Cumulative pregnancy and live birth rates through assisted reproduction in women 44–45 years of age: is there any hope?

Purpose

The purpose of the study is to calculate the cumulative pregnancy rate and cumulative live birth rate in women undergoing in vitro fertilization (IVF) at ages 44–45.

Methods

The study calculated cumulative live pregnancy rate and cumulative live birth rate of 124 women aged 44 to 45 years old who commenced IVF treatment.

Main outcome measures

The main outcome measures are cumulative live pregnancy rate and cumulative live birth rate.

Results

Cumulative live pregnancy rates following 1, 2, 3, and 4 cycles were 5.6, 11, 17, and 20%, respectively, with no additional pregnancies in further cycles. Cumulative live birth rates following 1, 2, and 3 cycles were 1.6, 3, and 7%, respectively, with no additional live births in further cycles.

Conclusions

The cumulative pregnancy rate rises during the first 4 cycles and cumulative live birth rate rises during the first 3 cycles, with no additional rise in pregnancies or deliveries thereafter, suggesting that it is futile to offer more than 3 cycles of treatment to 44–45-year-old women.

     

Bone age determination using only the index finger: a novel approach using a convolutional neural network compared with human radiologists

Background

Recently developed convolutional neural network (CNN) models determine bone age more accurately than radiologists.

Objective

The purpose of this study was to determine whether a CNN and radiologists can accurately predict bone age from radiographs using only the index finger rather than the whole hand.

Materials and methods

We used a public anonymized dataset provided by the Radiological Society of North America (RSNA) pediatric bone age challenge. The dataset contains 12,611 hand radiographs for training and 200 radiographs for testing. The index finger was cropped from these images to create a second dataset. Separate CNN models were trained using the whole-hand radiographs and the cropped second-digit dataset using the consensus ground truth provided by the RSNA bone age challenge. Bone age determination using both models was compared with ground truth as provided by the RSNA dataset. Separately, three pediatric radiologists determined bone age from the whole-hand and index-finger radiographs, and the consensus was compared to the ground truth and CNN-model-determined bone ages.

Results

The mean absolute difference between the ground truth and CNN bone age for whole-hand and index-finger was similar (4.7 months vs. 5.1 months, P=0.14), and both values were significantly smaller than that for radiologist bone age determination from the single-finger radiographs (8.0 months, P<0.0001).

Conclusion

CNN-model-determined bone ages from index-finger radiographs are similar to whole-hand bone age interpreted by radiologists in the dataset, as well as a model trained on the whole-hand radiograph. In addition, the index-finger model performed better than the ground truth compared to subspecialty trained pediatric radiologists also using only the index finger to determine bone age. The radiologist interpreting bone age can use the second digit as a reliable starting point in their search pattern.

     

Frequency of λ light chain subtypes in mouse antibodies to the 2,4-dinitrophenyl (DNP) group

Of the three λ chain subtypes made by inbred mice, chains of the λ1 subtype are much more frequent than those of the other subtypes (λ2,λ3) in antibodies (Ab) to those few antigenic structures that are known to elicit responses, in which λ chains are the predominant type of light chain [(4-hydroxy-3-nitrophenyl)acetyl (NP) and dextran]. The reasons for the frequency differences are not understood, and the large difference between the λ1 and λ3 frequencies is particularly puzzling, because in nearly all (about 95%) chains of these subtypes the N-terminal 97 or 98 amino acids are endoded by the same Vλ-gene segment. In an effort to identify an Ab response that has different λ subtype frequencies, we analyzed the light chains of the Ab made by BALB/c and B6 mice in response to 2,4-dinitrophenylated chicken gamma globulin (DNP-CGG). We found that approximately 40% of the elicited anti-DNP molecules had λ chains and of these approximately 40% were of the λ2 or λ3 subtype. Polyacrylamide gel electrophoresis indicated that the λ2 and λ3 chains were about equally abundant. Similar λ subtype frequencies were found in the anti-DNP Ab produced by the hybridomas made with spleen cells from the same immunized mice. In the anti-DNP Ab elicited by DNP-CGG and in the anti-NP Ab elicited by NP-CGG the different λ subtype frequencies (λ1/λ2 + λ3 = ca. 1.0-1.5 in anti-DNP and ca. 30 in anti-NP) were unaffected by immunizing mice with each of these antigens alone or with a mixture of the two. This finding, though preliminary, suggests that isotype-specific regulatory T cells are not responsible for the markedly different λ subtype frequencies in anti-DNP and anti-NP Ab.     

Genetic diversity of rabies virus in different host species and geographic regions of Zambia and Zimbabwe

Virus Genes - Rabies is endemic in Zambia and Zimbabwe. The previously investigated strains of rabies virus in central Zambia belong to the Africa 1b lineage, with similar circulating virus strains...     

Effect of tactile stimulation pulse characteristics on sensation threshold and power consumption

The psychophysical responses of human subjects to vibratory tactile stimulation of the skin were investigated experimentally. The parameters, of the waveform important to the minimization of power consumed by the tactile array of electromechanical vibrators and the maximization of the skin sensitivity to the stimulus were explored to develop optimum stimulation. Parameters investigated included the amplitude, frequency, and duty cycle of the current waveform used to drive the vibrators as well as the number of pulses per stimulating burst and the recovery time between bursts. Graphical techniques were used to determine, the optimal combination of the parameters which gave a stimulus that excited the skin to above tactile threshold while maintaining at a relative minimum the power required for the stimulus. The optimal stimulation waveform contains a burst of 10 rectangular pulses of 4% duty cycle separated by a period of nonstimulation of 2 s. Such a waveform can elicit a sensitivity of 29.4 mA⁻¹ consuming only 55 μW of power.     

Neuroblastic differentiation potential of the human retinoblastoma cell lines Y-79 and WERI-Rb1 maintained in an organ culture system. An immunohistochemical, electron microscopic, and biochemical study

The differentiation potential of the human retinoblastoma cell lines Y-79 and WERI-Rb1 was evaluated in vitro for up to 120 days in a matrix system and in rotary suspension for 30 days. Matrix cultures were grown with 10% fetal calf serum (FCS), with and without differentiation-promoting agents. The latter were applied for a total of 5-45 days (usually 30 days) and included 7S nerve growth factor, dibutyryl cyclic AMP, sodium butyrate, retinoic acid, hydrocortisone, and ascorbic acid. Fully defined, serum-free medium and medium containing 5 or 15% FCS were also used for matrix cultures, and medium with 5 or 10% FCS for suspension cultures. By immunoperoxidase (performed on matrix cultures, both untreated and treated for 30 days with differentiation-promoting agents), the cells of both lines were positive for neuron-specific enolase (NSE), microtubule-associated protein 2 (MAP2), class III beta-tubulin (human h beta 4) isotype, and synaptophysin. In addition, the WERI-Rb1 cells expressed 200 kd neurofilament protein (NFP-H) and retinal S-antigen. Both lines were invariably negative for glial fibrillary acidic (GFA) protein, myelin-associated glycoprotein, myelin basic protein, the epitope recognized by the Leu-7 monoclonal antibody, opsin, and hydroxy-indole-O-methyltransferase. In the Y-79 line the presence of NSE and the absence of NF proteins-H, -M and -L, of GFA protein, and of retinal S-antigen were confirmed biochemically. No differentiated features were found by electron microscopy in either line. Thus, in the matrix system employed, both lines exhibited solely a potential for neuroblastic differentiation, which was more advanced in the WERI-Rb1 line, as reflected by the antigenic expression of NFP-H and of retinal S-antigen.     

Hypotonicity stimulates translocation of ICln in neonatal rat cardiac myocytes

 Cell volume expansion stimulates the efflux of solutes, including the amino acid taurine, to accomplish a regulatory volume decrease (RVD). One protein that may play a role in taurine efflux is the cytosolic protein ICln. In rat neonatal cardiac myocytes under isotonic conditions, ICln is found predominantly (greater than 90%) in the cytosol. However, after cell volume expansion by exposure to hypotonic medium, ICln rapidly translocates to the particulate fraction (the Triton X-114-insoluble fraction). After 2 min in hypotonic medium the percentage of ICln in the particulate fraction increases to 30%, 46% at 5 min, 40% at 10 min, and 25% at 30 min. The time course of this response is similar to that of hypotonicity-stimulated taurine efflux. Hypotonicity-stimulated taurine efflux as well as ICln translocation parallel the reduction in medium osmolarity. As osmolarity decreases, taurine efflux and ICln movement increase. The movement of ICln from the particulate back to the cytosolic fraction is accelerated when volume-expanded cells are returned to isotonic medium. When ICln is analyzed under non-denaturing conditions, a dimer is detected in the particulate fraction of volume-expanded cells, along with the monomer. This dimer is not detected in the cytosol. Treatment of the particulate fraction from volume-expanded cells with the lyotropic agent KSCN caused release of ICln but not Na-K-ATPase into the soluble fraction, indicating that translocated ICln associates with membranes in the particulate fraction rather than inserting into them. Received: 31 October 1997 / Received after revision and accepted: 23 March 1998     

Continuous Biofeedback and Discrete Posttrial Verbal Feedback in Frontalis Muscle Relaxation Training

During training to relax the frontalis muscle, continuous biofeedback (BF) was compared to discrete verbal feedback (VF) delivered immediately after each trial. Both feedback modalities were based on frontalis electromyographic (EMG) activity. Training consisted of 3 consecutive daily session-each comprised of 3 baseline (nonfeedback) trials followed by 10 training trials of 128 see. The presence or absence of the two informationally positive feedback modalities were combined factorially to define four training conditions: BF + VF, NO BF + VF, BF + NO VF, and NO BF + NO VF. Results indicated that while VF alone facilitated muscle relaxation, BF was clearly prepotent ill effecting consistent decreases in EMG activity both across trials and days of training. Additionally, the facilitating effect of BF transferred to nonfeedback trials while VF did not affect performance on nonfeedback trials. Finally, accuracy of self-evaluations of performance on a trial by trial basis was markedly improved by BF, while VF improved accuracy only for trials having a very large absolute difference between levels of EMG activity. Ss receiving no feedback neither reduced muscle tension during training not were able to evaluate their performance accurately even when large absolute differences occurred between trials in frontalis EMG activity.     

Signaling pathways involved in Ca2+- and Pb2+-induced vesicular catecholamine release from rat PC12 cells

Since Pb(2+) substitutes for Ca(2+) in essential steps leading to exocytosis, we have investigated whether Ca(2+) and Pb(2+) induce exocytosis through similar pathways. Vesicular catecholamine release was measured from dexamethasone-differentiated PC12 cells using carbon fiber microelectrode amperometry. Effects of drugs known to modulate PKC (PMA, staurosporine), calcineurin (cyclosporin A), calmodulin (W7), and CaM kinase II (KN-62) activity were investigated in intact and in ionomycin-permeabilized PC12 cells. Activation of PKC and inhibition of calmodulin decrease the frequency of exocytotic events evoked by high K(+) stimulation in intact cells. In addition, inhibition of calmodulin enhances the frequency of basal exocytosis from intact cells. Activation of PKC and inhibition of calcineurin enhance the frequency of basal exocytosis in intact as well as in ionomycin-permeabilized cells. Inhibition of PKC and of CaM kinase II cause no significant effects. None of the treatments has a significant effect on vesicle contents. The combined results indicate that PKC and calcineurin enhance and inhibit exocytosis through direct effects on the exocytotic machinery, whereas calmodulin and CaM kinase II exert indirect effects only. Conversely, Pb(2+)-evoked exocytosis in permeabilized cells is strongly reduced by inhibition of CaM kinase II, but is not sensitive to modulation of PKC and calcineurin activity. Inhibition of calmodulin only reduces the delay to onset of Pb(2+)-evoked exocytosis. Synaptotagmin I- and II-deficient PC12-F7 cells exhibit vesicular catecholamine release following depolarization or superfusion with Pb(2+). However, the frequency of exocytosis and the contents of vesicles released are strongly reduced as compared to PC12 cells. It is concluded that Ca(2+)-evoked exocytosis is modulated mainly by PKC and calcineurin, whereas Pb(2+)-evoked exocytosis is mainly modulated by CaM kinase II.