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PubMed2003

Should single or distributed parameters be used to explain the steepness of tumour control probability curves?

Linear quadratic (LQ) modelling allows easy comparison of different fractionation schedules in radiotherapy. However, estimating the radiation effect of a single fractionated treatment introduces many questions with respect to the parameters to be used in the modelling process. Several studies have used tumour control probability (TCP) curves in order to derive the values for the LQ parameters that may be used further for the analysis and ranking of treatment plans. Unfortunately, little attention has been paid to the biological relevance of these derived parameters, either for the initial number of cells or their intrinsic radiosensitivity, or both. This paper investigates the relationship between single values for the TCP parameters and the resulting dose-response curve. The results of this modelling study show how clinical observations for the position and steepness of the TCP curve can be explained only by the choice of extreme values for the parameters, if they are single values. These extreme values are in contradiction with experimental observations. This contradiction suggests that single values for the parameters are not likely to explain reasonably the clinical observations and that some distributions of input parameters should be taken into consideration.

Cell Survival↗

PubMed2003

Mitochondrial theory of aging: importance to explain why females live longer than males.

Females live longer than males in many species, including humans. This can be explained on the basis of the mitochondrial theory of aging. Mitochondria from females produce significantly less hydrogen peroxide than those from males and have higher levels of mitochondrial reduced glutathione, manganese superoxide dismutase, and glutathione peroxidase than males. Oxidative damage to mitochondrial DNA is also fourfold higher in males than in females. These differences may be explained by estrogens. Ovariectomy abolishes the gender differences between males and females and estrogen replacement rescues the ovariectomy effect. The challenge for the future is to find molecules that have the beneficial effects of estradiol, but without its feminizing effects. Phytoestrogens or phytoestrogen-related molecules may be good candidates to meet this challenge.

Aging↗

PubMedDate not supplied

Can obesity explain the racial difference in stage of breast cancer at diagnosis between black and white women?

OBJECTIVE: Black women are more likely to be diagnosed at a more advanced stage of breast cancer than are white women. Traditionally, this has been attributed in part to social or cultural factors. Given that black women are more likely to be obese than white women and that being obese is associated with a more advanced stage at diagnosis, this study aims to assess to what extent the racial difference in stage at diagnosis can be explained by racial differences in obesity. METHODS: Incident cases of breast cancer between 1991 and 1997 (white, n = 585; black, n = 381) were identified from hospitals in the Baltimore metropolitan area. Information, including age, race, weight, height, and pathology reports, was obtained from hospital medical records. RESULTS: Black women were more likely than white women to be diagnosed with breast cancer at tumor-node-metastasis (TNM) stage II or greater (age-adjusted odds ratio [OR] = 1.51, 95% confidence interval [CI] 1.15-1.99). Further, black women were more likely than white women to be overweight or obese. A high body mass index (BMI) was significantly associated with an advanced stage of breast cancer at diagnosis. Adjustment for the higher prevalence of obesity in black women attenuated the risk estimate of more advanced stage of breast cancer at diagnosis in black women compared with white women by approximately 30%. CONCLUSIONS: Our results suggest that the higher prevalence of obesity among black women plays an important role in explaining their relative disadvantage in stage at diagnosis of breast cancer. Nonetheless, a racial difference in stage of breast cancer at diagnosis persists after adjustment for obesity.

Adult↗

PubMed2000

Racial disparity in pregnancy-related mortality associated with livebirth: can established risk factors explain it?

The authors conducted a nested case-control study to determine whether the fourfold increased risk of pregnancy-related mortality for US Black women compared with White women can be explained by racial differences in sociodemographic and reproductive factors. Cases were derived from a national surveillance database of pregnancy-related deaths and were restricted to White women (n = 840) and Black women (n = 448) whose pregnancies resulted in a livebirth and who died of a pregnancy-related cause between 1979 and 1986. Controls were derived from national natality data and were randomly selected White women and Black women who delivered live infants and did not die from a pregnancy-related cause (n = 5,437). Simultaneous adjustment for risk factors by using logistic regression did not explain the racial gap in pregnancy-related mortality. The largest racial disparity occurred among women with the lowest risk of pregnancy-related death: those of low to moderate parity who delivered normal-birth-weight babies (adjusted odds ratio = 3.53, 95% confidence interval: 2.9, 4.4). In contrast, no racial disparity was found among women with the highest risk of pregnancy-related death: high-parity women who delivered low-birth-weight babies. These findings indicate that reproductive health care professionals need to develop strategies to reduce pregnancy-related deaths among both high- and low-risk Black women.

Adolescent↗

PubMed2000

Does improvement in case ascertainment explain the increase in sporadic Creutzfeldt-Jakob disease since 1970 in the United Kingdom?

The aim of this study was to quantify the improvements in case ascertainment which are considered to explain the rise in the incidence of sporadic Creutzfeldt-Jakob disease. The numbers of cases, falling into five 10-year age groups starting at the age of 30 and three calendar periods of report since 1970, were analyzed by Poisson regression, assuming a constant age distribution. The age-period and age-cohort models were applied and discussed. The age-period model showed that underreporting in 1970-1979 was greater among patients aged 70 years or older. The age-cohort model indicated that a cohort factor increased over the first half of the 20th century (e.g., the incidence in the generation born in 1940 was almost twice that in the generation born in 1920); this increase was probably an artifact due to the past underascertainment pattern. However, from a statistical viewpoint, both models lead to a good fit; the cohort factor may appear to be as relevant as the period factor in describing the trends in incidence. Thus, one can imagine an unlikely worst case scenario, assuming that an unknown cohort factor is involved. In that case, the age-cohort model gives more optimistic predictions than Neilson's model (BMJ 1996;312:1038-9). These results are consistent with both interpretations: The rise in incidence is governed by improvements in case ascertainment, and is greater among old people (the most accepted interpretation); this rise may depend on a cohort factor as well, which may correspond to the zoonotic hypothesis (a totally hypothetical interpretation). Interpreting the increase of sporadic Creutzfeldt-Jakob disease over generations in terms of exposure to putative environmental factors is still a matter of debate; ongoing epidemiologic surveys may provide more information. Presently, this increase can be explained as an artifact due to the past underreporting pattern, with 79% (95% confidence interval: 56, 90) of the cases among persons aged > or =70 years being missed in 1970-1979.

Adult↗

PubMed2005

Explaining the decline in coronary heart disease mortality in Finland between 1982 and 1997.

In Finland since the 1980s, coronary heart disease mortality has declined more than might be predicted by risk factor reductions alone. The aim of this study was to assess how much of the decline could be attributed to improved treatments and risk factor reductions. The authors used the cell-based IMPACT mortality model to synthesize effectiveness of treatments and risk factor reductions with data on treatments administered to patients and trends in cardiovascular risk factors in the population. Cardiovascular risk factors were measured in random samples of patients in 1982 (n=8,501) and 1997 (n=4,500). Mortality and treatment data were obtained from the National Causes of Death Register, Hospital Discharge Register, social insurance data, and medical records. Estimated and observed changes in coronary heart disease mortality were used as main outcome measures. Between 1982 and 1997, coronary heart disease mortality rates declined by 63%, with 373 fewer deaths in 1997 than expected from baseline mortality rates in 1982. Improved treatments explained approximately 23% of the mortality reduction, and risk factors explained some 53-72% of the reduction. These findings highlight the value of a comprehensive strategy that promotes primary prevention programs and actively supports secondary prevention. It also emphasizes the importance of maximizing population coverage of effective treatments.

Adult↗

PubMed2007

A model explaining genotypic and ontogenetic variation of leaf photosynthetic rate in rice (Oryza sativa) based on leaf nitrogen content and stomatal conductance.

BACKGROUNDS AND AIMS: Identification of physiological traits associated with leaf photosynthetic rate (Pn) is important for improving potential productivity of rice (Oryza sativa). The objectives of this study were to develop a model which can explain genotypic variation and ontogenetic change of Pn in rice under optimal conditions as a function of leaf nitrogen content per unit area (N) and stomatal conductance (g(s)), and to quantify the effects of interaction between N and g(s) on the variation of Pn. METHODS: Pn, N and g(s) were measured at different developmental stages for the topmost fully expanded leaves in ten rice genotypes with diverse backgrounds grown in pots (2002) and in the field (2001 and 2002). A model of Pn that accounts for carboxylation and CO diffusion processes, and assumes that the ratio of internal conductance to g(s) is constant, was constructed, and its goodness of fit was examined. KEY RESULTS: Considerable genotypic differences in Pn were evident for rice throughout development in both the pot and field experiments. The genotypic variation of Pn was correlated with that of g(s) at a given stage, and the change of Pn with plant development was closely related to the change of N. The variation of g(s) among genotypes was independent of that of N. The model explained well the variation in Pn of the ten genotypes grown under different conditions at different developmental stages. Conclusions The response of Pn to increased N differs with g(s), and the increase in Pn of genotypes with low g(s) is smaller than that of genotypes with high g(s). Therefore, simultaneous improvements of these two traits are essential for an effective breeding of rice genotypes with increased Pn.

Electric Conductivity↗

PubMed2025

SetBERT: the deep learning platform for contextualized embeddings and explainable predictions from high-throughput sequencing.

MOTIVATION: High-throughput sequencing (HTS) is a modern sequencing technology used to profile microbiomes by sequencing thousands of short genomic fragments from the microorganisms within a given sample. This technology presents a unique opportunity for artificial intelligence to comprehend the underlying functional relationships of microbial communities. However, due to the unstructured nature of HTS data, nearly all computational models are limited to processing DNA sequences individually. This limitation causes them to miss out on key interactions between microorganisms, significantly hindering our understanding of how these interactions influence the microbial communities as a whole. Furthermore, most computational methods rely on post-processing of samples which could inadvertently introduce unintentional protocol-specific bias. RESULTS: Addressing these concerns, we present SetBERT, a robust pre-training methodology for creating generalized deep learning models for processing HTS data to produce contextualized embeddings and be fine-tuned for downstream tasks with explainable predictions. By leveraging sequence interactions, we show that SetBERT significantly outperforms other models in taxonomic classification with genus-level classification accuracy of 95%. Furthermore, we demonstrate that SetBERT is able to accurately explain its predictions autonomously by confirming the biological-relevance of taxa identified by the model. AVAILABILITY AND IMPLEMENTATION: All source code is available at https://github.com/DLii-Research/setbert. SetBERT may be used through the q2-deepdna QIIME 2 plugin whose source code is available at https://github.com/DLii-Research/q2-deepdna.

Deep Learning↗

PubMed1991

Multilevel modelling of longitudinal cephalometric data explained for orthodontists.

Multilevel modelling of longitudinal data is an important new statistical technique. In this article some of the basic concepts and ideas of multilevel modelling are explained. The model is introduced by showing how individual and average growth can be modelled. The intercept, linear and quadratic coefficient, between and within variance, fixed and random part, and other concepts of multilevel modelling are explained. Attention is also given to the reading of statistical tables of the results of multilevel analysis. In the conclusion some of the advantages of multilevel modelling of cephalometric data are mentioned.

Aging↗

PubMed1996

Explaining variations in the frequency of night visits in general practice.

BACKGROUND AND OBJECTIVE: The study identifies factors which explain variations in the frequency of night visits made by general practitioners, and is based on a cross-section regression analysis of practices in Lincolnshire in 1993. METHOD: The independent variables comprise 22 general practice characteristics, related to health and socio-demographic structure of practice lists, practice management and organization, location and social deprivation. RESULTS AND CONCLUSIONS: A final model containing 6 of the 22 variables originally entered succeeds in explaining 72 per cent of the variation in the frequency of night visits per GP per quarter-year. These variables are average list size per GP, frequency of home visits, maternity claims, list inflation owing to the influx of temporary residents, the number of proximate practices and unemployment.

Adult↗

PubMed2001

Explaining the role of sex on disability: a population-based study.

PURPOSE: There is no clear consensus about how sex influences prevalent disability and through what mechanisms. We investigated whether sex had a direct independent effect on disability or whether sex had an interactive effect on the relationship between chronic diseases/conditions and disability, and whether these effects differed in middle-aged versus older adults. DESIGN AND METHODS: We used baseline data from two nationally representative health interview surveys, the Health and Retirement Study (HRS) and the Study of Asset and Health Dynamics Among the Oldest Old (AHEAD), and disability and covariate measures that were nearly identical in both surveys. Logistic regression models tested the contributions of diseases, impairments, and demographic and social characteristics on difficulties with prevalent activities of daily living (ADLs), mobility, and strength. RESULTS: Models demonstrated no direct sex effect for ADL disability in either age group after adjusting for key covariates. However, sex did exert an indirect effect on ADL disability in older adults via musculoskeletal conditions and depressive symptoms. In contrast, female sex remained strongly associated with mobility and strength disability in both age groups, net of covariates. Major interactions were also significant, including a female sex/body mass index (BMI) interaction for mobility difficulty and several sex-disease interactions for strength disability in the middle-aged group. IMPLICATIONS: The effect of sex on ADL difficulty is largely explained by social and health-related covariates in middle-aged and older adults. In contrast, the independent association of female sex with decreased strength and mobility in both groups cannot be explained by our models' social or health-related variables. In addition, the positive association of BMI with mobility difficulty is significantly worse for women than for men.

Activities of Daily Living↗

PubMed2006

Does subfertility explain the risk of poor perinatal outcome after IVF and ovarian hyperstimulation?

BACKGROUND: The primary objective of this study was to investigate whether subfertility explains poor perinatal outcome after assisted conception. A secondary objective was to test the hypothesis that ovarian hyperstimulation rather than the IVF procedure may influence the perinatal outcome. METHODS: Using data from a Dutch population-based historical cohort of women treated for subfertility, we compared perinatal outcome of singletons conceived after controlled ovarian hyperstimulation (COHS) and IVF (IVF + COHS; n = 2239) with perinatal outcome in subfertile women who conceived spontaneously (subfertile controls; n = 6343) and in women who only received COHS (COHS only; n = 84). Furthermore, we compared perinatal outcome of singletons conceived after the transfer of thawed embryos with (Stim + Cryo; n = 66) and without COHS (Stim - Cryo; n = 73). RESULTS: The odds ratios (ORs) for very low birthweight (<1500 g) and low birthweight (1500-2500 g) were 2.8 [95% confidence interval (95% CI) 1.9-3.9] and 1.6 (95% CI 1.2-1.8) in the IVF + COHS group compared with the subfertile control group. The ORs for very preterm birth (<32 weeks) and for preterm birth (32-37 weeks) were 2.0 (95% CI 1.4-2.9) and 1.5 (95% CI 1.3-1.8), respectively. Adjustment for confounders did not materially change these risk estimates. The difference in risk between the COHS-only group and the subfertile group was significant only for very low birthweight (OR 3.5; 95% CI 1.1-11.4), but the association became weaker after adjustment for maternal age and primiparity (OR 3.1; 95% CI 1.0-10.4). No significant difference in birthweight and preterm delivery was found between the group of children conceived after ovarian stimulation/ovulation induction and (Stim + Cryo) and the group of children conceived after embryo transfer of thawed embryos in a spontaneous cycle without ovarian stimulation/ovulation induction (Stim - Cryo). CONCLUSIONS: The poor perinatal outcome in this database could not be explained by subfertility and suggests that other factors may be important in the known association between assisted conception and poor perinatal outcome.

Adult↗

PubMed1990

Can changes in the unemployment rates explain the recent changes in suicide rates in developed countries?

Data were collected on unemployment and suicide rates in 16 developed countries for 1973 and 1983 (suicide rates were three-year averages). Unemployment rates rose appreciably in men and women in all countries. Among men suicide rates rose in 14 of the countries whereas among women they did so in only seven. A mathematical model was developed to investigate, for those countries with increased suicide rates, how much of the increase could be contributed by an increase in the numbers unemployed. It was found that the proportion of the increase that could be 'explained' varied considerably between countries. In general the amount of the increase explained was small, and often a considerable increase in the suicide rates among those employed would be required to account for the observed increase in the suicide in the whole population. It is concluded that unemployment shows an inconsistent relationship with suicide. Further, if a relationship does exist in some countries the effect may be as much a generalized one on the whole population as a specific effect on the unemployed. Finally the possible effects of unemployment on suicide differ appreciably between men and women.

Adolescent↗

PubMed1995

Ways of seeing: explaining variations in use of acute hospital services.

BACKGROUND: In the US Medicare programme, hospitals are paid directly by activity. To provide incentives for efficiency, the US Federal Government has sought objective measures of inpatients' need for resources. In the UK National Health Service, resources are allocated for acute hospital services as part of a global budget to purchasers, who then contract with hospitals. To provide equity in resource allocation, the Department of Health in England, has sought objective measures of populations' need for resources. METHODS: Examination of policy and technology that has used variations in utilization of resources to derive objective measures of efficiency and equity. RESULTS: The technology of developing empirical measures of resources needed by patients has lacked information on outcomes, which is vital for measures of efficiency. The technology of developing empirical measures of resources needed by populations has relied on aggregate data. Analyses of specific procedures and conditions consistently find that these variations are explained by differences in medical practice and not by need. CONCLUSIONS: There is scope for multidisciplinary research to explain small area variations for specific procedures and conditions in resources used by populations. It seems unlikely, however, that governments will be interested in findings from this research.

Health Care Rationing↗

PubMed1996

Alcohol, fish, fibre and antioxidant vitamins intake do not explain population differences in coronary heart disease mortality.

BACKGROUND: Within the Seven Countries Study data we investigated whether population differences in 25-year mortality rates from coronary heart disease could be explained by population differences in alcohol, fish, fibre and antioxidant intake. METHODS: Baseline surveys were carried out between 1958 and 1964, on 12 763 middle-aged men constituting 16 cohorts in seven countries. In 1987 and 1988 equivalent food composites representing the average food intake of each cohort at baseline were collected locally and analysed for their fibre and antioxidant content in one central laboratory. The vital status of all participants was verified at regular intervals over 25 years. RESULTS: Alcohol and fish intake were inversely related to 25-year mortality from coronary heart disease in univariate analyses. These associations became non-significant when the confounding effects of saturated fatty acids, flavonoids and smoking were taken into account. Fibre and antioxidant vitamins intake were not related to coronary heart disease mortality in either uni- or multivariate analysis. CONCLUSION: These cross-cultural analyses show that alcohol, fish, fibre and antioxidant vitamins do not explain population differences in coronary heart disease mortality, independently of saturated fatty acids and flavonoids intake and cigarette smoking.

Adult↗

PubMed1999

Hepatitis B carriage explains the excess rate of hepatocellular carcinoma for Maori, Pacific Island and Asian people compared to Europeans in New Zealand.

BACKGROUND: The aim of this research was to determine the hepatitis B surface antigen (HBsAg) carrier prevalence among cases of hepatocellular carcinoma (HCC), and the population attributable risk of HBsAg carriage for HCC, by ethnicity in New Zealand. METHODS: The hospital notes of HCC cases registered with the New Zealand Cancer Registry, for the years 1987-1994 inclusive, were viewed to determine the HBsAg status. Results The HBsAg status was determined for 193 cases of HCC. The HBsAg carrier prevalence for non-Europeans with HCC was markedly higher than that for Europeans, being 76.7% for Maori, 80.0% for Pacific Island people, and 88.5% for Asians, compared to 6.0% for Europeans. In addition to the effect of ethnicity, HCC cases aged <60 years were more likely to be HBsAg carriers than those aged > or = 60 years. The estimated population attributable risk of HBsAg for HCC, within each ethnic group, was only marginally less than the HBsAg prevalence due to the high relative risk of HBsAg carriage for HCC. The standardized incidence rate ratios of HCC for Maori, Pacific Island people and Asians compared to Europeans were 9.6, 20.4, and 22.3, respectively. Hepatocellular carcinoma attributable to HBsAg carriage explained 79%, 83%, and 92% of the excess standardized rate of HCC, compared to Europeans, for Maori, Pacific Island people, and Asians, respectively. Conclusions The HBsAg carrier prevalence in non-European cases of HCC in New Zealand is between 75% and 90%. HBsAg carriage explains the majority of the excess rate of HCC in non-Europeans compared to Europeans in New Zealand.

Adolescent↗

PubMed2003

The survival benefit of measles immunization may not be explained entirely by the prevention of measles disease: a community study from rural Bangladesh.

OBJECTIVE: To examine whether the reduction in childhood mortality after immunization can be explained by the prevention of measles and its long-term effects. METHODS: and Data We re-analysed an existing data set from Matlab, Bangladesh. During 1982-1985, measles immunization was used from 9 months of age in half of the study area, and the other half was used as an unvaccinated control area. A total of 8134 immunized children had been matched by age with 8134 non-immunized children; 578 children died during the follow-up period of 3 years. Using these data, we calculated the vaccine effectiveness against death (VED) controlling for significant factors in a matched analysis. In the absence of measles, there should be no difference in mortality between immunized, uninfected children and non-immunized, uninfected children. We therefore calculated VED after the exclusion of all measles cases in the survival analysis. To assess the long-term effects of measles, we compared survival of unvaccinated children after measles disease with children who had not yet contracted measles. RESULTS: Prior to immunization and again after 1985, childhood mortality rates were 10% lower in the area that had received immunization. Though measles deaths only constituted 12.4% of the non-accidental deaths, the VED controlling for significant factors was 49% (95% CI: 38-58%). The vaccine was protective against measles death throughout the study, but it also had a marked effect against other causes of death, particularly diarrhoea and oedema. This effect may have been particularly strong in the first 6 months after immunization (VED = 74, 95% CI: 57-84%). The VED was only reduced from 49% to 43% (95% CI: 31-54%) when measles cases were excluded in the survival analysis. Controlling for background factors, mortality among measles cases was increased during the acute phase (0-45 days) (mortality ratio [MR] = 17.35, 95% CI: 11.9-25.3) and in the following 1(1/2) months (MR = 2.35, 95% CI: 0.95-5.84). However, post-measles cases had significantly lower mortality than uninfected, non-immunized children in the following 9 months (MR = 0.40, 95% CI: 0.16, 0.98). CONCLUSIONS: The non-randomized character of the original study and the possibility of uncontrolled confounding between the two areas prevent a precise estimate of the effectiveness of measles vaccine, but it is likely to have been substantial. Though there may have been some underreporting of cases of measles, the prevention of measles infection can only explain a limited part of the observed impact of measles immunization in Bangladesh. Furthermore, mortality may be reduced after the acute phase of measles infection. The observations from Bangladesh are consistent with recent research from Africa suggesting that measles immunization may have non-specific beneficial effects on survival.

Bangladesh↗

PubMed2003

Smoking at age 18-20 and suicide during 26 years of follow-up-how can the association be explained?

OBJECTIVES: Several studies have shown a relation between smoking and suicide. It is not clear if this relation should be considered causal, or if other risk factors for suicide, left unmeasured in many studies, might explain the smoking-suicide association. The aim of this cohort study was to analyse the role of smoking and other potential risk factors measured in adolescence on subsequent suicide. METHODS: Information on smoking, and other potential risk factors from childhood and adolescence was collected among 49 323 men, born 1949-1951, at conscription for compulsory military training in the years 1969-1970. Mortality data were obtained from the Swedish cause of death register for the years 1971-1996. RESULTS: There was a clear trend of increasing suicide risk with increasing intensity of smoking reported at conscription. Those smoking >20 cigarettes/day had a strongly increased relative risk of suicide (OR = 3.03, 95% CI: 1.72, 5.34) during the first 13 years of follow-up. From 14 to 26 years after conscription, the risk was only slightly weaker (OR = 2.53, 95% CI: 1.36, 4.72). When we adjusted for other risk factors for suicide measured at the conscription examination (psychiatric diagnosis, parental divorce, low emotional control, medication for nervous problems, contact with police and childcare, heavy alcohol consumption, drug use, and education) in a multivariate analysis, the trend with smoking intensity disappeared, and there was no longer an increased relative risk for the heavy smokers (follow-up years 1-13: OR = 0.98, 95% CI: 0.53, 1.82; years 14-26: OR = 1.31, 95% CI: 0.91, 1.87). CONCLUSION: The increased risk of suicide among smokers was almost entirely explained by an increased prevalence of heavy alcohol consumption and low mental well-being among smokers. That is, the association between smoking and suicide is probably due to confounding by these other factors. These results do not support the hypothesis that tobacco consumption itself is a risk factor for suicide.

Adolescent↗