The Political Ontology of Corporate Social Responsibility: Obscuring the Pluriverse in Place.

This article examines corporate social responsibility (CSR) through the lens of political ontology. We contend that CSR is not only a discursive mean of legitimization but an inherently ontological practice through which particular worlds become real. CSR enables the politics of place-making, connecting humans and nonhumans in specific territorial configurations in accordance with corporate needs and interests. We discuss three CSR mechanisms of singularization that create a particular corporate ontology in place: (1) community engagements that form 'stakeholders'; (2) CSR standards and certifications that produce singular sustainable environments; and (3) CSR reporting that erases ontological conflicts and enables the singularized representation (of the environment and the community) to travel to other locations of the corporate world. We argue that these ontological CSR practices obscure the pluriverse of other world and place-making practices that would create different kinds of sustainabilities based on less extractive and non-corporate ways of being in place.

Ethics at the Centre of Global and Local Challenges: Thoughts on the Future of Business Ethics.

To commemorate 40 years since the founding of the Journal of Business Ethics, the editors in chief of the journal have invited the editors to provide commentaries on the future of business ethics. This essay comprises a selection of commentaries aimed at creating dialogue around the theme Ethics at the centre of global and local challenges. For much of the history of the Journal of Business Ethics, ethics was seen within the academy as a peripheral aspect of business. However, in recent years, the stakes have risen dramatically, with global and local worlds destabilized by financial crisis, climate change, internet technologies and artificial intelligence, and global health crises. The authors of these commentaries address these grand challenges by placing business ethics at their centre. What if all grand challenges were framed as grand ethical challenges? Tanusree Jain, Arno Kourula and Suhaib Riaz posit that an ethical lens allows for a humble response, in which those with greater capacity take greater responsibility but remain inclusive and cognizant of different voices and experiences. Focussing on business ethics in connection to the grand(est) challenge of environmental emergencies, Steffen Böhm introduces the deceptively simple yet radical position that business is nature, and nature is business. His quick but profound side-step from arguments against human-nature dualism to an ontological undoing of the business-nature dichotomy should have all business ethics scholars rethinking their "business and society" assumptions. Also, singularly concerned with the climate emergency, Boudewijn de Bruin posits a scenario where, 40 years from now, our field will be evaluated by its ability to have helped humanity emerge from this emergency. He contends that Milieudefensie (Friends of the Earth) v. Royal Dutch Shell illustrates how human rights take centre stage in climate change litigation, and how business ethics enters the courtroom. From a consumer ethics perspective, Deirdre Shaw, Michal Carrington and Louise Hassan argue that ecologically sustainable and socially just marketplace systems demand cultural change, a reconsideration of future interpretations of "consumer society", a challenge to the dominant "growth logic" and stimulation of alternative ways to address our consumption needs. Still concerned with global issues, but turning attention to social inequalities, Nelarine Cornelius links the capability approach (CA) to global and corporate governance, arguing that CA will continue to lie at the foundation of human development policy, and, increasingly, CSR and corporate governance. Continuing debate on the grand challenges associated with justice and equality, Laurence Romani identifies a significant shift in the centrality of business ethics in debates on managing (cultural) differences, positing that dialogue between diversity management and international management can ground future debate in business ethics. Finally, the essay concludes with a commentary by Charlotte Karam and Michelle Greenwood on the possibilities of feminist-inspired theories, methods, and positionality for many spheres of business ethics, not least stakeholder theory, to broaden and deepen its capacity for nuance, responsiveness, and transformation. In the words of our commentators, grand challenges must be addressed urgently, and the Journal of Business Ethics should be at the forefront of tackling them.

Associations of early childhood medication exposure and molar incisor hypomineralization (MIH): A routine data analysis.

OBJECTIVES: Molar incisor hypomineralization (MIH) has become a major oral health problem of widely unknown origin. Besides genetic predisposition, exposure to certain drugs in early childhood are suspected to be associated with MIH. Aim of this routine data analysis was to examine associations of MIH and exposure to medication as well as perinatal factors. METHODS: Individuals with MIH were identified in claims data using a validated predefined specific treatment pattern. The database was a comprehensive routine data set of a major national health insurance company (BARMER, Germany). Based on this treatment pattern a MIH group and an unaffected control group were formed for analysis. Various medical data including medical diagnoses and prescriptions were available. Associations were examined comparing results for a set of variables in both groups. Differences between the groups were tested for significance using T-tests (P<0.01). RESULTS: Between 2010 to 2019, a total of 298,502 children between 6 and 9 years of age were included in this analysis. 22,947 were assigned to the MIH group. For individuals in this group, significantly larger prescription quantities in the main ATC (Anatomical, Therapeutic, Chemical) groups J (antiinfectives for systemic use), R (respiratory system) and S (sensory organs) were found in the first 4 years of life compared to MIH unaffected individuals. With antibiotics, there were both significantly larger prescription quantities and significantly higher numbers of respective prescriptions in the first 4 years of life. The differences amounted up to about 10.62% in frequently used antibiotics to be found in ATC J01D (other beta-lactam antibacterials) for the number of prescriptions in the 4th year of life. No association was found for premature birth, mode of delivery or the use of antipyretic or anti-inflammatory medication. CONCLUSIONS: While perinatal factors do not seem to be associated with MIH development, early life exposure to antibiotics might play a role. CLINICAL SIGNIFICANCE STATEMENT: Although causal relations can still not be proven, a responsible use of the unquestionably beneficial antibiotics is encouraged from a clinical point of view.

Performance of fixed dental prostheses up to 6 years-A massive data analysis.

STATEMENT OF PROBLEM: Metal and metal-ceramic fixed dental prostheses (FDPs) have been clinically determined to provide long-term durable restorations. However, data on their performance under practice conditions are sparse. PURPOSE: The purpose of this clinical study was to evaluate the longevity of FDPs under practice conditions by analyzing a large insurance claims database. MATERIAL AND METHODS: Data were extracted from the data warehouse of a major German national health insurance company (BARMER). The analysis focused on the FDP types with the lowest deductibles in the insurance system. All metal-based FDPs replacing up to 3 adjacent teeth were included. Ceramic veneering was optional and only approved on the labial surfaces of maxillary teeth mesial to the first molar and mandibular teeth mesial to the second premolar. Fee codes allowed clinical courses to be traced on a day count basis. Three groups with FDPs replacing 1 tooth, 2 teeth, and 3 teeth were formed. Kaplan-Meier survival analyses were conducted for the target events removal or extraction, indicating FDP failure and extraction of an abutment tooth. RESULTS: The sample comprised 124 660 FDPs that replaced 1 tooth (76.5%), 2 teeth (19.8%), or 3 teeth (3.7%). The cumulative survival rates for removal or extraction at 6 years differed significantly, with 83.0% for 1-pontic FDPs, 78.1% for 2-pontic FDPs, and 74.0% for 3-pontic FDPs. Thus, approximately 1 of 6 one-pontic FDPs, 1 of 5 two-pontic FDPs, and 1 of 4 three-pontic FDPs failed. The cumulative survival rates for extraction of an abutment tooth at 6 years showed no significant difference, with 96.0% for 1-pontic FDPs, 95.6% for 2-pontic FDPs, and 95.1% for 3-pontic FDPs. CONCLUSIONS: The survival rates of FDPs according to insurance data were lower than those reported by clinical studies, indicating a gap between efficacy and effectiveness.

Routine Data Analyses for Estimating the Caries Treatment Experience of Children.

Oral health surveys are considered the gold standard for assessing the caries experience of children. Analyses of routine data offer additional opportunities not yet fully explored. This study aimed at estimating the caries treatment experience by mining an insurance claims database. Comprehensive claims data sets were extracted from the data warehouse of a major health insurance company (BARMER, Germany). A surrogate variable for caries experience was formed that reflected the proportion of children without any former potentially caries-related treatment (filling, root canal treatment, and extraction) at ages from 1 to 14 years. The statistical calculations were based on Kaplan-Meier survival analyses. The evaluation for the permanent dentition comprised N = 593,330 children at 6 years and N = 114,568 at 12 years. At 12 years of age, 66.8% had not yet experienced potentially caries-related treatments. This value hints at a significantly higher caries experience at 12 years compared to available epidemiological data. For the deciduous dentition, the respective rates were 74.0% at 6 years and 45.8% at 10 years. Although various sources of bias have to be taken into account, the potential of routine data mining is evident. The approach is supplemental to oral health surveys. It can be useful in coming closer to reality when estimating the caries experience of children. From our results, we conclude that the oral health of up to 14-year-olds in Germany remains in urgent need of improvement.

Chemotherapy Induces Tumor-Associated Macrophages that Aid Adaptive Immune Responses in Ovarian Cancer.

Neoadjuvant chemotherapy (NACT) may stimulate anticancer adaptive immune responses in high-grade serous ovarian cancer (HGSOC), but little is known about effects on innate immunity. Using omental biopsies from HGSOC, and omental tumors from orthotopic mouse HGSOC models that replicate the human tumor microenvironment, we studied the impact of platinum-based NACT on tumor-associated macrophages (TAM). We found that chemotherapy reduces markers associated with alternative macrophage activation while increasing expression of proinflammatory pathways, with evidence of inflammasome activation. Further evidence of a shift in TAM functions came from macrophage depletion via CSF1R inhibitors (CSF1Ri) in the mouse models. Although macrophage depletion in established disease had no impact on tumor weight or survival, CSF1Ri treatment after chemotherapy significantly decreased disease-free and overall survival. This decrease in survival was accompanied by significant inhibition of adaptive immune response pathways in the tumors. We conclude that chemotherapy skews the TAM population in HSGOC toward an antitumor phenotype that may aid adaptive immune responses, and therapies that enhance or sustain this during remission may delay relapse.

Massive data analyses show negative impact of type 1 and 2 diabetes on the outcome of periodontal treatment.

OBJECTIVES: The aim was to evaluate the impact of diabetes on the outcome of periodontal treatment based on massive data analyses. MATERIALS AND METHODS: Data originated from the database of a major German National Health Insurance. Patients who underwent periodontal treatment were allocated to four groups according to their medical condition: type 1 diabetes (D1), type 2 diabetes with the intake of oral anti-diabetics (D2M), type 2 diabetes without the intake of oral anti-diabetics (D2), and a control group without diabetes (ND). Four-year Kaplan-Meier survival analyses on the patient level and multivariate regression analyses were conducted for tooth extraction. RESULTS: Of 415,718 patients, 4139 matched the criteria for D1, 22,430 for D2M, and 23,576 for D2. At 4 years, the cumulative survival rate (no extraction) was 51.7% in the D1 group, 54.0% in the D2M group, and 57.7% in the D2 group. The ND control group had a significantly higher survival rate of 65.9% (P < 0.0001). In the multivariate analyses, both diabetes types were significantly associated with further tooth loss after periodontal treatment. CONCLUSIONS: The diagnosis of diabetes type 1 or 2 seems to be associated with a higher risk of tooth loss after periodontal treatment. CLINICAL RELEVANCE: The long-term prognosis of teeth in diabetes patients should be judged carefully.

Six-year survival of single crowns - A massive data analysis.

OBJECTIVES: Numerous clinical trials have proven the long-term stability of metal and metal-ceramic crowns. However, data on their performance under practice conditions are rare. PURPOSE: To evaluate the longevity of crowns by means of massive data analyses. METHODS: The data were extracted from the data warehouse of a major German national health insurance company (BARMER, Berlin, Germany). The analysis focused on crown types with the lowest deductibles. Metal crowns and metal-ceramic crowns with ceramic veneering on the vestibular aspects of teeth 15-25 and 34-44 placed from 2012 to 2017 were included. The placement of the crowns, crown removals and tooth extractions were identified using the corresponding fee codes. Kaplan-Meier survival analyses were conducted for the outcomes "crown removal or extraction" and for "extraction". RESULTS: The cumulative six-year survival rates were 88.0 % for the outcome "crown removal or extraction" and 92.5 % for the outcome "extraction" (N = 192,868). The survival functions had slightly steepening but close to linear courses. CONCLUSIONS: The outcome of the treatment with metal and metal-ceramic crowns was moderately inferior in comparison to clinical trials. However, treatment with metal and metal-crowns is judged to be a reliable and safe option under practice conditions. CLINICAL SIGNIFICANCE STATEMENT: Clinicians must inform patients about potential treatment outcomes. Therefore, additional knowledge about single crown outcomes under general practice settings based on large database analyses is important.

Combining measures of immune infiltration shows additive effect on survival prediction in high-grade serous ovarian carcinoma.

BACKGROUND: In colorectal and breast cancer, the density and localisation of immune infiltrates provides strong prognostic information. We asked whether similar automated quantitation and combined analysis of immune infiltrates could refine prognostic information in high-grade serous ovarian carcinoma (HGSOC) and tested associations between patterns of immune response and genomic driver alterations. METHODS: Epithelium and stroma were semi-automatically segmented and the infiltration of CD45RO+, CD8+ and CD68+ cells was automatically quantified from images of 332 HGSOC patient tissue microarray cores. RESULTS: Epithelial CD8 [p = 0.027, hazard ratio (HR) = 0.83], stromal CD68 (p = 3 × 10-4, HR = 0.44) and stromal CD45RO (p = 7 × 10-4, HR = 0.76) were positively associated with survival and remained so when averaged across the tumour and stromal compartments. Using principal component analysis, we identified optimised multiparameter survival models combining information from all immune markers (p = 0.016, HR = 0.88). There was no significant association between PTEN expression, type of TP53 mutation or presence of BRCA1/BRCA2 mutations and immune infiltrate densities or principal components. CONCLUSIONS: Combining measures of immune infiltration provided improved survival modelling and evidence for the multiple effects of different immune factors on survival. The presence of stromal CD68+ and CD45RO+ populations was associated with survival, underscoring the benefits evaluating stromal immune populations may bring for prognostic immunoscores in HGSOC.

Participation in local food projects is associated with better psychological well-being: evidence from the East of England.

BACKGROUND: Studies suggest that local food may contribute to well-being, but do not use standardized measures, or control groups. METHODS: An online survey compared participants of local food initiatives (n = 302) with members of the general population (n = 157) in terms of scores on standardized measures of well-being and distress. Using hierarchical ordinary least squares regression models, we explored the relationship between participation and well-being via four mediators-nature connectedness, psychological need satisfaction, diet and physical activity. RESULTS: Participants scored higher than non-participants on life satisfaction (t(346) = 2.30, P = 0.02, ρr = 0.12) and the WEMWBS scale (t(335) = 2.12, P = 0.04, ρr = 0.10), but differences in psychological distress were insignificant. More actively engaged participants scored higher on positive well-being and longer duration participation was associated with higher life satisfaction and less psychological distress. Finally, we found that participation contributes to psychological need satisfaction, better diet and connection to nature, three known drivers of well-being. CONCLUSIONS: Well-being may be a co-benefit of local food initiatives beyond the physical and psychological benefits of growing food. Further research is needed to explore the mediators driving these effects, quantify benefits, and track impacts over time and across different social groups.

Pathological chemotherapy response score is prognostic in tubo-ovarian high-grade serous carcinoma: A systematic review and meta-analysis of individual patient data.

OBJECTIVE: There is a need to develop and validate biomarkers for treatment response and survival in tubo-ovarian high-grade serous carcinoma (HGSC). The chemotherapy response score (CRS) stratifies patients into complete/near-complete (CRS3), partial (CRS2), and no/minimal (CRS1) response after neoadjuvant chemotherapy (NACT). Our aim was to review current evidence to determine whether the CRS is prognostic in women with tubo-ovarian HGSC treated with NACT. METHODS: We established an international collaboration to conduct a systematic review and meta-analysis, pooling individual patient data from 16 sites in 11 countries. Patients had stage IIIC/IV HGSC, 3-4 NACT cycles and >6-months follow-up. Random effects models were used to derive combined odds ratios in the pooled population to investigate associations between CRS and progression free and overall survival (PFS and OS). RESULTS: 877 patients were included from published and unpublished studies. Median PFS and OS were 15 months (IQR 5-65) and 28 months (IQR 7-92) respectively. CRS3 was seen in 249 patients (28%). The pooled hazard ratios (HR) for PFS and OS for CRS3 versus CRS1/CRS2 were 0·55 (95% CI, 0·45-0·66; P < 0·001) and 0·65 (95% CI 0·50-0·85, P = 0·002) respectively; no heterogeneity was identified (PFS: Q = 6·42, P = 0·698, I2 = 0·0%; OS: Q = 6·89, P = 0·648, I2 = 0·0%). CRS was significantly associated with PFS and OS in multivariate models adjusting for age and stage. Of 306 patients with known germline BRCA1/2 status, those with BRCA1/2 mutations (n = 80) were more likely to achieve CRS3 (P = 0·027). CONCLUSIONS: CRS3 was significantly associated with improved PFS and OS compared to CRS1/2. This validation of CRS in a real-world setting demonstrates it to be a robust and reproducible biomarker with potential to be incorporated into therapeutic decision-making and clinical trial design.

Histopathologic response to neoadjuvant chemotherapy as a prognostic biomarker in tubo-ovarian high-grade serous carcinoma: updated Chemotherapy Response Score (CRS) results.

OBJECTIVE: The Chemotherapy Response Scoring (CRS) system was developed to enable reproducible reporting of histologic tumor response in interval debulking specimens following neoadjuvant chemotherapy in advanced stage tubo-ovarian high-grade serous carcinoma. This prognostic biomarker has been included in ovarian cancer pathology reporting guidelines (International Collaboration on Cancer Reporting, College of American Pathologists) and in the upcoming European Society for Medical Oncology-European Society of Gynaecological Oncology (ESMO-ESGO) guidelines for ovarian cancer management. We present follow-up data on the CRS validation initiatives and suggest research with novel therapeutic agents incorporating this biomarker. METHODS: The cohort on whom CRS was originally developed was analyzed after an extended follow-up of an additional 36 months. The CRS histopathologic scoring system was applied to omental sections obtained at interval surgery from all 80 patients. Progression-free and overall survival were re-calculated. RESULTS: After a median follow-up of 4.3 years the CRS score predicted progression-free survival with an HR of 0.39 (95% CI 0.21 to 0.70), p = 0.002 adjusted for age, stage, and debulking status (median 1.08 vs 2.27 years for CRS1/2 vs CRS3). CRS was also predictive of overall survival with an HR of 0.17 (95% CI 0.07 to 0.44), p = 0.0002 adjusted for age, stage, and debulking status (median 2.55 vs 5.47 years for CRS1/2 vs CRS3). CONCLUSION: CRS3 is a reproducible prognostic biomarker for improved progression-free and overall survival in stage 3C or 4 tubo-ovarian high-grade serous carcinoma after neoadjuvant chemotherapy. The score, obtained at interval debulking surgery, can help facilitate research and biomarker driven first-line treatment of patients with advanced ovarian cancer.

Tooth loss after periodontal treatment-Mining an insurance database.

OBJECTIVES: The aim of this study was to evaluate tooth loss after periodontal treatment. METHODS: The data was collected from the digital database of a major German national health insurance company. Periodontal treatment was the intervention in the treatment group. Kaplan-Meier survival analyses on the patient level with the primary outcome extraction were carried out over four years. A control group without treatment was matched and analysed. Differences were tested with the Log-Rank-test. Extraction incidences were calculated over a matched observation period six years before and four years after treatment for both treatment and control group. RESULTS: A total of 415,718 periodontal treatments could be traced. Focussing on the outcome "extraction", the cumulative four-year survival rate was 63.8% after periodontal treatment. The matched control group without periodontal treatment showed a survival rate of 72.5%. These differences were significant (p < 0.0001). The extraction incidence over time was higher in a four-year period after periodontal treatment compared to a six-year period before periodontal treatment. CONCLUSIONS: The outcome of periodontal treatment was acceptable. In about two thirds of the patients, extractions could be completely avoided within a four year period after treatment. CLINICAL SIGNIFICANCE STATEMENT: This study within the German national health insurance system shows that extractions were not observed after periodontal treatment in the majority of cases. Although periodontitis is a chronic disease, patients suffering from periodontitis have a considerable chance to prevent further tooth loss.

Deconstruction of a Metastatic Tumor Microenvironment Reveals a Common Matrix Response in Human Cancers.

We have profiled, for the first time, an evolving human metastatic microenvironment by measuring gene expression, matrisome proteomics, cytokine and chemokine levels, cellularity, extracellular matrix organization, and biomechanical properties, all on the same sample. Using biopsies of high-grade serous ovarian cancer metastases that ranged from minimal to extensive disease, we show how nonmalignant cell densities and cytokine networks evolve with disease progression. Multivariate integration of the different components allowed us to define, for the first time, gene and protein profiles that predict extent of disease and tissue stiffness, while also revealing the complexity and dynamic nature of matrisome remodeling during development of metastases. Although we studied a single metastatic site from one human malignancy, a pattern of expression of 22 matrisome genes distinguished patients with a shorter overall survival in ovarian and 12 other primary solid cancers, suggesting that there may be a common matrix response to human cancer.Significance: Conducting multilevel analysis with data integration on biopsies with a range of disease involvement identifies important features of the evolving tumor microenvironment. The data suggest that despite the large spectrum of genomic alterations, some human malignancies may have a common and potentially targetable matrix response that influences the course of disease. Cancer Discov; 8(3); 304-19. ©2017 AACR.This article is highlighted in the In This Issue feature, p. 253.

PD-1 Checkpoint Inhibitor Associated Autoimmune Encephalitis.

OBJECTIVE: To report first-hand narrative experience of autoimmune encephalitis and to briefly review currently available evidence of autoimmune encephalitis in cancer patients treated with immune checkpoint inhibitors. SETTING: A case study is presented on the management of a patient who developed autoimmune encephalitis during nivolumab monotherapy occurring after 28 weeks on anti-PD-1 monotherapy (nivolumab 3 mg/kg every 2 weeks) for non-small cell lung cancer. RESULTS: No substantial improvement was observed by antiepileptic treatment. After administration of 80 mg methylprednisolone, neurologic symptoms disappeared within 24 h and the patient fully recovered. CONCLUSIONS: Immune checkpoint inhibitor treatment can lead to autoimmune encephalitis. Clinical trial data indicate a frequency of autoimmune encephalitis of ≥0.1 to <1% with a higher probability during combined or sequential anti-CTLA-4/anti-PD-1 therapy than during anti-PD-1 or anti-PD-L1 monotherapy. Further collection of evidence and translational research is warranted.

A comparison of p53 and WT1 immunohistochemical expression patterns in tubo-ovarian high-grade serous carcinoma before and after neoadjuvant chemotherapy.

AIMS: The treatment of patients with tubo-ovarian high-grade serous carcinoma (HGSC) is increasingly based on diagnosis on small biopsy samples, and the first surgical sample is often taken post-chemotherapy. p53 and WT1 are important diagnostic markers for HGSC. The effect of neoadjuvant chemotherapy on p53 and WT1 expression has not been widely studied. We aimed to compare p53 and WT1 expression in paired pre-chemotherapy and post-chemotherapy samples of HGSC. METHODS AND RESULTS: Immunohistochemistry (IHC) was carried out for p53 and WT1 on paired omental HGSC samples pre-chemotherapy and post-chemotherapy. p53 IHC was recorded as normal (wild-type) or abnormal (mutation-type), and was further classified as overexpression, complete absence, or cytoplasmic. WT1 IHC was classified as positive or negative. A subset of cases were further assessed for the extent of nuclear immunoreactivity of WT1 by use of the H-score. Fifty-seven paired samples were stained with p53. Fifty-six of 57 (98%) cases showed mutation-type p53 staining. Pre-chemotherapy and post-chemotherapy IHC results were concordant in 55 of 57 (96%) cases. For WT1, pre-chemotherapy and post-chemotherapy IHC results were concordant in 56 of 58 (97%) cases. In 23 paired WT1 cases, the mean post-treatment H-score decreased from 227 [range 20-298, standard deviation (SD) 64] to 151 (range 0-288, SD 78) (P = 0.0008). CONCLUSIONS: Immunohistochemical expression of p53 (abnormal/mutation-type pattern) and WT1 in HGSC is almost universal and is largely concordant before and after chemotherapy. This finding underscores the reliability of these diagnostic markers in small samples and in surgical samples following neoadjuvant chemotherapy, with very few exceptions. A novel finding was the significant diminution in intensity of WT1 staining following chemotherapy.

Four-year outcomes of restored posterior tooth surfaces-a massive data analysis.

OBJECTIVES: There is only sparse knowledge concerning the outcomes of treatments with posterior permanent restorations in general practice settings. This study aimed at evaluating outcomes based on a large dataset by using a novel approach on a tooth surface basis. MATERIALS AND METHODS: The study based on routine data from a major German national health insurance company. Respective treatment fee codes allowed for tracking the clinical courses on a tooth surface level. The study intervention was defined as the placement of a restoration on an interproximal or occlusal posterior tooth surface regardless of its actual extension and material on which no information was available. All surfaces restored between January 1st, 2010 and December 31st, 2013 were included. Kaplan-Meier survival analyses were conducted to estimate four-year survival. The primary outcome was a restorative re-intervention on the same tooth surface. Separate analyses were performed for the secondary outcomes "crowning" and "extraction". RESULTS: Over ten million interproximal surfaces and eight million occlusal surfaces in nine million posterior teeth had been restored. At 4 years, the cumulative survival rates concerning the primary outcome "re-intervention" for mesial surfaces (81.4%; CI 81.3-81.5%) and distal surfaces (81.2%; CI 81.1-81.2%) differed significantly from those for occlusal surfaces (77.0%; CI 76.9-77.0%). Restored surfaces in premolars showed significantly higher survival rates compared to molars. Four-year survival rates for the secondary outcome "crowning" were 91.9% (CI 91.8-91.9%) for mesial surfaces, 92.1% (CI 92.1-92.2%) for distal surfaces and 93.3% (CI 93.2-93.3%) for occlusal surfaces. The respective rates for the secondary outcome "extraction" were 94.5% (CI 94.5-94.5%) for mesial surfaces, 94.8% (CI 94.7-94.8%) for distal surfaces and 95.4% (CI 95.4-95.5%) for occlusal surfaces. CONCLUSIONS: Re-interventions after restorative treatment play a significant role in general practice settings. Surface-related survival rates of restorations reveal a need for improvement. CLINICAL RELEVANCE: This study allows the estimation of the probability of re-interventions after restoring posterior tooth surfaces. It is based on several million cases from general practises under the terms and conditions of a national health insurance system.

A Strong B-cell Response Is Part of the Immune Landscape in Human High-Grade Serous Ovarian Metastases.

PURPOSE: In high-grade serous ovarian cancer (HGSOC), higher densities of both B cells and the CD8+ T-cell infiltrate were associated with a better prognosis. However, the precise role of B cells in the antitumor response remains unknown. As peritoneal metastases are often responsible for relapse, our aim was to characterize the role of B cells in the antitumor immune response in HGSOC metastases. EXPERIMENTAL DESIGN: Unmatched pre and post-chemotherapy HGSOC metastases were studied. B-cell localization was assessed by immunostaining. Their cytokines and chemokines were measured by a multiplex assay, and their phenotype was assessed by flow cytometry. Further in vitro and in vivo assays highlighted the role of B cells and plasma cell IgGs in the development of cytotoxic responses and dendritic cell activation. RESULTS: B cells mainly infiltrated lymphoid structures in the stroma of HGSOC metastases. There was a strong B-cell memory response directed at a restricted repertoire of antigens and production of tumor-specific IgGs by plasma cells. These responses were enhanced by chemotherapy. Interestingly, transcript levels of CD20 correlated with markers of immune cytolytic responses and immune complexes with tumor-derived IgGs stimulated the expression of the costimulatory molecule CD86 on antigen-presenting cells. A positive role for B cells in the antitumor response was also supported by B-cell depletion in a syngeneic mouse model of peritoneal metastasis. CONCLUSIONS: Our data showed that B cells infiltrating HGSOC omental metastases support the development of an antitumor response. Clin Cancer Res; 23(1); 250-62. ©2016 AACR.