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In the majority of cases, acromegaly is sporadic. However, it can also occur in a familial setting as a component of MEN-1, MEN-4, Carney complex (CNC) or as the extremely rare syndrome of isolated familial somatotropinoma (IFS), the latter belonging to familial isolated pituitary adenomas (FIPA). The diagnosis of IFS is based on the recognition of acromegaly/gigantism in at least two family members, given that the family is not affected by MEN-1, MEN-4 or CNC. The authors present a case study of two sisters: a 56 year-old patient (case no. 1) and a 61 year-old patient (case no. 2). In both sisters, acromegaly was recognised in the course of pituitary macroadenoma. Neither of the sisters showed features of MEN-1, MEN-4 or Carney complex. The authors suppose that the presented cases are manifestations of IFS. However, this diagnosis has not been confirmed yet because of the poor availability of genetic tests.  相似文献   

3.
《Endocrine practice》2007,13(4):396-402
ObjectiveTo present 2 cases of patients with acromegaly and severe hyperprolactinemia whose primary therapy with cabergoline resulted in hormonal normalization and a considerable reduction in the size of their somatotroph macroadenomas.MethodsWe summarize the clinical presentation and the pertinent laboratory findings in 2 patients with acromegaly, as well as their clinical response to the therapy with cabergoline. A review of the literature regarding the use of cabergoline in acromegaly is also presented.ResultsA 48-year-old man (case 1) and a 26-year-old woman (case 2) were found to have acromegaly associated with very high levels of serum prolactin (2,700 and 5,250 ng/mL, respectively). These patients received first-line therapy with cabergoline that resulted not only in clinical improvement and normalization of growth hormone, prolactin, and insulin-like growth factor-I levels but also in a substantial reduction in the size of their somatotroph macroadenomas. By 6 months after the patients began to take cabergoline, tumor shrinkage of 94% (in case 1) and of 70% (in case 2) was demonstrated by magnetic resonance imaging.ConclusionOur findings demonstrate that cabergoline should be considered for medical treatment of adenomas cosecreting growth hormone and prolactin, even in the presence of large tumors with appreciable suprasellar extension, because substantial tumor shrinkage is possible with this therapy. (Endocr Pract. 2007;13:396-402)  相似文献   

4.
《Endocrine practice》2009,15(7):725-731
ObjectiveTo identify and present cases of acromegaly in which pituitary apoplexy resulted in remission of acromegaly, with normalization of insulinlike growth factor-I and growth hormone levels.MethodsWe present a case history of a personal patient and review the related literature in PubMed and Ovid MEDLINE.ResultsA 34-year-old man with classic acromegaly had spontaneous pituitary apoplexy, resulting in remission of his acromegaly and diabetes. Moreover, we identified 21 other similar cases in the literature and analyze the clinical presentations, possible apoplexy triggers, and hormonal sequelae. All these patients were “cured” of acromegaly, and 68% of them experienced other pituitary hormone insufficiencies after pituitary apoplexy, including 2 cases of panhypopituitarism.ConclusionPituitary apoplexy can result in remission of acromegaly and in partial or complete anterior or posterior (or both) pituitary insufficiency. Thus, after suspected or confirmed pituitary apoplexy, pituitary hormone secretion must be reevaluated. This assessment may result in initiation of appropriate substitution therapy, a change in management of growth hormone overproduction, or both interventions. (Endocr Pract. 2009;15:725-731)  相似文献   

5.
《Endocrine practice》2004,10(4):348-352
ObjectiveTo describe a case of acromegaly in a young woman using oral contraceptives who had nonspecific symptoms and persistent hyperphosphatemia and to analyze the reasons for delay in diagnosis.MethodsA 31-year-old woman underwent evaluation for failure of menstrual flow to resume after discontinued use of oral contraceptives. Clinical and laboratory findings are summarized, and atypical manifestations of acromegaly are discussed.ResultsThe patient complained of weight gain, acne, and increased facial hair growth, and laboratory tests showed a low estradiol level and hyperinsulinemia. “Postpill amenorrhea” and polycystic ovary syndrome were considered possible diagnoses. During subsequent endocrinology consultation, hyperphosphatemia was present on three occasions during a 7-month period. Hormonal studies for evaluation of pituitary function revealed increased insulin-like growth factor-I and growth hormone (GH) levels. Acromegaly was suspected, and the increased GH level failed to suppress after a glucose load. Magnetic resonance imaging revealed a pituitary macroadenoma with suprasellar extension. Visual field testing showed bitemporal abnormalities. Transsphenoidal resection successfully removed the GH-producing tumor, and hormone replacement therapy was initiated postoperatively.ConclusionThe textbook presentation of GH excess is a late feature of acromegaly. The diagnosis in a young woman can be easily missed when clinicopathologic findings are not classic and the picture is further clouded by factors such as oral contraceptive use. Features may also resemble polycystic ovary syndrome, a more common condition in women of childbearing age. This case also illustrates that hyperphosphatemia, overlooked in this patient, can precede the full-blown clinical manifestations of acromegaly and serve as a subtle clue to the underlying disease. Awareness of these situations and screening for high GH levels in patients with unexplained, persistent hyperphosphatemia are advisable for making an early correct diagnosis and providing appropriate therapy. (Endocr Pract. 2004;10:348-352)  相似文献   

6.
Kim HJ  Kwon SH  Kim SW  Park DJ  Shin CS  Park KS  Kim SY  Cho BY  Lee HK 《Hormone research》2001,56(3-4):117-123
OBJECTIVE: To investigate the diagnostic value of serum insulin-like growth factor-I (IGF-I) and insulin-like growth factor-binding protein-3 (IGFBP-3) measurements in adult patients with acromegaly and GH deficiency (GHD). METHODS: Serum IGF-I and IGFBP-3 levels were measured in 39 active acromegalic patients, 34 adult patients with GHD and 150 healthy adults. Disease activity in patients with acromegaly was confirmed by nadir GH levels during an oral glucose tolerance test (OGTT). Among patients with acromegaly, 15 had not been treated previously and 24 had been treated but not cured. GHD in adults was diagnosed by an insulin tolerance test (ITT). Among patients with GHD, 15 were aged 20-40 years (9 men and 6 women) and 19 were aged over 40 years (9 men and 10 women). One hundred and fifty healthy subjects were recruited as a control group. To compare the individual serum IGF-I and IGFBP-3 levels of patients with the results of the gold standard, we calculated age- and sex-corrected standard deviation scores (SDS) for individual IGF-I and IGFBP-3 levels. The sensitivities of serum IGF-I and IGFBP-3 measurements for the disease diagnosis were analyzed using the mean +/- 2 SD of the values of healthy control subjects as a diagnostic cutoff, defining 95% specificity. RESULTS: The mean IGF-I and IGFBP-3 SDS levels were significantly higher in active acromegalic patients, both untreated and treated but not cured, than in the control subjects (p < 0.05). The sensitivities of serum IGF-I and IGFBP-3 measurements for the diagnosis of acromegaly were 97.4 and 81.8%, respectively. In untreated patients with acromegaly, the sensitivities of serum IGF-I and IGFBP-3 measurements for the diagnosis of disease were 100 and 100%, while these were 95.8 and 72.7% in treated patients with acromegaly. In adult patients with GHD, the mean IGF-I and IGFBP-3 SDS were significantly lower than those of the control subjects (IGF-I, -2.2 +/- 0.8 vs. 0.0 +/- 1.0 SDS, p < 0.0001); IGFBP-3, -1.7 +/- 1.2 vs. 0.0 +/- 1.0 SDS, p < 0.0001), but there was a considerable overlap between GHD in adults and the controls. In all patients with GHD, the sensitivities of serum IGF-I and IGFBP-3 measurements were 64.7 and 52.9%, respectively. In the group of women aged 20-40 years, the sensitivity of IGF-I measurement for the diagnosis of GHD was 100%, although the number of patients was only 6. CONCLUSION: Both serum IGF-I and IGFBP-3 measurements are comparable to an oral glucose tolerance test in patients with untreated acromegaly, but in acromegalic patients that have undergone surgery and/or radiotherapy, serum IGF-I is more valuable for determining disease activity than serum IGFBP-3. Serum IGF-I and IGFBP-3 measurements are not valuable for the diagnosis of GHD in adults, but in women aged 20-40 years serum IGF-I measurement appears to be useful in the diagnosis of GHD.  相似文献   

7.
《Endocrine practice》2011,17(1):79-84
ObjectiveTo present a case of acromegaly due to ectopic growth hormone-releasing hormone (GHRH) secretion from a pancreatic neuroendocrine tumor in the context of multiple endocrine neoplasia type 1 (MEN 1).MethodsWe describe the clinical, imaging, and pathologic findings of the study patient.ResultsA 46 year old woman presented with clinical and biochemical findings diagnostic of acromegaly. Magnetic resonance imaging showed a 1.2-cm sellar mass. Following resection of the macroadenoma, serum insulinlike growth factor 1 (IGF-1) and growth hormone (GH) levels remained unchanged. Pathologic examination revealed adenomatous changes, including a nonsecretory focus and a prolactin immunopositive area (GH stain negative in both). Octreotide long-acting release was ineffective. Search for an ectopic tumor included normal octreoscan and abdominal computed tomography. GHRH was greater than 1000 pg/mL. Repeated abdominal computed tomography documented a 6.2-cm mass in the tail and body of the pancreas. Distal pancreatectomy revealed a pancreatic neuroendocrine tumor that stained positive for GHRH. Postoperatively, serum GHRH and IGF-1 normalized. Re-evaluation of the initial pituitary pathologic specimen revealed additional somatotroph hyperplasia of the adjacent, normal pituitary gland. Primary hyperparathyroidism was diagnosed, and multigland parathyroid hyperplasia was noted at surgery. Genetic testing was positive for a mutation in the MEN1 gene.ConclusionThis patient’s acromegaly was resistant to somatostatin analogue therapy, reflecting the negative octreoscan imaging. In addition, this case is novel because the patient presented with pituitary adenomatous changes, which were presumably associated with MEN 1 and/or possibly the elevated GHRH levels. (Endocr Pract. 2011; 17:79-84)  相似文献   

8.
Cell culture of human pituitary tissue has been used to diagnose a patient with Cushing's syndrome due to ectopic secretion of corticotrophin-releasing factor (CRF; case 1) and a case of acromegaly associated with ectopic secretion of a growth-hormone releasing factor (GRF; case 2). In both patients a pituitary tumour was not detected. Case 1 had a small cell carcinoma and symptoms of the ectopic ACTH syndrome, but in culture the carcinoma failed to secrete detectable ACTH. However, the culture medium used to maintain this carcinoma in vitro was found to contain a substance which stimulated ACTH secretion by human pituitary corticotrophs in cell culture. Radioimmunoassays and HPLC indicated that this substance had similar elution characteristics to human CRF and cross-reacted with antiserum to ovine CRF. Case 2 was found to have a lung tumour, the removal of which led to regression of her acromegalic symptoms. In culture, this tumour did not secrete GH, but did secrete a GRF. We conclude that the Cushing's syndrome and acromegaly, in cases 1 and 2, respectively, were due to ectopic secretion of CRF and GRF leading to hyperstimulation of the pituitary gland.  相似文献   

9.
Acromegaly is a pathological condition that is caused by over-secretion of growth hormone (GH) and develops primarily from a pituitary adenoma. Excess GH exposure over a prolonged period of time leads to a wide range of systemic manifestations and comorbidities. Studying the effect of excess GH on the cellular level could help to understand the underlying causes of acromegaly health complications and comorbidities. In our previous publications, we have shown that excess GH reduces body side population (SP) stem cells and induces signs of premature ageing in an acromegaly zebrafish model. Here, we study acromegaly ageing in greater depth at the level of gene expression. We investigated whether acromegaly induces an ageing genetic signature in different organs. Using the GenAge database, our acromegaly model showed a significant enrichment of ageing genetic datasets in the muscle but not in other organs. Likewise, the hierarchical clustering of wild type (WT), acromegaly and aged RNA data from various organs revealed the similarity of gene expression profiles between the acromegaly and the aged muscles. We therefore identified overlapping differentially expressed genes (DEGs) in different organs between acromegaly and aged zebrafish. Importantly, about half of the muscle, liver and brain acromegaly DEGs overlapped with aged zebrafish DEGs. Interestingly, overlapping was observed in the same way; acromegaly-up DEGs overlapped with aged zebrafish up DEGs, not down DEGs, and vice versa. We then identified the biological functions of overlapping DEGs. Enrichment database analysis and gene ontology showed that most overlapping muscle genes were involved in ageing metabolism, while overlapping liver DEGs were involved in metabolic pathways, response to hypoxia and endoplasmic reticulum stress. Thus, this study provides a full ageing genetic signature of acromegaly at the gene expression level.  相似文献   

10.
《Endocrine practice》2016,22(11):1327-1335
Objective: Acromegaly, a rare endocrine disorder, results from excessive growth hormone secretion, leading to multisystem-associated morbidities. Using 2 large nationwide databases, we estimated the annual incidence and prevalence of acromegaly in the U.S.Methods: We used 2008 to 2013 data from the Truven Health MarketScan® Commercial Claims and Encounters Database and IMS Health PharMetrics healthcare insurance claims databases, with health plan enrollees <65 years of age. Study patients had ≥2 claims with acromegaly (International Classification of Diseases, 9th Revision, Clinical Modification Code [ICD-9CM] 253.0), or 1 claim with acromegaly and 1 claim for pituitary tumor, pituitary surgery, or cranial stereotactic radiosurgery. Annual incidence was calculated for each year from 2009 to 2013, and prevalence in 2013. Estimates were stratified by age and sex.Results: Incidence was up to 11.7 cases per million person-years (PMPY) in MarketScan and 9.6 cases PMPY in PharMetrics. Rates were similar by sex but typically lowest in ≤17 year olds and higher in >24 year olds. The prevalence estimates were 87.8 and 71.0 per million per year in MarketScan and PharMetrics, respectively. Prevalence consistently increased with age but was similar by sex in each database.Conclusion: The current U.S. incidence of acromegaly may be up to 4 times higher and prevalence may be up to 50% higher than previously reported in European studies. Our findings correspond with the estimates reported by a recent U.S. study that used a single managed care database, supporting the robustness of these estimates in this population. Our study indicates there are approximately 3,000 new cases of acromegaly per year, with a prevalence of about 25,000 acromegaly patients in the U.S.Abbreviations:CT = computed tomographyGH = growth hormoneIGF-1 = insulin-like growth factor 1ICD-9-CM Code = International Classification of Diseases, 9th Revision, Clinical Modification CodesMRI = magnetic resonance imagingPMPY = per million person-years  相似文献   

11.
Fourteen patients with acromegaly were treated with bromocryptine (CB 154, Sandoz), 4 X 2.5 mg, for periods of up to eleven months. One patient did not tolerate the drug, ten of the remaining thirteen experienced considerable clinical improvement. There was a dose-dependent suppression of plasma growth hormone levels, but growth hormone response to TRH injection and to glucose administration was still present during therapy although reduced. TSH response to TRH was not significantly altered. The suppressive power of bromocryptine on growth hormone appears to be related to the mechanism by which TRH stimulates growth hormone secretion in acromegaly, but long-term administration of this drug may be successful in spite of an absent response to TRH in some cases. Bromocryptine appears to be a safe and effective drug for the treatment of acromegaly.  相似文献   

12.
《Endocrine practice》2005,11(1):18-22
ObjectiveTo describe a case of muscle weakness in a patient with acromegaly and to review the pathophysiologic features of this disorder.MethodsWe present the clinical, laboratory, electromyographic, and muscle biopsy findings in our patient and review related reports in the literature.ResultsA 58-year-old woman with acromegaly presented with complaints of bilateral hip pain, weakness, and instability 8 months after transsphenoidal resection of a growth hormone (GH)-secreting pituitary macroadenoma. She had biochemically normal thyroid and adrenal function and no evidence of any neuropathy, inflammatory myopathy, or rheumatologic disorder to explain her symptoms. Investigations revealed increased levels of GH, insulin-like growth factor-I, serum creatine kinase (CK), and the MB fraction of CK, normal results of nerve conduction studies, and nonspecific findings on electromyography and muscle biopsy. A review of the literature revealed that although muscle weakness is a well-recognized feature of acromegaly, only a few cases similar to ours have been reported since acromegaly was first described in the late 1800s. Little is known about the natural history, best diagnostic approach, and optimal therapy for this debilitating complication.ConclusionMuscle weakness in acromegaly is common and may result from a combination of the direct effect of GH excess on muscle and other metabolic derangements (hypothyroidism, hypoadrenalism, or diabetes). Mechanical factors may also contribute, such as joint laxity in conjunction with hypermobility. Affected patients may benefit from a reduction in GH levels and physiotherapy for adaptive training. Persistently increased serum CK levels in a patient with diabetes, for whom no other cause is found, should prompt an investigation for acromegaly. More research into this aspect of acromegaly is needed for enhancement of our understanding of, and therapy for, this debilitating condition. (Endocr Pract. 2005;11:18-22)  相似文献   

13.
The sebum excretion rate (S.E.R.) was measured in 20 patients with acromegaly. Eleven were untreated at the time of the measurement and nine had previously undergone surgical hypophysectomy or had received pituitary irradiation by yttrium-90 or radiotherapy. In five patients the S.E.R. was measured before and after such treatment. The mean S.E.R. in the untreated acromegalics was much greater than in a normal population and decreased significantly after successful pituitary ablation. No significant decrease in mean S.E.R. occurred in the group of patients with a poor clinical response to ablation. The correlations between S.E.R. and log serum growth hormone, plasma 11-hydroxycorticosteroid levels, and heel-pad thickness were significant, but there was no significant correlation between S.E.R. and serum protein-bound iodine levels. This suggests that the changes in S.E.R. were due to pituitary ablation but could not necessarily be attributed solely to changes in growth hormone, thyroid-stimulating hormone, or adrenocorticotrophic hormone. The association between the clinical state of the acromegaly and the S.E.R. was better than the association between acromegaly and serum growth hormone. We conclude that the S.E.R. is a useful addition to the clinical and endocrinological data used in assessing acromegaly.  相似文献   

14.
Clinical and pathological findings in 100 cases of acromegaly were reviewed. Great individual variation in manifestations of the disease was apparent. The chronic course was evidenced by 30 patients presenting symptoms unrelated to acromegaly. Headache, visual disturbances, arthritis and elevated blood pressure were common. The incidence of diabetes mellitus, thyroid and adrenal dysfunction was similar to that reported in other series. Gonadal disturbances were frequent. Two patients had galactorrhea and two had hyperparathyroidism. Radiologically, pituitary fossae were normal in 24. Pituitary histology in 29 cases revealed four eosinophilic adenomas, but most were mixed eosinophilic-chromophobic. Fifty-two patients received radiation therapy. Rhinorrhea and optic nerve fibrosis were seen in this group. Twenty-four patients were operated upon, with no operative deaths since 1945 and no morbidity since 1952. Visual failure was the clearest indication for surgery. Treatment will be difficult to evaluate until an index of growth hormone secretion is generally available.  相似文献   

15.
Carl‐Ulrik Schierup 《Ethnos》2013,78(3-4):173-198
This article analyzes the role of self‐control, moral and ethical doctrines in the rise of individualist world‐view in Finland. In the Finnish case, the formation of the modern individual was closely linked with the temperance movement, the ideology of which is therefore used as an illustrative example. The guiding line in the article is not to treat self‐control as a theoretical concept used in analyzing individual behavior, but as a legitimation of an increasing use of a utilitarian framework. The author discusses the developments in Finnish individualist world‐view by analyzing the main turning points in Finnish notions about drinking. First he discusses the end of the 19th century and the beginning of the 20th century, the era of the strength of Finnish temperance movement. Secondly he analyzes the way in which conceptions about drinking changed when the temperance movement lost its appeal to the masses.  相似文献   

16.
ObjectiveAcromegaly is characterized by chronic growth hormone (GH) and insulin-like growth factor 1 (IGF-1) hypersecretion, often caused by a GH-secreting pituitary adenoma. Even though surgery remains the first line of treatment, medical therapy is essential if surgery is contraindicated, does not achieve remission, or does not prevent recurrence despite apparent surgical remission. Oral octreotide capsules (OOCs) that combine octreotide with a transient permeability enhancer technology are the first oral somatostatin receptor ligands (SRLs) approved in the United States for acromegaly.MethodsWe review the literature and clinical trial data on OOC therapy in patients with acromegaly and discuss the clinical assessment of OOC use, potential drug–drug interactions, drug initiation, dose titration, and monitoring of drug efficacy and tolerability.ResultsIn 4 pivotal clinical trials involving 238 patients with acromegaly treated with OOC, effective suppression of serum GH and IGF-1 levels, maintenance of disease control, decreased breakthrough symptoms and symptomatic improvement with non-inferiority of OOCs to injectable SRLs in maintaining biochemical response was seen. Additionally, the safety profile of OOC therapy is comparable to that of injectable SRLs. Most patients who completed the clinical trials of OOCs have also expressed preference for oral compared with injectable SRL administration.ConclusionOOCs are an effective treatment option for patients with acromegaly who previously responded to injectable SRLs, with the benefits of avoiding injection-related side effects. This article provides a review of the pharmacology, safety, and efficacy and offers practical recommendations on the use of OOCs to treat injectable SRL-responsive patients with acromegaly.  相似文献   

17.
Different types of treatment, including surgery, medical therapy and radiotherapy, are possible in achieving control of acromegaly. Of the medical therapies available, somatostatin analogues are effective in the majority of patients and can induce pituitary tumour shrinkage. The rationale and outcome of somatostatin analogue treatment before surgery in patients with acromegaly is briefly presented. In summary, the benefits of somatostatin analogues given preoperatively should be considered carefully as optimisation of cardiovascular, respiratory and metabolic functions is clinically relevant for perioperative morbidity. Somatostatin analogues also induce significant shrinkage of GH-secreting pituitary tumours, although this does not seem to be helpful in terms of improved surgical outcome.  相似文献   

18.
Plasma prolactin response to thyrotropin-releasing-hormone (TRH) stimulation was diminished in 30 patients with prolactinomas and 9 patients with acromegaly who had normal serum prolactin levels. There was no overlap of prolactin responses when compared with 32 control patients. Responses of ten patients with adrenocorticotropin (ACTH)-secreting pituitary tumors were similar to those of controls. Plasma growth hormone concentrations after TRH stimulation changed significantly in 28% of normal control and 20%, 25% and 50% of patients with prolactin-, growth hormone- and ACTH-secreting pituitary tumors, respectively. Our data suggest that the blunted TRH-induced rise in plasma prolactin levels in patients with prolactinomas and those with acromegaly may be related to humoral factor(s) affecting TRH receptor or postreceptor function. Growth hormone responses to TRH are nonspecific and should not be considered a marker for active acromegaly.  相似文献   

19.
《Endocrine practice》2021,27(10):1034-1039
ObjectiveAcromegaly is associated with increased morbidity and mortality. Limited data are available on these patients’ utilization and costs of health care. This study assessed the impact of acromegaly on employees’ health benefit (direct and indirect) costs and absenteeism.MethodsA retrospective analysis was conducted of drug and medical claims and employer data (from January 2010 to April 2019) of patients with an acromegaly diagnosis and matched controls from a U.S. employee database. Patient claims were tracked for 12 months postdiagnosis (or matched) date. Outcomes were analyzed using separate 2-part regression models, controlling for clinical, demographic, and job-related variables.ResultsForty-seven patients with acromegaly and 940 controls were identified. Cohorts were similar in most demographic and job-related variables. Patients with acromegaly had a significantly higher Charlson comorbidity index score and higher incidence of claims for several comorbidities. Acromegaly drugs represented 16.3% of the acromegaly cohort’s total costs. Total health benefit costs were $54 821 higher (P < .05) for patients compared with controls, with direct costs representing 79.8% of the difference. Total indirect costs were higher for patients with acromegaly, with short-term and long-term disability comprising most of the difference between the acromegaly and control groups. Patients with acromegaly had significantly more short-term disability days than controls, but total sick days were similar for the 2 groups.ConclusionThe presence of acromegaly was associated with increased direct and indirect employee health benefit costs and increased work absenteeism.  相似文献   

20.
Unbiased estimation of individual asymmetry   总被引:1,自引:0,他引:1  
The importance of measurement error (ME) for the estimation of population level fluctuating asymmetry (FA) has long been recognized. At the individual level, however, this aspect has been studied in less detail. Recently, it has been shown that the random slopes of a mixed regression model can estimate individual asymmetry levels that are unbiased with respect to ME. Yet, recent studies have shown that such estimates may fail to reflect heterogeneity in these effects. In this note I show that this is not the case for the estimation of individual asymmetry. The random slopes adequately reflect between‐individual heterogeneity in the underlying developmental instability. Increased levels of ME resulted in, on average, lower estimates of individual asymmetry relative to the traditional unsigned asymmetry. This well‐known shrinkage effect in Bayesian analysis adequately corrected for ME and heterogeneity in ME resulting in unbiased estimates of individual asymmetry that were more closely correlated with the true underlying asymmetry.  相似文献   

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