Management Approaches in WHO Grade III Meningioma: A National Oncology Trainees' Collaborative for Healthcare Research (NOTCH) UK Multi-Centre Retrospective Study.

AIMS: WHO Grade 3 (G3) meningiomas are rare tumours with limited data to guide management. This retrospective study documents UK management approaches across 14 centres over 11 years. MATERIALS AND METHODS: Patients with WHO G3 meningioma between 01/01/2008 and 31/12/2018 were identified. Data were collected on demographics, management strategy, adjuvant radiotherapy, approach in recurrence setting and survival. RESULTS: 84 patients were identified. 21.4% transformed from lower-grade disease. 96.4% underwent primary surgical resection, with 20.8% having evidence of residual disease on their post-op MRI. 59.3% of patients underwent adjuvant radiotherapy (RT) following surgical resection. Overall median PFS and OS were 12.6 months and 28.2 months, respectively. Median OS in the group who underwent complete surgical resection was 34.9 months, compared to 27.5 months for those who had incomplete resection (HR 0.58, 95% CI 0.27-1.23, p = 0.15). Median OS was 33.1 months for those who underwent adjuvant RT and 14.0 months for those who did not (HR 0.48, 95% CI 0.27-0.84, p = 0.004). Median adjuvant RT dose delivered was 60Gy (range 12Gy-60Gy), 45.8% of adjuvant RT was delivered using IMRT. At disease relapse, 31% underwent salvage surgery and 29.3% underwent salvage RT. Of those treated with salvage RT, 64.7% were re-treats and all were treated with hypofractionated RT. CONCLUSION: Surgery continues to be the preferred primary management strategy. Post-operative MRI within 48 hours is indicated to assess presence of residual disease and guide further surgical options. Adjuvant radiotherapy plays an important part of the management paradigm in these patients with the data supporting an attached survival advantage. Further surgery and re-irradiation is an option in the disease recurrence setting with radiosurgery frequently utilised in this context.

Assessing the use of minimally invasive self-sampling at home for long-term monitoring of the microbiota within UK families.

Monitoring the presence of commensal and pathogenic respiratory microorganisms is of critical global importance. However, community-based surveillance is difficult because nasopharyngeal swabs are uncomfortable and painful for a wide age range of participants. We designed a methodology for minimally invasive self-sampling at home and assessed its use for longitudinal monitoring of the oral, nasal and hand microbiota of adults and children within families. Healthy families with two adults and up to three children, living in and near Liverpool, United Kingdom, self-collected saliva, nasal lining fluid using synthetic absorptive matrices and hand swabs at home every two weeks for six months. Questionnaires were used to collect demographic and epidemiological data and assess feasibility and acceptability. Participants were invited to take part in an exit interview. Thirty-three families completed the study. Sampling using our approach was acceptable to 25/33 (76%) families, as sampling was fast (76%), easy (76%) and painless (60%). Saliva and hand sampling was acceptable to all participants of any age, whereas nasal sampling was accepted mostly by adults and children older than 5 years. Multi-niche self-sampling at home can be used by adults and children for longitudinal surveillance of respiratory microorganisms, providing key data for design of future studies.

Rare and declining bird species benefit most from designating protected areas for conservation in the UK.

There have been recent renewed commitments to increase the extent of protected areas to combat the growing biodiversity crisis but the underpinning evidence for their effectiveness is mixed and causal connections are rarely evaluated. We used data gathered by three large-scale citizen science programmes in the UK to provide the most comprehensive assessment to date of whether national (Sites of Special Scientific Interest) and European (Special Protection Areas/Special Areas of Conservation) designated areas are associated with improved state (occurrence, abundance), change (rates of colonization, persistence and trend in abundance), community structure and, uniquely, demography (productivity) on a national avifauna, while controlling for differences in land cover, elevation and climate. We found positive associations with state that suggest these areas are well targeted and that the greatest benefit accrued to the most conservation-dependent species since positive associations with change were largely restricted to rare and declining species and habitat specialists. We suggest that increased productivity provides a plausible demographic mechanism for positive effects of designation.

Estimating the Health Effects of Adding Bicycle and Pedestrian Paths at the Census Tract Level: Multiple Model Comparison.

BACKGROUND: Adding additional bicycle and pedestrian paths to an area can lead to improved health outcomes for residents over time. However, quantitatively determining which areas benefit more from bicycle and pedestrian paths, how many miles of bicycle and pedestrian paths are needed, and the health outcomes that may be most improved remain open questions. OBJECTIVE: Our work provides and evaluates a methodology that offers actionable insight for city-level planners, public health officials, and decision makers tasked with the question "To what extent will adding specified bicycle and pedestrian path mileage to a census tract improve residents' health outcomes over time?" METHODS: We conducted a factor analysis of data from the American Community Survey, Center for Disease Control 500 Cities project, Strava, and bicycle and pedestrian path location and use data from two different cities (Norfolk, Virginia, and San Francisco, California). We constructed 2 city-specific factor models and used an algorithm to predict the expected mean improvement that a specified number of bicycle and pedestrian path miles contributes to the identified health outcomes. RESULTS: We show that given a factor model constructed from data from 2011 to 2015, the number of additional bicycle and pedestrian path miles in 2016, and a specific census tract, our models forecast health outcome improvements in 2020 more accurately than 2 alternative approaches for both Norfolk, Virginia, and San Francisco, California. Furthermore, for each city, we show that the additional accuracy is a statistically significant improvement (P<.001 in every case) when compared with the alternate approaches. For Norfolk, Virginia (n=31 census tracts), our approach estimated, on average, the percentage of individuals with high blood pressure in the census tract within 1.49% (SD 0.85%), the percentage of individuals with diabetes in the census tract within 1.63% (SD 0.59%), and the percentage of individuals who had >2 weeks of poor physical health days in the census tract within 1.83% (SD 0.57%). For San Francisco (n=49 census tracts), our approach estimates, on average, that the percentage of individuals who had a stroke in the census tract is within 1.81% (SD 0.52%), and the percentage of individuals with diabetes in the census tract is within 1.26% (SD 0.91%). CONCLUSIONS: We propose and evaluate a methodology to enable decision makers to weigh the extent to which 2 bicycle and pedestrian paths of equal cost, which were proposed in different census tracts, improve residents' health outcomes; identify areas where bicycle and pedestrian paths are unlikely to be effective interventions and other strategies should be used; and quantify the minimum amount of additional bicycle path miles needed to maximize health outcome improvements. Our methodology shows statistically significant improvements, compared with alternative approaches, in historical accuracy for 2 large cities (for 2016) within different geographic areas and with different demographics.

Multidrug-resistant OXA-48/CTX-M-15 Klebsiella pneumoniae cluster in a COVID-19 intensive care unit: salient lessons for infection prevention and control during the COVID-19 pandemic.

BACKGROUND: Wards caring for COVID-19 patients, including intensive care units (ICUs), have an important focus on preventing transmission of SARS-CoV-2 to other patients and healthcare workers. AIM: To describe an outbreak of carbapenemase-producing Enterobacterales (CPE) in a COVID-19 ICU and to discuss key infection control measures enabling prompt termination of the cluster. METHODS: CPE were isolated from clinical specimens and screening swabs from intensive care patients with COVID-19 disease and from environmental screening. Whole-genome sequencing analysis was instrumental in informing phylogenetic relationships. FINDINGS: Seven clinical isolates and one environmental carbapenemase-producing Klebsiella pneumoniae isolate - all carrying OXA-48, CTX-M-15 and outer membrane porin mutations in ompK35/ompK36 - were identified with ≤1 single nucleotide polymorphism difference, indicative of clonality. A bundle of infection control interventions including careful adherence with contact precautions and hand hygiene, twice weekly screening for multidrug-resistant organisms, strict antimicrobial stewardship, and enhanced cleaning protocols promptly terminated the outbreak. CONCLUSION: Prolonged use of personal protective equipment is common with donning and doffing stations at the ward entrance, leaving healthcare workers prone to reduced hand hygiene practices between patients. Minimizing transmission of pathogens other than SARS-CoV-2 by careful adherence to normal contact precautions including hand hygiene, even during high patient contact manoeuvres, is critical to prevent outbreaks of multidrug-resistant organisms. Appropriate antimicrobial stewardship and screening for multidrug-resistant organisms must also be maintained throughout surge periods to prevent medium-term escalation in antimicrobial resistance rates. Whole-genome sequencing is highly informative for multidrug-resistant Enterobacterales surveillance strategies.

Persistent influence of precession on northern ice sheet variability since the early Pleistocene.

Prior to ~1 million years ago (Ma), variations in global ice volume were dominated by changes in obliquity; however, the role of precession remains unresolved. Using a record of North Atlantic ice rafting spanning the past 1.7 million years, we find that the onset of ice rafting within a given glacial cycle (reflecting ice sheet expansion) consistently occurred during times of decreasing obliquity whereas mass ice wasting (ablation) events were consistently tied to minima in precession. Furthermore, our results suggest that the ubiquitous association between precession-driven mass wasting events and glacial termination is a distinct feature of the mid to late Pleistocene. Before then (increasing), obliquity alone was sufficient to end a glacial cycle, before losing its dominant grip on deglaciation with the southward extension of Northern Hemisphere ice sheets since ~1 Ma.

Control of three gastrointestinal illness outbreaks in a British Role 1 facility in Afghanistan: a primary care perspective.

INTRODUCTION: In 2019, Camp Qargha (QAA), a British-led multinational military camp in Kabul, had three of the largest outbreaks of gastrointestinal illness (GI) experienced by the British Military since 2003. This paper discusses the incidence, the response of the British-led Role 1 (R1) medical treatment facility, identifies potential causative and exacerbating factors, and explains the control measures initiated. METHOD: GI in QAA results in local and UK military-wide data collection including in the form of local GI questionnaires, FMed85 forms and EpiNATO returns. The data from these was used to identify trends during and after outbreaks and produce environmental health (EH) and local outbreak reports. RESULTS: Overall, among the outbreaks 56% of stool samples tested positive for norovirus. In each outbreak incidence peaked within the first 3 days, and hardened multiperson rooms were worst affected. 206 patient presentations occurred during the three outbreaks, 706 working days were lost in isolation, with QAA shut down while in quarantine for 27 days. DISCUSSION: Significant strain was placed on QAA and the R1. Causative factors may include close interaction with the local national (LN) population, a high population density and accommodation being limited by specific national infrastructure protocols in an operational environment. CONCLUSION: Early recognition of GI, positive standard operating procedures and good hygiene habits are essential to prevent the spread of GI such as norovirus. An early awareness of LN population illness patterns will allow the R1 and command to be better prepared for outbreaks in the future.

Clinical likelihood ratios and balanced accuracy for 44 in silico tools against multiple large-scale functional assays of cancer susceptibility genes.

PURPOSE: Where multiple in silico tools are concordant, the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) framework affords supporting evidence toward pathogenicity or benignity, equivalent to a likelihood ratio of ~2. However, limited availability of "clinical truth sets" and prior use in tool training limits their utility for evaluation of tool performance. METHODS: We created a truth set of 9,436 missense variants classified as deleterious or tolerated in clinically validated high-throughput functional assays for BRCA1, BRCA2, MSH2, PTEN, and TP53 to evaluate predictive performance for 44 recommended/commonly used in silico tools. RESULTS: Over two-thirds of the tool-threshold combinations examined had specificity of <50%, thus substantially overcalling deleteriousness. REVEL scores of 0.8-1.0 had a Positive Likelihood Ratio (PLR) of 6.74 (5.24-8.82) compared to scores <0.7 and scores of 0-0.4 had a Negative Likelihood Ratio (NLR) of 34.3 (31.5-37.3) compared to scores of >0.7. For Meta-SNP, the equivalent PLR = 42.9 (14.4-406) and NLR = 19.4 (15.6-24.9). CONCLUSION: Against these clinically validated "functional truth sets," there was wide variation in the predictive performance of commonly used in silico tools. Overall, REVEL and Meta-SNP had best balanced accuracy and might potentially be used at stronger evidence weighting than current ACMG/AMP prescription, in particular for predictions of benignity.

Auroral Energy Flux and Joule Heating Derived From Global Maps of Field-Aligned Currents.

We calculate auroral energy flux and Joule heating in the high-latitude ionosphere for 27 geomagnetically active days using two-dimensional maps of field-aligned currents determined by the Active Magnetosphere and Planetary Response Experiment. The energy input to the ionosphere due to Joule heating increases more rapidly with geomagnetic activity than that due to precipitating particles. The energy flux varies more smoothly with time than Joule heating, which is impulsive in nature on time scales from minutes to tens of minutes. These impulsive events correlate well with recoveries in the Sym-H index, with the maximum correlation when compared to Sym-H recoveries 70 min later. Because of prior studies that have associated transient recoveries of Sym-H with substorm expansions, the delay found here suggests that dissipation of energy in the ionosphere occurs during the substorm growth phase prior to the release of magnetic energy caused by diversion of tail currents.

Criticality assessment for a regional maritime economy.

OBJECTIVE: To identify and assess the criticality for infrastructure assets and better understand their dependencies, interdependencies, and supply chain reliance. DESIGN: This study used a modified mission impact, symbolism, history, accessibility, recognizability, population, and proximity model combined with a deliberative process with regional subject matter experts. SETTING: Hampton roads Virginia maritime area. PARTICIPANTS: Emergency managers, US Corps of Engineers, US Coast Guard, law enforcement, railroad industry, intelligence community, Virginia Department of Emergency Management, Virginia Department of Transportation, and Virginia Port. MAIN OUTCOME: A prioritized list of one-to-n critical assets in the maritime area and identification of up and down-stream dependencies. RESULTS: The final most highly critical grouping included 26 out of 277 assets including especially important road bridges and tunnels, rail bridges and choke points, shipping channels, and marine terminals. CONCLUSIONS: Subject matter experts identified 277 critical infrastructure assets in the Hampton Roads Maritime Area (HRMA). From these, 26 assets that were deemed to be significantly more critical than others. From this reduced list, 12 were further assessed to be most important. The selection process provided significant support to those responsible for providing protection, mitigating potential damage, and planning recovery and allows informed, objective expenditures of limited funding. Additional key findings include the following: Proximity, or the potential for an asset that has been damaged or destroyed to cause direct harm to adjacent assets in the surrounding community, drives criticality in the HRMA more than any other factor in the model. A small group of 26 out of 277 assets exerts an outsized impact in the HRMA-nearly 20 percent of criticality-due to the potential consequences associated with their destruction or disruption. Road transportation, particularly tunnels, represents the primary dependency among critical assets. Major road and maritime transportation assets rely heavily on federal and state organizations to maintain their function. Supply chain: The critical asset group supports or supplies many missions and industries both nationally and internationally, including defense, manufacturing, commercial enterprise, and the movement of raw commodities.

Machine learning predictions of concentration-specific aggregate hazard scores of inorganic nanomaterials in embryonic zebrafish.

The possibility of employing computational approaches like nano-QSAR or nano-read-across to predict nanomaterial hazard is attractive from both a financial, and most importantly, where in vivo tests are required, ethical perspective. In the present work, we have employed advanced Machine Learning techniques, including stacked model ensembles, to create nano-QSAR tools for modeling the toxicity of metallic and metal oxide nanomaterials, both coated and uncoated and with a variety of different core compositions, tested at different dosage concentrations on embryonic zebrafish. Using both computed and experimental descriptors, we have identified a set of properties most relevant for the assessment of nanomaterial toxicity and successfully correlated these properties with the associated biological responses observed in zebrafish. Our findings suggest that for the group of metal and metal oxide nanomaterials, the core chemical composition, concentration and properties dependent upon nanomaterial surface and medium composition (such as zeta potential and agglomerate size) are significant factors influencing toxicity, albeit the ranking of different variables is sensitive to the exact analysis method and data modeled. Our generalized nano-QSAR ensemble models provide a promising framework for anticipating the toxicity potential of new nanomaterials and may contribute to the transition out of the animal testing paradigm. However, future experimental studies are required to generate comparable, similarly high quality data, using consistent protocols, for well characterized nanomaterials, as per the dataset modeled herein. This would enable the predictive power of our promising ensemble modeling approaches to be robustly assessed on large, diverse and truly external datasets.

Exploring the relationship between generalised anxiety/depression scales and asthma-specific quality of life/control questionnaires in a specialist asthma clinic.

INTRODUCTION: Psychological issues are common in patients with chronic disabling diseases such as asthma. National guidance recommends that specialist asthma clinic attendees should complete questionnaires screening for psychological comorbidities. However, completing these in addition to asthma specific questionnaires can be burdensome. In order to investigate whether anxiety and depression questionnaires can be used in a targeted manner, this study investigates the correlation between the respective scores. We hypothesize that there is correlation between asthma-specific and anxiety/depression questionnaire scores. METHODS: Three-hundred individuals with poorly controlled asthma attending a specialist clinic were asked to complete Asthma Control Questionnaire (ACQ), mini-Asthma Quality of Life Questionnaire (mini-AQLQ), Generalized Anxiety Disorder (GAD-7) and Patient Health Questionnaires (PHQ-9). A Pearson correlation coefficient was generated and area under ROC and confusion matrices were used to assess correlation. RESULTS: 49% and 47% of patients completing the GAD-7 or PHQ-9 questionnaires, respectively had scores above the screening level for co-morbid anxiety and depression. Additional questionnaires were often incomplete (GAD-7 = 150 and PHQ-9 = 140). GAD-7 and PHQ-9 correlated with ACQ and mini-AQLQ (all p = <0.001, r values 0.53-0.65). Asthma-specific questionnaire scores were predictive of GAD-7 and PHQ-9 scores (AUCs of 0.78 to 0.84). 75% of patients with a mini-AQLQ score of <3 met the threshold GAD-7 and PHQ-9 score of 10. CONCLUSIONS: ACQ and mini-AQLQ correlate with GAD-7 and PHQ-9 amongst specialist asthma clinic attendees. A mini-AQLQ >3 suggests patients are unlikely to have anxiety or depression. These findings could be used to identify patients requiring formal screening for psychological co-morbidity.

Aflatoxin and ochratoxin A residues in supplementary foods used for wild birds.

Provision of supplementary food for garden birds is practiced on a large scale in multiple countries. While this resource has benefits for wild bird populations, concern has been expressed regarding the potential for contamination of foodstuffs by mycotoxins, and the implications this might have for wildlife health. We investigated whether aflatoxin (AF) and ochratoxin A (OA) residues are present in foodstuffs sold for wild bird consumption at point of sale in Great Britain using high pressure liquid chromatography analyses. The hypothesis that production of these mycotoxins occurs in British climatic conditions, or under storage conditions after the point of sale, was tested under experimental conditions but was not proved by our study. While the majority of peanut samples were negative for AF residues, 10% (10/98) of samples at point of sale and 11% (13/119) of those across the storage and climate exposure treatment replicates contained AFB1 that exceeded the maximum permitted limit of 20 µg/kg. No significant difference was found in the detection of either mycotoxin between branded and non-branded products. The clinical significance, if any, of exposure of wild birds to mycotoxins requires further investigation. Nevertheless, the precautionary principle should be adopted and best practice steps to reduce the likelihood of wild bird exposure to mycotoxins are recommended.

Survival of a long-lived single island endemic, the Raso lark Alauda razae, in relation to age, fluctuating population and rainfall.

Estimating and understanding variation in survival rates is crucial for the management of threatened species, especially those with limited population sizes and/or restricted ranges. Using a capture-resighting dataset covering 2004-2017, we estimate adult survival in the Raso lark Alauda razae, a Critically Endangered single-island Cape Verdean endemic, whose population varied 25-fold during the study. Average annual adult survival was similar for males (0.813 ± 0.011) and females (0.826 ± 0.011) over the period. These values are high for a temperate passerine but not unusual for an insular tropical species like the lark. The oldest bird was recorded 13 years after first ringing. There was strong evidence that survival varied among years (between 0.57 and 0.95), being generally higher in wetter years. Survival, especially of males, was lower when the population was large, but only in drier years. Survival declined with age but there was no evidence that this decline was other than linear. High survival, even in the face of dry conditions, at least when the population is depressed, has probably contributed to the persistence of the species on its 7 km2 island home over several centuries.

Impact of endometritis on post-partum ovarian cyclicity in dairy cows.

Endometritis in dairy cows is a major global issue and has been associated with a decrease in reproductive performance. The aim of this study was to quantify the effect of endometritis (as defined by the presence of any abnormal vaginal discharge after 21 days post-partum) on post-partum ovarian cyclicity in dairy cows. Milk progesterone analysis was used to monitor reproductive cyclicity in 170 dairy cows across three different commercial herds. Associations between the occurrence of endometritis and the incidence risk of a variety of atypical cycle profiles during the calving to conception period were investigated to establish the importance of endometritis on post-partum ovarian activity. Endometritis increased the incidence odds of atypical ovarian profiles (P < 0.05) with prolonged luteal activity being the most affected (P < 0.05), but also showed prolonged time (3 days) to onset of luteal activity after parturition (P < 0.05). Using milk progesterone analysis, we found a relatively low incidence odds for reproductive cycle problems in healthy cows during the calving to conception period. However, the incidence odds of cycle problems, in particular prolonged luteal activity, were high in cows that had experienced endometritis, which would have significantly impaired reproductive function.

Association between testosterone, semen parameters, and live birth in men with unexplained infertility in an intrauterine insemination population.

OBJECTIVE: To determine whether men with unexplained infertility and low total T (TT) have abnormal spermatogenesis and lower fecundity. DESIGN: Secondary analysis of the prospective, randomized, multicenter clinical trial, Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS). SETTING: Infertility clinics. PATIENT(S): Nine hundred couples with unexplained infertility enrolled in AMIGOS. Semen analysis with an ejaculate of at least 5 million total motile sperm was required for enrollment. For inclusion in this secondary analysis, a fasting TT was required. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Logistic regression, adjusted for age and body mass index, assessed the association between low TT (defined as <264 ng/dL), semen parameters, and pregnancy outcome. RESULT(S): Seven hundred eighty-one men (mean age, 34.2 ± 5.7 years) with a median (interquartile range) TT of 411 (318-520) ng/dL were included. Men with TT <264 ng/dL were less likely to have normal (≥4% strict Kruger) morphology (unadjusted odds ratio [OR], 0.56; 95% confidence interval [CI], 0.34, 0.92; adjusted OR, 0.59; 95% CI, 0.35, 0.99). There was no association between low TT and semen volume < 1.5 mL, sperm concentration < 15 × 106/mL, or motility < 40%. Among couples whose male partner had low TT, 21 (18.8%) had a live birth, compared with 184 (27.5%) live births in couples with a male partner having TT > 264 ng/dL. The odds of live birth decreased by 40% in couples whose male partner had low TT (unadjusted OR, 0.60; 95% CI, 0.36, 1.00; adjusted OR, 0.65; 95% CI, 0.38, 1.12). CONCLUSION(S): In couples with unexplained infertility, low TT in the male partner was associated with abnormal sperm morphology and lower live birth rates. CLINICAL TRIAL REGISTRATION NUMBER: NCT01044862.

Regulating landfills using measured methane emissions: An English perspective.

Methane emissions from landfills are an important source of greenhouse gases in the UK and worldwide. This paper considers how measurements of methane emissions could be used to regulate landfills in England in order to reduce the contribution of landfilling to climate change. The paper presents the results of a number of UK studies undertaken to quantify methane emissions from landfills. The methods used have included the DIAL (Differential Absorption Lidar) technique and a tracer gas dispersion method. A method based on aerial measurements has been developed. Methane emission rates were measured at 15 biodegradable waste landfills. All of the landfills where measurements took place had an active landfill gas extraction system. A methane collection index (MCI) is calculated for each landfill using the ratio of the methane collection rate to the sum of the collection and emission rates. The values of the index in the campaigns reported here ranged from 0.28 to 0.90. The modern operational landfills surveyed achieved MCI values with a much narrower range of between 0.64 and 0.90 with an average of 0.76. This has demonstrated that it is possible for these landfills to collect a high proportion of the landfill gas. A proposed approach is presented for regulating landfills using the measured MCI. This would involve an annual measurement campaign to quantify the methane emissions and the use of the data provided by these surveys to develop an achievable but challenging MCI limit. A limit value of 0.75 for the MCI is used to illustrate the approach. An MCI that falls below the limit would trigger actions to reduce the methane emissions from the landfill.

Business models and provider satisfaction in in vitro fertilization centers in the USA.

PURPOSE: The number of in vitro fertilization (IVF) cycles is increasing and the majority of patients undergoing IVF pay out of pocket. Reproductive endocrinology and infertility practitioners employ different business models to help create financial pathways for patients needing IVF but details regarding the different types of business models being used and physician satisfaction with those models have not been described previously. METHODS: A cross-sectional survey was sent to members of the Society of Reproductive Endocrinology and Infertility. The survey included 30 questions designed to assess demographics, practice patterns, and business models utilized. RESULTS: A total of 222/736 (30%) physicians responded to the survey. The majority of physicians offer a-la-carte (67%), bundled services (69%), grants (57%), and cost/risk-sharing (50%). The majority answered that the single ideal business model is bundled services (53%). There was no significant association between financial package offered and region of practice or state-mandated insurance. The largest barrier to care reported was cost with or without state-mandated coverage (94% and 99%, respectively). The majority of practices are satisfied with their business model (75%). Higher physician satisfaction was associated with private practice [69% vs 27%; OR (95%CI) = 3.8 (1.7, 8.6)], male gender [59% vs 30%; OR = 2.4 (1.1, 5.4)], and offering bundled services [83% vs 59%; OR = 2.8 (1.2, 6.7)]. CONCLUSIONS: Physicians utilize a variety of business models and most are satisfied with their current model. Cost is the major barrier to care in states with and without mandated coverage.

Molecular fingerprint-derived similarity measures for toxicological read-across: Recommendations for optimal use.

Computational approaches are increasingly used to predict toxicity due, in part, to pressures to find alternatives to animal testing. Read-across is the "new paradigm" which aims to predict toxicity by identifying similar, data rich, source compounds. This assumes that similar molecules tend to exhibit similar activities i.e. molecular similarity is integral to read-across. Various of molecular fingerprints and similarity measures may be used to calculate molecular similarity. This study investigated the value and concordance of the Tanimoto similarity values calculated using six widely used fingerprints within six toxicological datasets. There was considerable variability in the similarity values calculated from the various molecular fingerprints for diverse compounds, although they were reasonably concordant for homologous series acting via a common mechanism. The results suggest generic fingerprint-derived similarities are likely to be optimally predictive for local datasets, i.e. following sub-categorisation. Thus, for read-across, generic fingerprint-derived similarities are likely to be most predictive after chemicals are placed into categories (or groups), then similarity is calculated within those categories, rather than for a whole chemically diverse dataset.