RESUMEN
Germline mutations in succinate dehydrogenase B (SDHB) predispose to hereditary paraganglioma (PGL) syndrome type 4. The risk of developing PGL or pheochromocytoma (PHEO) in SDHB mutation carriers is subject of recent debate. In the present nationwide cohort study of SDHB mutation carriers identified by the clinical genetics centers of the Netherlands, we have calculated the penetrance of SDHB associated tumors using a novel maximum likelihood estimator. This estimator addresses ascertainment bias and missing data on pedigree size and structure. A total of 195 SDHB mutation carriers were included, carrying 27 different SDHB mutations. The 2 most prevalent SDHB mutations were Dutch founder mutations: a deletion in exon 3 (31% of mutation carriers) and the c.423+1G>A mutation (24% of mutation carriers). One hundred and twelve carriers (57%) displayed no physical, radiological or biochemical evidence of PGL or PHEO. Fifty-four patients had a head and neck PGL (28%), 4 patients had a PHEO (2%), 26 patients an extra-adrenal PGL (13%). The overall penetrance of SDHB mutations is estimated to be 21% at age 50 and 42% at age 70 when adequately corrected for ascertainment. These estimates are lower than previously reported penetrance estimates of SDHB-linked cohorts. Similar disease risks are found for different SDHB germline mutations as well as for male and female SDHB mutation carriers.
Asunto(s)
Neoplasias de las Glándulas Suprarrenales/genética , Mutación de Línea Germinal , Paraganglioma/genética , Feocromocitoma/genética , Succinato Deshidrogenasa/genética , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Países Bajos , Penetrancia , Fenotipo , Estudios RetrospectivosRESUMEN
In the Netherlands, the majority of hereditary paragangliomas (PGL) is caused by SDHD, SDHB and SDHAF2 mutations. Founder mutations in SDHD are particularly prevalent, but several SDHB founder mutations have also been described. Here, we describe an extended PGL family with a Dutch founder mutation in SDHB, c.201-4429_287-933del. The proband presented with apparently sporadic head and neck paraganglioma at advanced age. Subsequently, evaluation of the family identified several unaffected mutation carriers, asymptomatic and symptomatic PGL patients, and patients presenting with early-onset malignant pheochromocytoma. The calculated penetrance of the SDHB mutation in this kindred is lower than the risk suggested for SDHB mutations in the literature. This may represent a characteristic of this particular SDHB mutation, but may also be a reflection of the inclusion of relatively large numbers of asymptomatic mutation carriers in this family and adequate statistical correction for ascertainment bias. The low penetrance of SDHB mutations may obscure the hereditary nature of SDHB-linked disease and is important in the counseling of SDHB-linked patients. Risk estimates should preferably be based on the specific mutation involved.
Asunto(s)
Exones , Mutación de Línea Germinal , Paraganglioma/genética , Penetrancia , Feocromocitoma/genética , Eliminación de Secuencia , Succinato Deshidrogenasa/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Femenino , Genotipo , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Paraganglioma/diagnóstico , Paraganglioma/mortalidad , Linaje , Fenotipo , Feocromocitoma/diagnóstico , Feocromocitoma/mortalidad , Adulto JovenRESUMEN
BACKGROUND: Up to 53% of cancer survivors (CSs) experiences job loss during or after treatment. To support CSs with job loss in the Netherlands, a tailored return to work (RTW) program was developed. The objective of this study was to assess the effectiveness of the program on duration until sustainable RTW in CSs with job loss. MATERIAL AND METHODS: This study employed a two-armed (intervention/control) randomized controlled design with one-year follow-up. The primary outcome measure was duration until sustainable RTW. The secondary outcome measures were: rate of RTW, fatigue, quality of life, and participation in society. Descriptive analyses, Kaplan-Meier estimators and Cox regression analyses were conducted. RESULTS: Participants (N = 171) had a mean age of 48.4 years (SD = 8.6). The majority was female (69%) and breast cancer survivor (40%). The crude hazard ratio (HR) for duration until sustainable RTW was 0.86 (95% CI 0.46-1.62; p = 0.642). In the adjusted model, the intervention group had a slight, but statistically non-significant, improvement in duration until sustainable RTW compared to the control group (HR 1.16; 95% CI 0.59-2.31; p = 0.663). The program did not have any significant effects on secondary outcome measures. CONCLUSION: As the tailored RTW program did not demonstrate a statistically significant effect on duration until sustainable RTW in CSs with job loss, implementation of the program in its current form is not recommended.
Asunto(s)
Supervivientes de Cáncer/estadística & datos numéricos , Neoplasias/rehabilitación , Evaluación de Programas y Proyectos de Salud , Reinserción al Trabajo/estadística & datos numéricos , Apoyo Social , Adulto , Fatiga/etiología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/complicaciones , Países Bajos , Calidad de VidaRESUMEN
BACKGROUND: Offspring of consanguineous couples are at increased risk of congenital disorders. The risk increases as parents are more closely related. Individuals that have the same degree of relatedness according to their pedigree, show variable genomic kinship coefficients. To investigate whether we can differentiate between couples with high- and low risk for offspring with congenital disorders, we have compared the genomic kinship coefficient of consanguineous parents with a child affected with an autosomal recessive disorder with that of consanguineous parents with only healthy children, corrected for the degree of pedigree relatedness. METHODS: 151 consanguineous couples (73 cases and 78 controls) from 10 different ethnic backgrounds were genotyped on the Affymetrix platform and passed quality control checks. After pruning SNPs in linkage disequilibrium, 57,358 SNPs remained. Kinship coefficients were calculated using three different toolsets: PLINK, King and IBDelphi, yielding five different estimates (IBDelphi, PLINK (all), PLINK (by population), King robust (all) and King homo (by population)). We performed a one-sided Mann Whitney test to investigate whether the median relative difference regarding observed and expected kinship coefficients is bigger for cases than for controls. Furthermore, we fitted a mixed effects linear model to correct for a possible population effect. RESULTS: Although the estimated degrees of genomic relatedness with the different toolsets show substantial variability, correlation measures between the different estimators demonstrated moderate to strong correlations. Controls have higher point estimates for genomic kinship coefficients. The one-sided Mann Whitney test did not show any evidence for a higher median relative difference for cases compared to controls. Neither did the regression analysis exhibit a positive association between case-control status and genomic kinship coefficient. CONCLUSIONS: In this case-control setting, in which we compared consanguineous couples corrected for degree of pedigree relatedness, a higher degree of genomic relatedness was not significantly associated with a higher likelihood of having an affected child. Further translational research should focus on which parts of the genome and which pathogenic mutations couples are sharing. Looking at relatedness coefficients by determining genome-wide SNPs does not seem to be an effective measure for prospective risk assessment in consanguineous parents.
Asunto(s)
Anomalías Congénitas/genética , Consanguinidad , Genes Recesivos , Genoma Humano/genética , Secuencia de Bases , Estudios de Casos y Controles , Femenino , Genotipo , Humanos , Masculino , Linaje , Polimorfismo de Nucleótido Simple , Análisis de Secuencia de ADN , Estadísticas no ParamétricasRESUMEN
BACKGROUND: Birt-Hogg-Dubé (BHD) syndrome is an autosomal dominant condition caused by germline FLCN mutations, and characterised by fibrofolliculomas, pneumothorax and renal cancer. The renal cancer risk, cancer phenotype and pneumothorax risk of BHD have not yet been fully clarified. The main focus of this study was to assess the risk of renal cancer, the histological subtypes of renal tumours and the pneumothorax risk in BHD. METHODS: In this study we present the clinical data of 115 FLCN mutation carriers from 35 BHD families. RESULTS: Among 14 FLCN mutation carriers who developed renal cancer 7 were <50 years at onset and/or had multifocal/bilateral tumours. Five symptomatic patients developed metastatic disease. Two early-stage cases were diagnosed by surveillance. The majority of tumours showed characteristics of both eosinophilic variants of clear cell and chromophobe carcinoma. The estimated penetrance for renal cancer and pneumothorax was 16% (95% minimal confidence interval: 6-26%) and 29% (95% minimal confidence interval: 9-49%) at 70 years of age, respectively. The most frequent diagnosis in families without identified FLCN mutations was familial multiple discoid fibromas. CONCLUSION: We confirmed a high yield of FLCN mutations in clinically defined BHD families, we found a substantially increased lifetime risk of renal cancer of 16% for FLCN mutation carriers. The tumours were metastatic in 5 out of 14 patients and tumour histology was not specific for BHD. We found a pneumothorax risk of 29%. We discuss the implications of our findings for diagnosis and management of BHD.
Asunto(s)
Síndrome de Birt-Hogg-Dubé/genética , Predisposición Genética a la Enfermedad , Neoplasias Renales/genética , Mutación , Neumotórax/genética , Proteínas Proto-Oncogénicas/genética , Proteínas Supresoras de Tumor/genética , Adulto , Anciano , Síndrome de Birt-Hogg-Dubé/complicaciones , Femenino , Humanos , Neoplasias Renales/complicaciones , Masculino , Persona de Mediana Edad , Neumotórax/complicacionesRESUMEN
For many diseases, it seems that the age at onset is genetically influenced. Therefore, the age-at-onset data are often collected in order to map the disease gene(s). The ages are often (right) censored or truncated, and therefore, many standard techniques for linkage analysis cannot be used. In this paper, we present a correlated frailty model for censored survival data of siblings. The model is used for testing heritability for the age at onset and linkage between the loci and the gene(s) that influence(s) the survival time. The model is applied to interval-censored migraine twin data. Heritability (obtained from the frailties rather than actual onset times) was estimated as 0.42; this value was highly significant. The highest lod score, a score of 1.9, was found at the end of chromosome 19.
Asunto(s)
Ligamiento Genético , Predisposición Genética a la Enfermedad/epidemiología , Trastornos Migrañosos/genética , Distribuciones Estadísticas , Edad de Inicio , Protocolos Clínicos , Femenino , Predisposición Genética a la Enfermedad/genética , Humanos , Funciones de Verosimilitud , Estudios Longitudinales , Masculino , Trastornos Migrañosos/epidemiología , Modelos Genéticos , Países Bajos , Linaje , Sitios de Carácter Cuantitativo , Valores de Referencia , Proyectos de Investigación/estadística & datos numéricos , Análisis de Supervivencia , Estudios en Gemelos como Asunto/métodosRESUMEN
Family survival data can be used to estimate the degree of genetic and environmental contributions to the age at onset of a disease or of a specific event in life. The data can be modeled with a correlated frailty model in which the frailty variable accounts for the degree of kinship within the family. The heritability (degree of heredity) of the age at a specific event in life (or the onset of a disease) is usually defined as the proportion of variance of the survival age that is associated with genetic effects. If the survival age is (interval) censored, heritability as usually defined cannot be estimated. Instead, it is defined as the proportion of variance of the frailty associated with genetic effects. In this paper we describe a correlated frailty model to estimate the heritability and the degree of environmental effects on the age at which individuals contact a social worker for the first time and to test whether there is a difference between the survival functions of this age for twins and non-twins.
Asunto(s)
Edad de Inicio , Ambiente , Modelos Genéticos , Modelos Estadísticos , Carácter Cuantitativo Heredable , Gemelos/genética , Adolescente , Adulto , Familia , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Países Bajos , Adulto JovenRESUMEN
AIM: Salivary duct carcinoma (SDC), an aggressive subtype of salivary gland cancer, is androgen receptor (AR)-positive in 67-96% of cases. In patients with locally recurrent and metastatic (R/M) AR-positive SDC, androgen deprivation therapy (ADT) has an overall response rate of 18-64.7%. In this study, we describe the efficacy of adjuvant ADT in patients with poor-risk (stage 4a) AR-positive SDC. METHODS: This is a retrospective cohort study in which patients with stage 4a AR-positive SDC were offered adjuvant ADT, i.e. bicalutamide, luteinizing hormone-releasing hormone (LHRH) analogue or a combination of these after tumour resection. In the control group, data were collected on patients with stage 4a SDC who underwent a tumour resection but did not receive adjuvant ADT. RESULTS: Twenty-two AR-positive SDC patients were treated with adjuvant ADT for a median duration of 12 months. The control group consisted of 111 SDC patients. After a median follow-up of 20 months in the ADT-treated patients and 26 months in the control group, the 3-year disease-free survival (DFS) was estimated as 48.2% (95% confidence interval [CI] 14.0-82.4%) and 27.7% (95% CI 18.5-36.9%) (P = 0.037). Multivariable Cox regression analysis showed a hazard ratio of 0.138 (95% CI 0.025-0.751, P = 0.022) for DFS and 0.064 (95% CI 0.005-0.764, P = 0.030) for overall survival (OS) in favour of the ADT-treated patients. CONCLUSION: Poor-risk, AR-positive SDC patients who received adjuvant ADT have a significantly longer DFS compared with patients in the control group, who did not receive adjuvant ADT. For OS, this was just below and above the significance level, in case there was or was no correction for confounders.
Asunto(s)
Antagonistas de Andrógenos/uso terapéutico , Antineoplásicos Hormonales/uso terapéutico , Neoplasias de las Glándulas Salivales/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Quimioterapia Adyuvante , Femenino , Humanos , Masculino , Persona de Mediana Edad , Receptores Androgénicos/metabolismo , Factores de Riesgo , Conductos Salivales , Resultado del TratamientoRESUMEN
BACKGROUND AND PURPOSE: Precise in vivo measurement of deep GM volume change is a highly demanded prerequisite for an adequate evaluation of disease progression and new treatments. However, quantitative data on the reproducibility of deep GM structure volumetry are not yet available. In this paper we aim to investigate this reproducibility using a large multicenter dataset. MATERIALS AND METHODS: We have assessed the reproducibility of 2 automated segmentation software packages (FreeSurfer and the FMRIB Integrated Registration and Segmentation Tool) by quantifying the volume changes of deep GM structures by using back-to-back MR imaging scans from the Alzheimer Disease Neuroimaging Initiative's multicenter dataset. Five hundred sixty-two subjects with scans at baseline and 1 year were included. Reproducibility was investigated in the bilateral caudate nucleus, putamen, amygdala, globus pallidus, and thalamus by carrying out descriptives as well as multilevel and variance component analysis. RESULTS: Median absolute back-to-back differences varied between GM structures, ranging from 59.6-156.4 µL for volume change, and 1.26%-8.63% for percentage volume change. FreeSurfer had a better performance for the outcome of longitudinal volume change for the bilateral amygdala, putamen, left caudate nucleus (P < .005), and right thalamus (P < .001). For longitudinal percentage volume change, Freesurfer performed better for the left amygdala, bilateral caudate nucleus, and left putamen (P < .001). Smaller limits of agreement were found for FreeSurfer for both outcomes for all GM structures except the globus pallidus. Our results showed that back-to-back differences in 1-year percentage volume change were approximately 1.5-3.5 times larger than the mean measured 1-year volume change of those structures. CONCLUSIONS: Longitudinal deep GM atrophy measures should be interpreted with caution. Furthermore, deep GM atrophy measurement techniques require substantially improved reproducibility, specifically when aiming for personalized medicine.
Asunto(s)
Enfermedad de Alzheimer/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Sustancia Gris/diagnóstico por imagen , Procesamiento de Imagen Asistido por Computador/métodos , Neuroimagen/métodos , Adulto , Enfermedad de Alzheimer/patología , Atrofia/patología , Encéfalo/patología , Conjuntos de Datos como Asunto , Progresión de la Enfermedad , Femenino , Sustancia Gris/patología , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Programas InformáticosRESUMEN
BACKGROUND: There is a wide practice variation of used methods and outcomes in IUI in fertility laboratories. Standardization of the IUI procedure is important for reducing inconsistency among laboratories in counseling infertile couples and in pregnancy results. The aim of the study was to evaluate the currently used laboratory procedures of IUI in Dutch fertility laboratories and their effect on IUI pregnancy results. Additionally, the methods for semen analysis (SA) were evaluated, as SA is related to IUI in terms of inseminated sperm number and IUI counseling. MATERIAL AND METHODS: This questionnaire survey study was sent to laboratories participating in the Dutch external quality control program for semen analysis (SKML) and consisted of 46 questions concerning laboratory management, methods for semen analysis and IUI, and clinical results. The results were analyzed using univariable and multivariable logistic regression models. RESULTS: A total of 52 laboratories (out of 99) provided information on used methodologies for SA or laboratory procedures of IUI and the organization of the laboratory. A wide variability was confirmed in used methods for both SA and IUI. Evaluation of pregnancy results obtained during 3 years (2013-2015) showed that specific used laboratory methods have a significant effect on the probability of becoming pregnant. DISCUSSION AND CONCLUSION: Important to remark is that in this survey study cycle-specific data, including variables of the individual couples (age, stimulation protocol, etc), were not included and may have effects on the results. The reported results provide an overview of the current practice performance; however, the organization of fertility laboratories is changing rapidly. The use of standardized methods in IUI is important for optimizing the performance of care and improving pregnancy results. The knowledge on used procedures, however, is limited, and further research on factors involving SA and the IUI procedure is necessary.
Asunto(s)
Inseminación Artificial Homóloga/métodos , Resultado del Embarazo , Femenino , Humanos , Masculino , Embarazo , Análisis de Semen/métodos , Encuestas y CuestionariosRESUMEN
BACKGROUND AND OBJECTIVES: Birt-Hogg-Dubé syndrome is an autosomal dominant disorder characterized by skin fibrofolliculomas, lung cysts, spontaneous pneumothorax and renal cell cancer due to germline folliculin (FLCN) mutations (Menko et al. in Lancet Oncol 10(12):1199-1206, 2009). The aim of this study was to evaluate the incidence of spontaneous pneumothorax in patients with BHD during or shortly after air travel and diving. METHODS: A questionnaire was sent to a cohort of 190 BHD patients and the medical files of these patients were evaluated. The diagnosis of BHD was confirmed by FLCN mutations analysis in all patients. We assessed how many spontaneous pneumothoraces (SP) occurred within 1 month after air travel or diving. RESULTS: In total 158 (83.2 %) patients returned the completed questionnaire. A total of 145 patients had a history of air travel. Sixty-one of them had a history of SP (42.1 %), with a mean of 2.48 episodes (range 1-10). Twenty-four (35.8 %) patients had a history of pneumothorax on both sides. Thirteen patients developed SP < 1 month after air travel (9.0 %) and two patients developed a SP < 1 month after diving (3.7 %). We found in this population of BHD patients a pneumothorax risk of 0.63 % per flight and a risk of 0.33 % per episode of diving. Symptoms possible related to SP were perceived in 30 patients (20.7 %) after air travel, respectively in ten patients (18.5 %) after diving. CONCLUSION: Based on the results presented in this retrospective study, exposure of BHD patients to considerable changes in atmospheric pressure associated with flying and diving may be related to an increased risk for developing a symptomatic pneumothorax. Symptoms reported during or shortly after flying and diving might be related to the early phase of pneumothorax. An individualized advice should be given, taking also into account patients' preferences and needs.
RESUMEN
The purpose of this research was to model the familial clustering of breast cancer and to provide an accurate risk estimate for individuals from the general population, based on their family history of breast and ovarian cancer. We constructed a genetic model as an extension of a model by Claus et al. (E. B. Claus et al., Am. J. Hum. Genet., 48: 232-242, 1991), with three breast cancer genes, BRCA1, BRCA2, and a hypothetical BRCAu, in two variants, one in which BRCAu was dominant and one in which BRCAu was recessive. The model parameters were estimated using published estimates of population incidence and relative risks. Risk estimation was performed for a set of 196 counselees and for a set of simulated counselees with both the dominant BRCAu and the recessive BRCAu model, and compared relating to medical management. Estimates of the model parameters were found. Relative risks among family members were comparable between the model of Claus et al. (E. B. Claus et al., Am. J. Hum. Genet., 48: 232-242, 1991) and our model. The dominant and the recessive model provided approximately similar lifetime risks for breast cancer. Our model is suitable for breast cancer risk estimation in a health care setting.
Asunto(s)
Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/genética , Genes BRCA1 , Genes BRCA2 , Predisposición Genética a la Enfermedad/epidemiología , Adulto , Distribución por Edad , Anciano , Análisis por Conglomerados , Femenino , Pruebas Genéticas , Heterocigoto , Humanos , Incidencia , Persona de Mediana Edad , Modelos Genéticos , Países Bajos/epidemiología , Linaje , Pronóstico , Medición de RiesgoRESUMEN
Risk estimation in breast cancer families is often estimated by use of the Claus tables. We analyzed the family histories of 196 counselees; compared the Claus tables with the Claus, the BRCA1/2, the BRCA1/2/ models; and performed linear regression analysis to extend the Claus tables with characteristics of hereditary breast cancer. Finally, we compared the Claus extended method with the Claus, the BRCA1/2, and the BRCA1/2/u models. We found 47% agreement for Claus table versus Claus model; 39% agreement for Claus table versus BRCA1/2 model; 48% agreement for Claus table versus BRCA1/2/u model; 37% agreement for Claus extended method versus Claus model; 44% agreement for Claus extended model versus BRCA1/2 model; and 66% agreement for Claus extended method versus BRCA1/2/u model. The regression formula (Claus extended method) for the lifetime risk for breast cancer was 0.08 + 0.40 (*) Claus Table + 0.07 (*) ovarian cancer + 0.08 (*) bilateral breast cancer + 0.07 (*) multiple cases. This new method for risk estimation, which is an extension of the Claus tables, incorporates information on the presence of ovarian cancer, bilateral breast cancer, and whether there are more than two affected relatives with breast cancer. This extension might offer a good alternative for breast cancer risk estimation in clinical practice.
Asunto(s)
Neoplasias de la Mama/etiología , Familia , Genes BRCA1 , Genes BRCA2 , Modelos Logísticos , Neoplasias Ováricas/etiología , Medición de Riesgo/métodos , Femenino , Humanos , MasculinoRESUMEN
In the literature 3-methylhistidine (3-MeHis) is mentioned as a parameter for the determination of meat content. Because of the variable molar ratio of 3-MeHis in the myofibrillar protein myosin, this indicator cannot be used without some restriction. However, the content of 3-MeHis in the myofibrillar protein actin is constant. Moreover, actin is relatively heat-stable in comparison with other muscle proteins. These facts made actin an interesting parameter for determination of the meat (protein) content of heated and raw meat products. Fast protein liquid chromatography (FPLC) was used to separate from a meat extract an actin-containing fraction without myosin. The actin content of the meat was calculated from its content in the fraction. The latter was determined by means of a 3-MeHis method. Several muscles of the beef and pig carcass were examined for their actin contents. Generally, the actin values were comparable with the data reported in the literature. The influence of heat treatment was also studied on one type of beef muscle. The determined actin content was not affected up to a temperature of 85°C.
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Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/genética , Atención Primaria de Salud/estadística & datos numéricos , Adulto , Factores de Edad , Proteína BRCA1/genética , Proteína BRCA2/genética , Salud de la Familia , Femenino , Frecuencia de los Genes , Humanos , Incidencia , Tamizaje Masivo/métodos , Persona de Mediana Edad , Modelos Genéticos , Mutación , Países Bajos/epidemiología , Penetrancia , PrevalenciaAsunto(s)
Neoplasias de la Mama/genética , Pruebas Genéticas/métodos , Adulto , Anciano , Anciano de 80 o más Años , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias de la Mama/diagnóstico , Salud de la Familia , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Modelos Genéticos , Mutación , Linaje , Fenotipo , Factores de Riesgo , Sensibilidad y EspecificidadRESUMEN
Studies on population history are often based on incomplete records of life histories. For instance, in studies using data obtained from family reconstitution, the date of death is right censored (by migration) and the censoring time is never observed. Several methods for the correction of mortality estimates are proposed in the literature, most of which first estimate the number of individuals at risk and then use standard techniques to estimate mortality. Other methods are based on statistical models. In this paper all methods are reviewed, and their merits are compared by applying them to simulated and to seventeenth-century data from the English parish of Reigate. An ad hoc method proposed by Ruggles performs reasonably well. Methods based on statistical models, provided they are sufficiently realistic, give comparable accuracy and allow the estimation of several other quantities of interest, such as the distribution of migration times.
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Recolección de Datos/métodos , Demografía , Sesgo , Simulación por Computador , Recolección de Datos/estadística & datos numéricos , Familia , Humanos , Modelos Estadísticos , Sistema de RegistrosRESUMEN
We consider the estimation of life length of people who were born in the seventeenth or eighteenth century in England. The data consist of a sequence of times of life events that is either ended by a time of death or is right-censored by an unobserved time of migration. We propose a semi parametric model for the data and use a maximum likelihood method to estimate the unknown parameters in this model. We prove the consistency of the maximum likelihood estimators and describe an algorithm to obtain the estimates numerically. We have applied the algorithm to data and the estimates found are presented.
Asunto(s)
Funciones de Verosimilitud , Longevidad , Modelos Estadísticos , Mortalidad/tendencias , Algoritmos , Inglaterra , Femenino , Historia del Siglo XVII , Historia del Siglo XVIII , Humanos , Esperanza de Vida , MasculinoRESUMEN
Quality regulations of the Guelders ring sausage are applied in the Netherlands. One of the quality parameters is the content of CFMP (collagen-free muscle protein) in the product. The purpose of this research is to substitute the usual indirect method by a direct analytical method for CFMP. The proposed direct method is composed of separation and determination of actin. Actin was well separated from the sausage product by SDS-gel-filtration chromatography, which was checked by SDS-polyacrylamide-gel electrophoresis. Actin was determined by its 3-methylhistidine content, but this result was smaller than expected. It was caused by the presence of salt during the 3-methylhistidine analysis. Finally, a method for the determination of actin by 3-methylhistidine was developed for the direct procedure. The relations of 3 MH (3-methylhistidine) with respective CFMP and MP (muscle protein) are formulated. Both formulae give a reasonably good estimation of 3 MH, CFMP or MP, one of these parameters of the Guelders ring sausage being known.
Asunto(s)
Actinas/análisis , Productos de la Carne/análisis , Carne/análisis , Animales , Cromatografía en Gel , Metilhistidinas/análisis , Proteínas Musculares/análisis , Control de Calidad , PorcinosRESUMEN
The purpose of this study was to find experimental conditions for the complete solubility of collagen-free muscle proteins (CFMP) using acetone powder of Guelders ring sausage. Preliminary experiments were carried out to choose the best procedure for preparing the acetone dry powder. Two different methods of acetone extraction of minced sausage were compared. The acetone dry mass (ADM) method using continuous extraction in a Soxhlet [2] apparatus gave better results than the acetone powder (ACP) method, which used a blender [1]. The ADM method was used for further investigations. ADM was extracted with two types of sodium dodecyl sulphate (SDS), containing solvents A and B. Solvent A contains a Tris-boric acid buffer (pH 8.2) with 1.5% (m/v) SDS and 0.05% (m/v) dithioerythreitol [3]. Solvent B is a borate-chloric acid buffer (pH 9.0) with 2.0% (m/v) SDS and 1.0% (m/v) mercapto-ethanol [2]. Both solvents showed a linear relationship between the quantities of CFMP in ADM and the dissolved CFMP. The linear relationships were found between quantities of 10.0 and 30.0 mg (solution A) and of 5.0 and 30.0 mg ADM (solution B) per ml solvent. The solubility of CFMP was better in solvent B than in solution A. Completely dissolved CFMP from ADM was only obtained in the case of 5.0 mg ADM in 1.0 ml solution B. These conditions will be used in liquid chromatography experiments, the results of which will be reported later.