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Classification of sleep stage with period analysis features derived from the EEG.

This paper details our experience with the use of regression analysis and discriminant analyses, combined with a Bayes classifier, to evaluate the usefulness of a series of features derived in real time from a single channel of EEG. These features were 1) the number of zero crossings, 2) the number of zero crossings of the first derivative of the EEG, and 3) the number of zero crossings of the second derivative and five additional "histogram" measures. Each histogram measure represented the number of occurrences of a zero crossing interval falling within an arbitrarily selected range of values. The distributions of several measures conditioned on sleep stage are presented along with night-to-night and subject-to-subject variations in the measures. These details provide a basis for understanding effectiveness and limitations of zero crossing measures and the regression and discriminant analysis techniques. Our results permitted a range of 57-90% accurate classification with just zero crossing measures with the cross-correlation between computer- and hand-scored nightly sleep patterns ranging from 0.63-0.94. We consider these to be good and acceptable accuracies for this type of analysis.

Electroencephalography↗

Spectral analysis vs. period-amplitude analysis of narrowband EEG activity: a comparison based on the sleep delta-frequency band.

This paper presents a comparison of spectral analysis with period-amplitude analysis when applied to the quantification of narrowband electroencephalographic (EEG) activity. In particular, it examines their respective usefulness in quantifying on the average the electrographic content within the delta-frequency band of EEG epochs during human stage 4 sleep. It is shown that while the power spectrum efficiently quantifies the overall power trends in the EEG data, period-amplitude analysis seems to offer more resolution than the power spectrum in detecting electrographic details in amplitude and incidence within relatively narrow frequency bands. Examples are given of the sensitivity of spectral analysis ot both wave amplitude and incidence, and of the fact that--due to the inherent averaging process in the power spectrum generation--spectral analysis cannot differentiate between low-amplitude, high-incidence EEG activity and high-amplitude, low-incidence EEG activity, in contradistinction to period-amplitude analysis. It is also shown that although two EEG epochs may exhibit similar power spectrum plots, their corresponding period-amplitude plots may not be similar. It is emphasized that discrepancies may exist when comparing spectral to period-amplitude analysis due to differences in the definition of "frequency" in the two techniques.

Adult↗

Long-term survival of children with neuroblastoma prior to the neuroblastoma screening project in Germany.

BACKGROUND: In the last decades, prognosis of children with neuroblastoma has improved only slightly. Traditional estimates of survival reflect the survival experience of children diagnosed many years ago, and may thus not capture more recent progress in prognosis. We applied a new method of survival analysis, denoted period analysis, to provide more up-to-date estimates of long-term prognosis. We selected the cases diagnosed before the German neuroblastoma screening project in 1995, allowing to assess the method by comparing the 1994 projected survival estimates with the observations made today (2000). PROCEDURE: The data comes from the population based German Childhood Cancer Registry. We included all 1,353 children diagnosed with neuroblastoma below age 15 between 1980 and 1994. We derived 5-, 10-, and 15-year survival estimates using traditional analysis or period analysis as needed. Where possible we compared the period analysis estimates with the later obtained actual estimates. We showed trends in survival for the sample as a whole and for prognostic subgroups. RESULTS: Survival probabilities increased over time especially in the subgroups with poor prognosis. Short-term survival probabilities improved more than long-term survival probabilities. Evaluation of the period-analysis estimates showed them to provide accurate and timely projections of prognosis of newly diagnosed patients. CONCLUSIONS: The results suggest major improvements in prognosis of children with neuroblastoma, even prior to the start of the German neuroblastoma screening project, especially in advanced disease. This could have been disclosed with the application of the period analysis method in 1995 even then with considerable accuracy. We recommend a more widespread application of this method especially in population-based cancer registries.

Adolescent↗

The temporal variations of (7)Be, (210)Pb and (210)Po in air in England.

We have conducted measurements of naturally occurring radionuclides (7)Be, (210)Pb and (210)Po in air at ground level at Chilton, Oxfordshire, England. The sampling and analysis regime for the latter two isotopes has been optimised to minimise uncertainties in measurement due to decay of (210)Po and in-growth of (210)Pb during the sampling and analysis period. Analysis times were reduced by using Cerenkov counting to assay the (210)Bi daughter of (210)Pb. Monthly data collected over a four-year period are presented and discussed. (7)Be activity concentrations appear to peak in spring. (210)Pb activity concentrations also follow a seasonal trend reflecting different (222)Rn emanation rates from soil during winter and summer. Data for (210)Po show no such trend.

Air Pollutants, Radioactive↗

Long-term cancer patient survival achieved by the end of the 20th century: most up-to-date estimates from the nationwide Finnish cancer registry.

A new method of survival analysis, denoted period analysis, has recently been developed, which has been shown to provide more up-to-date estimates of long-term survival rates than traditional methods of survival analysis. We applied period analysis to data from the nationwide Finnish cancer registry to provide up-to-date estimates of 5-, 10-, 15- and 20-year relative survival rates (RSR) achieved by the end of the 20th century. For most forms of cancer, period estimates of long-term survival are much higher than corresponding traditional survival estimates which suggests that for these cancers there has been ongoing major progress in survival rates in recent years which so far has remained undisclosed by traditional methods of survival analysis. For example, period analysis reveals that 10 year RSR have come close to (or even exceed) 80% for cancer of the corpus uteri and melanoma, 75% for breast cancer, 70% for bladder cancer, 65% for cancer of the cervix uteri, and 55% for cancer of the colon and prostate. Period analysis further reveals that 20 year RSR have now come close to (or even exceed) 75% for endometrial cancer and melanoma, 60% for breast cancer and cervical cancer, 55% for colon cancer and bladder cancer, and 40%-50% for cancer of the rectum, the ovaries, kidneys and nervous system.

Age Factors↗

More up-to-date monitoring of long-term survival rates by cancer registries: an empirical example.

A few years ago, a new method of survival analysis, denoted period analysis, has been developed to derive more up-to-date estimates of long-term survival rates of cancer patients, but this method has rarely been applied so far. Using empirical examples from the Saarland Cancer Registry, we illustrate how seriously traditional long-term survival estimates may lag behind survival expectations of newly diagnosed cancer patients in the case of recent improvement in prognosis, and to what extent this problem may be reduced by period analysis of survival. We conclude that period analysis should be more widely used for deriving more up-to-date long-term survival estimates.

Aged↗

An alternative approach to statistical age-period-cohort analysis.

Age-period-cohort analysis has generated considerable interest in epidemiology, but the model has fundamental problems which have been discussed by Kupper et al. While one can agree that the age-period-cohort model should be used with caution, it should also be noted that some useful inferences can be made with the model. The problems raised by Kupper et al. are discussed in terms of estimable functions of the parameters, which are not affected by arbitrary constraints on the parameters. The use of these methods are illustrated and specific examples presented where age-period-cohort models can be used effectively.

Aging↗

Long-term survival of children with leukemia achieved by the end of the second millennium.

BACKGROUND: The prognosis for patients with childhood leukemia has improved steadily over the last decades due to major progress in therapy. Much of this progress remains unaccounted for in traditional estimates of long-term survival rates, which essentially reflect the survival experience of patients who were diagnosed many years ago. METHODS: The authors applied a new method of survival analysis, called period analysis, to provide up-to-date estimates of long-term survival rates. The analysis is based on data from the nationwide German Childhood Cancer Registry and includes 8059 children who were diagnosed with leukemia between 1981 and 1998. The most up-to-date 5-year, 10-year, and 15-year survival estimates were obtained by period analysis and were compared with to the most up-to-date survival estimates from traditional methods of survival analysis. RESULTS: Period estimates (95% confidence intervals) of 5-year, 10-year, and 15-year survival rates achieved by 1998 were 81% (79-83%), 77% (74-79%), and 73% (70-76%), respectively, for all patients with leukemia combined; 86% (84-88%), 81% (79-84%), and 77% (74-81%), respectively, for patients with acute lymphocytic leukemia; and 59% (53-65%), 59% (53-65%), and 57% (49-64%), respectively, for patients with acute nonlymphocytic leukemia. Substantially lower estimates would have been obtained with traditional methods of survival analysis. CONCLUSIONS: These results from one of the world's largest childhood cancer registries reveal that cure rates of childhood leukemia achieved by the end of the second millennium are higher than suggested by previous estimates based on traditional methods of survival analysis.

Adolescent↗

Hybrid analysis for up-to-date long-term survival rates in cancer registries with delayed recording of incident cases.

Up-to-date monitoring of long-term survival is an important task of population-based and clinical cancer registries. A few years ago, a new method of survival analysis, denoted period analysis, was introduced to provide more up-to-date estimates of long-term survival. However, a prototypical period analysis may not be applicable in situations with delayed recording of incident cases. We introduce herein a hybrid type of analysis that combines elements of both traditional and period analyses which may still be feasible in such settings. The performance of the hybrid type of analysis compared with other design options is empirically evaluated and illustrated for children diagnosed with cancer in the United States. The empirical evaluation indicates that hybrid analysis may be useful to derive more up-to-date estimates of long-term survival compared with traditional design options if there is a strong improvement of survival over time, even in situations with a substantial delay in recording of incident cases.

Adolescent↗

Tropomyosin has discrete actin-binding sites with sevenfold and fourteenfold periodicities.

Analysis of the periodic distribution of amino acids in tropomyosin has revealed the presence of seven or 14 quasi-equivalent actin-binding sites. We tested the hypothesis of periodic actin-binding sites by making deletions of chicken striated alpha-tropomyosin cDNA using oligonucleotide-directed mutagenesis. The deletions corresponded to one-half (amino acid residues 47 to 67), two-thirds (residues 47 to 74) and one actin-binding site (residues 47 to 88), on the basis of there being seven sites. The mutant cDNAs were expressed as fusion and non-fusion proteins in Escherichia coli and analyzed for actin binding and regulatory function. Fusion tropomyosin binds to actin with an affinity similar to that of muscle tropomyosin. Of the mutant fusion tropomyosins, only that with a full site deleted retained actin affinity and the ability to inhibit the actomyosin S1 ATPase, though it was less effective than wild-type. We conclude that an integral number of half-turns of the tropomyosin coiled-coil, and the consequential sevenfold periodicity, as well as the correct orientation of the ends with respect to each other, are important for actin binding. On the other hand, non-fusion tropomyosin binds well to actin only in the presence of troponin, and the binding is calcium-sensitive. Assay of non-fusion mutant tropomyosins showed that mutants with deletion of one-half and one actin binding site both had high affinity for actin, equal to or slightly less than wild-type. The ability of these two mutants to regulate the actomyosin or acto-S1 ATPase with troponin in the absence of calcium was indistinguishable from that of the wild-type. The normal regulatory function of the mutant with a 1/14 deletion (removal of a quarter turn or half a site) indicates that a 14-fold periodicity is adequate for regulation, consistent with the presence of two sets of seven alpha and seven beta quasi-equivalent actin-binding sites. An alternative explanation is that the alpha-sites are of primary importance and that proper alignment of the alpha-sites in every second tropomyosin, as when half a site is deleted, is sufficient for normal regulatory function. Deletion of a non-integral period (2/3 of a site) severely compromised actin-binding and regulatory function, presumably due to the inability of the mutant to align properly on the actin filament.

Actins↗

Combining cohort and period methods for retrospective time trend analyses of long-term cancer patient survival rates.

Assessing trends in long-term cancer patient survival is an essential component of monitoring progress against cancer by cancer registries. Traditional assessment of long-term survival ('cohort analysis') is very useful to disclose trends in long-term survival rates of patients diagnosed many years ago, but it does not allow the disclosure of recent trends in long-term survival rates. The latter can be achieved by an alternative method of survival analysis ('period analysis'), which has been proposed a few years ago. On the other hand, unlike cohort analysis, period analysis does not provide estimates of long-term survival rates for patients diagnosed in the early years after initiation of cancer registration. In this paper, a method of retrospective analysis of time trends in long-term survival rates is introduced, which combines the advantages of both cohort and period analysis ('mixed analysis'). This method thereby allows for a comprehensive monitoring of trends in long-term survival over an extended time span from the earliest to the most recent years of cancer registration. The use of the method is illustrated for retrospective time trend analyses of long-term survival of cancer patients in the United States with the 1973-1999 database of the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute.

Cohort Studies↗

An empirical evaluation of period survival analysis using data from the Canadian Cancer Registry.

OBJECTIVE: To provide an empirical evaluation of the performance of period analysis in comparison to traditional methods of survival analysis for predicting future 5-year cancer survival using data from the Canadian Cancer Registry. METHODS: 5-year relative survival estimates were derived by period and traditional methods of analysis using data available at the conclusion of 1997. The extent to which these estimates agreed with survival later observed for cancer cases diagnosed in 1997 was quantified by calculating the squared difference of the estimate to the corresponding relative survival ratio actually observed. RESULTS: Period analysis was observed to be superior to, or comparable with, cohort analysis in predicting the average 5-year relative survival observed later for virtually all individual cancer sites studied. The improvement in survival estimation was most pronounced for prostate cancer. Where period estimates did not match the eventually observed value, they were predominantly on the lower side. Complete analysis estimates were generally observed to be in between the cohort and period values. CONCLUSIONS: The period method of survival analysis provides more up-to-date estimates of 5-year survival than do traditional cohort-based methods.

Adolescent↗

The effect of increased prescription drug cost-sharing on medical care utilization and expenses of elderly health maintenance organization members.

OBJECTIVES: The nature and extent of prescription drug benefits for the elderly are a continuing concern for health-care managers and policy makers. This study examined the impact of increased prescription drug cost-sharing on the drug and medical care utilization and expenses of the elderly. METHODS: Two groups of well-insured Medicare risk-based members of a large health maintenance organization (HMO) had their copayments increased in different years during a 3-year period. Four 2-year analysis periods were established for comparing these elderly groups. During one analysis period, copayments did not change in either group. RESULTS: Moderate increases of from $1 to $3, from $3 to $5 per copayment, and from 50% per dispensing to 70% per dispensing with a maximum payment per dispensing resulted in lower annual per capita prescription drug use and expenses. No consistent annual changes were observed in either medical care utilization (office visits, emergency room visits, home health-care visits, hospitalizations) or total medical care expenses across analysis periods. CONCLUSIONS: No consistent relationships were observed between increased copayments per dispensing and medical care utilization and expense. Future research needs to address the impact on the classes of medications received and related health status, and the impact of larger increases in copayments per dispensing on medical care and health-related factors.

Aged↗

Analysis of mortality data from the former USSR: age-period-cohort analysis.

The objective of this article is to review research on age-period-cohort (APC) analysis of mortality and to trace the effects of contemporary and historical factors on mortality change in the former USSR. Several events in USSR history have exerted a lasting influence on its people. These influences may be captured by an APC model in which the period effects measure the impact of contemporary factors and the cohort effects the past history of individuals which cannot be attributed to age or stage in the life cycle. APC models are extensively applied in the study of mortality. This article presents the statistical theory of the APC models and shows that they belong to the family of generalized linear models. The parameters of the APC model may therefore be estimated by any package of loglinear analysis that allows for hybrid loglinear models.

Adolescent↗