Stoichiometry-Controlled Reversible Lithiation Capacity in Nanostructured Silicon Nitrides Enabled by in Situ Conversion Reaction.

In modern Li-based batteries, alloying anode materials have the potential to drastically improve the volumetric and specific energy storage capacity. For the past decade silicon has been viewed as a "Holy Grail" among these materials; however, severe stability issues limit its potential. Herein, we present amorphous substoichiometric silicon nitride (SiNx) as a convertible anode material, which allows overcoming the stability challenges associated with common alloying materials. Such material can be synthesized in a form of nanoparticles with seamlessly tunable chemical composition and particle size and, therefore, be used for the preparation of anodes for Li-based batteries directly through conventional slurry processing. Such SiNx materials were found to be capable of delivering high capacity that is controlled by the initial chemical composition of the nanoparticles. They exhibit an exceptional cycling stability, largely maintaining structural integrity of the nanoparticles and the complete electrodes, thus delivering stable electrochemical performance over the course of 1000 charge/discharge cycles. Such stability is achieved through the in situ conversion reaction, which was herein unambiguously confirmed by pair distribution function analysis of cycled SiNx nanoparticles revealing that active silicon domains and a stabilizing Li2SiN2 phase are formed in situ during the initial lithiation.

Anodes for Li-ion batteries prepared from microcrystalline silicon and enabled by binder's chemistry and pseudo-self-healing.

Silicon, while suffering from major degradation issues, has been recognized as a next promising material to replace currently used graphite in the anodes of Li-ion batteries. Several pathways to mitigate the capacity fading of silicon has been proposed, including optimization of the electrode composition. Within the present work we evaluated different binder formulations to improve the long-term performance of the Li-ion batteries' anodes based on industrial grade silicon (Si) which is typically characterized by a particle sizes ranging from 100 nm to 5.5 microns. The decrease of pH in a binder formulation was found to detrimental for the cycling performance of Si due to enhanced formation of an ester-type bonding between the carboxylic group of the binder and hydroxyl group on the Si surface as well as cross-linking. Furthermore, the present work was focused on the use of the industrial grade Si with very high loading of Si material (up to 80% by weight) to better highlight the effects of the surface chemistry of Si and its influence on the performance of Si-based anodes in Li-ion batteries. The tested system allowed to establish a pseudo self-healing effect that manifests itself through the restoration of the anode capacity by approximately 25% and initiates after approximately 20 cycles. The stabilization of the capacity is attributed to self-limiting lithiation process. Such effect is closely related to SEI formation and transport properties of an electrode prepared from silicon of industrial grade.

Comparative study of the implementation of tin and titanium oxide nanoparticles as electrodes materials in Li-ion batteries.

Transition metal oxides potentially present higher specific capacities than the current anodes based on carbon, providing an increasing energy density as compared to commercial Li-ion batteries. However, many parameters could influence the performance of the batteries, which depend on the processing of the electrode materials leading to different surface properties, sizes or crystalline phases. In this work a comparative study of tin and titanium oxide nanoparticles synthesized by different methods, undoped or Li doped, used as single components or in mixed ratio, or alternatively forming a composite with graphene oxide have been tested demonstrating an enhancement in capacity with Li doping and better cyclability for mixed phases and composite anodes.

Morphology engineering of silicon nanoparticles for better performance in Li-ion battery anodes.

Amorphous silicon nanoparticles were synthesized through pyrolysis of silane gas at temperatures ranging from 575 to 675 °C. According to the used temperature and silane concentration, two distinct types of particles can be obtained: at 625 °C, spherical particles with smooth surface and a low degree of aggregation, but at a higher temperature (650 °C) and lower silane concentration, particles with extremely rough surfaces and high degree of aggregation are found. This demonstrates the importance of the synthesis temperature on the morphology of silicon particles. The two types of silicon nanoparticles were subsequently used as active materials in a lithium half cell configuration, using LiPF6 in an alkylcarbonate-based electrolyte, in order to investigate the impact of the particles morphology on the cycling performances of silicon anode material. The difference in morphology of the particles resulted in different volume expansions, which impacts the solid electrolyte interface (SEI) formation and, as a consequence, the lifetime of the electrode. Half-cells fabricated from spherical particles demonstrated almost 70% capacity retention for over 300 cycles, while the cells made from the rough, aggregated particles showed a sharp decrease in capacity after the 20th cycle. The cycling results underline the importance of Si particle engineering and its influence on the lifetime of Si-based materials.

Silicon-Carbon composite anodes from industrial battery grade silicon.

In this work, silicon/carbon composites for anode electrodes of Li-ion batteries are prepared from Elkem's Silgrain® line. Gentle ball milling is used to reduce particle size of Silgrain, and the resulting Si powder consists of micrometic Si with some impurities. Silicon/carbon composite with CMC/SBR as a dual binder can achieve more than 1200 cycles with a capacity of 1000 mAh g-1 of Si. This excellent electrochemical performance can be attributed to the use of a buffer as a solvent to control the pH of the electrode slurry, and hence the bonding properties of the binder to the silicon particles. In addition, the use of FEC as an electrolyte additive is greatly contributing to a stabilized cycling by creating a more robust SEI layer. This work clearly demonstrates the potential of industrial battery grade silicon from Elkem.

Substoichiometric Silicon Nitride - An Anode Material for Li-ion Batteries Promising High Stability and High Capacity.

Silicon is often regarded as a likely candidate to replace graphite as the main active anode material in next-generation lithium ion batteries; however, a number of problems impacting its cycle stability have limited its commercial relevance. One approach to solving these issues involves the use of convertible silicon sub-oxides. In this work we have investigated amorphous silicon sub-nitride as an alternative convertible silicon compound by comparing the electrochemical performance of a-SiNx thin films with compositions ranging from pure Si to SiN0.89. We have found that increasing the nitrogen content gradually reduces the reversible capacity of the material, but also drastically increases its cycling stability, e.g. 40 nm a-SiN0.79 thin films exhibited a stable capacity of more than 1,500 mAh/g for 2,000 cycles. Consequently, by controlling the nitrogen content, this material has the exceptional ability to be tuned to satisfy a large range of different requirements for capacity and stability.

Evaluating different breast tumor progression models using screening data.

BACKGROUND: Mammography screening is used to detect breast cancer at an early treatable stage, reducing breast cancer mortality. Traditionally, breast cancer has been seen as a disease with only progressive lesions, and here we examine the validity of this assumption by testing if incidence levels after introducing mammography screening can be reproduced assuming only progressive tumors. METHODS: Breast cancer incidence data 1990-2009 obtained from the initially screened Norwegian counties (Akershus, Oslo, Rogaland and Hordaland) was included, covering the time-period before, during and after the introduction of mammography screening. From 1996 women aged 50-69 were invited for biennial public screening. Using estimates of tumor growth and screening sensitivity based on pre-screening and prevalence screening data (1990-1998), we simulated incidence levels during the following period (1999-2009). RESULTS: The simulated incidence levels during the period with repeated screenings were markedly below the observed levels. The results were robust to changes in model parameters. Adjusting for hormone replacement therapy use, we obtained levels closer to the observed levels. However, there was still a marked gap, and only by assuming some tumors that undergo regressive changes or enter a markedly less detectable state, was our model able to reproduce the observed incidence levels. CONCLUSIONS: Models with strictly progressive tumors are only able to partly explain the changes in incidence levels observed after screening introduction in the initially screened Norwegian counties. More complex explanations than a time shift in detection of future clinical cancers seem to be needed to reproduce the incidence trends, questioning the basis for many over-diagnosis calculations. As data are not randomized, similar studies in other populations are wanted to exclude effect of unknown confounders.

Long-term Cyclability of Substoichiometric Silicon Nitride Thin Film Anodes for Li-ion Batteries.

Silicon has been the subject of an extensive research effort aimed at developing new anode materials for lithium ion batteries due to its large specific and volumetric capacity. However, commercial use is limited by a number of degradation problems, many of which are related to the large volume change the material undergoes during cycling in combination with limited lithium-diffusivity. Silicon rich silicon oxides (SiOx), which converts into active silicon and inactive lithium oxide during the initial lithiation, have attracted some attention as a possible solution to these issues. In this work we present an investigation of silicon rich amorphous silicon nitride (a-SiNx) as an alternative convertible anode material. Amorphous SiN0.89 thin films deposited by plasma enhanced chemical vapour deposition show reversible reactions with lithium when cycled between 0.05 and 1.0 V vs. Li+/Li. This material delivers a reversible capacity of approximately 1,200 mAh/g and exhibits excellent cycling stability, with 41 nm a-SiN0.89 thin film electrodes showing negligible capacity degradation over more than 2,400 cycles.

Bias in Observational Studies of the Association between Menopausal Hormone Therapy and Breast Cancer.

BACKGROUND: During the period 1985-2000 the breast cancer incidence rates increased 50% in the age group invited to mammography screening in Norway and Sweden. Simultaneously, use of hormone replacement treatment therapy (HT) increased 5 times. Several influential observational studies showed that HT was associated with 50% to 100% increased risk of breast cancer and most for those using combined (estrogen plus progestin) hormone replacement therapy (CHT). In contrast, the randomized WHI trial reported that CHT increased the risk by 10% for those not having previously used hormones and 24% when including previous users in the analyses. In another randomized trial, estrogen use only was not associated with any increased risk at all. After the WHI trial was published in 2003, use of HT dropped 70% within 5 years in Norway and Sweden while breast cancer rates were essentially unchanged. After 2008, HT use has dropped further and breast cancer incidence rates have started increasing again. The study objective is to calculate and to explain potential bias in the observational study design. METHODS AND FINDINGS: Here we use data from the randomized WHI trial and analyze these data as done in the observational studies to calculate the magnitude of the potential biases in the observational study design. Time varying effect of hormones and categorization of the follow-up time may increase the hazard ratio for long-term users from 1.10 to 1.48. Selective retrospective reporting of hormone use may further increase the hazard ratio to 1.68. CONCLUSIONS: We suggest that the mechanism causing higher hazard ratio of breast cancer (compared to the observational studies) is the time-varying effect of CHT on the breast cancer risk and selective retrospective reporting of hormone use. Other risk factors for the increase in breast cancer risk in the age group 50-69 years should be considered, for example, overdiagnosis.

Apolipoprotein E allelotype is associated with neuropathological findings in Alzheimer's disease.

In a consecutive hospital-based autopsy series, we examined the relationship between apolipoprotein E (apoE) and Alzheimer's disease (AD) and investigated the clinicopathological relationship in AD. The study population included 99 patients (mean age 81 years) with AD-related neuropathological findings at death, of whom 83 were diagnosed with AD according to the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) classification, and a control group of patients without neurodegenerative disease (n = 1429). The patients were apoE genotyped and the density of ß-amyloid senile plaques, neuritic plaques and neurofibrillary tangles was estimated in the cortex and hippocampus. The utility of immunohistochemical staining using an antibody directed against apoE4 in paraffin-embedded tissue was also evaluated. Among patients with "definite AD" according to CERAD, 65 % were ε4 carriers, compared to 32 % among controls (p < 0.001). The risk of ε4 carriers to develop AD was higher (odds ratio = 4.65, p = 0.001) than for non-ε4 carriers. The amount of ß-amyloid deposition and neurofibrillary pathology differed significantly (p < 0.01) between the genotypes, with increasing densities from ε2 carriers to homozygous ε4 carriers. The effect of ε4 on the presence of clinical symptoms was attenuated and non-significant after adjusting for AD-related neuropathological findings. There was an association between these findings and the presence of clinical symptoms of AD, with neurofibrillary tangles separating patients with and without symptoms of AD markedly better than ß-amyloid. In addition, we found a strong relationship between genotype and immunohistochemical apoE4-staining intensity. In conclusion, this Scandinavian autopsy study shows that the apoE polymorphism is associated with the probability of AD and influences the deposition of ß-amyloid and neurofibrillary pathology. Our findings suggest that the association between apoE and clinical manifestations of AD is mediated mainly through the neuropathological features of AD. Further, we found a relationship between AD-related findings and clinical symptoms of AD with neurofibrillary tangles associating most strongly with clinical symptoms. Finally, immunohistochemical staining in brain specimens is useful for determining ε4- or non-ε4-carrier status.

Staphylococcal α-hemolysin is neurotoxic and causes lysis of brain cells in vivo and in vitro.

Formation of a bacterial brain abscess entails loss of brain cells and formation of pus. The mechanisms behind the cell loss are not fully understood. Staphylococcus aureus, a common cause of brain abscesses, produces various exotoxins, including α-hemolysin, which is an important factor in brain abscess formation. α-Hemolysin may cause cytolysis by forming pores in the plasma membrane of various eukaryotic cells. However, whether α-hemolysin causes lysis of brain cells is not known. Nor is it known whether α-hemolysin in the brain causes cell death through pore formation or by acting as a chemoattractant, recruiting leukocytes and causing inflammation. Here we show that α-hemolysin injected into rat brain causes cell damage and edema formation within 30 min. Cell damage was accompanied by an increase in extracellular concentrations of zinc, GABA, glutamate, and other amino acids, indicating plasma membrane damage, but leukocytic infiltration was not seen 0.5-12h after α-hemolysin injection. This was in contrast to injection of S. aureus, which triggered extensive infiltration with neutrophils within 8h. In vitro, α-hemolysin caused concentration-dependent lysis of isolated nerve endings and cultured astrocytes. We conclude that α-hemolysin contributes to the cell death inherent in staphylococcal brain abscess formation as a pore-forming neurotoxin.

Breast cancer stromal elastosis is associated with mammography screening detection, low Ki67 expression and favourable prognosis in a population-based study.

BACKGROUND: Mammography screen-detected breast cancers have a better prognosis than predicted from established prognostic markers. A search for additional features that are characteristic for these tumours and their prognosis is needed to reduce overtreatment, a recognized challenge in breast cancer patient management today. Here, we have investigated the occurrence and importance of tumour elastosis. METHODS: We performed a population based retrospective study of breast cancers detected in the Norwegian Breast Cancer Screening Programme in Vestfold County during 2004-2009. In total, 197 invasive screen-detected cancers and 75 interval cancers in patients aged 50-69 years were compared with regard to standard clinico-pathological parameters and tumour shape, as well as ER, PR, HER2 and Ki67 expression. In particular, the presence of elastotic material in tumours was graded on a 4-tiered scale (score 0-3). RESULTS: Screen-detected cancers had a significantly higher content of stromal elastosis than interval cancers (p < 0.001). High content of elastosis (score 3) correlated strongly with stellate tumour shape, low histological grade, and ER+/HER2- status. Further, high elastosis score was significantly associated with lower Ki67 expression. In survival analyses, cases with high elastosis demonstrated increased recurrence free (p = 0.03) and disease-specific survival (p = 0.11) compared to cases with low elastosis. CONCLUSION: There is a strong correlation between the presence of tumour elastosis, stellate tumour shape and mammography detection of breast cancers. To our knowledge, this is the first time elastosis has been studied in relation to breast cancer detection method. Presence of elastosis is associated with low tumour cell proliferation (Ki67) and a good prognosis. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_230.

Brain infection with Staphylococcus aureus leads to high extracellular levels of glutamate, aspartate, γ-aminobutyric acid, and zinc.

Staphylococcal brain infections may cause mental deterioration and epileptic seizures, suggesting interference with normal neurotransmission in the brain. We injected Staphylococcus aureus into rat striatum and found an initial 76% reduction in the extracellular level of glutamate as detected by microdialysis at 2 hr after staphylococcal infection. At 8 hr after staphylococcal infection, however, the extracellular level of glutamate had increased 12-fold, and at 20 hr it had increased >30-fold. The extracellular level of aspartate and γ-aminobutyric acid (GABA) also increased greatly. Extracellular Zn(2+) , which was estimated at ∼2.6 µmol/liter in the control situation, was increased by 330% 1-2.5 hr after staphylococcal infection and by 100% at 8 and 20 hr. The increase in extracellular glutamate, aspartate, and GABA appeared to reflect the degree of tissue damage. The area of tissue damage greatly exceeded the area of staphylococcal infiltration, pointing to soluble factors being responsible for cell death. However, the N-methyl-D-aspartate receptor antagonist MK-801 ameliorated neither tissue damage nor the increase in extracellular neuroactive amino acids, suggesting the presence of neurotoxic factors other than glutamate and aspartate. In vitro staphylococci incubated with glutamine and glucose formed glutamate, so bacteria could be an additional source of infection-related glutamate. We conclude that the dramatic increase in the extracellular concentration of neuroactive amino acids and zinc could interfere with neurotransmission in the surrounding brain tissue, contributing to mental deterioration and a predisposition to epileptic seizures, which are often seen in brain abscess patients.

Loss of lysosomal membrane protein NCU-G1 in mice results in spontaneous liver fibrosis with accumulation of lipofuscin and iron in Kupffer cells.

Human kidney predominant protein, NCU-G1, is a highly conserved protein with an unknown biological function. Initially described as a nuclear protein, it was later shown to be a bona fide lysosomal integral membrane protein. To gain insight into the physiological function of NCU-G1, mice with no detectable expression of this gene were created using a gene-trap strategy, and Ncu-g1(gt/gt) mice were successfully characterized. Lysosomal disorders are mainly caused by lack of or malfunctioning of proteins in the endosomal-lysosomal pathway. The clinical symptoms vary, but often include liver dysfunction. Persistent liver damage activates fibrogenesis and, if unremedied, eventually leads to liver fibrosis/cirrhosis and death. We demonstrate that the disruption of Ncu-g1 results in spontaneous liver fibrosis in mice as the predominant phenotype. Evidence for an increased rate of hepatic cell death, oxidative stress and active fibrogenesis were detected in Ncu-g1(gt/gt) liver. In addition to collagen deposition, microscopic examination of liver sections revealed accumulation of autofluorescent lipofuscin and iron in Ncu-g1(gt/gt) Kupffer cells. Because only a few transgenic mouse models have been identified with chronic liver injury and spontaneous liver fibrosis development, we propose that the Ncu-g1(gt/gt) mouse could be a valuable new tool in the development of novel treatments for the attenuation of fibrosis due to chronic liver damage.

Postmortem heart weight: relation to body size and effects of cardiovascular disease and cancer.

BACKGROUND: Gender, body weight, and cardiovascular disease (CVD) are all variables known to influence human heart weight. The impact of cancer is less studied, and the influence of age is not unequivocal. We aimed to describe the relationship between body size and heart weight in a large autopsy cohort and to compare heart weight in patients with cancer, CVD, and other diseases. METHODS AND RESULTS: Registered information, including cause of death, evidence of cancer and/or CVD, heart weight, body weight, and height, was extracted from the autopsy reports of 1410 persons (805 men, mean age 66.5 years and 605 women, mean age 70.6 years). The study population was divided in four groups according to cause of death; cancer (n=349), CVD (n=470), mixed group who died from cancer and CVD and/or lung disease (n=263), and a reference group with patients who did not die from any of these conditions (n=328). In this last group, heart weight correlated only slightly better with body surface area than body weight, and nomograms based on body weight are presented. Compared to the reference group (mean heart weight: 426 g and 351 g in men and women, respectively), heart weight was significantly lower (men: P<.05, women: P<.001) in cancer patients (men: 392 g, women: 309 g) and higher (P<.001) in patients who died from CVD (men: 550 g, women: 430 g). Similar results were obtained in linear regression models adjusted for body weight and age. Among CVD, heart valve disease had the greatest impact on heart weight, followed by old myocardial infarction, coronary atherosclerosis, and hypertension. Absolute heart weight decreased with age, but we demonstrated an increase relative to body weight. CONCLUSION: The weight of the human heart is influenced by various disease processes, in addition to body weight, gender, and age. While the most prevalent types of CVD are associated with increased heart weight, patients who die from cancer have lower average heart weight than other patient groups. The latter finding, however, is diminished when adjusting for body weight. SUMMARY: The present study demonstrates that the weight of the human heart is influenced by various disease processes like cancer and CVD, in addition to body weight, gender and, possibly, age.

Unaltered lactate and glucose transporter levels in the MPTP mouse model of Parkinson's disease.

BACKGROUND: Metabolic impairment contributes to development of Parkinson's disease (PD). Mitochondrial dysfunction is involved in degeneration of nigral dopamine neurons. Also, in PD there are alterations in glucose metabolism in nigro-striatal pathways, and increased cerebral lactate levels have been found. OBJECTIVES: We raise the question of whether changes in the amount transporters of energy substrates are involved in the pathogenesis of PD. METHODS: We have used confocal immunofluorescence and immunogold postembedding electron microscopic techniques to study whether there are altered levels of the transporters for monocarboxylates (MCT1 and MCT2) and glucose (GLUT1) in the MPTP mouse model of PD. RESULTS: We found that MCT1 and GLUT1 were densely located in blood vessel endothelium, while MCT2 was present in perivascular astrocytic end feet processes in the substantia nigra and the striatum of control mice. We found that the localisation and densities of MCTs and GLUT1 were unaltered in the PD model. DISCUSSION: This is the first study reporting on the distribution of metabolic transporters in PD. Our results suggest that, although there are metabolic impairments in PD, the levels of MCT1, MCT2 and GLUT1 is not changed following dopaminergic neurodegeneration. This is in contrast to findings in other neurodegenerative disease, such as mesial temporal lobe epilepsy, where there are large alterations in MCT levels.

Hormone therapy use and breast cancer incidence by histological subtypes in Sweden and Norway.

Mammography screening and postmenopausal hormone therapy (HT) both influence breast cancer incidence. While breast cancer incidence increased by around 50% during the introduction of screening, a smaller decline in incidence has been reported in several countries after 2002 when the sales of HT started to decline. Data suggest that HT increases the risk of the second most common type of breast cancer, invasive lobular carcinoma (ILC) but not the most common, invasive ductal carcinoma (IDC). Breast cancer incidences stratified on histological subtypes were obtained from the national cancer registries. HT sales data from drug consumption statistics and information on the county-level introduction of mammography screening were combined, and breast cancer incidence trends were estimated using Poisson regression models, focusing on the period after 2002. From 2002 to 2007 the annual decrease in breast cancer incidence rates for women aged 50-69 was 1.5% (95% CI -2.3% to -0.7%) in Sweden and 0.8% (95% CI -2.8% to 1.2%) in the part of Norway not confounded by prevalence screening. Most of the decline was in the rates of ILC which dropped by 4.7% (95% CI -6.6% to -2.7%) and 7.0% (95% CI -12.8% to -0.9%) per year, respectively. The rates of IDC were stable in this period. Breast cancer incidence has declined in Sweden and Norway since 2002, but the reduction is moderate compared with the large increase that occurred during the introduction of mammography screening. Declining rates of ILC, but not of IDC, support the hypothesis that the drop in breast cancer incidence is associated with reduced HT use.

The apolipoprotein E polymorphism and cardiovascular diseases--an autopsy study.

BACKGROUND: Numerous studies have addressed the association between the apolipoprotein E polymorphism and cardiovascular disease, but only a few reports are based on findings at autopsy. In the present retrospective study, we have used autopsy findings from a general hospital population to further investigate this issue. METHODS AND RESULTS: We collected information from 1522 consecutive autopsy reports (886 men, mean age 65.7 years; 636 women, mean age 69.7 years) conducted at Oslo University Hospital, Norway, in the period from 1996 to 2000. Cause of death and signs related to cardiovascular disease including the degree of atherosclerosis in the aorta and the coronary arteries, signs of myocardial infarction, heart weight, and signs of cerebrovascular disease were recorded. The patients were genotyped, and the apolipoprotein E allele frequencies (ɛ2, 8.0%; ɛ3, 72.6%; and ɛ4, 19.4%) were not statistically different from a group of healthy controls. Approximately 35% of the patients died from a cardiovascular disease. Genotypes differed significantly (P<.05), with more ɛ4-carriers (34.3% vs. 29.6%) and fewer ɛ2-carriers (11.8% vs. 13.9%) among patients who died from cardiovascular disease compared to those who died from other causes. A similar distribution of genotypes was seen in patients recorded with myocardial infarction or cerebrovascular disease. There was an association between the presence of ɛ4 and atherosclerosis in the aorta and coronary arteries, but this did not reach statistical significance. Among patients with signs of coronary heart disease, standardized heart weights were significantly higher in ɛ2-carriers compared to ɛ4-carriers. CONCLUSION: The present autopsy study suggests that the risk of developing and dying from cardiovascular disease, including coronary heart disease and cerebrovascular disease, is influenced by the apolipoprotein E polymorphism.

Overdiagnosis of breast cancer after 14 years of mammography screening.

BACKGROUND: In 2004 we wrote in Tidsskriftet that mammography screening resulted in massive over-diagnosis and over-treatment of breast cancer. Our study was criticised because we had only five years of follow-up time and did not take account of the fact that increased use of hormone replacement therapy could lead to more breast cancer. We have now been screening women for 14 years, and during a period when the use of hormones has fallen by 70 %. MATERIAL AND METHOD: Age-specific incidence rates, detection rates and interval rates for breast cancer in the period 1991-2009 have been computed for 40-79 year-old women. Incidence trends have been calculated using Poisson regression. RESULTS: The incidence of breast cancer in the age group 40-49 was stable throughout the period, but rose by 50 % in the age group 50-69 years immediately after the start of screening. There was no significant reduction in the incidence of breast cancer in the age group 70-74. The number of new cases of breast cancer in the period increased from around 2000 to 2750. About 300 cases of ductal carcinoma in situ (DCIS) were also diagnosed. Today a total of some 1050 more women have been diagnosed than before screening started. Our calculations indicate that in the absence of screening, around 800 of these women would never have become breast cancer patients. INTERPRETATION: The figures from 14 years of mammography screening indicate that all increase in the incidence of breast cancer is due to over-diagnosis: findings of tumours that in the absence of screening would never have given rise to clinical illness.

The value of autopsies for determining the cause of death.

BACKGROUND: Death certificates are the only source of information on the underlying cause of death in more than 90 % of cases. Supplementary information is available for only a small proportion of them, as a rule from a medical or forensic autopsy. We wished to investigate how frequently the findings of medical autopsies influence determination of the underlying cause of death. MATERIAL AND METHOD: Using the Norwegian Cause of Death Register as our basis, we determined from the death certificate the underlying cause of death for deaths for which a medical autopsy was carried out in 2005. Then we investigated whether the underlying cause of death was changed when we took account of the autopsy findings. RESULTS: There were 41,152 deaths in Norway in 2005. The Cause of Death Registry received the results of medical autopsies for 1 773 persons who died at the age of 2 or older. Autopsy findings led to changes in the underlying cause of death in 1,077 cases (61 %). In 567 cases (32 %), the change was a major one, resulting in a change in the ICD 10 chapter for cause of death. The percentage of changed causes of death was greatest for the youngest and oldest age groups and for women. INTERPRETATION: Medical autopsies provide an important corrective to the determination of underlying cause of death.