Please cite this paper as: Adams S, Eberhard‐Gran M, Eskild A. Fear of childbirth and duration of labour: a study of 2206 women with intended vaginal delivery. BJOG 2012;119:1238–1246.
Objective To ...assess the association between fear of childbirth and duration of labour.
Design A prospective study of women from 32 weeks of gestation through to delivery.
Setting Akershus University Hospital, Norway.
Population A total of 2206 pregnant women with a singleton pregnancy and intended vaginal delivery during the period 2008–10.
Methods Fear of childbirth was assessed by the Wijma Delivery Expectancy Questionnaire (W‐DEQ) version A at 32 weeks of gestation, and defined as a W‐DEQ sum score ≥ 85. Information on labour duration, use of epidural analgesia and mode of delivery was obtained from the maternal ward electronic birth records.
Main outcome measures Labour duration in hours: from 3–4 cm cervical dilatation and three uterine contractions per 10 minutes lasting ≥1 minute, until delivery of the child.
Results Fear of childbirth (W‐DEQ sum score ≥ 85) was present in 7.5% (165) of women. Labour duration was significantly longer in women with fear of childbirth compared with women with no such fear using a linear regression model (crude unstandardised coefficient 1.54; 95% confidence interval 0.87–2.22, corresponding to a difference of 1 hour and 32 minutes). After adjustment for parity, counselling for pregnancy concern, epidural analgesia, labour induction, labour augmentation, emergency caesarean delivery, instrumental vaginal delivery, offspring birthweight and maternal age, the difference attenuated, but remained statistically significant (adjusted unstandardised coefficient 0.78; 95% confidence interval 0.20–1.35, corresponding to a 47‐minute difference).
Conclusion Duration of labour was longer in women with fear of childbirth than in women without fear of childbirth.
In 2014, we described a method to quantify percentage of tumor-infiltrating lymphocytes (TILs) on hematoxylin and eosin-stained slides of breast cancer samples using light microscopy that could be ...performed easily by pathologists with no extra stains. The aim of detailing the method was to facilitate independent research groups replicating our prognostic findings using TIL quantity in early-stage breast cancers. A global working group of breast pathologists was convened to standardize, test reproducibility, and refine the method. A website was also established which allowed free training (www.tilsinbreastcancer.org). As a result of this work, TIL data have been collected in over 20 000 primary breast cancer samples worldwide and the robust associations with better prognoses in triple-negative breast cancer (TNBC) and HER2+ BC have been confirmed. This has resulted in the inclusion of the TIL biomarker in several international breast cancer guidelines as well as in national criteria for routine pathology reporting. TIL therefore represents the first biological prognostic biomarker for early-stage TNBCs, and here its prognostic effect is linear, with values of 30%-50% being suggested as suitable for use in potential chemotherapy de-escalation studies. The efficacy of immune checkpoint-targeted agents in breast cancer now provides direct evidence that host immune responses can modify tumor growth in some patients. With the recent granting of accelerated approvals for the first PD-1/PD-L1 targeting agents in early and advanced TNBC, our focus has now moved to investigating the clinical utility of TIL in the setting of immune checkpoint agents, with or without PD-L1 protein assessment. Emerging data suggest that TIL quantity can help clinicians identify patients with breast cancer who benefit most from PD-1/PD-L1 inhibition. In patients with advanced TNBC and HER2+ disease a TIL cut-off of 5% or 10%, with PD-L1 expression can define ‘immune-enriched’ tumors and currently seems to have the most clinical relevance in this context.
•TILs is a strong prognostic biomarker in some breast cancer subtypes in early-stage setting.•Our method of quantifying TIL published 5+ years ago has been standardized, is reproducible, and has been adopted worldwide.•TIL quantity has shown to be predictive of benefit from agents targeting PD-1/PD-L1 in the metastatic setting.•TIL quantity correlates with many other immune biomarkers. TIL and PD-L1 expression together can identify ‘immune-rich’ tumors.•Investigating the relevant immune subsets important for prognosis and immunotherapy response is ongoing.
Rechargeable all‐solid‐state lithium Li‐ion batteries (AS‐LIBs) are attractive power sources for electrochemical applications; due to their potentiality in improving safety and stability over ...conventional batteries with liquid electrolytes. AS‐LIBs require a Li‐fast ion conductor (FIC) as the solid electrolyte. Finding a solid electrolyte with high ionic conductivity and compatibility with other battery components is a key factor in building high performance AS‐LIBs. There have been numerous studies, e.g., on lithium rich sulfide glasses as solid electrolytes. However, the limited current density remains a major obstacle in developing competitive batteries based on the known solid electrolytes. Here we prepare argyrodite‐type Li6PS5X (X = Cl, Br, I) using mechanical milling followed by annealing. XRD characterization reveals the formation and growth of Li6PS5X crystals in samples under varying annealing conditions. For Li6PS5Cl an ionic conductivity of the order of 10−4 S/cm is reached at room temperature, which is close to the Li mobility in conventional liquid electrolytes (LiPF6 in various carbonates) and well suitable for AS‐LIBs.
Treatment options for previously treated metastatic triple-negative breast cancer (mTNBC) are limited. In cohort A of the phase II KEYNOTE-086 study, we evaluated pembrolizumab as second or later ...line of treatment for patients with mTNBC.
Eligible patients had centrally confirmed mTNBC, ≥1 systemic therapy for metastatic disease, prior treatment with anthracycline and taxane in any disease setting, and progression on or after the most recent therapy. Patients received pembrolizumab 200 mg intravenously every 3 weeks for up to 2 years. Primary end points were objective response rate in the total and PD-L1–positive populations, and safety. Secondary end points included duration of response, disease control rate (percentage of patients with complete or partial response or stable disease for ≥24 weeks), progression-free survival, and overall survival.
All enrolled patients (N = 170) were women, 61.8% had PD-L1–positive tumors, and 43.5% had received ≥3 previous lines of therapy for metastatic disease. ORR (95% CI) was 5.3% (2.7–9.9) in the total and 5.7% (2.4–12.2) in the PD-L1–positive populations. Disease control rate (95% CI) was 7.6% (4.4–12.7) and 9.5% (5.1–16.8), respectively. Median duration of response was not reached in the total (range, 1.2+–21.5+) and in the PD-L1–positive (range, 6.3–21.5+) populations. Median PFS was 2.0 months (95% CI, 1.9–2.0), and the 6-month rate was 14.9%. Median OS was 9.0 months (95% CI, 7.6–11.2), and the 6-month rate was 69.1%. Treatment-related adverse events occurred in 103 (60.6%) patients, including 22 (12.9%) with grade 3 or 4 AEs. There were no deaths due to AEs.
Pembrolizumab monotherapy demonstrated durable antitumor activity in a subset of patients with previously treated mTNBC and had a manageable safety profile.
ClinicalTrials.gov, NCT02447003
Standard first-line treatment of metastatic triple-negative breast cancer (mTNBC) is chemotherapy. However, outcomes are poor, and new treatment options are needed. In cohort B of the phase II ...KEYNOTE-086 study, we evaluated pembrolizumab as first-line therapy for patients with PD-L1-positive mTNBC.
Eligible patients had centrally confirmed mTNBC, no prior systemic anticancer therapy for metastatic disease, measurable disease at baseline per RECIST v1.1 by central review, no radiographic evidence of central nervous system metastases, and a tumor PD-L1 combined positive score ≥1. Patients received pembrolizumab 200 mg intravenously every 3 weeks for up to 2 years. The primary end point was safety. Secondary end points included objective response rate, disease control rate (percentage of patients with complete or partial response or stable disease for ≥24 weeks), duration of response, progression-free survival and overall survival.
All 84 patients enrolled were women, and 73 (86.9%) received prior (neo)adjuvant therapy. Fifty-three (63.1%) patients had treatment-related adverse events (AEs), including 8 patients (9.5%) with grade 3 severity; no patients experienced grade 4 AEs or died because of treatment-related AEs. Four patients had a complete response and 14 had a partial response, for an objective response rate of 21.4% (95% CI 13.9–31.4). Of the 13 patients with stable disease, 2 had stable disease lasting ≥24 weeks, for a disease control rate of 23.8% (95% CI 15.9–34.0). At data cut-off, 8 of 18 (44.4%) responses were ongoing, and median duration of response was 10.4 months (range 4.2 to 19.2+). Median progression-free survival was 2.1 months (95% CI 2.0–2.2), and median overall survival was 18.0 months (95% CI 12.9–23.0).
Pembrolizumab monotherapy had a manageable safety profile and showed durable antitumor activity as first-line therapy for patients with PD-L1-positive mTNBC.
ClinicalTrials.gov, NCT02447003.
We study coherent excitation hopping in a spin chain realized using highly excited individually addressable Rydberg atoms. The dynamics are fully described in terms of an XY spin Hamiltonian with a ...long range resonant dipole-dipole coupling that scales as the inverse third power of the lattice spacing, C(3)/R(3). The experimental data demonstrate the importance of next neighbor interactions which are manifest as revivals in the excitation dynamics. The results suggest that arrays of Rydberg atoms are ideally suited to large scale, high-fidelity quantum simulation of spin dynamics.
•Metaplastic breast carcinomas (MPBC) are rare tumors with poor clinical outcomes.•MPBC are associated with EMT and stem-cell like features.•MPBC are genetically heterogeneous and commonly harbor ...mutations in TP53 and PTEN.•Emerging data suggest a role of targeted therapies/immunotherapies in this subtype.
Metaplastic breast carcinomas (MPBC) are rare, aggressive and relatively chemorefractory tumors with a high unmet need. While most are “triple negative” and lack expression of estrogen, progesterone and HER2 receptors, MPBC are associated with worse outcomes compared to conventional triple negative invasive tumors. MPBCs are genetically heterogeneous and harbor somatic mutations, most frequently in TP53, PIK3CA and PTEN, with emerging studies suggesting a role for novel targeted therapies. These tumors have also been associated with overexpression of PD-L1 and tumor-infiltrating lymphocytes suggesting an endogenous immune response and therefore a rationale for treatment with immunotherapies. Here, we focus on therapeutic options for this difficult to treat breast cancer subtype and encourage physicians to consider targeted therapies/immunotherapies as part of ongoing clinical trials.
Knowledge about the ability of vitamin D to function outside its established role in skeletal homeostasis is not a new phenomenon. Nonclassical immunomodulatory and antiproliferative responses ...triggered by active 1,25-dihydroxyvitamin D were first reported more than a quarter of a century ago. It is only in recent years, however, that there has been a significant improvement in our understanding of how these nonclassical effects of vitamin D can influence the pathophysiology and possible prevention of human disease. Three particular strands of evidence have been prominent: firstly, population studies have revised our interpretation of normal vitamin D status in humans, suggesting, in turn, that vitamin D insufficiency is a clinical problem of global proportions; secondly, epidemiology has linked vitamin D status with disease susceptibility and/or mortality; and, thirdly, expression of the machinery required to synthesize 1,25-dihydroxyvitamin D in normal human tissue seems to be much more widespread than originally thought. Collectively, these observations suggest that nonclassical metabolism and response to vitamin D might have a significant role in human physiology beyond skeletal and calcium homeostasis. Specific examples of this will be detailed in the current Review, with particular emphasis on the immunomodulatory properties of vitamin D.
Alongside the well-known chemical modes of cell-cell communication, we find an important and powerful system of bioelectrical signaling: changes in the resting voltage potential (Vₘₑₘ) of the plasma ...membrane driven by ion channels, pumps and gap junctions. Slow Vₘₑₘ changes in all cells serve as a highly conserved, information-bearing pathway that regulates cell proliferation, migration and differentiation. In embryonic and regenerative pattern formation and in the disorganization of neoplasia, bioelectrical cues serve as mediators of large-scale anatomical polarity, organ identity and positional information. Recent developments have resulted in tools that enable a high-resolution analysis of these biophysical signals and their linkage with upstream and downstream canonical genetic pathways. Here, we provide an overview for the study of bioelectric signaling, focusing on state-of-the-art approaches that use molecular physiology and developmental genetics to probe the roles of bioelectric events functionally. We highlight the logic, strategies and well-developed technologies that any group of researchers can employ to identify and dissect ionic signaling components in their own work and thus to help crack the bioelectric code. The dissection of bioelectric events as instructive signals enabling the orchestration of cell behaviors into large-scale coherent patterning programs will enrich on-going work in diverse areas of biology, as biophysical factors become incorporated into our systems-level understanding of cell interactions.
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