Avelumab first-line maintenance treatment for advanced urothelial carcinoma: review of evidence to guide clinical practice.

The JAVELIN Bladder 100 phase III trial led to the incorporation of avelumab first-line (1L) maintenance treatment into international guidelines as a standard of care for patients with advanced urothelial carcinoma (UC) without progression after 1L platinum-based chemotherapy. JAVELIN Bladder 100 showed that avelumab 1L maintenance significantly prolonged overall survival (OS) and progression-free survival in this population compared with a 'watch-and-wait' approach. The aim of this manuscript is to review clinical studies of avelumab 1L maintenance in patients with advanced UC, including long-term efficacy and safety data from JAVELIN Bladder 100, subgroup analyses in clinically relevant subpopulations, and 'real-world' data obtained outside of clinical trials, providing a comprehensive resource to support patient management. Extended follow-up from JAVELIN Bladder 100 has shown that avelumab provides a long-term efficacy benefit, with a median OS of 23.8 months measured from start of maintenance treatment, and 29.7 months measured from start of 1L chemotherapy. Longer OS was observed across subgroups, including patients who received 1L cisplatin + gemcitabine, patients who received four or six cycles of 1L chemotherapy, and patients with complete response, partial response, or stable disease as best response to 1L induction chemotherapy. No new safety signals were seen in patients who received ≥1 year of avelumab treatment, and toxicity was similar in those who had received cisplatin or carboplatin with gemcitabine. Other clinical datasets, including noninterventional studies conducted in Europe, USA, and Asia, have confirmed the efficacy of avelumab 1L maintenance. Potential subsequent treatment options after avelumab maintenance include antibody-drug conjugates (enfortumab vedotin or sacituzumab govitecan), erdafitinib in biomarker-selected patients, platinum rechallenge in suitable patients, nonplatinum chemotherapy, and clinical trial participation; however, evidence to determine optimal treatment sequences is needed. Ongoing trials of avelumab-based combination regimens as maintenance treatment have the potential to evolve the treatment landscape for patients with advanced UC.

[Real-life results of anti-VEGF treatment in fellow eyes with nAMD]. / Real-life-Ergebnisse der Anti-VEGF-Therapie bei nAMD der Partneraugen.

PURPOSE: Neovascular age-related macular degeneration (nAMD) often affects both eyes. This study compared real-life outcomes of the first affected eye (1st eye) and the last affected eye (2nd eye) after anti-vascular endothelial growth factor (anti-VEGF) treatment. MATERIAL AND METHODS: For this retrospective monocenter study 3217 eyes from 2793 patients with nAMD were identified, who received at least 3 anti-VEGF injections between 2006 and 2014 at the University Eye Hospital of Munich. Included in the study were patients with bilateral nAMD when the 1st and 2nd eyes were not previously treated and there was a strict adherence with continuous follow-up for at least 5 years. Corrected visual acuity, number of intravitreal injections and visits as well as central macular thickness were compared. RESULTS: A total of 72 eyes of 36 patients were included in this analysis. Before anti-VEGF therapy, the group of 2nd eyes showed significantly better mean visual acuity than the 1st eyes (p < 0.001). This difference in visual acuity between 1st and 2nd eyes was noted at all time points throughout the follow-up period (p < 0.05). The mean number of cumulative injections was higher in the group of 2nd eyes (p = 0.04) with a comparable number of visits between both groups. In more than half of all patients the 2nd eye became affected by nAMD within 12 months following treatment initiation of the 1st eye and the majority (83%) followed within 3 years. CONCLUSION: In unilateral nAMD, regular monitoring of the fellow eye is essential to avoid severe bilateral vision loss. Early diagnosis with rapid initiation of treatment can preserve visual acuity and quality of life.

Deubiquitinase USP10 regulates Notch signaling in the endothelium.

Notch signaling is a core patterning module for vascular morphogenesis that codetermines the sprouting behavior of endothelial cells (ECs). Tight quantitative and temporal control of Notch activity is essential for vascular development, yet the details of Notch regulation in ECs are incompletely understood. We found that ubiquitin-specific peptidase 10 (USP10) interacted with the NOTCH1 intracellular domain (NICD1) to slow the ubiquitin-dependent turnover of this short-lived form of the activated NOTCH1 receptor. Accordingly, inactivation of USP10 reduced NICD1 abundance and stability and diminished Notch-induced target gene expression in ECs. In mice, the loss of endothelial Usp10 increased vessel sprouting and partially restored the patterning defects caused by ectopic expression of NICD1. Thus, USP10 functions as an NICD1 deubiquitinase that fine-tunes endothelial Notch responses during angiogenic sprouting.

Ventricular assist device therapy and heart transplantation: Benefits, drawbacks, and outlook.

End-stage heart failure is associated with significant morbidity and mortality. Heart transplantation has the potential to offer a return to daily activities for critically ill patients and is the gold standard therapy. However, heart transplantations are decreasing yearly with a historic low in Germany in 2017. By striking contrast, both waiting list numbers and waiting time have increased owing to a lack of acceptable donor organs. Ventricular assist devices (VAD) represent a reasonable therapeutic alternative for patients on heart transplantation waiting lists. Patients ineligible for transplantation may undergo VAD implantation as a destination therapy. However, the necessity for life-long anticoagulation must be weighed against bleeding complications in potential VAD candidates. VAD-dependent patients also face risks of driveline infections, in addition to restricted activities of daily living owing to limited battery capacities. Given Germany's low transplantation rate, VAD implantation may serve as a middle ground. With the recent events in transplantation medicine, trust among the German population has declined. Transplant centers must ensure graft quality and ongoing care, define minimum caseload for accreditation, and implement specialty care units in heart failure. Furthermore, the legislation shift from extended consent to dissent solution has the potential to end donor organ shortage.

Effects of the Cardio First AngelTM on chest compression performance.

BACKGROUND: Survival rates of out-of-hospital cardiac arrest remain poor. Bystander cardiopulmonary resuscitation (CPR) is crucial for survival and feedback devices could improve its quality. OBJECTIVE: We investigated the quality of chest compression when using the Cardio First AngelTM (CFA) feedback device compared to standard basic life support (BLS). The analysis focused on laymen. METHODS: Laymen without (n= 43) and with (n= 96) explanation of the device, medical students (n= 128) and medical staff (n= 27) performed 60 seconds of standard versus assisted chest compression using the CFA on a resuscitation manikin. Compression frequency, depth and position were analyzed according to current guidelines. RESULTS: Laymen showed significantly better success rates regarding correct compression depth when using the CFA (23.3% vs. 55.8%, p= 0.004 and 25.0% vs. 52.1%, p< 0.001, laymen without and with explanation of the device, respectively). Medical students likewise improved (22.7% vs. 42.2%, p= 0.004). Hand positioning was 100% correct in all groups with the device. Improvement in frequency yielded by the CFA was more pronounced for probands with fears of contact (p= 0.02). The benefit of using the device did not differ significantly in laymen with or without explanation. CONCLUSIONS: Chest compression as performed by laymen was significantly improved with regard to compression depth when using the CFA for guidance and feedback. With the device, no cases of incorrect hand positioning occurred in any group.

Bacterial Zoonoses Transmitted by Household Pets: State-of-the-Art and Future Perspectives for Targeted Research and Policy Actions.

The close contact between household pets and people offers favourable conditions for bacterial transmission. In this article, the aetiology, prevalence, transmission, impact on human health and preventative measures are summarized for selected bacterial zoonoses transmissible by household pets. Six zoonoses representing distinct transmission routes were selected arbitrarily based on the available information on incidence and severity of pet-associated disease caused by zoonotic bacteria: bite infections and cat scratch disease (physical injuries), psittacosis (inhalation), leptospirosis (contact with urine), and campylobacteriosis and salmonellosis (faecal-oral ingestion). Antimicrobial resistance was also included due to the recent emergence of multidrug-resistant bacteria of zoonotic potential in dogs and cats. There is a general lack of data on pathogen prevalence in the relevant pet population and on the incidence of human infections attributable to pets. In order to address these gaps in knowledge, and to minimize the risk of human infection, actions at several levels are recommended, including: (1) coordinated surveillance of zoonotic pathogens and antimicrobial resistance in household pets, (2) studies to estimate the burden of human disease attributable to pets and to identify risk behaviours facilitating transmission, and (3) education of those in charge of pets, animal caretakers, veterinarians and human medical healthcare practitioners on the potential zoonotic risks associated with exposure to pets. Disease-specific recommendations include incentives to undertake research aimed at the development of new diagnostic tests, veterinary-specific antimicrobial products and vaccines, as well as initiatives to promote best practices in veterinary diagnostic laboratories and prudent antimicrobial usage.

Workshop report: the 2012 antimicrobial agents in veterinary medicine: exploring the consequences of antimicrobial drug use: a 3-D approach.

Antimicrobial resistance is a global challenge that impacts both human and veterinary health care. The resilience of microbes is reflected in their ability to adapt and survive in spite of our best efforts to constrain their infectious capabilities. As science advances, many of the mechanisms for microbial survival and resistance element transfer have been identified. During the 2012 meeting of Antimicrobial Agents in Veterinary Medicine (AAVM), experts provided insights on such issues as use vs. resistance, the available tools for supporting appropriate drug use, the importance of meeting the therapeutic needs within the domestic animal health care, and the requirements associated with food safety and food security. This report aims to provide a summary of the presentations and discussions occurring during the 2012 AAVM with the goal of stimulating future discussions and enhancing the opportunity to establish creative and sustainable solutions that will guarantee the availability of an effective therapeutic arsenal for veterinary species.

Species-specific quantification of probiotic lactobacilli in yoghurt by quantitative real-time PCR.

AIMS: Lactobacilli strains with probiotic effects have been widely used in dairy products such as yoghurts as well as in food additives and pharmaceuticals. Despite their successful commercial application, the current species identification and quantification methods of the genus Lactobacillus are time-consuming and labour-intensive. METHODS AND RESULTS: To fulfil the requirements of a robust quality management, we have developed a quantitative real-time PCR assay based on the heat shock protein 60 gene (hsp60) for accurate identification and quantification of five commercially important Lactobacillus species. The developed assay allows an unambiguous species-specific detection of the species Lact. acidophilus, Lact. brevis, Lact. delbrueckii subsp. bulgaricus, Lact. helveticus and Lact. reuteri from bacterial cultures as well as directly from dairy products for instance yoghurt. CONCLUSIONS: With the assay, we were able to specifically detect lactobacilli strains down to 10(5)  CFU ml(-1) directly from yoghurt, which is a sufficient detection limit as commercial products usually contain 10(6) -10(12)  CFU ml(-1) of probiotic strains. SIGNIFICANCE AND IMPACT OF THE STUDY: The real-time PCR assay developed here might become a convenient tool enabling an accurate, fast and sensitive detection of probiotic lactobacilli commercially used in food.

Mirion--a software package for automatic processing of mass spectrometric images.

Mass spectrometric imaging (MSI) techniques are of growing interest for the Life Sciences. In recent years, the development of new instruments employing ion sources that are tailored for spatial scanning allowed the acquisition of large data sets. A subsequent data processing, however, is still a bottleneck in the analytical process, as a manual data interpretation is impossible within a reasonable time frame. The transformation of mass spectrometric data into spatial distribution images of detected compounds turned out to be the most appropriate method to visualize the results of such scans, as humans are able to interpret images faster and easier than plain numbers. Image generation, thus, is a time-consuming and complex yet very efficient task. The free software package "Mirion," presented in this paper, allows the handling and analysis of data sets acquired by mass spectrometry imaging. Mirion can be used for image processing of MSI data obtained from many different sources, as it uses the HUPO-PSI-based standard data format imzML, which is implemented in the proprietary software of most of the mass spectrometer companies. Different graphical representations of the recorded data are available. Furthermore, automatic calculation and overlay of mass spectrometric images promotes direct comparison of different analytes for data evaluation. The program also includes tools for image processing and image analysis.

The European Virus Archive: a new resource for virology research.

The European Virus Archive (EVA) was conceived as a direct response to the need for a coordinated and readily accessible collection of viruses that could be made available to academia, public health organisations and industry, initially within Europe, but ultimately throughout the world. Although scientists worldwide have accumulated virus collections since the early twentieth century, the quality of the collections and the viruses collected may vary according to the personal interests and agenda of the scientists. Moreover, when laboratories are re-organised or closed, collections are no longer maintained and gradually cease to exist. The tragedy of 9/11 and other disruptive activities have also meant that some previously available biological reagents are no longer openly exchanged between countries. In 2008, funding under the FP7-EU infrastructure programme enabled the initiation of the EVA. Within three years, it has developed from a consortium of nine European laboratories to encompass associated partners in Africa, Russia, China, Turkey, Germany and Italy. There is every reason to believe that EVA will continue to expand and ultimately exist as a globally networked, quality-controlled non-profit archive for the benefit of science. Organizations or individuals who would like to be considered as contributors are invited to contact the EVA coordinator, Jean-Louis Romette, at jean-louis.romette@univmed.fr.

Extended-spectrum ß-lactamase-producing and AmpC-producing Escherichia coli from livestock and companion animals, and their putative impact on public health: a global perspective.

The possible zoonotic spread of antimicrobial-resistant bacteria is controversial. This review discusses global molecular epidemiological data combining both analyses of the chromosomal background, using multilocus sequence typing (MLST), and analyses of plasmid (episomal) extended-spectrum ß-lactamase (ESBL)/AmpC genes in Escherichia coli present in humans and animals. For consideration of major epidemiological differences, animals were separated into livestock and companion animals. MLST revealed the existence of ESBL-producing isolates thoughout the E. coli population, with no obvious association with any ancestral EcoR group. A similar distribution of major ESBL/AmpC types was apparent only in human isolates, regardless of their geographical origin from Europe, Asia, or the Americas, whereas in animals this varied extensively between animal groups and across different geographical areas. In contrast to the diversity of episomal ESBL/AmpC types, isolates from human and animals mainly shared identical sequence types (STs), suggesting transmission or parallel micro-evolution. In conclusion, the opinion that animal ESBL-producing E. coli is a major source of human infections is oversimplified, and neglects a highly complex scenario.

High-throughput microRNAome analysis in human germ cell tumours.

Testicular germ cell tumours (GCTs) of adolescents and adults can be subdivided into seminomas (referred to as dysgerminomas of the ovary) and non-seminomas, all referred to as type II GCTs. They originate from carcinoma in situ (CIS), being the malignant counterparts of primordial germ cells (PGCs)/gonocytes. The invasive components mimic embryogenesis, including the stem cell component embryonal carcinoma (EC), the somatic lineage teratoma (TE), and the extra-embryonic tissues yolk sac tumour (YST) and choriocarcinoma (CH). The other type is the so-called spermatocytic seminomas (SS, type III GCT), composed of neoplastic primary spermatocytes. We reported previously that the miRNAs hsa-miR 371-373 cluster is involved in overruling cellular senescence induced by oncogenic stress, allowing cells to become malignant. Here we report the first high-throughput screen of 156 microRNAs in a series of type II and III GCTs (n = 69, in duplicate) using a quantitative PCR-based approach. After normalization to allow inter-sample analysis, the technical replicates clustered together, and the previous hsa-miRNA 371-373 cluster finding was confirmed. Unsupervised cluster analysis demonstrated that the cell lines are different from the in vivo samples. The in vivo samples, both normal and malignant, clustered predominantly based on their maturation status. This parallels normal embryogenesis, rather than chromosomal anomalies in the tumours. miRNAs within a single cluster showed a similar expression pattern, implying common regulatory mechanisms. Normal testicular tissue expressed most discriminating miRNAs at a higher level than SE and SS. Moreover, differentiated non-seminomas showed overexpression of discriminating miRNAs. These results support the model that miRNAs are involved in regulating differentiation of stem cells, retained in GCTs.

Rises in [Ca2+]i mediate capsaicin- and proton-induced heat sensitization of rat primary nociceptive neurons.

Capsaicin (CAPS) as well as acidic pH induces Ca2+ influx in a subset of rat dorsal root ganglion neurons. Here we show that CAPS as well as three different approaches to induce experimental tissue acidification (phosphate buffered solution pH 5.4, CO2-gassed solution pH 6.1 and NPE-caged protons) yielded a transient heat sensitization of peripheral nociceptive terminals in rat skin in vitro. The heat sensitization induced by CAPS (1 microM) could be prevented by preloading the neurons with the neuroprotective calcium chelator BAPTA-AM (1 mM). However, this pretreatment had no effect on the sensitization following exposure to acidic solutions (pH 5.4 and pH 6.1). Therefore, the membrane-permeant proton buffer SNARF-AM (200 microM) was used together with BAPTA-AM in order to prevent changes in intracellular pH. Under these conditions heat sensitization by low pH did not occur. To investigate the underlying membrane mechanisms, current recordings together with simultaneous calcium measurements using FURA-2 were performed in neurons isolated from rat dorsal root ganglia. In a subset of these neurons, an increase in [Ca2+]i and concomitant facilitation of heat-activated ionic currents was observed after application of CAPS as well as pH 5.6. Rises in [Ca2+]i thus appear to play an essential role in plastic changes not only of central neurons but also of peripheral nociceptive terminals which may account for heat hyperalgesia.

Role of [Ca2+]i in the ATP-induced heat sensitization process of rat nociceptive neurons.

In inflamed tissue, nociceptors show increased sensitivity to noxious heat, which may account for heat hyperalgesia. In unmyelinated nociceptive afferents in rat skin in vitro, a drop of heat threshold and an increase in heat responses were induced by experimental elevation of intracellular calcium ([Ca2+]i) levels with the calcium ionophore ionomycin (10 microM). Similar results were obtained in experiments employing [Ca2+]i release from preloaded "caged calcium" (NITR-5/AM) via UV photolysis. In both cases, sensitization was prevented by preventing rises in [Ca2+]i with the membrane-permeant calcium chelator BAPTA-AM (1 mM). No pronounced change of mechanical sensitivity was observed. Heat-induced membrane currents (Iheat) were investigated with patch-clamp recordings, and simultaneous calcium measurements were performed in small sensory neurons isolated from adult rat dorsal root ganglia (DRG). Ionomycin-induced rises in [Ca2+]i resulted in reversible sensitization of Iheat. In the same subset of DRG neurons, the endogenous algogen ATP (100 microM) was used to elevate [Ca2+]i, which again resulted in significant sensitization of Iheat. In correlative recordings from the skin-nerve preparation, ATP induced heat sensitization of nociceptors, which again could be blocked by preincubation with BAPTA-AM. Rises in [Ca2+]i in response to inflammatory mediators, e.g., ATP, thus appear to play a central role in plastic changes of nociceptors, which may account for hypersensitivity of inflamed tissue.

Spectrometric investigations in ocular hypertension and early stages of primary open angle glaucoma and of low tension glaucoma--multisubstance analysis.

The approximation of logarithmic difference spectra between the reflectance of the normal fundus and the fundus reflectance in different stages of glaucoma is demonstrated by a model. The influences of fundus pigments like oxihemoglobin, melanin, xanthophyll and rhodopsin as well as the intensity and the exponent of the scattered light are optimized. Glaucomatous alterations in the extinction of these pigments and of the scattering parameters are different in the macula, in the papillo-macular bundle and in the parapapillary region temporal to the optic disc. A lack of oxihemoglobin only in the papillo-macular bundle in first relative losses in the visual field function points to a damaged microcirculation in early POAG. In progressive glaucoma the extinction spectrum of xanthophyll is detectable in the papillo-macular bundle. A decreased intensity of the scattered light and an altered scattering exponent are suggestive of a damage in the nerve fiber layer at early stages of glaucoma.

Variability of resting respiratory drive and timing in healthy subjects.

Studies of breathing pattern have focused primarily on changes in the mean values of the breathing pattern components, whereas there has been minimal investigation of breath-to-breath variability, which should provide information on the constancy with which respiration is controlled. In this study we examined the variability of breathing pattern both on a breath-to-breath and day-to-day basis by calculating the coefficient of variation (i.e., the standard deviation expressed as a percentage of the mean). By examining breath-to-breath data, we found that the coefficients of variation of tidal volume (VT) and fractional inspiratory time (TI/TT, an index of timing) obtained with an inductive plethysmograph and spirometer were within 1% of each other. Examination of breath-to-breath variability in breathing pattern over a 15-min period in 65 subjects revealed large coefficients of variation, indicating the need to base calculations on a relatively large number of breaths. Less breath-to-breath variability was observed in respiratory frequency [f, 20.8 +/- 11.5% (SD)] and TI/TT (17.9 +/- 6.5%) than in VT (33 +/- 14.9%) and mean inspiratory flow (VT/TI, an index of drive; 31.6 +/- 12.6%; P less than 0.0001). Older subjects (60-81 yr) displayed greater breath-to-breath variability than young subjects (21-50 yr). Use of a mouthpiece did not affect the degree of variability.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of gynecologic health care problems between lesbians and bisexual women. A survey of 2,345 women.

A survey of reproductive system problems was conducted in a large group of lesbians (n = 1,921) and bisexual women (n = 424) in a nonclinical setting. Demographically the groups were similar: the majority of respondents were white, urban and well educated. A history of heterosexual coitus was common in both groups (bisexuals, 95%; lesbians, 77%). Bisexuals were more likely than lesbians to report an abnormal Papanicolaou smear, cystitis, genital herpes, gonorrhea and vaginal infections. When sexual orientation was controlled for, most, but not all, of these differences were associated with a difference in reported frequency of (prior) coitus. Despite the lower risk of certain problems, however, the lesbians who reported no previous coitus did report the occurrence of vaginitis, abnormal Papanicolaou smears and genital herpes. There were no differences in past oral contraceptive use, endometriosis, menstrual dysfunction or breast disease. The lesbian group reported a greater percentage of hysterectomies. These data suggest that, overall, the sexual behaviors of lesbians are associated with a lower risk of most sexually transmitted diseases.

Does rib cage-abdominal paradox signify respiratory muscle fatigue?

Studies suggesting that abnormal motion of the rib cage (RC) and abdomen (Ab) may indicate respiratory muscle fatigue have not separated the influence of respiratory load from that of fatigue in its pathogenesis. We hypothesized that abnormalities on RC-Ab motion are primarily related to increased load rather than fatigue. We tested this hypothesis in subjects breathing against resistive loads while maintaining 30 and 60% of maximum mouth pressure (Pmmax). RC-Ab asynchrony and paradox and the degree of variation in compartmental contribution to tidal volume were measured by inductive plethysmography and quantitated by the Konno-Mead method of analysis. Comparing measurements of base line and 30 and 60% of Pmmax indicated that the degree of asynchrony, paradox, and variation in compartmental contribution were significantly related to the level of the load; significant abnormalities were observed at even 30% of Pmmax, a target pressure that can be sustained indefinitely. In another group of subjects, fatigue was induced by sustaining 60% of Pmmax to the limits of tolerance. Indexes of abnormal RC-Ab motion increased from base line during the 1st min of loaded breathing but displayed no progression from the beginning to the end of the fatigue run. Immediately on discontinuation of the load, the indexes returned to levels similar to base line despite persistence of the fatigue state. These results in healthy subjects breathing against severe resistances indicate that RC-Ab asynchrony and paradox and variation in compartmental contribution to tidal volume are predominantly due to increases in respiratory load rather than muscle fatigue.

Konno-Mead analysis of ribcage-abdominal motion during successful and unsuccessful trials of weaning from mechanical ventilation.

Respiratory muscle fatigue is considered a common cause of weaning failure but its detection is hampered by the lack of a satisfactory diagnostic test. Abdominal paradox has been proposed as a valuable clinical index of fatigue and thus its presence may lead to curtailment of weaning trials. However, sensitivity and specificity of this sign as a predictor of weaning outcome is unknown. We hypothesize that abnormal ribcage-abdominal (RC-Ab) motion is a common finding in the early stages of weaning and its presence does not inevitably imply an unsuccessful weaning outcome. We tested this hypothesis in patients undergoing a weaning trial: one group had a successful weaning outcome and were extubated (n = 10) and the other group failed the trial (n = 7). Normal RC-Ab motion was separately characterized in 17 healthy subjects. Employing a calibrated respiratory inductive plethysmograph, quantitative assessment of asynchrony and paradox was obtained by computing several indices from series of breaths at fixed time periods using the Konno-Mead method of analysis. During the weaning trial, both groups of patients displayed significant increases in asynchrony and Ab paradox compared to normal values. As a group, patients who failed the trial displayed significantly greater asynchrony and paradox of the RC and Ab than patients with a successful outcome. However, there was considerable overlap between the individual patients in the 2 study groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Parenting desires among bisexual women and lesbians.

Parenting desires were ascertained among a large group of lesbians (n = 1,921) and bisexual women (n = 424) recruited in a nonclinical setting. More than 50% of each sexual-orientation group had considered having a child since recognizing their current sexual identity. Lesbians were more likely than bisexuals to favor adoption and donor insemination as options, whereas bisexuals were more likely to consider intercourse with either a cooperative or unsuspecting man. Overall, however, 47 women (2%) reported success in obtaining a child through one of these options.