The end of fertility: age, fecundity and fecundability in women

Onset of capacity for childbearing in women is dated biologically by menarche, although actual onset may be delayed. The end of childbearing is less understood but recent demographic and biological research on fertility at older ages is clarifying the end of fertility. The demographic view of declining fertility with age is based on age-specific fertility in natural fertility populations, artificial insemination and pregnancy rates by age and World Fertility Survey data. New data from the Demographic and Health Surveys on exposure to the risk of pregnancy shows that whereas older women biologically need longer exposure to pregnancy, exposure declines on behavioural grounds such as duration of marriage. Actual fecundity is obscured by factors of fecundability. Recent research on medically assisted conception is adding to the understanding of declining fecundity with age, especially the relative contributions of endometrial and ovarian ageing. This paper reviews the available information on declining fertility with age and discusses the implications of the extension of fertility through new medical technologie

Nodal-Stage Classification in Invasive Lobular Breast Carcinoma: Influence of Different Interpretations of the pTNM Classification

Purpose Application of current nodal status classification is complicated in lobular breast carcinoma metastases. The aim of this study was to define the optimal interpretation of the pTNM classification in sentinel node (SN) -positive patients to select patients with limited or with a high risk of non-SN involvement. Patients and Methods SN metastases of 392 patients with lobular breast carcinoma were reclassified according to interpretations of the European Working Group for Breast Screening Pathology (EWGBSP) and guidelines by Turner et al, and the predictive power for non-SN involvement was assessed. Results Reclassification according to definitions of EWGBSP and Turner et al resulted in different pN classification in 73 patients (19%). The rate of non-SN involvement in the 40 patients with isolated tumor cells according to Turner et al and with micrometastases according to EWGBSP was 20%, which is comparable to the established rate for micrometastases. The rate of non-SN involvement in the 29 patients with micrometastases according to Turner et al and with macrometastases according to EWGBSP was 48%, which is comparable to the established rate for macrometastases. Therefore, the EWGBSP method to classify SN tumor load better reflected the risk of non-SN involvement than the Turner et al system. Conclusion Compared with the guidelines by Turner et al, the EWGBSP definitions better reflect SN metastatic tumor load and allow better differentiation between patients with lobular breast carcinoma who have a limited or a high risk of non-SN metastases. Therefore, we suggest using the EWGBSP definitions in these patients to select high-risk patients who may benefit from additional local and/or systemic therapy

Reproducibility and predictive value of scoring stromal tumour infiltrating lymphocytes in triple-negative breast cancer : a multi-institutional study

Several studies have demonstrated a prognostic role for stromal tumour infiltrating lymphocytes (sTILs) in triple-negative breast cancer (TNBC). The reproducibility of scoring sTILs is variable with potentially excellent concordance being achievable using a software tool. We examined agreement between breast pathologists across Europe scoring sTILs on H&E-stained sections without software, an approach that is easily applied in clinical practice. The association between sTILs and response to anthracycline-taxane NACT was also examined. Pathologists from the European Working Group for Breast Screening Pathology scored sTILs in 84 slides from 75 TNBCs using the immune-oncology biomarker working group guidance in two circulations. There were 16 participants in the first and 19 in the second circulation. Moderate agreement was achieved for absolute sTILs scores (intraclass correlation coefficient (ICC) = 0.683, 95% CI 0.601-0.767, p-value = 25% (kappa = 0.53) and for LPBC (kappa = 0.49), but poor for sTILs as 10% increments (kappa = 0.24). Increasing sTILs was significantly associated with an increased likelihood of a pathological complete response (pCR) on multivariable analysis. Increasing sTILs in TNBCs improves the likelihood of a pCR. However, inter-observer agreement is such that H&E-based assessment is not sufficiently reproducible for clinical application. Other methodologies should be explored, but may be at the cost of ease of application.Non peer reviewe

Hydrogen peroxide bleaching of cellulose pulps obtained from brewer’s spent grain

Brewer’s spent grain (BSG) was evaluated for bleached pulp production. Two cellulose pulps with different chemical compositionswere produced by soda pulping: one from the original raw material and the other from material pretreated by dilute acid. Both of them were bleached by a totally chlorine-free sequence performed in three stages, using 5% hydrogen peroxide in the two initial, and a 0.25 NNaOHsolution in the last one. Chemical composition, kappa number, viscosity, brightness and yield of bleached and unbleached pulps were evaluated. The high hemicellulose (28.4% w/w) and extractives (5.8% w/w) contents in original BSG affected the pulping and bleaching processes.However, soda pulping of acid pretreated BSG gave a celluloserich pulp (90.4% w/w) with low hemicellulose and extractives contents (7.9% w/w and <3.4% w/w, respectively), which was easily bleached achieving a kappa number of 11.21, viscosity of 3.12 cp, brightness of 71.3%, cellulose content of 95.7% w/w, and residual lignin of 3.4% w/w. Alkaline and oxidative delignification of acid pretreated BSG was found as an attractive approach for producing high-purity, chlorine-free cellulose pulp.FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo), Brazil.CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico).Capes (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior)

P2X7 nucleotide receptors mediate caspase-8/9/3-dependent apoptosis in rat primary cortical neurons

Apoptosis is a major cause of cell death in the nervous system. It plays a role in embryonic and early postnatal brain development and contributes to the pathology of neurodegenerative diseases. Here, we report that activation of the P2X7 nucleotide receptor (P2X7R) in rat primary cortical neurons (rPCNs) causes biochemical (i.e., caspase activation) and morphological (i.e., nuclear condensation and DNA fragmentation) changes characteristic of apoptotic cell death. Caspase-3 activation and DNA fragmentation in rPCNs induced by the P2X7R agonist BzATP were inhibited by the P2X7R antagonist oxidized ATP (oATP) or by pre-treatment of cells with P2X7R antisense oligonucleotide indicating a direct involvement of the P2X7R in nucleotide-induced neuronal cell death. Moreover, Z-DEVD-FMK, a specific and irreversible cell permeable inhibitor of caspase-3, prevented BzATP-induced apoptosis in rPCNs. In addition, a specific caspase-8 inhibitor, Ac-IETD-CHO, significantly attenuated BzATP-induced caspase-9 and caspase-3 activation, suggesting that P2X7R-mediated apoptosis in rPCNs occurs primarily through an intrinsic caspase-8/9/3 activation pathway. BzATP also induced the activation of C-jun N-terminal kinase 1 (JNK1) and extracellular signal-regulated kinases (ERK1/2) in rPCNs, and pharmacological inhibition of either JNK1 or ERK1/2 significantly reduced caspase activation by BzATP. Taken together, these data indicate that extracellular nucleotides mediate neuronal apoptosis through activation of P2X7Rs and their downstream signaling pathways involving JNK1, ERK and caspases 8/9/3

Measurement of branching fractions and direct CPCP asymmetries for B→KπB \to K\pi and B→ππB\to\pi\pi decays at Belle II

We report measurements of the branching fractions and direct $\it{CP}$ asymmetries of the decays $B^0 \to K^+ \pi^-$, $B^+ \to K^+ \pi^0$, $B^+ \to K^0 \pi^+$, and $B^0 \to K^0 \pi^0$, and use these for testing the standard model through an isospin-based sum rule. In addition, we measure the branching fraction and direct $\it{CP}$ asymmetry of the decay $B^+ \to \pi^+\pi^0$ and the branching fraction of the decay $B^0 \to \pi^+\pi^-$. The data are collected with the Belle II detector from $e^+e^-$ collisions at the $\Upsilon(4S)$ resonance produced by the SuperKEKB asymmetric-energy collider and contain $387\times 10^6$ bottom-antibottom meson pairs. Signal yields are determined in two-dimensional fits to background-discriminating variables, and range from 500 to 3900 decays, depending on the channel. We obtain $-0.03 \pm 0.13 \pm 0.04$ for the sum rule, in agreement with the standard model expectation of zero and with a precision comparable to the best existing determinations

Measurement of the τ\tau-lepton mass with the Belle~II experiment

We present a measurement of the $\tau$-lepton mass using a sample of about 175 million $e^+e^- \to \tau^+\tau^-$ events collected with the Belle II detector at the SuperKEKB $e^+e^-$ collider at a center-of-mass energy of $10.579\,\mathrm{Ge\kern -0.1em V}$. This sample corresponds to an integrated luminosity of $190\,\mathrm{fb^{-1}}$. We use the kinematic edge of the $\tau$ pseudomass distribution in the decay ${\tau^-\to\pi^-\pi^+\pi^-\nu_\tau}$ and measure the $\tau$ mass to be $1777.09 \pm 0.08 \pm 0.11 \,\mathrm{Me\kern -0.1em V\!/c^2}$, where the first uncertainty is statistical and the second systematic. This result is the most precise to date

Observation of B→D(∗)K−KS0{B\to D^{(*)} K^- K^{0}_S} decays using the 2019-2022 Belle II data sample

We present a measurement of the branching fractions of four $B^{0,-}\to D^{(*)+,0} K^- K^{0}_S$ decay modes. The measurement is based on data from SuperKEKB electron-positron collisions at the $\Upsilon(4S)$ resonance collected with the Belle II detector and corresponding to an integrated luminosity of ${362~\text{fb}^{-1}}$. The event yields are extracted from fits to the distributions of the difference between expected and observed $B$ meson energy to separate signal and background, and are efficiency-corrected as a function of the invariant mass of the $K^-K_S^0$ system. We find the branching fractions to be: $$\text{B}(B^-\to D^0K^-K_S^0)=(1.89\pm 0.16\pm 0.10)\times 10^{-4},$$ $$\text{B}(\overline B{}^0\to D^+K^-K_S^0)=(0.85\pm 0.11\pm 0.05)\times 10^{-4},$$ $$\text{B}(B^-\to D^{*0}K^-K_S^0)=(1.57\pm 0.27\pm 0.12)\times 10^{-4},$$ $$\text{B}(\overline B{}^0\to D^{*+}K^-K_S^0)=(0.96\pm 0.18\pm 0.06)\times 10^{-4},$$ where the first uncertainty is statistical and the second systematic. These results include the first observation of $\overline B{}^0\to D^+K^-K_S^0$, $B^-\to D^{*0}K^-K_S^0$, and $\overline B{}^0\to D^{*+}K^-K_S^0$ decays and a significant improvement in the precision of $\text{B}(B^-\to D^0K^-K_S^0)$ compared to previous measurements

Measurement of the integrated luminosity of the Phase 2 data of the Belle II experiment

From April to July 2018, a data sample at the peak energy of the γ(4S) resonance was collected with the Belle II detector at the SuperKEKB electron-positron collider. This is the first data sample of the Belle II experiment. Using Bhabha and digamma events, we measure the integrated luminosity of the data sample to be (496.3 ± 0.3 ± 3.0) pb-1, where the first uncertainty is statistical and the second is systematic. This work provides a basis for future luminosity measurements at Belle II

Postoperative outcomes in oesophagectomy with trainee involvement

BACKGROUND: The complexity of oesophageal surgery and the significant risk of morbidity necessitates that oesophagectomy is predominantly performed by a consultant surgeon, or a senior trainee under their supervision. The aim of this study was to determine the impact of trainee involvement in oesophagectomy on postoperative outcomes in an international multicentre setting. METHODS: Data from the multicentre Oesophago-Gastric Anastomosis Study Group (OGAA) cohort study were analysed, which comprised prospectively collected data from patients undergoing oesophagectomy for oesophageal cancer between April 2018 and December 2018. Procedures were grouped by the level of trainee involvement, and univariable and multivariable analyses were performed to compare patient outcomes across groups. RESULTS: Of 2232 oesophagectomies from 137 centres in 41 countries, trainees were involved in 29.1 per cent of them (n = 650), performing only the abdominal phase in 230, only the chest and/or neck phases in 130, and all phases in 315 procedures. For procedures with a chest anastomosis, those with trainee involvement had similar 90-day mortality, complication and reoperation rates to consultant-performed oesophagectomies (P = 0.451, P = 0.318, and P = 0.382, respectively), while anastomotic leak rates were significantly lower in the trainee groups (P = 0.030). Procedures with a neck anastomosis had equivalent complication, anastomotic leak, and reoperation rates (P = 0.150, P = 0.430, and P = 0.632, respectively) in trainee-involved versus consultant-performed oesophagectomies, with significantly lower 90-day mortality in the trainee groups (P = 0.005). CONCLUSION: Trainee involvement was not found to be associated with significantly inferior postoperative outcomes for selected patients undergoing oesophagectomy. The results support continued supervised trainee involvement in oesophageal cancer surgery