 glottic carcinoma were treated with telecobalt therapy at the Department of Radiology, Osaka University Medical School. Of 295 patients, 219 patients treated with 2 Gy per day were evaluated. The median of total doses was 60 Gy (42 to 72 Gy). Overall treatment times of patients with tumor clearance at 40 Gy were significantly shorter than those with tumor persistence at 40 Gy. RESULTS: According to the univariate analysis, there were no statistically significant factors for local control except tumor response during treatment. Of 124 patients treated with a total dose of 60 Gy and the overall treatment time of 40 to 46 days, local control rates of patients treated with the overall treatment time of 40 to 42 days and 43 to 46 days were 88% and 78%, respectively (p = 0.3072). For 91 patients with tumor clearance at 40 Gy, local control rates of patients treated with the overall treatment time of 40 to 42 days and 43 to 46 days were 96% and 82%, respectively (p = 0.1645). Corresponding figures for 31 patients with tumor persistence at 40 Gy were 63% and 65%, respectively (p = 0.4227). CONCLUSION: We compare the treatment results of patients treated with the same total dose and the same tumor response during radiotherapy. We concluded that the overall treatment time was not a prognostic factor for T1 glottic tumor treated with overall time of 40 to 46 days.

Carcinoma↗

[Prolongation of latency or overall treatment time by unplanned radiation pauses. The clinical importance of compensation].

BACKGROUND AND PURPOSE: Local tumor control after radiotherapy does not only depend on total dose, dose per fraction and physical parameters but also on the time interval between surgery and begin of radiotherapy and on overall time of fractionated irradiation. This study summarizes the evidence for an impact of delay and overall time of radiotherapy on locoregional tumor control. METHODS: Published reports of the last 30 years were reviewed for evidence of a time factor, i.e., for an influence of overall treatment time on local tumor control. Overall, 33 nonrandomized studies and twelve randomized trials addressing this question were identified. RESULTS: Prolongation of waiting time between surgery and radiotherapy, dependent on tumor type and residual burden, decreases local control. Postoperative radiotherapy should be initiated early, whenever medically appropriate. Almost all nonrandomized and randomized trials indicate that prolongation of overall time of fractionated irradiation decreases local tumor control, particularly of squamous cell carcinoma of the head and neck and cervix, but also of non-small cell and small cell lung cancer. In these tumors prolongation of overall treatment time by 1 week results in a decrease of local control between 1-16%. CONCLUSION: Prescription of radiotherapy may not be limited to total dose and dose per fraction, but needs to include the parameter overall treatment time. Unscheduled treatment interruptions such as holidays, machine breakdown or patient-related factors, leading to protraction of the overall treatment time, decrease the chance of cure for the patient. Therefore, unplanned gaps need to be compensated by appropriate measures such as additional fractions at weekends or by applications of a second fraction per day.

Dose Fractionation, Radiation↗

Overall connectivity--a next generation molecular connectivity.

The development of molecular connectivity concept and some of its key elements - Randić's inverse-square-root function and the detailed subgraph characterization - are analyzed. The concept of overall connectivity recently advanced is presented as a next step in unfolding the ideas of molecular connectivity by combining them with those of molecular complexity. Definitions of overall connectivity index, eth-order overall connectivities, and overall connectivity vector are presented along with formulae for calculating these sets of topological indices for several classes of graphs of chemical relevance. Based on sums of adjacencies over all subgraphs (or up to a limiting subgraph size in large molecules), the overall connectivities increase both with molecule size and complexity, as expressed in branching and cyclicity of molecular skeleton. When applied to molecules containing heteroatoms, valence overall connectivities are constructed employing the Kier and Hall scheme. The usefulness of the novel indices is demonstrated by modeling physicochemical properties of alkane compounds. A detailed comparison is made with other models derived for the same set of compounds, proceeding from molecular connectivity, as well as with two other probe connectivity functions--the overall connectivity versions of the second Zagreb index, and a derivative inverse function of this index. The favorable comparisons indicate the need of molecular connectivity paradigm revisiting, and show the potential of the overall connectivity indices for QSPR/QSAR applications.

Alkanes↗

The addition of bicalutamide 150 mg to radiotherapy significantly improves overall survival in men with locally advanced prostate cancer.

PURPOSE: Castration therapy adjuvant to radiotherapy can significantly improve overall survival compared with radiotherapy alone in patients with locally advanced prostate cancer. Although many of the adverse effects of castration therapy are manageable, they can have a detrimental effect on quality of life. Here we evaluate the efficacy and tolerability of the non-castration-based therapy bicalutamide ('Casodex') 150 mg adjuvant to radiotherapy in patients with T1-4, M0, any n prostate cancer. METHODS: The subset of patients within the early prostate cancer (EPC) program who received radiotherapy with curative intent (n = 1,370) were included in the analysis. These patients were randomized to receive oral bicalutamide 150 mg once daily (n = 699) or placebo (n = 671). RESULTS: The median follow-up for patients included in this analysis was 7.2 years. In patients with locally advanced disease (n = 305), bicalutamide adjuvant to radiotherapy significantly improved: progression-free survival (PFS), reducing the risk of objective progression by 44% compared with radiotherapy alone [hazard ratio (HR) 0.56; 95% confidence interval (CI) 0.40, 0.78; P < 0.001). Prostate-specific antigen (PSA)-PFS, reducing the risk of PSA progression by 59% compared with radiotherapy alone (HR 0.41; 95% CI 0.30, 0.55; P < 0.001). Overall survival, reducing the risk of death by 35% compared with radiotherapy alone (HR 0.65; 95% CI 0.44, 0.95; P = 0.03). This significant overall survival benefit for bicalutamide was driven by a lower risk of prostate cancer-related deaths (16.1 vs 24.3%, respectively). There was no significant difference in PFS or overall survival in patients with localized disease (n = 1,065). CONCLUSIONS: In patients with locally advanced disease, bicalutamide 150 mg adjuvant to radiotherapy demonstrates significant clinical benefits in terms of overall survival, PFS and PSA-PFS compared with radiotherapy alone. The overall survival benefit in these patients is consistent with prior studies evaluating castration-based therapies adjuvant to radiotherapy (Bolla et al. in Lancet 360:103-108, 2002; Pilepich et al. in Int J Radiat Oncol Biol Phys 61:1285-1290, 2005). In addition, the clinical benefit of bicalutamide 150 mg in locally advanced patients, but not in those with localized disease, is consistent with the overall results from the EPC program (McLeod et al. BJU Int 97:247-254, 2006). Given the quality-of-life advantages of bicalutamide relative to castration, bicalutamide 150 mg adjuvant to radiotherapy is an attractive alternative for men with locally advanced prostate cancer.

Aged↗

Carcinoma of the uterine cervix. II. Lack of impact of prolongation of overall treatment time on morbidity of radiation therapy.

PURPOSE: Several reports document a negative impact of prolongation of overall treatment time in a course of irradiation on tumor control and survival. A correlation has been documented of incidence of significant treatment sequelae with increasing doses of irradiation, volume of the specific organ, and dose per fraction. However, no data were found on the potential correlation of overall irradiation treatment time with significant sequelae. METHODS AND MATERIALS: Records were reviewed of 1,269 patients with carcinoma of the cervix (Stage IB to HI) treated with definitive irradiation (combination of external beam and two intracavitary insertions). Follow-up was obtained in 97% of patients (median, 12 years; minimum, 3 years; maximum, 28 years). The relationships between overall treatment time and time of brachytherapy and incidence of treatment sequelae were analyzed for each stage. RESULTS: Overall incidence of Grades 2 (moderate) sequelae was 7% and of Grade 3 (severe) sequelae, 11%. There was no significant correlation of various incidences of Grade 2 and 3 sequelae with overall treatment times (8% in patients treated in less than 7 weeks, 9% in 7.1 to 9 weeks, and 12% when treatment time was longer than 9 weeks) (p = 0.08). In patients with Stage IB and IIA tumors, incidence of rectal toxicity (mostly proctitis) was comparable in patients treated in less than 7 or 7.1 to 9 weeks (4.1 and 6%, respectively) and slightly higher in those treated in longer periods (11.5%) (p = 0.24). In patients with Stage IIB and III, the incidence of Grade 2 and 3 small bowel morbidity was 2% in those treated in less than 7 weeks, 6% for 7.1 to 9 weeks, and 4.9% for longer times (p < or = 0.01). This increased morbidity was also correlated with total dose of irradiation to the lateral pelvic wall: 5 of 257 (2%) for less than 60 Gy and 21 of 438 (4.8%) for higher doses (p < or = 0.01). There was no significant correlation between the timing of brachytherapy (usually two low dose rate intracavitary insertions performed within 4.5 to 6.5 weeks of initiation of external beam therapy) and significant treatment sequelae. CONCLUSIONS: We observed a varied average incidence of Grade 2 and 3 morbidity in the bladder, rectum, and small intestine with different overall treatment times, without a definite pattern to suggest an impact of prolongation of treatment time on morbidity. Likewise, there was no significant correlation with the timing of intracavitary insertions and morbidity of therapy. Because prolongation of the overall treatment time has a well-documented detrimental effect on pelvic tumor control and survival in carcinoma of the cervix with no significant impact on morbidity, it is imperative to deliver radiation therapy in the shortest possible time and without schedule interruptions.

Aged↗

Influence of fraction size, total dose, and overall time on local control of T1-T2 glottic carcinoma.

PURPOSE: To evaluate the influence of fraction size, overall time, total dose, and other prognostic factors on local control of T1 and T2 glottic carcinomas. METHODS AND MATERIALS: Between 1956 and 1995, 398 consecutive patients with early glottic carcinoma (315 T1 and 83 T2) were treated with once-a-day definitive radiotherapy at the University of California, San Francisco, and associated institutions. Treatment was delivered 5 days per week. Minimum tumor dose ranged from 46.6 to 77.6 Gy (median: 63 Gy). The fraction size was < 1.8 Gy in 146; 1.8-1.99 Gy in 128; 2.0-2.24 Gy in 62, and > or = 2.25 Gy in 62 patients. Overall time ranged from 34 to 75 days (median: 50 days). The majority of patients treated with a fraction size of 2.25 Gy completed therapy within 43 days. Median follow-up of all alive patients was 116 months (range 3-436 months). RESULTS: Five-year local control was 85% for T1 and 70% for T2 glottic carcinomas (p = 0.0004). For T1 lesions, within the dose and time range evaluated, there was no apparent relationship between fraction size, overall time, total dose, and local control on multivariate analysis. Treatment era was the only significant prognostic factor (p = 0.02), and anterior commissure (AC) involvement was of borderline significance (p = 0.056). Five-year local control was 77% for patients treated between 1956-1970, 89% for between 1971-1980, and 91% for between 1981-1995; 80% for patients with AC involvement and 88% for those without. For T2 lesions, prognostic factors for local control on multivariate analysis were: overall time (p = 0.003), fraction size (p = 0.003), total dose (p = 0.01), impaired vocal cord mobility (p = 0.02), and subglottic extension (p = 0.04). Five-year local control was 100% for T2 lesions treated with overall time < or = 43 days vs. 84% for overall time > 43 days; 100% for fraction size > or = 2.25 Gy vs. 44% for fraction size < 1.8 Gy; 78% for total dose > 65 Gy vs. 60% for total dose < or = 65 Gy; 79% for normal cord mobility vs. 45% for impaired cord mobility, and 58% for lesions with subglottic extension vs. 77% for those without. The severe complication rate for the entire group was low: 1.8%. CONCLUSIONS: Total dose, fraction size, and overall time were significant factors for local control of T2 but not T1 glottic carcinomas. Anterior commissure involvement was associated with decreased local control for T1 but not T2 lesions. For T1 lesions, local control improved over the treatment era. For T2 lesions, local control decreased with impaired cord mobility and subglottic extension.

Adult↗

Relationship of domain-specific measures of health to perceived overall health among older subjects.

The associations between nine domain-specific measures of health (e.g., depressive symptoms, psychological distress, mental health, physical functioning, role functioning, social functioning, bodily pain, somatic symptoms, and chronic medical morbidity) and a single-item measure for perceived overall health were studied in an extensive community-based sample of elderly persons (n = 5279). The results showed that: (1) the discriminative power of perceived overall health compared to domain-specific measures of health was moderate to large only at the fair/poor end of the perceived overall health spectrum; (2) a single-item measure of perceived overall health did not cover domain-specific measurements of health since only 41.8% of the variance in perceived overall health was explained by all domain-specific measures; and (3) the affective domains of functioning (psychological distress, mental health) were weakly related to perceived overall health. Bodily pain, chronic medical morbidity and, to a lesser extent, physical functioning were more strongly related to perceived overall health. These results were fairly consistent for men and women and for three age groups. We conclude that a global, single-item measure of perceived health and domain-specific health measures are not exchangeable in evaluation, survey, or epidemiological research.

Activities of Daily Living↗

Measurement uncertainty associated with overall migration testing.

The results from a single laboratory that took part in a series of check-sample exercises for overall migration were used to calculate the measurement uncertainty for the overall migration methodology. The results span 10 years of proficiency testing and cover a range of plastic materials tested using a variety of time and temperature test conditions. Twelve sets of results for overall migration into olive oil and 10 sets of results for overall migration into volatile simulants were used. The measurement uncertainty associated with the determination of overall migration from plastics into olive oil was estimated as +/- 2.6 mg dm-2 for results between 1.2 and 15.4 mg dm-2. The measurement uncertainty associated with the determination of overall migration into volatile simulants was estimated as +/- 1.4 mg dm-2 for results between 2.1 and 13 mg dm-2. These estimates are within the analytical tolerances set in European Union regulations, of 3 and 2 mg dm-2, respectively. The performance of all laboratories participating in these 22 check sample exercises was also evaluated. A very large majority (93%) of the participants used official test methods, sometimes with minor modifications as stated. For the simulant olive oil, an average of 81% of laboratories (13 rounds with an average of 21 participants in each) using official methods was within the tolerance specified in regulations. For the volatile food simulants, an average of 87% of laboratories (11 rounds with an average of 38 participants in each) using official methods was within the tolerance specified. It is concluded from this evaluation of within- and between-laboratory data that the official European Standard methods for overall migration testing are suitable for the analysis of routine samples.

Dietary Fats, Unsaturated↗

The time of day of food intake influences overall intake in humans.

Circadian and diurnal rhythms affect food intake, and earlier research has suggested that meal sizes increase, whereas the after-meal intervals and satiety ratios decrease over the day. We hypothesized that the time of day of food intake would be related to total intake such that intake early in the day would tend to reduce overall intake, whereas intake later in the day would tend to increase intake over the entire day. The intakes of 375 male and 492 female free-living individuals, previously obtained via 7-d diet diaries, were reanalyzed. The total and meal intakes of food energy, the amounts of the macronutrients ingested and the density of intake occurring during five 4-h periods (0600-0959, 1000-1359, 1400-1759, 1800-2159 and 2200-0159 h) were identified and related to overall and meal intakes during the entire day. The proportion of intake in the morning was negatively correlated with overall intake (r=-0.13, P<0.01), whereas the proportion ingested late in the evening was positively correlated with overall intake (r=0.14, P<0.01). The energy densities of intake during all periods of the day were positively related to overall intake (range, r=0.13-0.23, P<0.01). The results suggest that low energy density intake during any portion of the day can reduce overall intake, that intake in the morning is particularly satiating and can reduce the total amount ingested for the day, and that intake in the late night lacks satiating value and can result in greater overall daily intake.

Adult↗