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Article ; Online: Novel predictions of invasive breast cancer risk in mammography screening cohorts.

Strandberg, Rickard / Czene, Kamila / Hall, Per / Humphreys, Keith

2023 Volume 42, Issue 21, Page(s) 3816–3837

Abstract: Mammography screening programs are aimed at reducing mortality due to breast cancer by detecting tumors at an early stage. There is currently interest in moving away from the age-based screening programs, and toward personalized screening based on ... ...

Abstract	Mammography screening programs are aimed at reducing mortality due to breast cancer by detecting tumors at an early stage. There is currently interest in moving away from the age-based screening programs, and toward personalized screening based on individual risk factors. To accomplish this, risk prediction models for breast cancer are needed to determine who should be screened, and when. We develop a novel approach using a (random effects) continuous growth model, which we apply to a large population-based, Swedish screening cohort. Unlike existing breast cancer prediction models, this approach explicitly incorporates each woman's individual screening visits in the prediction. It jointly models invasive breast cancer tumor onset, tumor growth rate, symptomatic detection rate, and screening sensitivity. In addition to predicting the overall risk of invasive breast cancer, this model can make separate predictions regarding specific tumor sizes, and the mode of detection (eg, detected at screening, or through symptoms between screenings). It can also predict how these risks change depending on whether or not a woman will attend her next screening. In our study, we predict, given a future diagnosis, that the probability of having a tumor less than (as opposed to greater than) 10-mm diameter, at detection, will be, on average, 2.6 times higher if a woman in the cohort attends their next screening. This indicates that the model can be used to evaluate the short-term benefit of screening attendance, at an individual level.
MeSH term(s)	Humans ; Female ; Breast Neoplasms/diagnostic imaging ; Breast Neoplasms/pathology ; Early Detection of Cancer ; Mammography ; Mass Screening ; Sweden/epidemiology
Language	English
Publishing date	2023-06-19
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	843037-8
ISSN	1097-0258 ; 0277-6715
ISSN (online)	1097-0258
ISSN	0277-6715
DOI	10.1002/sim.9834
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Article ; Online: Studying the association between longitudinal mammographic density measurements and breast cancer risk: a joint modelling approach.

Illipse, Maya / Czene, Kamila / Hall, Per / Humphreys, Keith

Breast cancer research : BCR

2023 Volume 25, Issue 1, Page(s) 64

Abstract: Background: Researchers have suggested that longitudinal trajectories of mammographic breast density (MD) can be used to understand changes in breast cancer (BC) risk over a woman's lifetime. Some have suggested, based on biological arguments, that the ... ...

Abstract	Background: Researchers have suggested that longitudinal trajectories of mammographic breast density (MD) can be used to understand changes in breast cancer (BC) risk over a woman's lifetime. Some have suggested, based on biological arguments, that the cumulative trajectory of MD encapsulates the risk of BC across time. Others have tried to connect changes in MD to the risk of BC. Methods: To summarize the MD-BC association, we jointly model longitudinal trajectories of MD and time to diagnosis using data from a large ([Formula: see text]) mammography cohort of Swedish women aged 40-80 years. Five hundred eighteen women were diagnosed with BC during follow-up. We fitted three joint models (JMs) with different association structures; Cumulative, current value and slope, and current value association structures. Results: All models showed evidence of an association between MD trajectory and BC risk ([Formula: see text] for current value of MD, [Formula: see text] and [Formula: see text] for current value and slope of MD respectively, and [Formula: see text] for cumulative value of MD). Models with cumulative association structure and with current value and slope association structure had better goodness of fit than a model based only on current value. The JM with current value and slope structure suggested that a decrease in MD may be associated with an increased (instantaneous) BC risk. It is possible that this is because of increased screening sensitivity rather than being related to biology. Conclusion: We argue that a JM with a cumulative association structure may be the most appropriate/biologically relevant model in this context.
MeSH term(s)	Female ; Humans ; Breast Neoplasms/diagnostic imaging ; Breast Neoplasms/epidemiology ; Breast Density ; Breast/diagnostic imaging ; Mammography ; Research ; Risk Factors
Language	English
Publishing date	2023-06-09
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2015059-3
ISSN	1465-542X ; 1465-5411
ISSN (online)	1465-542X
ISSN	1465-5411
DOI	10.1186/s13058-023-01667-8
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Zs.A 5494: Show issues

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Article ; Online: Familial adversity: association with discontinuation of adjuvant hormone therapy and breast cancer prognosis.

Zeng, Erwei / He, Wei / Sjölander, Arvid / Bergqvist, Jenny / Fang, Fang / Czene, Kamila

Journal of the National Cancer Institute

2024

Abstract: Background: Many studies have examined patient-related factors affecting adjuvant hormone therapy adherence in breast cancer patients. Our study aimed to examine associations of family-related factors with adjuvant hormone therapy discontinuation and ... ...

Abstract	Background: Many studies have examined patient-related factors affecting adjuvant hormone therapy adherence in breast cancer patients. Our study aimed to examine associations of family-related factors with adjuvant hormone therapy discontinuation and breast cancer-specific mortality. Methods: By cross-linking seven Swedish health registers, we performed a cohort study including all breast cancer patients who initiated adjuvant hormone therapy during 2006-2019 in Sweden (N = 10,701). A group-based multi-trajectory model was used to identify familial adversity groups based on three dimensions: material deprivation, negative family dynamics, and loss or threat of loss. Cox proportional hazard models were used to investigate associations of familial adversity with hormone therapy discontinuation and breast cancer-specific mortality. Results: We identified five distinctive familial adversity groups among the cohort participants. Compared to women with low familial adversity, higher risks to discontinue adjuvant hormone therapy were observed among women with material deprivation (hazard ratio (HR), 1.31; 95% CI, 1.20-1.43), negative family dynamics (HR, 1.16; 95% CI, 1.06-1.28), loss or threat to loss (HR, 1.15; 95% CI, 1.00-1.32), or high familial adversity (HR, 1.53; 95% CI, 1.40-1.68). Furthermore, women with material deprivation (HR, 1.37; 95% CI, 1.05-1.79), negative family dynamics (HR, 1.41; 95% CI, 1.01-1.97), or high adversity (HR, 1.67; 95% CI, 1.26-2.23) were at higher risks of dying from breast cancer. Conclusion: Familial adversity is associated with a higher risk of adjuvant hormone therapy discontinuation and breast cancer-specific mortality. Family-related factors identified in our study may help identify high-risk patients for interventions to prevent treatment discontinuation and subsequently improve breast cancer outcomes.
Language	English
Publishing date	2024-03-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	2992-0
ISSN	1460-2105 ; 0027-8874 ; 0198-0157
ISSN (online)	1460-2105
ISSN	0027-8874 ; 0198-0157
DOI	10.1093/jnci/djae061
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Article ; Online: Influence of mammographic density and compressed breast thickness on true mammographic sensitivity: a cohort study.

Strandberg, Rickard / Illipse, Maya / Czene, Kamila / Hall, Per / Humphreys, Keith

Scientific reports

2023 Volume 13, Issue 1, Page(s) 14194

Abstract: Understanding the detectability of breast cancer using mammography is important when considering nation-wide screening programmes. Although the role of imaging settings on image quality has been studied extensively, their role in detectability of cancer ... ...

Abstract	Understanding the detectability of breast cancer using mammography is important when considering nation-wide screening programmes. Although the role of imaging settings on image quality has been studied extensively, their role in detectability of cancer at a population level is less well studied. We wish to quantify the association between mammographic screening sensitivity and various imaging parameters. Using a novel approach applied to a population-based breast cancer screening cohort, we specifically focus on sensitivity as defined in the classical diagnostic testing literature, as opposed to the screen-detected cancer rate, which is often used as a measure of sensitivity for monitoring and evaluating breast cancer screening. We use a natural history approach to model the presence and size of latent tumors at risk of detection at mammography screening, and the screening sensitivity is modeled as a logistic function of tumor size. With this approach we study the influence of compressed breast thickness, x-ray exposure, and compression pressure, in addition to (percent) breast density, on the screening test sensitivity. When adjusting for all screening parameters in addition to latent tumor size, we find that percent breast density and compressed breast thickness are statistically significant factors for the detectability of breast cancer. A change in breast density from 6.6 to 33.5% (the inter-quartile range) reduced the odds of detection by 61% (95% CI 48-71). Similarly, a change in compressed breast thickness from 46 to 66 mm reduced the odds by 42% (95% CI 21-57). The true sensitivity of mammography, defined as the probability that an examination leads to a positive result if a tumour is present in the breast, is associated with compressed breast thickness after accounting for mammographic density and tumour size. This can be used to guide studies of setups aimed at improving lesion detection. Compressed breast thickness-in addition to breast density-should be considered when assigning complementary screening modalities and personalized screening intervals.
MeSH term(s)	Humans ; Female ; Breast Density ; Cohort Studies ; Mammography ; Breast/diagnostic imaging ; Breast Neoplasms/diagnostic imaging
Language	English
Publishing date	2023-08-30
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-41356-2
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Random effects models of lymph node metastases in breast cancer: quantifying the roles of covariates and screening using a continuous growth model

Isheden, Gabriel / Czene, Kamila / Humphreys, Keith

Biometrics. 2022 Mar., v. 78, no. 1

2022

Abstract: We recently described a joint model of breast cancer tumor size and number of affected lymph nodes, which conditions on screening history, mammographic density, and mode of detection, and can be used to infer growth rates, time to symptomatic detection, ... ...

Abstract	We recently described a joint model of breast cancer tumor size and number of affected lymph nodes, which conditions on screening history, mammographic density, and mode of detection, and can be used to infer growth rates, time to symptomatic detection, screening sensitivity, and rates of lymph node spread. The model of lymph node spread can be estimated in isolation from measurements of tumor volume and number of affected lymph nodes, giving inference identical to the joint model. Here, we extend our model to include covariate effects. We also derive theoretical results in order to study the role of screening on lymph node metastases at diagnosis. We analyze the association between hormone replacement therapy (HRT) and breast cancer lymph node spread, using data from a case‐control study designed specifically to study the effects of HRT on breast cancer. Using our method, we estimate that women using HRT at time of diagnosis have a 36% lower rate of lymph node spread than nonusers (95% confidence interval [CI] =(8%,58%)). This can be contrasted with the effect of HRT on the tumor growth rate, estimated here to be 15% slower in HRT users (95% CI = (−34%,+7%)). For screen‐detected cancers, we illustrate how lead time can relate to lymph node spread; and using symptomatic cancers, we illustrate the potential consequences of false negative screens in terms of lymph node spread.
Keywords	breast neoplasms ; case-control studies ; confidence interval ; growth models ; hormone replacement therapy ; lymph ; lymph nodes
Language	English
Dates of publication	2022-03
Size	p. 376-387.
Publishing place	John Wiley & Sons, Ltd
Document type	Article
Note	JOURNAL ARTICLE
ZDB-ID	213543-7
ISSN	0099-4987 ; 0006-341X
ISSN	0099-4987 ; 0006-341X
DOI	10.1111/biom.13430
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Biomarkers and Disease Trajectories Influencing Women's Health: Results from the UK Biobank Cohort.

Yang, Haomin / Pawitan, Yudi / Fang, Fang / Czene, Kamila / Ye, Weimin

Phenomics (Cham, Switzerland)

2022 Volume 2, Issue 3, Page(s) 184–193

Abstract: Women's health is important for society. Despite the known biological and sex-related factors influencing the risk of diseases among women, the network of the full spectrum of diseases in women is underexplored. This study aimed to systematically examine ...

Abstract	Women's health is important for society. Despite the known biological and sex-related factors influencing the risk of diseases among women, the network of the full spectrum of diseases in women is underexplored. This study aimed to systematically examine the women-specific temporal pattern (trajectory) of the disease network, including the role of baseline physical examination indexes, and blood and urine biomarkers. In the UK Biobank study, 502,650 participants entered the cohort from 2006 to 2010, and were followed up until 2019 to identify disease incidence via linkage to the patient registers. For those diseases with increased risk among women, conditional logistic regression models were used to estimate odds ratios (ORs), and the binomial test of direction was further used to build disease trajectories. Among 301 diseases, 82 diseases in women had ORs > 1.2 and Supplementary information: The online version contains supplementary material available at 10.1007/s43657-022-00054-1.
Language	English
Publishing date	2022-05-12
Publishing country	Switzerland
Document type	Journal Article
ISSN	2730-5848
ISSN (online)	2730-5848
DOI	10.1007/s43657-022-00054-1
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Article ; Online: Cancer risks among first-degree relatives of women with a genetic predisposition to breast cancer.

Xiao, Qingyang / Mao, Xinhe / Ploner, Alexander / Grassmann, Felix / Rodriguez, Juan / Eriksson, Mikael / Hall, Per / Czene, Kamila

Journal of the National Cancer Institute

2024

Abstract: Background: Associations between germline alterations in women and cancer risks among their relatives are largely unknown.: Methods: We used women from two Swedish cohorts (KARMA and pKARMA), including 28,362 women with genotyping data and 13,226 ... ...

Abstract	Background: Associations between germline alterations in women and cancer risks among their relatives are largely unknown. Methods: We used women from two Swedish cohorts (KARMA and pKARMA), including 28,362 women with genotyping data and 13,226 with sequencing data. Using Swedish Multi-Generation Register, we linked these women to 133,389 first-degree relatives. Associations between protein-truncating variants (PTVs) in 8 risk genes and breast cancer polygenic risk score (PRS) in index women and cancer risks among their relatives were modeled via Cox regression. Results: Female relatives of index women who were PTV carriers in any of the 8 risk genes had an increased breast cancer risk compared to those of non-carriers (HR1.85, 95% CI: 1.52-2.27), with the strongest association found for PTVs in BRCA1/2. These relatives had a statistically higher risk of early-onset than late-onset breast cancer (P = .001). Elevated breast cancer risk was also observed in female relatives of index women with higher PRS (HR per SD: 1.28, 95% CI: 1.23-1.32). The estimated lifetime risk was 22.3% for female relatives of PTV carriers and 14.4% for those related to women in the top PRS quartile. Moreover, relatives of index women with PTV presence (HR: 1.30, 95% CI: 1.06-1.59) or higher PRS (HR per SD: 1.04, 95% CI: 1.01-1.07) were also at higher risk of non-breast-HBOC cancers, including prostate, ovarian, pancreatic cancer, and melanoma. Conclusions: Both PTVs of risk genes and higher PRS in index women are associated with an increased risk of breast and other HBOC-related cancers among relatives.
Language	English
Publishing date	2024-02-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	2992-0
ISSN	1460-2105 ; 0027-8874 ; 0198-0157
ISSN (online)	1460-2105
ISSN	0027-8874 ; 0198-0157
DOI	10.1093/jnci/djae030
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Article ; Online: Adjuvant Hormone Therapy-Related Hot Flashes Predict Treatment Discontinuation and Worse Breast Cancer Prognosis.

Zeng, Erwei / He, Wei / Smedby, Karin E / Czene, Kamila

Journal of the National Comprehensive Cancer Network : JNCCN

2022 Volume 20, Issue 6, Page(s) 683–689.e2

Abstract: Background: Clinical trials have shown that adjuvant hormone therapy (AHT)-related hot flashes can predict better breast cancer outcomes. This population-based cohort study investigated whether this result can be generalized to a real-world setting.: ... ...

Abstract	Background: Clinical trials have shown that adjuvant hormone therapy (AHT)-related hot flashes can predict better breast cancer outcomes. This population-based cohort study investigated whether this result can be generalized to a real-world setting. Patients and methods: By linking the National Quality Registry for Breast Cancer, Prescribed Drug Register, and Cause-of-Death Register, we identified 7,152 chemotherapy-free patients with breast cancer who initiated AHT in Stockholm from 2006 through 2019, and followed them until 2020. Hot flashes were defined as new use of drugs for hot flashes within 6 months after initiating AHT. We used Cox models to compare disease-free survival and treatment discontinuation among patients with and without hot flashes. Results: Patients who newly used drugs for hot flashes shortly after AHT initiation had worse disease-free survival (adjusted hazard ratio [HR], 1.67; 95% CI, 1.11-2.52) and a higher treatment discontinuation rate (adjusted HR, 1.47; 95% CI, 1.21-1.78). The association between drugs for hot flashes and discontinuation of AHT differed by patient characteristics, with stronger associations among low-income patients (HR, 1.91; 95% CI, 1.41-2.59) and those without first-degree relatives who had cancer (HR, 1.81; 95% CI, 1.39-2.35) or died from cancer (HR, 1.71; 95% CI, 1.37-2.12). Conclusions: AHT-related hot flashes predict worse, rather than better, breast cancer outcomes among patients in clinical routine practice. The identification of adverse effects by the initiation of hot flash medications may identify a subset of patients with more severe hot flashes who are more likely to discontinue AHT and need more support for treatment adherence.
MeSH term(s)	Humans ; Female ; Breast Neoplasms/complications ; Breast Neoplasms/drug therapy ; Cohort Studies ; Hot Flashes/epidemiology ; Hot Flashes/etiology ; Chemotherapy, Adjuvant/adverse effects ; Prognosis ; Hormones/therapeutic use
Chemical Substances	Hormones
Language	English
Publishing date	2022-04-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	2250759-0
ISSN	1540-1413 ; 1540-1405
ISSN (online)	1540-1413
ISSN	1540-1405
DOI	10.6004/jnccn.2021.7116
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Article ; Online: Baseline breast tissue characteristics determine the effect of tamoxifen on mammographic density change.

Gabrielson, Marike / Hammarström, Mattias / Bergqvist, Jenny / Lång, Kristina / Rosendahl, Ann H / Borgquist, Signe / Hellgren, Roxanna / Czene, Kamila / Hall, Per

International journal of cancer

2024

Abstract: Tamoxifen prevents recurrence of breast cancer and is also approved for preventive, risk-reducing, therapy. Tamoxifen alters the breast tissue composition and decreases the mammographic density. We aimed to test if baseline breast tissue composition ... ...

Abstract	Tamoxifen prevents recurrence of breast cancer and is also approved for preventive, risk-reducing, therapy. Tamoxifen alters the breast tissue composition and decreases the mammographic density. We aimed to test if baseline breast tissue composition influences tamoxifen-associated density change. This biopsy-based study included 83 participants randomised to 6 months daily intake of placebo, 20, 10, 5, 2.5, or 1 mg tamoxifen. The study is nested within the double-blinded tamoxifen dose-determination trial Karolinska Mammography Project for Risk Prediction of Breast Cancer Intervention (KARISMA) Study. Ultrasound-guided core-needle breast biopsies were collected at baseline before starting treatment. Biopsies were quantified for epithelial, stromal, and adipose distributions, and epithelial and stromal expression of proliferation marker Ki67, oestrogen receptor (ER) and progesterone receptor (PR). Mammographic density was measured using STRATUS. We found that greater mammographic density at baseline was positively associated with stromal area and inversely associated with adipose area and stromal expression of ER. Premenopausal women had greater mammographic density and epithelial tissue, and expressed more epithelial Ki67, PR, and stromal PR, compared to postmenopausal women. In women treated with tamoxifen (1-20 mg), greater density decrease was associated with higher baseline density, epithelial Ki67, and stromal PR. Women who responded to tamoxifen with a density decrease had on average 17% higher baseline density and a 2.2-fold higher PR expression compared to non-responders. Our results indicate that features in the normal breast tissue before tamoxifen exposure influences the tamoxifen-associated density decrease, and that the age-associated difference in density change may be related to age-dependant differences in expression of Ki67 and PR.
Language	English
Publishing date	2024-03-30
Publishing country	United States
Document type	Journal Article
ZDB-ID	218257-9
ISSN	1097-0215 ; 0020-7136
ISSN (online)	1097-0215
ISSN	0020-7136
DOI	10.1002/ijc.34939
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Article ; Online: Reply to T. Suemasu et al.

Eriksson, Mikael / Czene, Kamila / Hall, Per

Journal of clinical oncology : official journal of the American Society of Clinical Oncology

2021 Volume 39, Issue 26, Page(s) 2966–2968

Language	English
Publishing date	2021-06-14
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	604914-x
ISSN	1527-7755 ; 0732-183X
ISSN (online)	1527-7755
ISSN	0732-183X
DOI	10.1200/JCO.21.01166
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