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Objective To assess the relationship between the ethnicity of women and the clinical success of in vitro fertilisation ( IVF) or intracytoplasmic sperm injection ( ICSI) treatment. Design Observational cohort study. Setting Nottingham University Research and Treatment Unit in Reproduction ( NURTURE), UK. Sample A total of 1517 women, of which 1291 were white Europeans and 226 belonged to an ethnic minority group. All the women were undergoing their first cycle of assisted reproductive technology ( ART) between 2006 and 2011. Methods All of the women underwent their first cycle of ART between 2006 and 2011. Main outcome measures Live birth rates following IVF or ICSI treatment. Results Although pre-treatment ovarian reserve variables [mean age, basal follicle stimulating hormone ( FSH), and total antral follicle count] were significantly favourable in the ethnic group, the live birth rates were significantly lower in this group (35%) compared with the white European group (43.8%) (relative risk 0.8; 95% CI 0.66-0.97). On logistic regression analysis, ethnicity was an independent predictor of live birth rate ( OR 0.688; 95% CI 0.513-0.924). After controlling for the other independent variables (age and FSH), the significant association between ethnicity and live birth rate remained strong ( OR 0.591; 95% CI 0.425-0.822) on multivariate logistic regression analysis. Conclusions Live birth rates following IVF or ICSI treatment were significantly lower in the ethnic minority group compared with white European women, which suggests that ethnicity is a major determinant of live birth following IVF treatment. [ABSTRACT FROM AUTHOR]

Objectives: Oral contraceptive pills suppress the hypothalomo-pituitary axis, which can affect the ultrasound and endocrine markers used to examine ovarian reserve. The objective of this study was to quantify the ultrasound and endocrine markers of functional ovarian reserve in women using a combined oral contraceptive pill (COCP) for more than a year. Methods: This was a prospective case-control study involving healthy volunteers: 34 women using for more than a year a COCP with hormone-free interval (HFI) were compared to 36 normo-ovulatory, age-matched controls who had not used hormonal contraception within the last year. Volunteers using a COCP underwent a 3D ultrasound examination and had a blood sample taken within the first 4 days of active pill ingestion and those in the control group had the scan and blood test in the early follicular phase (days 2-5) of menstrual cycle. The main outcome measure was the difference in antral follicle counts stratified according to size and anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2) levels. Results: There were no significant differences in the number of small antral follicles measuring 2-6 mm. The COCP group had significantly fewer antral follicles measuring ≥ 6 mm (P < 0.001) and had significantly smaller ovaries (P < 0.001), which also had lower vascular indices than the control group (P < 0.05). While serum FSH, LH and E2 levels were significantly lower in the COCP group (P < 0.05), there was no significant difference in serum AMH levels between the two groups. Conclusions: Prolonged use of COCP suppressed pituitary gonadotropins and antral follicle development beyond 6 mm, but had no effect on levels of serum AMH and number of small antral follicles. [ABSTRACT FROM AUTHOR]

Objective: To compare the reliability of our recently introduced technique for first-trimester embryo volume measurement, the 'semiautomated technique' using both Virtual Organ Computer-aided AnaLysis (VOCAL(™) ) and Sonography-based Automated Volume Count (SonoAVC) with a manual technique using VOCAL alone. Methods: Seventy-four subjects with viable, singleton first-trimester in-vitro fertilization (IVF) pregnancies were recruited. Each subject underwent transvaginal sonography, at which a three-dimensional ultrasound dataset of the entire gestational sac was acquired. Each embryo volume was measured by two techniques, each performed twice. In the semiautomated technique VOCAL was used to calculate the volume of the gestational and yolk sacs, and SonoAVC was used to quantify the fluid volume within the amniotic and extra-amniotic cavities. Embryo volume was calculated by subtracting the sum of yolk sac, amniotic and extra-amniotic fluid volumes from gestational sac volume. In the manual technique, VOCAL was used to delineate the entire embryo using 9° rotations. Reliability was assessed using limits of agreement and intraclass correlation coefficient. Results: Datasets were included from 52 eligible subjects. Median gestational age was 7 + 4 weeks; median crown-rump length (CRL) was 13 (range, 2-29) mm; and median embryo volume was 1.8 (range, 0.03-8.1) cm(3) using the semiautomated technique and 0.7 (range 0.009-3.6) cm(3) using the manual technique. There was a significant discrepancy in the volumes measured by the two different techniques. Assessment of the limits of agreement suggested that the semiautomated technique (-15.8% to 14.0% of the mean embryo volume) was more reliable than was the manual technique (-22.4% to 26.6%). Conclusion: The semiautomated technique is more reliable than is the manual technique for embryo volume measurement. However, the discrepancy in measurements between the two methods raises concerns over the validity of the semiautomated technique that require further investigation. [ABSTRACT FROM AUTHOR]

Objective: To assess the reliability of automated measurements of the total antral follicle count (AFC) made using Sono-Automatic Volume Count (SonoAVC), and to compare these to two-dimensional (2D) and manual three-dimensional (3D) techniques. Methods: Fifty-five subjects aged under 40 years who had 3D transvaginal ultrasound examination in the early follicular phase of their menstrual cycle were prospectively recruited. 3D datasets were acquired and subsequently analyzed. The total AFC (2-10 mm antral follicles) was calculated by two observers using three independent methods: 2D real-time equivalent (2D-RTE), 3D manual multiplanar view (3D-MPV), and SonoAVC. For measurements made using SonoAVC, the initial automated count (sAVC-AA) was recorded and postprocessing (sAVC-PP) then applied to identify follicles that had been missed or incorrectly included. Intraclass correlation and limits of agreement were used to evaluate the methods. Results: The intra- and interobserver reliability of measurements of total AFC was best with SonoAVC with postprocessing followed by 3D-MPV and 2D-RTE. The initial count calculated by sAVC-AA missed follicles and this was reflected in the significantly lower mean total AFC (6.51 +/- 4.79) than that made after postprocessing techniques (sAVC-PP, 18.42 +/- 10.53, P < 0.001; 3D-MPV, 19.38 +/- 10.85, P < 0.001; and 2D-RTE, 19.26 +/- 10.55, P < 0.001). The mean total AFC became more comparable with postprocessing (sAVC-PP) but still remained significantly lower than counts made with 2D-RTE and 3D-MPV (P < 0.05). Conclusion: SonoAVC with postprocessing is a reliable method for measuring total AFC. It takes longer to perform, because of the need for postprocessing, and obtains values that are lower than those obtained by the 2D and 3D-MPV techniques. However, the AFC obtained by sAVC-PP is likely to be lower because this method measures and color codes each follicle preventing recounting. [ABSTRACT FROM AUTHOR]

In women there is a gradual rise in the basal level of follicle stimulating hormone (FSH) in the years prior to the menopause (pre-menopause) which is thought to be due to a relative lack of ovarian factors reflecting the number of antral follicles present in the ovaries. Experimental animal models for this phenomenon, particularly in mono-ovulatory species, have been lacking due to most animals; relatively short life span. We have available a group of experimental ewes in which the right ovary was removed and the left ovary was autotransplanted to the neck at least 10 years previously, which have been maintained in good health until an age of 12-13 years. Two experiments were conducted with these animals to determine the endocrine and follicular effects of age: a retrospective experiment in the same Finn-Merino ewes (n= 5) when the animals were 6-7 or 12-13 years of age; and a cohort experiment in old (12-13 years, n = 6) and young (2 years, n = 5) ewes of the same breed. In both retrospective and cohort experiments, the concentrations of FSH were significantly higher (P < 0.05) in older animals during the luteal phase when oestradiol secretion was low. This increase in FSH was associated with a decrease in the concentration of inhibin A (P < 0.05) in older animals in both the follicular and luteal stages of the cycle but the concentrations of oestradiol were similar between ages. Although there were significantly fewer antral follicles P < 0.05) available for development in older ewes during the early luteal phase of the cycle, the ovulation rate was similar to that observed in younger animals (2.0 ± 0 vs 2.0 ± 4; P > 0.05) but the interval from luteal regression to the onset of the LH surge was lower (P < 0.05) in older animals. In conclusion, the endocrine changes associated with increasing reproductive age in sheep are therefore similar to those observed in women, suggesting that the sheep could be a useful animal model to study the effect of age on human fertility. [ABSTRACT FROM PUBLISHER]

A California-sponsored, 18-month, tobacco-free intervention in residential substance use disorder (SUD) programs was associated with increases in tobacco-free grounds and tobacco-related client services. The current study examined whether positive results would be replicated in 11 programs participating subsequently. Program directors ( N  = 11) completed surveys of tobacco-related policies pre- and post-intervention. Pre- ( n  = 163) and post-intervention ( n  = 128) cross-sectional staff surveys examined tobacco-related training, beliefs, practices, smoking policy, and smoking status. Directors reported increases in tobacco-free grounds (from 3 to 8 programs), tobacco-related staff training (1 to 10 programs), tobacco cessation staff services (1 to 9 programs) and nicotine replacement therapy (NRT) provision (6 to 10 programs). At post-intervention, staff were more likely to report smoke-free workplaces ( p  = 0.008), positive beliefs about treating tobacco use ( p  = 0.017) and less likely to report current smoking ( p  = 0.003). Clinical staff were more likely to report tobacco-related training receipt ( p  = 0.001), program-level NRT provision ( p  = 0.009) and conducting tobacco-related client services ( p  < 0.0001) post-intervention. Findings of increases in tobacco-free grounds and tobacco cessation client services corroborated prior results. These and the additional finding of decreases in staff smoking strengthen evidence that initiatives supporting tobacco-free policies can be successfully implemented in SUD treatment.

Introduction: Polycystic ovary syndrome (PCOS) seems to be associated with increased ovarian sympathetic nerve activity and in rodent models of PCOS reducing the sympathetic drive to the ovary, through denervation or neuromodulation, improves ovulation rate. We hypothesised that sympathetic nerves work with gonadotropins to promote development and survival of small antral follicles to develop a polycystic ovary phenotype., Methods: Using a clinically realistic ovine model we showed a rich sympathetic innervation to the normal ovary and reinnervation after ovarian transplantation. Using needlepoint diathermy to the nerve plexus in the ovarian vascular pedicle we were able to denervate the ovary resulting in reduced intraovarian noradrenaline and tyrosine hydroxylase immunostained sympathetic nerves. We developed an acute polycystic ovary (PCO) model using gonadotrophin releasing hormone (GnRH) agonist followed infusion of follicle stimulating hormone (FSH) with increased pulsatile luteinising hormone (LH). This resulted in increased numbers of smaller antral follicles in the ovary when compared to FSH infusion suggesting a polycystic ovary., Results: Denervation had no effect of the survival or numbers of follicles in the acute PCO model and did not impact on ovulation, follicular and luteal hormone profiles in a normal cycle., Discussion: Although the ovary is richly inervated we did not find evidence for a role of sympathetic nerves in ovarian function or small follicle growth and survival., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Duncan, Nicol, O’Hare, Witherington, Miranda, Campbell, Thomas and Rae.)

Tobacco-related morbidity and mortality disproportionately affect people with substance use disorders (SUD). Encouraging overall wellness may support tobacco use cessation. We investigated relationships between wellness (health status, physical activity, sugar-sweetened beverage (SSB) consumption), cigarette smoking, and smoking cessation among SUD treatment patients to inform clinical care. Cross-sectional surveys were conducted with 395 patients in 20 California residential SUD programs. Using multivariate regression, we examined associations between smoking status and wellness. Among smokers, we examined associations between lifetime smoking exposure, cessation behaviors and attitudes, and wellness. Compared to nonsmokers (n = 121), smokers (n = 274) reported more SSB consumption, poorer physical health, and more respiratory symptoms. Among smokers, SSB consumption and respiratory symptoms increased per ten pack-years of smoking. Smokers with respiratory symptoms reported higher motivation to quit and more use of nicotine replacement therapy (NRT). Smokers with more days of poor mental health reported lower motivation to quit. Overall, cigarette smoking was associated with other health-risk behaviors among SUD treatment patients. Respiratory symptoms may increase, and poor mental health may decrease, SUD patients' intent to quit smoking. To reduce chronic disease risk among SUD patients, treatment programs should consider promoting overall wellness concurrently with smoking cessation.

Background: Smoking prevalence is high among people in substance use disorder (SUD) treatment, and program interventions to address smoking are often complex and lengthy. This cluster-randomized trial tested whether a brief multi-component intervention impacted tobacco outcomes among staff and clients., Methods: Seven SUD treatment programs were randomly assigned to the multi-component intervention or to waitlist control. The 6-month intervention included a leadership motivation assessment, program incentives, 4 staff training sessions and a leadership learning community session. Survey data were collected from staff and clients at pre- and post-intervention. Outcomes were first compared across condition (intervention vs waitlist control), and then examined pre- to post-intervention with condition collapsed., Results: Staff in the intervention (n = 48) and control conditions (n = 26) did not differ at post-intervention on smoking prevalence, self-efficacy to help clients quit, or practices used to help clients quit smoking. Intervention clients (n = 113) did not differ from controls (n = 61) in smoking prevalence or receipt of tobacco services. Pre-post comparisons collapsed across condition showed a decrease in client and staff smoking prevalence, which could not be attributed to the intervention, and a decrease in client receipt of cessation medication., Conclusion: The brief multi-component intervention did not support changes in smoking prevalence or in tobacco-related services received by clients. Other intervention features are needed to reduce smoking among SUD clients., Trial Registration: Randomization occurred at the program level and outcomes measured are program-level measures. Accordingly, the trial is not registered., (© 2023. The Author(s).)

Introduction: Interest in wellness interventions in substance use disorder (SUD) treatment is growing although evidence remains limited. This study evaluated nutrition, physical activity, nutrition and physical activity counseling, and relationships of counseling with wellness behavior before and after a wellness-oriented, tobacco-free policy intervention in 17 residential SUD programs., Methods: Clients completed cross-sectional surveys reporting sugar-sweetened beverage consumption, physical activity, and receipt of nutrition and physical activity counseling before (n= 434) and after (n = 422) an 18-month intervention. Multivariable regression models assessed pre-post-intervention differences in these variables and examined associations of nutrition counseling with sugar-sweetened beverage consumption and physical activity counseling with physical activity., Results: Post-intervention clients were 83% more likely than pre-intervention clients to report nutrition counseling (p = 0.024). There were no pre-post- differences for other variables. Past week sugar-sweetened beverage consumption was 22% lower among clients reporting nutrition counseling than for those who did not (p = 0.008) and this association did not vary by time (pre/post). There was a significant interaction of physical activity counseling receipt by time on past week physical activity (p = 0.008). Pre-intervention clients reporting physical activity counseling had 22% higher physical activity than those who did not; post-intervention clients reporting physical activity counseling had 47% higher physical activity., Conclusion: A wellness policy intervention was associated with increased nutrition counseling. Nutrition counseling predicted lower sugar-sweetened beverage consumption. Physical activity counseling predicted higher physical activity, an association that was greater post-intervention. Adding wellness components to tobacco-related interventions may promote health among SUD clients., Competing Interests: None., (© 2023 The Authors. Published by Elsevier B.V.)

Targeted therapies for cancers have improved primary tumor response rates, but concomitantly, brain metastases (BM) have become the most common brain tumors in adults and are associated with a dismal prognosis of generally less than 6 months, irrespective of the primary cancer type. They most commonly occur in patients with primary breast, lung, or melanoma histologies; however, they also appear in patients with other primary cancers including, but not limited to, prostate cancer, colorectal cancer, and renal cell carcinoma. Historically, molecular biomarkers have normally been identified from primary tumor resections. However, clinically informative genomic alterations can occur during BM development and these potentially actionable alterations are not always detected in the primary tumor leading to missed opportunities for effective targeted therapy. The molecular mechanisms that facilitate and drive metastasis to the brain are poorly understood. Identifying the differences between the brain and other extracranial sties of metastasis, and between primary tumors and BM, is essential to improving our understanding of BM development and ultimately patient management and survival. In this review, we present the current data on the genomic landscape of BM from various primary cancers which metastasize to the brain and outline potential mechanisms which may play a role in promoting the formation of the distant metastases in the brain.

Background: Disease recurrence is common following prostatectomy in patients with localised prostate cancer with high-risk features. Although androgen deprivation therapy increases the rates of organ-confined disease and negative surgical margins, there is no significant benefit on disease recurrence. Multiple lines of evidence suggest that (Fibroblast Growth Factor/Fibroblast Growth Factor Receptor) FGF/FGFR-signalling is important in supporting prostate epithelial cell survival in hostile conditions, including acute androgen deprivation. Given the recent availability of oral FGFR inhibitors, we investigated whether combination therapy could improve tumour response in the neo-adjuvant setting., Methods: We conducted an open label phase II study of the combination of erdafitinib (3 months) and androgen deprivation therapy (4 months) in men with localised prostate cancer with high-risk features prior to prostatectomy using a Simon's 2 stage design. The co-primary endpoints were safety and tolerability and pathological response in the prostatectomy specimen. The effect of treatment on residual tumours was explored by global transcriptional profiling with RNA-sequencing., Results: Nine patients were enrolled in the first stage of the trial. The treatment combination was poorly tolerated. Erdafitinib treatment was discontinued early in six patients, three of whom also required dose interruptions/reductions. Androgen deprivation therapy for 4 months was completed in all patients. The most common adverse events were hyperphosphataemia, taste disturbance, dry mouth and nail changes. No patients achieved a complete pathological response, although patients who tolerated erdafitinib for longer had smaller residual tumours, associated with reduced transcriptional signatures of epithelial cell proliferation., Conclusions: Although there was a possible enhanced anti-tumour effect of androgen deprivation therapy in combination with erdafitnib in treatment naïve prostate cancer, the poor tolerability in this patient population prohibits the use of this combination in this setting., (Copyright © 2022. Published by Elsevier Inc.)

Introduction: Implementing tobacco-free policies in substance use disorders (SUD) treatment may reduce tobacco-related, health disparities. This study examined adoption of tobacco-related policy and practices in six residential programs participating in a California-sponsored, 18-month, tobacco-free policy intervention., Methods: Directors (N=6) completed surveys of tobacco-related policies before and after the intervention. Staff completed cross-sectional surveys assessing tobacco-related training, beliefs, practices, workplace smoking policy, tobacco cessation program services, and smoking status pre- (n=135) and post-intervention (n=144)., Results: Director surveys indicated no programs had tobacco-free grounds, one provided tobacco-related staff training, and two provided nicotine replacement therapy (NRT) pre-intervention. At post-intervention, 5 programs had implemented tobacco-free grounds, 6 provided tobacco cessation training, and 3 provided NRT. Across all programs, staff were more likely to report smoke-free workplaces (AOR = 5.76, 95% CI1.14,29.18) post- versus pre-intervention. Staff positive beliefs towards addressing tobacco use were higher post-intervention (p<0.001). Odds of clinical staff reporting tobacco-related training participation (AOR = 19.63, 95% CI14.21,27.13) and program-level provision of NRT (AOR = 4.01, 95% CI 1.54, 10.43) increased post- versus pre-intervention. Clinical staff reporting they provided tobacco cessation services were also higher post-intervention (p= 0.045). There were no changes in smoking prevalence or quit intention among smoking staff., Conclusion: A tobacco-free policy intervention in SUD treatment was associated with implementation of tobacco-free grounds, tobacco-related training among staff, more positive staff beliefs towards and delivery of tobacco cessation services to clients. The model may be improved with greater emphasis on staff policy awareness, facilitating availability of NRT, and reducing staff smoking., Competing Interests: The authors state that they have no conflicts of interest., (© 2022 The Authors. Published by Elsevier B.V.)

Prostate cancer (PCa) is a hormone driven cancer, characterised by defects in androgen receptor signalling which drive the disease process. As such, androgen targeted therapies have been the mainstay for PCa treatment for over 70 years. High-risk PCa presents unique therapeutic challenges, namely in minimising the primary tumour, and eliminating any undetected micro metastases. Trials of neoadjuvant androgen deprivation therapy aim to address these challenges. Patients typically respond well to neoadjuvant treatment, showing regression of the primary tumour and negative surgical margins at the time of resection, however the majority of patients relapse and progress to metastatic disease. The mechanisms affording this resistance are largely unknown. This commentary attempts to explore theories of resistance more broadly, namely, clonal evolution, cancer stem cells, cell persistence, and drug tolerance. Moreover, it aims to explore the application of these theories in the PCa setting. This commentary also highlights the distinction between castration resistant PCa, and neoadjuvant resistant disease, and identifies the markers and characteristics of neoadjuvant resistant disease presented by current literature.

Background: Co-use of tobacco and cannabis has been associated with greater dependence on and lower quit rates for both substances. Tobacco/cannabis co-use among individuals with substance use disorders (SUDs), a population with high rates of cigarette smoking, may hinder the effectiveness of smoking cessation interventions. We examined rates of lifetime (i.e., ever vs. never) cannabis use among current cigarette smokers in SUD treatment, and we identified the subgroup who had used tobacco and cannabis together in the form of blunts and/or spliffs. We then examined variables associated with lifetime use of blunts and/or spliffs., Methods: We surveyed 562 clients in 20 residential SUD treatment programs in California, USA, in 2019. Measures included demographics, lifetime use of any cannabis product, lifetime use of blunt/spliffs, patterns of tobacco use, and smoking cessation-related questions. We asked current cigarette smokers who also reported lifetime cannabis use whether they had ever used blunts and/or spliffs. We then assessed relationships of demographic, tobacco use, use of cannabis/tetrahydrocannabinol (THC) in e-cigarettes/vape pens, and smoking cessation-related variables with ever use versus never use of blunts/spliffs., Results: Among 340 current cigarette smokers, 93.2% (n = 317) reported lifetime use of any cannabis product. Among current cigarette smokers with lifetime cannabis use, 64.4% reported lifetime blunt/spliff use. Compared to those who had never used blunts/spliffs, lifetime blunt/spliff users were more likely to be younger (OR = 0.93, 95% CI 0.90-0.95), more likely to report lifetime use of cigars/cigarillos (OR = 2.95, CI 1.37-6.32), and to have ever used cannabis/THC in e-cigarettes/vape pens (OR = 4.26, CI 1.54-11.80). They were less often ready to quit smoking within 30 days (OR = 0.37, CI 0.23-0.60), but more likely to want help with smoking cessation (OR = 2.39, CI 1.52-3.77)., Conclusion: Current cigarette smokers in SUD treatment reported a high prevalence of lifetime cannabis use. Smokers with a history of blunt/spliff use were more likely to report lifetime use of e-cigarettes/vape pens for cannabis/THC delivery. They wanted help to quit smoking, but felt less prepared to quit in the next 30 days. Cannabis co-use may warrant clinicians' attention when providing smoking cessation interventions during SUD treatment., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Natriuretic peptides (NPs) have been reported to have critical roles in follicular development and oocyte maturation in rodents. This study aimed to extend our current understanding of NP-mediated signalling pathways and mechanisms of action in the follicles of a monovulatory species. Ovine granulosa cells (GCs) and theca cells (TCs) were cultured under conditions designed to allow gonadotrophin-stimulated cell differentiation. Gene expression analysis was performed by qualitative (q)PCR for NPs and NPRs (between 16 and 96 h of culture) and VEGF120 and VEGF164 (between 16 and 144 h of culture). A qualitative analysis of the production of NP/NPR family members and NP ligand/receptor associations was carried out utilising a highly sensitive immunological approach known as 'proximity ligation assay' (PLA). All NPRs were observed in GCs, while NPRA was absent in TCs. In GCs, gene expression of NPRA, NPRB and NPRC was apparent but only active BNP and CNP and not ANP, were detected. Also in GCs, ANP but not CNP was able to significantly (P < 0.05) reduce oestradiol and increase (P < 0.05) progesterone. Inhibition of VEGF164 by ANP and CNP (P < 0.01) after 48 h of culture preceded up-regulation of VEGF120 by ANP (P < 0.01) after 144 h, but not CNP. Taken together, these findings appear to demonstrate that NP responsiveness in the GC compartment of sheep follicles is multi-facilitated, utilising both autocrine and paracrine stimulation pathways.

The aim was to define the pattern and physiological concentrations of FSH and LH required for the selection of a single dominant follicle in mono-ovulatory species. A series of five experiments was carried out using gonadotrophin-releasing hormone agonist-induced hypogonadal heifers. Animals were infused with different patterns of either FSH and/or LH followed by an ovulatory dose of human chorionic gonadotrophin. Follicular response was monitored by ultrasound scanning and blood samples were collected to measure concentrations of FSH, LH, oestradiol and progesterone. The main findings were: (1) physiological concentrations of FSH given as a continuous infusion and for an adequate duration, in the presence of basal LH, with or without LH pulses, are capable of inducing a superovulatory response, (2) initial exposure to FSH followed by LH pulses alone stimulate the development of multiple preovulatory follicles, confirming that ovarian follicles are capable of transferring dependence on gonadotrophins from FSH to LH, (3) while LH pulses appear not to have a major effect on the pattern of preovulatory follicle development, adequate LH pulsatile support is required for full oestradiol synthesis and (4) the duration of initial exposure to FSH and the ability to transfer the dependence from FSH to LH are critical for the selection of a single dominant follicle. In conclusion, this experimental series confirms that the duration of initial exposure to FSH and the ability of the selected follicle to transfer its gonadotrophic dependence from FSH to LH are critical for the selection of a single dominant follicle in cattle.

Introduction: We examined rates of use, health risk perceptions and reasons for use of combustible and non-combustible tobacco products among clients enrolled in addictions treatment across the United States., Methods: Participants (N = 1153) completed tobacco use surveys and rated health risk perception of all products. Users of non-cigarette products reported their main reason for use of each product. Logistic regression analyses examined associations between health risk perceptions and product use, including combustible cigarette use, and between reasons for use and non-cigarette product use., Results: Cigarette smoking was reported by 77.5%, followed by use of e-cigarettes (26.6%), little filtered cigars (LFCs)/cigarillos (15.4%), smokeless tobacco (11.4%), and cigars (8.4%). Lower perceived health risk of cigarettes was associated with smoking cigarettes (OR = 0.985, 95% CI: 0.975-0.995, p = 0.005). Lower perceived health risk of e-cigarettes was associated with e-cigarette use (OR = 0.991, 95% CI: 0.984-0.998, p = 0.023). Users of cigars and users of LFC/cigarillos (versus other product use) were more likely to report their main reason for use as "enjoying flavor/ taste", and smokeless tobacco users were more likely to report "at times when can't smoke" as their main reason for use compared with other reasons. E-cigarette users were more likely to report to "reduce/quit cigarettes" as their main reason for use as compared to all other reasons except "reduce health risk"., Conclusion: Treating smoking in addictions treatment should assess all tobacco product use, accuracy of health risk perceptions, and use of e-cigarettes to reduce/quit smoking, in order to promote cessation of combustible tobacco., (Copyright © 2018 Elsevier Ltd. All rights reserved.)