Controlling a new plasma regime.

Success of the UK's Spherical Tokamak for Energy Production (STEP) programme requires a robust plasma control system. This system has to guide the plasma from initiation to the burning phase, maintain it there, produce the desired fusion power for the desired duration and then terminate the plasma safely. This has to be done in a challenging environment with limited sensors and without overloading plasma-facing components. The plasma parameters and the operational regime in the STEP prototype will be very different from tokamaks, which are presently in operation. During fusion burn, the plasma regime in STEP will be self-organizing, adding further complications to the plasma control system design. This article describes the work to date on the design of individual controllers for plasma shape and position, magneto hydrodynamic instabilities, heat load and fusion power. Having studied 'normal' operation, the article discusses the philosophy of how the system will handle exceptions, when things do not go exactly as planned. This article is part of the theme issue 'Delivering Fusion Energy - The Spherical Tokamak for Energy Production (STEP)'.

Relationship Between Extreme Rainfall Occurrences and Galactic Cosmic Rays over Natal/RN, Brazil: A Case Study.

The increase in Galactic Cosmic Rays (GCR) flux intensity induces the Condensation Nuclei (CN) production, which intensifies rainfall occurrences. Then, the objective of this study was to analyze the rainfall distribution in the NEB and the impact of GCR flux on extreme rainfall events occurred in July 1998 in Natal/RN, Brazil. We used historical rainfall, Sea Surface Temperature (SST) and GCR flux data for Natal/RN. We used R software for statistical analysis. The results indicate that the GCR flux is important for intensifying extremes rainfall occurrences. This fact is observed when analyzing the relationship between rainfall greater than 10 mm and GCR flux above 6,390 counts/min. Pearson correlation coefficient between rainfall and GCR flux was 0.94 (p-value = 0.0005) and SST was -0.76 (p-value = 0.0263), both statistically significant. The rate between GCR flux and rainfall was +2.87 mm/count/min, while the rate between SST and rainfall was -7.91 mm/°C. The variance proportion explained by regression was 94.41%, with relative importance degree corresponding to 62.0% for GCR flux and 32.4% for SST, respectively. The results show that GCR flux had a greater contribution to extreme rainfall occurrence in the metropolitan region of Natal/RN and it is important in climatological studies.

Genome sequencing reveals underdiagnosis of primary ciliary dyskinesia in bronchiectasis.

BACKGROUND: Bronchiectasis can result from infectious, genetic, immunological and allergic causes. 60-80% of cases are idiopathic, but a well-recognised genetic cause is the motile ciliopathy, primary ciliary dyskinesia (PCD). Diagnosis of PCD has management implications including addressing comorbidities, implementing genetic and fertility counselling and future access to PCD-specific treatments. Diagnostic testing can be complex; however, PCD genetic testing is moving rapidly from research into clinical diagnostics and would confirm the cause of bronchiectasis. METHODS: This observational study used genetic data from severe bronchiectasis patients recruited to the UK 100,000 Genomes Project and patients referred for gene panel testing within a tertiary respiratory hospital. Patients referred for genetic testing due to clinical suspicion of PCD were excluded from both analyses. Data were accessed from the British Thoracic Society audit, to investigate whether motile ciliopathies are underdiagnosed in people with bronchiectasis in the UK. RESULTS: Pathogenic or likely pathogenic variants were identified in motile ciliopathy genes in 17 (12%) out of 142 individuals by whole-genome sequencing. Similarly, in a single centre with access to pathological diagnostic facilities, 5-10% of patients received a PCD diagnosis by gene panel, often linked to normal/inconclusive nasal nitric oxide and cilia functional test results. In 4898 audited patients with bronchiectasis, <2% were tested for PCD and <1% received genetic testing. CONCLUSIONS: PCD is underdiagnosed as a cause of bronchiectasis. Increased uptake of genetic testing may help to identify bronchiectasis due to motile ciliopathies and ensure appropriate management.

Magseed localisation of non-palpable breast lesions: experience from a single centre.

AIM: To prospectively analyse patients undergoing magnetic seed (Magseed) localisation (MSL) to evaluate the outcome, and to retrospectively compare re-excision rates for MSL with previous wire-guided localisation (WGL) to assess the hypothesis that the introduction of MSL may lead to a lower re-excision rate. MATERIALS AND METHODS: MSL commenced at University Hospital Crosshouse in December 2017. No other changes were made to radiological or surgical practice during this time. Data were collected prospectively on all patients undergoing MSL between December 2017 and December 2019, in a single breast unit. Data were gathered retrospectively on patients who had undergone localised breast procedures between January 2016 and December 2019 for comparison of re-excision rates. RESULTS: Two hundred and fifty-five patients underwent MSL surgery between December 2017 and December 2019. Of those, 98% (n=250) patients underwent successful MSL at the first attempt. The Magseed was identified intraoperatively in 100% patients and surgical excision was performed. The re-excision rate reduced from 18.9% in 2016/2017, to 11.6% in 2018/2019 (p=0.098). CONCLUSION: In conclusion, Magseed localisation has proved to be a safe and effective way of localising breast lesions, with the advantage of high accuracy. The reduction in re-excision rates at University Hospital Crosshouse with the introduction of Magseed® localisation is a potential benefit, which requires further study.

Improved Constraints on Primordial Gravitational Waves using Planck, WMAP, and BICEP/Keck Observations through the 2018 Observing Season.

We present results from an analysis of all data taken by the BICEP2, Keck Array, and BICEP3 CMB polarization experiments up to and including the 2018 observing season. We add additional Keck Array observations at 220 GHz and BICEP3 observations at 95 GHz to the previous 95/150/220 GHz dataset. The Q/U maps now reach depths of 2.8, 2.8, and 8.8 µK_{CMB} arcmin at 95, 150, and 220 GHz, respectively, over an effective area of ≈600 square degrees at 95 GHz and ≈400 square degrees at 150 and 220 GHz. The 220 GHz maps now achieve a signal-to-noise ratio on polarized dust emission exceeding that of Planck at 353 GHz. We take auto- and cross-spectra between these maps and publicly available WMAP and Planck maps at frequencies from 23 to 353 GHz and evaluate the joint likelihood of the spectra versus a multicomponent model of lensed ΛCDM+r+dust+synchrotron+noise. The foreground model has seven parameters, and no longer requires a prior on the frequency spectral index of the dust emission taken from measurements on other regions of the sky. This model is an adequate description of the data at the current noise levels. The likelihood analysis yields the constraint r_{0.05}<0.036 at 95% confidence. Running maximum likelihood search on simulations we obtain unbiased results and find that σ(r)=0.009. These are the strongest constraints to date on primordial gravitational waves.

Norwich COVID-19 testing initiative pilot: evaluating the feasibility of asymptomatic testing on a university campus.

BACKGROUND: There is a high prevalence of COVID-19 in university-age students, who are returning to campuses. There is little evidence regarding the feasibility of universal, asymptomatic testing to help control outbreaks in this population. This study aimed to pilot mass COVID-19 testing on a university research park, to assess the feasibility and acceptability of scaling up testing to all staff and students. METHODS: This was a cross-sectional feasibility study on a university research park in the East of England. All staff and students (5625) were eligible to participate. All participants were offered four PCR swabs, which they self-administered over two weeks. Outcome measures included uptake, drop-out rate, positivity rates, participant acceptability measures, laboratory processing measures, data collection and management measures. RESULTS: 798 (76%) of 1053 who registered provided at least one swab; 687 (86%) provided all four; 792 (99%) of 798 who submitted at least one swab had all negative results and 6 participants had one inconclusive result. There were no positive results. 458 (57%) of 798 participants responded to a post-testing survey, demonstrating a mean acceptability score of 4.51/5, with five being the most positive. CONCLUSIONS: Repeated self-testing for COVID-19 using PCR is feasible and acceptable to a university population.

New Measurement of

Carbon and oxygen burning reactions, in particular, ^{12}C+^{12}C fusion, are important for the understanding and interpretation of the late phases of stellar evolution as well as the ignition and nucleosynthesis in cataclysmic binary systems such as type Ia supernovae and x-ray superbursts. A new measurement of this reaction has been performed at the University of Notre Dame using particle-γ coincidence techniques with SAND (a silicon detector array) at the high-intensity 5U Pelletron accelerator. New results for ^{12}C+^{12}C fusion at low energies relevant to nuclear astrophysics are reported. They show strong disagreement with a recent measurement using the indirect Trojan Horse method. The impact on the carbon burning process under astrophysical scenarios will be discussed.

First Direct Measurement of

Type-I x-ray bursts can reveal the properties of an accreting neutron star system when compared with astrophysics model calculations. However, model results are sensitive to a handful of uncertain nuclear reaction rates, such as ^{22}Mg(α,p). We report the first direct measurement of ^{22}Mg(α,p), performed with the Active Target Time Projection Chamber. The corresponding astrophysical reaction rate is orders of magnitude larger than determined from a previous indirect measurement in a broad temperature range. Our new measurement suggests a less-compact neutron star in the source GS1826-24.

Immune response to temperature stress in three bivalve species: Pacific oyster Crassostrea gigas, Mediterranean mussel Mytilus galloprovincialis and mud cockle Katelysia rhytiphora.

Summer mortality of some bivalve species is often associated with the change of environmental temperature. This study compares the response of immunological parameters to temperature change in three marine bivalves: Pacific oyster Crassostrea gigas, Mediterranean mussel Mytilus galloprovincialis and mud cockle Katelysia rhytiphora. Each species was exposed to three temperatures, 15 °C, 20 °C and 25 °C for 14 days. The total haemocyte count (THC), phagocytosis, reactive oxygen species (ROS) and the activity of antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT) were used as indicators to measure the response of each species to different temperatures. The highest temperature (25 °C) significantly increased the THC and phagocysis of haemocytes in all species. The SOD and CAT activities in the haemocytes of M. galloprovincialis and K. rhytiphora rapidly increased with temperature elevation, concomitantly with the increase of ROS ions. In contrast, the increases of ROS and SOD in C. gigas only occurred from 20 °C to 25 °C, suggesting that this intertidal species is more adaptive to different temperature levels. This study indicates that the activities of antioxidant enzymes can reflect the immune response of marine bivalves to thermal stress. Intertidal species such as Pacific oysters have a greater tolerance to thermal stress than subtidal species (e.g. Mediterranean mussel) and demersal species buried in sand (e.g. cockle).

Identification of pathological complete response after neoadjuvant chemotherapy for breast cancer: comparison of greyscale ultrasound, shear wave elastography, and MRI.

AIM: To assess the value of post-treatment shear-wave elastography (SWE) parameters (maximum stiffness [Emax], mean stiffness [Emean], and standard deviation [SD]) compared to greyscale ultrasonography (US) and magnetic resonance imaging (MRI) in identifying pathological complete response (pCR) to neoadjuvant chemotherapy (NACT) in breast cancer. MATERIALS AND METHODS: In a prospective cohort study, 80 patients receiving NACT for breast cancer underwent baseline and post-treatment US, SWE, and MRI examinations. Four SWE images in two orthogonal planes were obtained. Maximum greyscale US diameter and maximum diameter of lesion enhancement on MRI were measured. Percentage reductions between baseline and post-treatment scans were calculated for MRI and greyscale US diameter, and Emean, Emax, and SD. The percentage reduction in Emean and US diameter were also analysed as a combination. Analysis was undertaken using receiver operating characteristic (ROC) curves and the chi-squared test. RESULTS: pCR occurred in 21 of 80 (26%) women. The area under the ROC curve (AUC) for pCR of percentage reductions in Emean, Emax, SD, and greyscale US diameter were 0.89, 0.85, 0.75, and 0.86, respectively. The combination of percentage reductions in Emean and greyscale ultrasound diameter yielded an AUC of 0.92, which is similar to the AUC for MRI of 0.96 (p=0.28). CONCLUSIONS: SWE combined with greyscale US shows promise for end-of-treatment identification of response to NACT in women with breast cancer, with accuracies similar to breast MRI. This technique could be used to inform surgical decision-making after NACT.

A systematic review of interventions to increase physical activity among South Asian adults.

OBJECTIVES: To identify interventions aimed at increasing physical activity (PA) levels among South Asian (SA) adults and identify the specific changes in the content and delivery mode of interventions designed to increase PA levels among SA people aged ≥18 years. DESIGN: A systematic review of quantitative studies. DATA SYNTHESIS: Extracted data were synthesized using a narrative approach. DATA SOURCES: ASSIA, CINHAL, EMBASE, Medline, SPORTDiscus and PsychINFO were searched. Included articles met the following criteria: (1) population: community-dwelling SA adults aged ≥18 years and (2) outcome: reporting determinants of PA, exercise, or a combination of the two, measured objectively or using self-report. The search was restricted to articles published in the English language up to 31 January 2017. RESULTS: Fifteen trials/programmes (16 articles) met the review criteria. The findings show that involving the target community in developing culturally appropriate interventions appears to be important in their acceptability, delivery and uptake. Using community-based participation in intervention planning, evaluation and research appears to produce culturally and linguistically tailored interventions that address core values, attitudes, beliefs and norms, and encourage participation in PA. Furthermore, the use of community health workers and underpinning the interventions with a psychological theory show promise in increasing PA uptake. CONCLUSIONS: This systematic review suggests that making cultural adaptations to PA interventions shows promise, but the evidence base presented is not strong. This does not mean that adopting such an approach is ineffective but that the evidence base is currently lacking.

A narrative meta-review of a series of systematic and meta-analytic reviews on the intervention outcome for children with developmental co-ordination disorder.

BACKGROUND: Systematic reviews and meta-analyses are considered to be the 'gold standards' for synthesizing research evidence in particular areas of enquiry. However, such reviews are only useful if they themselves are conducted to a sufficiently high standard. The aim of this study was to conduct a narrative meta-review of existing analyses of the effectiveness of interventions designed for children with developmental co-ordination disorder (DCD). METHODS: A narrative meta-review of systematic and meta-analytic reviews aimed at evaluating the effectiveness of intervention for children with DCD was conducted on studies published between 1950 and 2014. We identified suitable reviews, using a modification of the Population, Intervention, Comparison, Outcome (PICO) system and evaluated their methodological quality using the Assessment of Multiple Systematic Reviews (AMSTAR). In addition, the consistency of the quality of evidence and classification of intervention approaches was assessed independently by two assessors. RESULTS: The literature search yielded a total of four appropriate reviews published in the selected time span. The Assessment of Multiple Systematic Reviews percentage quality scores assigned to each review ranged from 0% (low quality) to 55% (medium quality). Evaluation of the quality of evidence and classification of intervention approaches yielded a discrepancy rate of 25%. All reviews concluded that some kind of intervention was better than none at all. CONCLUSIONS: Although the quality of the reviews progressively improved over the years, the shortcomings identified need to be addressed before concrete evidence regarding the best approach to intervention for children with DCD can be specified.

Robust anti-obesity and metabolic effects of a dual GLP-1/glucagon receptor peptide agonist in rodents and non-human primates.

AIMS: To characterize the pharmacology of MEDI0382, a peptide dual agonist of glucagon-like peptide-1 (GLP-1) and glucagon receptors. MATERIALS AND METHODS: MEDI0382 was evaluated in vitro for its ability to stimulate cAMP accumulation in cell lines expressing transfected recombinant or endogenous GLP-1 or glucagon receptors, to potentiate glucose-stimulated insulin secretion (GSIS) in pancreatic ß-cell lines and stimulate hepatic glucose output (HGO) by primary hepatocytes. The ability of MEDI0382 to reduce body weight and improve energy balance (i.e. food intake and energy expenditure), as well as control blood glucose, was evaluated in mouse models of obesity and healthy cynomolgus monkeys following single and repeated daily subcutaneous administration for up to 2 months. RESULTS: MEDI0382 potently activated rodent, cynomolgus and human GLP-1 and glucagon receptors and exhibited a fivefold bias for activation of GLP-1 receptor versus the glucagon receptor. MEDI0382 produced superior weight loss and comparable glucose lowering to the GLP-1 peptide analogue liraglutide when administered daily at comparable doses in DIO mice. The additional fat mass reduction elicited by MEDI0382 probably results from a glucagon receptor-mediated increase in energy expenditure, whereas food intake suppression results from activation of the GLP-1 receptor. Notably, the significant weight loss elicited by MEDI0382 in DIO mice was recapitulated in cynomolgus monkeys. CONCLUSIONS: Repeated administration of MEDI0382 elicits profound weight loss in DIO mice and non-human primates, produces robust glucose control and reduces hepatic fat content and fasting insulin and glucose levels. The balance of activities at the GLP-1 and glucagon receptors is considered to be optimal for achieving weight and glucose control in overweight or obese Type 2 diabetic patients.

Mapping and evaluation of physical activity interventions for school-aged children.

OBJECTIVES: A high degree of de-regulation, organisational fragmentation and funding cuts throughout UK schools in recent years has obscured the definitive structure and effectiveness of physical activity (PA) provision offered to children. This pilot study aimed to map the current structure and context of PA provision offered to school children in Southampton, and its alignment with existing empirical evidence about the likely effectiveness of such interventions. STUDY DESIGN: Utilising a qualitative approach, the study focused upon school-based PA provision, since this setting was conjectured to show greater diversity when compared to settings outside of school, lending itself to further interventions than non-school PA provision. METHODS: Interventions offered across nine schools (three junior, two primary, four secondary) were investigated and mapped through semi-structured interviews. Findings were benchmarked against other cities similar to Southampton in indices of multiple deprivation status via interviews with city council workers. RESULTS: Interviews highlighted only three formal PA specific interventions currently operating, and a hand full of informal interventions. Limited PA provision was attributed to a lack of time, money, and priority devoted towards PA within schools. Considerable disparity exists between the high prevalence of sport-oriented provision compared with the low prevalence of PA specific provision. Interviews with Portsmouth and Bristol city councils suggest that such findings may not be unique to Southampton. CONCLUSIONS: In contrast to the extensive literature base detailing numerous PA interventions in school-aged children, our data suggest that a very small amount of such knowledge appears to translate into PA provision offered in Southampton schools. Our data highlight a significant discrepancy between sport and PA provision across schools. It is possible that the inability to successfully differentiate between sport and PA may present a further obstacle to the successful uptake of PA in the future. An extension of the PA mapping carried out, both countywide and nationally, provides a possible avenue for future research to confirm or contrast these initial insights.

Component reductions in oxygen delivery generate variable haemodynamic and stress hormone responses.

BACKGROUND: In clinical practice, global oxygen delivery (DO2) is often considered as a whole; however pathological and adaptive responses after a decrease in individual constituents of the DO2 equation (cardiac output, haemoglobin, oxyhaemoglobin saturation) are likely to be diverse. We hypothesized that an equivalent decrease in DO2 after reductions in each separate component of the equation would result in different haemodynamic, tissue oxygenation, and stress hormonal responses. METHODS: Anaesthetized, fluid-resuscitated male Wistar rats were subjected to circulatory, anaemic, or hypoxic hypoxia (by haemorrhage, isovolaemic haemodilution, and breathing a hypoxic gas mix, respectively), produced either rapidly over 5 min or graded over 30 min, to a targeted 50% decrease in global oxygen delivery. Sham-operated animals acted as controls. Measurements were made of haemodynamics, skeletal muscle tissue oxygen tension, blood gas analysis, and circulating stress hormone levels. RESULTS: Whereas haemorrhage generated the largest decrease in cardiac output, and the greatest stress hormone response, haemodilution had the most marked effect on arterial pressure. In contrast, rapid hypoxaemia produced a minor impact on global haemodynamics yet induced the greatest decrease in regional oxygenation. A greater degree of hyperlactataemia was observed with graded insults compared with those administered rapidly. CONCLUSIONS: Decreasing global oxygen delivery, achieved by targeted reductions in its separate components, induces varying circulatory, tissue oxygen tension, and stress hormone responses. We conclude that not all oxygen delivery is the same; this disparity should be emphasized in classical teaching and re-evaluated in patient management.

The "Lollypop" technique for polyethylene exchange in total ankle replacement.

UNLABELLED: We describe a simple technique for the removal of the polyethylene meniscus bearing surface in patients undergoing re-operation and meniscus bearing exchange following a previous total ankle replacement. LEVEL OF EVIDENCE: Level V.

MicroRNA profiling of peripheral nerve sheath tumours identifies miR-29c as a tumour suppressor gene involved in tumour progression.

BACKGROUND: Neurofibromatosis type 1 is one of the most common familial diseases, the hallmark of which is the development of multiple neurofibromas. These are benign nerve sheath tumours, which can transform into malignant peripheral nerve sheath tumours (MPNST). METHODS: The aim of this study was to identify differentially expressed microRNA (miRNA) in neurofibromas and MPNST obtained from patients with neurofibromatosis type 1 using microarray analysis. Differential expression was validated by reverse transcription quantitative-PCR, and functional studies were performed after transfection of miRNA oligonucleotide mimics into MPNST cells. RESULTS: Sixteen miRNA were significantly differentially expressed in MPNST compared with NF, and of these fourteen were downregulated in MPNST: these included miR-30e*, miR-29c*, miR-29c, miR-340*, miR-30c, miR-139-5p, miR-195, miR-151-5p, miR-342-5p, miR-146a, miR-150, miR-223, let-7 a and let-7 g with a false discovery rate of q=8.48E-03 for the least significant miRNA. In contrast, miR-210 and miR-339-5p were upregulated in MPNST compared with neurofibromas. Prediction softwares/algorithms identified a list of genes targeted by miR-29c including extracellular matrix genes and matrix metalloproteinase (MMP)-2, all of which are reported to be involved in cell migration and invasion. Functional studies in a MPNST cell line, sNF96.2, using a mimic of the mature miR-29c showed reduced invasion, whereas there was no change in proliferation. Zymography of the manipulated cells showed that MMP2 activity was also reduced when miR-29c expression was forced in sNF96.2. CONCLUSION: We provide evidence that reduction of miR-29c has a pivotal role in the progression of nerve sheath tumours and results by increasing the invasive/migratory properties of nerve sheath tumours.

Nfasc155H and MAG are specifically susceptible to detergent extraction in the absence of the myelin sphingolipid sulfatide.

Mice incapable of synthesizing the myelin lipid sulfatide form paranodes that deteriorate with age. Similar instability also occurs in mice that lack contactin, contactin-associated protein or neurofascin155 (Nfasc155), the proteins that cluster in the paranode and form the junctional complex that mediates myelin-axon adhesion. In contrast to these proteins, sulfatide has not been shown to be enriched in the paranode nor has a sulfatide paranodal binding partner been identified; thus, it remains unclear how the absence of sulfatide results in compromised paranode integrity. Using an in situ extraction procedure, it has been reported that the absence of the myelin sphingolipids, galactocerebroside and sulfatide, increased the susceptibility of Nfasc155 to detergent extraction. Here, employing a similar approach, we demonstrate that in the presence of galactocerebroside but in the absence of sulfatide Nfasc155 is susceptible to detergent extraction. Furthermore, we use this in situ approach to show that stable association of myelin-associated glycoprotein (MAG) with the myelin membrane is sulfatide dependent while the membrane associations of myelin/oligodendrocyte glycoprotein, myelin basic protein and cyclic nucleotide phosphodiesterase are sulfatide independent. These findings indicate that myelin proteins maintain their membrane associations by different mechanisms. Moreover, the myelin proteins that cluster in the paranode and require sulfatide mediate myelin-axon adhesion. Additionally, the apparent dependency on sulfatide for maintaining Nfasc155 and MAG associations is intriguing since the fatty acid composition of sulfatide is altered and paranodal ultrastructure is compromised in multiple sclerosis. Thus, our findings present a potential link between sulfatide perturbation and myelin deterioration in multiple sclerosis.

The genomic landscape of familial glioma.

Glioma is a rare brain tumor with a poor prognosis. Familial glioma is a subset of glioma with a strong genetic predisposition that accounts for approximately 5% of glioma cases. We performed whole-genome sequencing on an exploratory cohort of 203 individuals from 189 families with a history of familial glioma and an additional validation cohort of 122 individuals from 115 families. We found significant enrichment of rare deleterious variants of seven genes in both cohorts, and the most significantly enriched gene was HERC2 (P = 0.0006). Furthermore, we identified rare noncoding variants in both cohorts that were predicted to affect transcription factor binding sites or cause cryptic splicing. Last, we selected a subset of discovered genes for validation by CRISPR knockdown screening and found that DMBT1, HP1BP3, and ZCH7B3 have profound impacts on proliferation. This study performs comprehensive surveillance of the genomic landscape of familial glioma.

Activin B is produced early in antral follicular development and suppresses thecal androgen production.

Little is known about the role of activin B during folliculogenesis. This study investigated the expression levels of activin/inhibin subunits (ßA, ßB, and α), steroid enzyme, and gonadotrophin receptors in theca (TC) and granulosa cells (GC) by QPCR and activin A and B and inhibin A protein levels in follicular fluid (FF) of developing sheep follicles during estrus and anestrus. The effect of activin B on androgen production from primary TC cultures in vitro was also assessed. During folliculogenesis, in anestrus and estrus, FF activin B concentrations and thecal and GC activin ßB mRNA levels decreased as follicle diameter increased from 1-3 to >6  mm regardless of estrogenic status. Estrogenic preovulatory follicles had reduced concentrations of FF activins B and A, and TC and GCs expressed higher levels of activin ßA mRNA at 3-4  mm, and TCs more inhibin α mRNA at >4  mm stages of development compared with nonestrogenic follicles. Activin B decreased androstenedione production from primary TCs in vitro, an effect blocked by inhibin A. Thus, sheep follicles 1-3  mm in diameter contained high FF levels of activin B, which decreased as the follicle size increased, and, like activin A, suppressed thecal androgen production in vitro, an effect blocked by inhibin. Furthermore, the theca of large estrogenic follicles expressed high levels of inhibin α and activin ßA mRNA suggesting local thecal derived inhibin A production. This would inhibit the negative effects of thecal activins B and A ensuring maximum androgen production for enhanced estradiol production by the preovulatory follicle(s).