The V-ATPase/ATG16L1 axis is controlled by the V1H subunit.

Defects in organellar acidification indicate compromised or infected compartments. Recruitment of the autophagy-related ATG16L1 complex to pathologically neutralized organelles targets ubiquitin-like ATG8 molecules to perturbed membranes. How this process is coupled to proton gradient disruption is unclear. Here, we reveal that the V1H subunit of the vacuolar ATPase (V-ATPase) proton pump binds directly to ATG16L1. The V1H/ATG16L1 interaction only occurs within fully assembled V-ATPases, allowing ATG16L1 recruitment to be coupled to increased V-ATPase assembly following organelle neutralization. Cells lacking V1H fail to target ATG8s during influenza infection or after activation of the immune receptor stimulator of interferon genes (STING). We identify a loop within V1H that mediates ATG16L1 binding. A neuronal V1H isoform lacks this loop and is associated with attenuated ATG8 targeting in response to ionophores in primary murine and human iPSC-derived neurons. Thus, V1H controls ATG16L1 recruitment following proton gradient dissipation, suggesting that the V-ATPase acts as a cell-intrinsic damage sensor.

Multilayered regulation of autophagy by the Atg1 kinase orchestrates spatial and temporal control of autophagosome formation.

Autophagy is a conserved intracellular degradation pathway exerting various cytoprotective and homeostatic functions by using de novo double-membrane vesicle (autophagosome) formation to target a wide range of cytoplasmic material for vacuolar/lysosomal degradation. The Atg1 kinase is one of its key regulators, coordinating a complex signaling program to orchestrate autophagosome formation. Combining in vitro reconstitution and cell-based approaches, we demonstrate that Atg1 is activated by lipidated Atg8 (Atg8-PE), stimulating substrate phosphorylation along the growing autophagosomal membrane. Atg1-dependent phosphorylation of Atg13 triggers Atg1 complex dissociation, enabling rapid turnover of Atg1 complex subunits at the pre-autophagosomal structure (PAS). Moreover, Atg1 recruitment by Atg8-PE self-regulates Atg8-PE levels in the growing autophagosomal membrane by phosphorylating and thus inhibiting the Atg8-specific E2 and E3. Our work uncovers the molecular basis for positive and negative feedback imposed by Atg1 and how opposing phosphorylation and dephosphorylation events underlie the spatiotemporal regulation of autophagy.

Does that sound right? A novel method of evaluating models of reading aloud : Rating nonword pronunciations.

Nonword pronunciation is a critical challenge for models of reading aloud but little attention has been given to identifying the best method for assessing model predictions. The most typical approach involves comparing the model's pronunciations of nonwords to pronunciations of the same nonwords by human participants and deeming the model's output correct if it matches with any transcription of the human pronunciations. The present paper introduces a new ratings-based method, in which participants are shown printed nonwords and asked to rate the plausibility of the provided pronunciations, generated here by a speech synthesiser. We demonstrate this method with reference to a previously published database of 915 disyllabic nonwords (Mousikou et al., 2017). We evaluated two well-known psychological models, RC00 and CDP++, as well as an additional grapheme-to-phoneme algorithm known as Sequitur, and compared our model assessment with the corpus-based method adopted by Mousikou et al. We find that the ratings method: a) is much easier to implement than a corpus-based method, b) has a high hit rate and low false-alarm rate in assessing nonword reading accuracy, and c) provided a similar outcome as the corpus-based method in its assessment of RC00 and CDP++. However, the two methods differed in their evaluation of Sequitur, which performed much better under the ratings method. Indeed, our evaluation of Sequitur revealed that the corpus-based method introduced a number of false positives and more often, false negatives. Implications of these findings are discussed.

Sentiment analysis as a measure of conservation culture in scientific literature.

Culturomics is emerging as an important field within science, as a way to measure attitudes and beliefs and their dynamics across time and space via quantitative analysis of digitized data from literature, news, film, social media, and more. Sentiment analysis is a culturomics tool that, within the last decade, has provided a means to quantify the polarity of attitudes expressed within various media. Conservation science is a crisis discipline; therefore, accurate and effective communication are paramount. We investigated how conservation scientists communicate their findings through scientific journal articles. We analyzed 15,001 abstracts from articles published from 1998 to 2017 in 6 conservation-focused journals selected based on indexing in scientific databases. Articles were categorized by year, focal taxa, and the conservation status of the focal species. We calculated mean sentiment score for each abstract (mean adjusted z score) based on 4 lexicons (Jockers-Rinker, National Research Council, Bing, and AFINN). We found a significant positive annual trend in the sentiment scores of articles. We also observed a significant trend toward increasing negativity along the spectrum of conservation status categories (i.e., from least concern to extinct). There were some clear differences in the sentiments with which research on different taxa was reported, however. For example, abstracts mentioning lobe finned fishes tended to have high sentiment scores, which could be related to the rediscovery of the coelacanth driving a positive narrative. Contrastingly, abstracts mentioning elasmobranchs had low scores, possibly reflecting the negative sentiment score associated with the word shark. Sentiment analysis has applications in science, especially as it pertains to conservation psychology, and we suggest a new science-based lexicon be developed specifically for the field of conservation.

El Análisis de Opinión como Medida de la Cultura de Conservación en la Literatura Científica Lennox et al. Resumen La culturomía está emergiendo como un campo importante dentro de la ciencia pues es una manera de medir las actitudes, creencias y sus dinámicas a través del tiempo y el espacio por medio de un análisis cuantitativo de datos digitalizados a partir de la literatura, las noticias, las películas, las redes sociales y otros medios. El análisis de opinión es una herramienta de la culturomía que, en la última década, ha proporcionado los medios para cuantificar la polaridad de las actitudes expresadas en varios medios. La ciencia de la conservación es una disciplina de crisis; por lo tanto, la comunicación certera y efectiva es de suma importancia. Investigamos cómo los científicos de la conservación comunican sus hallazgos por medio de los artículos en las revistas científicas. Analizamos 15,001 resúmenes de artículos publicados entre 1998 y 2017 en seis revistas enfocadas en la conservación que fueron seleccionados con base en los índices de las bases de datos científicos. Categorizamos los artículos por año, taxón de enfoque y el estado de conservación de la especie focal. Calculamos la opinión promedio para cada resumen (puntaje z ajustado a la media) con base en cuatro lexicones (Jockers-Rinker, National Research Council, Bing y AFINN). Encontramos una significativa tendencia positiva anual en los puntajes de opinión de los artículos. También observamos una tendencia significativa hacia el incremento en la negatividad a lo largo del espectro de categorías de estado de conservación (es decir, de aquellas de menos preocupación a aquellas en peligro crítico o extintas). Sin embargo, hubo algunas diferencias claras en las opiniones con las cuales se reportaron las investigaciones sobre los diferentes taxones. Por ejemplo, los resúmenes que mencionaron a los peces de aletas lobuladas tendieron hacia los puntajes altos de opinión, lo que podría relacionarse con el redescubrimiento del celacanto como causa de una narrativa positiva. En contraste, los resúmenes que mencionaron a los elasmobranquios tuvieron puntajes bajos, lo que refleja el puntaje de opinión negativa asociado con la palabra tiburón. El análisis de opinión tiene aplicaciones en la ciencia, especialmente como parte de la psicología de la conservación, y sugerimos que se desarrolle un nuevo lexicón basado en la ciencia específicamente para el campo de la conservación.

Googling endometriosis: a systematic review of information available on the Internet.

BACKGROUND: The demand for health information online is increasing rapidly without clear governance. OBJECTIVE: We aim to evaluate the credibility, quality, readability, and accuracy of online patient information concerning endometriosis. STUDY DESIGN: We searched 5 popular Internet search engines: aol.com, ask.com, bing.com, google.com, and yahoo.com. We developed a search strategy in consultation with patients with endometriosis, to identify relevant World Wide Web pages. Pages containing information related to endometriosis for women with endometriosis or the public were eligible. Two independent authors screened the search results. World Wide Web pages were evaluated using validated instruments across 3 of the 4 following domains: (1) credibility (White Paper instrument; range 0-10); (2) quality (DISCERN instrument; range 0-85); and (3) readability (Flesch-Kincaid instrument; range 0-100); and (4) accuracy (assessed by a prioritized criteria developed in consultation with health care professionals, researchers, and women with endometriosis based on the European Society of Human Reproduction and Embryology guidelines [range 0-30]). We summarized these data in diagrams, tables, and narratively. RESULTS: We identified 750 World Wide Web pages, of which 54 were included. Over a third of Web pages did not attribute authorship and almost half the included pages did not report the sources of information or academic references. No World Wide Web page provided information assessed as being written in plain English. A minority of web pages were assessed as high quality. A single World Wide Web page provided accurate information: evidentlycochrane.net. Available information was, in general, skewed toward the diagnosis of endometriosis. There were 16 credible World Wide Web pages, however the content limitations were infrequently discussed. No World Wide Web page scored highly across all 4 domains. CONCLUSION: In the unlikely event that a World Wide Web page reports high-quality, accurate, and credible health information it is typically challenging for a lay audience to comprehend. Health care professionals, and the wider community, should inform women with endometriosis of the risk of outdated, inaccurate, or even dangerous information online. The implementation of an information standard will incentivize providers of online information to establish and adhere to codes of conduct.

Is There Asymmetry Between the Concave and Convex Pedicles in Adolescent Idiopathic Scoliosis? A CT Investigation.

BACKGROUND: Adolescent idiopathic scoliosis is a complex three-dimensional deformity of the spine characterized by deformities in the sagittal, coronal, and axial planes. Spinal fusion using pedicle screw instrumentation is a widely used method for surgical correction in severe (coronal deformity, Cobb angle > 45°) adolescent idiopathic scoliosis curves. Understanding the anatomic difference in the pedicles of patients with adolescent idiopathic scoliosis is essential to reduce the risk of neurovascular or visceral injury through pedicle screw misplacement. QUESTIONS/PURPOSES: To use CT scans (1) to analyze pedicle anatomy in the adolescent thoracic scoliotic spine comparing concave and convex pedicles and (2) to assess the intra- and interobserver reliability of these measurements to provide critical information to spine surgeons regarding size, length, and angle of projection. METHODS: Between 2007 and 2009, 27 patients with adolescent idiopathic scoliosis underwent thoracoscopic anterior correction surgery by two experienced spinal surgeons. Preoperatively, each patient underwent a CT scan as was their standard of care at that time. Twenty-two patients (mean age, 15.7 years; SD, 2.4 years; range, 11.6-22 years) (mean Cobb angle, 53°; SD, 5.3°; range, 42°-63°) were selected. Inclusion criteria were a clinical diagnosis of adolescent idiopathic scoliosis, female, and Lenke type 1 adolescent idiopathic scoliosis with the major curve confined to the thoracic spine. Using three-dimensional image analysis software, the pedicle width, inner cortical pedicle width, pedicle height, inner cortical pedicle height, pedicle length, chord length, transverse pedicle angle, and sagittal pedicle angles were measured. Randomly selected scans were remeasured by two of the authors and the reproducibility of the measurement definitions was validated through limit of agreement analysis. RESULTS: The concave pedicle widths were smaller compared with the convex pedicle widths at T7, T8, and T9 by 37% (3.44 mm ± 1.16 mm vs 4.72 mm ± 1.02 mm; p < 0.001; mean difference, 1.27 mm; 95% CI, 0.92 mm-1.62 mm), 32% (3.66 mm ± 1.00 mm vs 4.82 mm ± 1.10 mm; p < 0.001; mean difference, 1.16 mm; 95% CI, 0.84 mm-1.49 mm), and 25% (4.10 mm ± 1.57 mm vs 5.12 mm ± 1.17 mm; p < 0.001; mean difference, 1.02 mm; 95% CI, 0.66 mm-1.39 mm), respectively. The concave pedicle heights were smaller than the convex at T5 (9.43 mm ± 0.98 vs 10.63 mm ± 1.10 mm; p = 0.002; mean difference, 1.02 mm; 95% CI, 0.59 mm-1.45 mm), T6 (8.87 mm ± 1.37 mm vs 10.88 mm ± 0.81 mm; p < 0.001; mean difference, 2.02 mm; 95% CI, 1.40 mm-2.63 mm), T7 (9.09 mm ± 1.24 mm vs 11.35 mm ± 0.84 mm; p < 0.001; mean difference, 2.26 mm; 95% CI, 1.81 mm-2.72 mm), and T8 (10.11 mm ± 1.05 mm vs 11.86 mm ± 0.88 mm; p < 0.001; mean difference, 1.75 mm; 95% CI, 1.30 mm-2.19 mm). Conversely, the concave transverse pedicle angle was larger than the convex at levels T6 (11.37° ± 4.48° vs 8.82° ± 4.31°; p = 0.004; mean difference, 2.54°; 95% CI, 1.10°-3.99°), T7 (12.69° ± 5.93° vs 8.65° ± 3.79°; p = 0.002; mean difference, 4.04°; 95% CI, 1.90°-6.17°), T8 (13.24° ± 5.28° vs 7.66° ± 4.87°; p < 0.001; mean difference, 5.58°; 95% CI, 2.99°-8.17°), and T9 (19.95° ± 5.69° vs 8.21° ± 4.02°; p < 0.001; mean difference, 4.74°; 95% CI, 2.68°-6.80°), indicating a more posterolateral to anteromedial pedicle orientation. CONCLUSIONS: There is clinically important asymmetry in the morphologic features of pedicles in individuals with adolescent idiopathic scoliosis. The concave side of the curve compared with the convex side is smaller in height and width periapically. Furthermore, the trajectory of the pedicle is more acute on the convex side of the curve compared with the concave side around the apex of the curve. Knowledge of these anatomic variations is essential when performing scoliosis correction surgery to assist with selecting the correct pedicle screw size and trajectory of insertion to reduce the risk of pedicle wall perforation and neurovascular injury.

Variation in outcome reporting in endometriosis trials: a systematic review.

OBJECTIVE: We reviewed the outcomes and outcome measures reported in randomized controlled trials and their relationship with methodological quality, year of publication, commercial funding, and journal impact factor. DATA SOURCES: We searched the following sources: (1) Cochrane Central Register of Controlled Trials, (2) Embase, and (3) MEDLINE from inception to November 2014. STUDY ELIGIBILITY: We included all randomized controlled trials evaluating a surgical intervention with or without a medical adjuvant therapy for the treatment of endometriosis symptoms. STUDY DESIGN: Two authors independently selected trials, assessed methodological quality (Jadad score; range, 1-5), outcome reporting quality (Management of Otitis Media with Effusion in Cleft Palate criteria; range, 1-6), year of publication, impact factor in the year of publication, and commercial funding (yes or no). Univariate and bivariate analyses were performed using Spearman Rh and Mann-Whitney U tests. We used a multivariate linear regression model to assess relationship associations between outcome reporting quality and other variables. RESULTS: There were 54 randomized controlled trials (5427 participants), which reported 164 outcomes and 113 outcome measures. The 3 most commonly reported primary outcomes were dysmenorrhea (10 outcome measures; 23 trials), dyspareunia (11 outcome measures; 21 trials), and pregnancy (3 outcome measures; 26 trials). The median quality of outcome reporting was 3 (interquartile range 4-2) and methodological quality 3 (interquartile range 5-2). Multivariate linear regression demonstrated a relationship between outcome reporting quality with methodological quality (ß = 0.325; P = .038) and year of publication (ß = 0.067; P = .040). No relationship was demonstrated between outcome reporting quality with journal impact factor (Rho = 0.190; P = .212) or commercial funding (P = .370). CONCLUSION: Variation in outcome reporting within published endometriosis trials prohibits comparison, combination, and synthesis of data. This limits the usefulness of research to inform clinical practice, enhance patient care, and improve patient outcomes. In the absence of a core outcome set for endometriosis we recommend the use of the 3 most common pain (dysmenorrhea, dyspareunia, and pelvic pain) and subfertility (pregnancy, miscarriage, and live birth) outcomes. International consensus among stakeholders is needed to establish a core outcome set for endometriosis trials.

Development of a Reagentless Biosensor for Inorganic Phosphate, Applicable over a Wide Concentration Range.

A fluorescent reagentless biosensor for inorganic phosphate (Pi), based on the E. coli PstS phosphate binding protein, was redesigned to allow measurements of higher Pi concentrations and at low, substoichiometric concentrations of biosensor. This was achieved by weakening Pi binding of the previous biosensor, and different approaches are described that could enable this change in properties. The readout, providing response to the Pi concentration, is delivered by tetramethylrhodamine fluorescence. In addition to two cysteine mutations for rhodamine labeling at positions 17 and 197, the final variant had an I76G mutation in the hinge region between the two lobes that make up the protein. Upon Pi binding, the lobes rotate on this hinge and the mutation on the hinge lowers affinity ∼200-fold, with a dissociation constant now in the tens to hundreds micromolar range, depending on solution conditions. The signal change on Pi binding was up to 9-fold, depending on pH. The suitability of the biosensor for steady-state ATPase assays was demonstrated with low biosensor usage and its advantage in ability to cope with Pi contamination.

Preoperative assessment and diagnosis of endometriosis: are we any closer?

PURPOSE OF REVIEW: The management of endometriosis has progressed vastly with medical treatments providing a large role in controlling endometriosis symptoms. Despite these advances we still lack an accurate noninvasive test to diagnose endometriosis. This has a large role in the delay to diagnosis, management and progression of the disease amongst a population that is choosing to conceive later. RECENT FINDINGS: Endometriosis is now thought to affect 1 in 10 women with patient annual healthcare costs estimated at &OV0556;9579. The diagnosis of this disease is still delayed by an average of 6-9 years allowing disease and symptom progression. Researchers have assessed a wide variety of noninvasive markers from urinary derivatives to MRI. There has been limited success in producing a highly sensitive and specific preoperative test for endometriosis. Novel markers such as miRNA provide the most encouraging diagnostic accuracy. SUMMARY: The development of a noninvasive accurate marker for endometriosis is a research target and priority of the European Society of Human Reproduction and Embryology. The current markers in use have moderate sensitivity and sensitivity. The inflammatory basis for the disease underpins many biomarkers but also many other concomitant diseases reducing accuracy and increasing false positive results.

Review of the management of ovarian endometriosis: paradigm shift towards conservative approaches.

PURPOSE OF REVIEW: To describe the current consensus regarding the modern management of ovarian endometriosis and summarize the recent evidence that led to a shift in the management recommendations. RECENT FINDINGS: The vast majority of the recent studies demonstrate an adverse effect of surgery on ovarian reserve markers, whereas convincing evidence of a benefit of surgery on fertility outcomes is lacking. Current research is focussing on identifying the optimal surgical technique that affords minimal injury to ovarian function. New medical treatment options in the form of aromatase inhibitors are emerging, whereas the evidence for a role of ultrasound-guided drainage and sclerotherapy is scarce and unconvincing. SUMMARY: Consensus from Europe and the USA is for a conservative approach to the treatment of ovarian endometriosis, with early recourse to assisted reproductive technology for subfertility. Surgery is currently only being advised for severe pain or difficult access to growing follicles and only after careful counselling regarding the potential adverse effect on ovarian reserve. Research has still not identified the optimal technique for treating ovarian endometriosis. Laparoscopic ovarian cystectomy not only offers the lowest risk of recurrence and the highest chance of spontaneous pregnancy rate, but also risks significant injury to ovarian function. Medical treatment offers temporary symptom relief but does not improve the fertility outcomes, and the role of ultrasound-guided drainage remains to be established.

A behavioral database for masked form priming.

Reading involves a process of matching an orthographic input with stored representations in lexical memory. The masked priming paradigm has become a standard tool for investigating this process. Use of existing results from this paradigm can be limited by the precision of the data and the need for cross-experiment comparisons that lack normal experimental controls. Here, we present a single, large, high-precision, multicondition experiment to address these problems. Over 1,000 participants from 14 sites responded to 840 trials involving 28 different types of orthographically related primes (e.g., castfe-CASTLE) in a lexical decision task, as well as completing measures of spelling and vocabulary. The data were indeed highly sensitive to differences between conditions: After correction for multiple comparisons, prime type condition differences of 2.90 ms and above reached significance at the 5% level. This article presents the method of data collection and preliminary findings from these data, which included replications of the most widely agreed-upon differences between prime types, further evidence for systematic individual differences in susceptibility to priming, and new evidence regarding lexical properties associated with a target word's susceptibility to priming. These analyses will form a basis for the use of these data in quantitative model fitting and evaluation and for future exploration of these data that will inform and motivate new experiments.

Structural basis for AMP binding to mammalian AMP-activated protein kinase.

AMP-activated protein kinase (AMPK) regulates cellular metabolism in response to the availability of energy and is therefore a target for type II diabetes treatment. It senses changes in the ratio of AMP/ATP by binding both species in a competitive manner. Thus, increases in the concentration of AMP activate AMPK resulting in the phosphorylation and differential regulation of a series of downstream targets that control anabolic and catabolic pathways. We report here the crystal structure of the regulatory fragment of mammalian AMPK in complexes with AMP and ATP. The phosphate groups of AMP/ATP lie in a groove on the surface of the gamma domain, which is lined with basic residues, many of which are associated with disease-causing mutations. Structural and solution studies reveal that two sites on the gamma domain bind either AMP or Mg.ATP, whereas a third site contains a tightly bound AMP that does not exchange. Our binding studies indicate that under physiological conditions AMPK mainly exists in its inactive form in complex with Mg.ATP, which is much more abundant than AMP. Our modelling studies suggest how changes in the concentration of AMP ([AMP]) enhance AMPK activity levels. The structure also suggests a mechanism for propagating AMP/ATP signalling whereby a phosphorylated residue from the alpha and/or beta subunits binds to the gamma subunit in the presence of AMP but not when ATP is bound.

'So Help Me God'? Does oath swearing in courtroom scenarios impact trial outcomes?

In countries such as Britain and the US, court witnesses must declare they will provide truthful evidence and are often compelled to publicly choose between religious ("oath") and secular ("affirmation") versions of this declaration. Might defendants who opt to swear an oath enjoy more favourable outcomes than those who choose to affirm? Two preliminary, pre-registered survey studies using minimal vignettes (Study 1, N = 443; Study 2, N = 913) indicated that people associate choice of the oath with credible testimony; and that participants, especially religious participants, discriminate against defendants who affirm. In a third, Registered Report study (Study 3, N = 1821), we used a more elaborate audiovisual mock trial paradigm to better estimate the real-world influence of declaration choice. Participants were asked to render a verdict for a defendant who either swore or affirmed, and were themselves required to swear or affirm that they would try the defendant in good faith. Overall, the defendant was not considered guiltier when affirming rather than swearing, nor did mock-juror belief in God moderate this effect. However, jurors who themselves swore an oath did discriminate against the affirming defendant. Exploratory analyses suggest this effect may be driven by authoritarianism, perhaps because high-authoritarian jurors consider the oath the traditional (and therefore correct) declaration to choose. We discuss the real-world implications of these findings and conclude the religious oath is an antiquated legal ritual that needs reform.

Autophagosome membrane expansion is mediated by the N-terminus and cis-membrane association of human ATG8s.

Autophagy is an essential catabolic pathway which sequesters and engulfs cytosolic substrates via autophagosomes, unique double-membraned structures. ATG8 proteins are ubiquitin-like proteins recruited to autophagosome membranes by lipidation at the C-terminus. ATG8s recruit substrates, such as p62, and play an important role in mediating autophagosome membrane expansion. However, the precise function of lipidated ATG8 in expansion remains obscure. Using a real-time in vitro lipidation assay, we revealed that the N-termini of lipidated human ATG8s (LC3B and GABARAP) are highly dynamic and interact with the membrane. Moreover, atomistic MD simulation and FRET assays indicate that N-termini of LC3B and GABARAP associate in cis on the membrane. By using non-tagged GABARAPs, we show that GABARAP N-terminus and its cis-membrane insertion are crucial to regulate the size of autophagosomes in cells irrespectively of p62 degradation. Our study provides fundamental molecular insights into autophagosome membrane expansion, revealing the critical and unique function of lipidated ATG8.

Can the fall in serum FSH during coasting in IVF/ICSI predict clinical outcomes?

This retrospective cohort study determined whether the total falls in serum FSH and oestradiol concentrations from start to end of coasting in IVF/intracytoplasmic sperm injection could predict clinical outcomes. Ninety-nine cycles, with gonadotrophin-releasing hormone-agonist down-regulation where coasting with serial serum oestradiol and FSH monitoring was adopted due to risk of severe ovarian hyperstimulation syndrome, were consecutively included. The primary clinical outcome was live-birth rate (LBR); other outcomes measured were number of oocytes retrieved and fertilization, implantation and clinical pregnancy rates. LBR for FSH fall>10 IU/l compared with 5-10 and<5 IU/l were 45.4% versus 22.0% and 25.0%, respectively. Mean serum FSH fall was similar with and without live birth (8.4 ± 6.2 versus 7.3 ± 5.0 IU/l) as were mean oestradiol and FSH concentrations on HCG administration, oestradiol fall, percentage fall in FSH/oestradiol and duration of coasting. None of the variables efficiently predicted live birth on regression analysis. The AUC of FSH fall was 0.53 at 11.0 IU/l. Basal FSH, starting and total gonadotrophin dose and duration of coasting were positively correlated with FSH fall. A potentially clinically important association between live birth and FSH fall during coasting was apparent, which requires further evaluation. The purpose of this retrospective cohort study was to determine whether the magnitude of fall in the serum FSH and oestradiol concentrations from start to end of coasting in IVF/intracytoplasmic sperm injection cycles could predict the clinical outcomes. Gonadotrophin-releasing hormone-agonist down-regulated cycles (n=99), where coasting with serial serum oestradiol and FSH monitoring was adopted due to risk of ovarian hyperstimulation, were consecutively included. Live birth was the primary clinical outcome measured; number of oocytes retrieved and fertilization, implantation and clinical pregnancy rates were the other outcomes examined. Live-birth rate tended to be high when FSH fall was >10 IU/l, compared with 5-10 IU/l and <5 IU/l, although not statistically significantly. Mean serum FSH fall were similar in live-birth and no-live-birth cycles (8.4 ± 6.2 versus 7.3 ± 5.0) as were mean oestradiol and FSH concentrations on hCG administration, oestradiol fall, percentage fall in FSH and oestradiol and duration of coasting. None of the variables efficiently predicted live birth. The area under the curve of FSH fall was 0.53. FSH fall of <11.0 IU/l was found to be more likely to predict negative outcome (specificity 84.72%) than predicting positive outcome when FSH fall was >11 IU/l (sensitivity 34.48%). Women's basal FSH, starting and total gonadotrophin dose of ovarian stimulation and duration of coasting had direct positive correlation with the magnitude of FSH fall. A potentially clinically important rise in live birth in association with greater FSH fall during coasting was apparent, which requires further evaluation.

Does minimally invasive surgery for endometriosis improve pelvic symptoms and quality of life?

PURPOSE OF REVIEW: Endometriosis is a common gynaecological disorder estimated to affect over 70 million women worldwide. In this review we aim to give an overview of postoperative symptoms and look at factors influencing therapeutic choices and surgical techniques. RECENT FINDINGS: A wide range of physical and psychological factors contribute to the symptoms of disease. Patients suffer from impaired quality of life, depression, anxiety and chronic and acute pain. Validated questionnaires have been used to assess patient response. Surgical excision of endometriosis improves dyspareunia and the quality of sex life of patients. It is superior in outcomes to medical therapy in achieving increased pregnancy rates. Catastrophizing and biopsychosocial variables are implicated in the severity of pain experienced in patients with endometriosis. Patients with endometriosis score lower on quality of life assessments and the addition of psychosomatic therapy to medical treatments has shown to improve the emotional status of patients with improved treatment outcomes. SUMMARY: Despite its prevalence, there is no optimal treatment for endometriosis; recurrence of disease is a common problem. Laparoscopic surgery compared with medical therapies shows improved patient satisfaction outcomes in general health, quality of life and emotional wellbeing. Management of this varied aetiology improves in the context of a multidisciplinary team.

Update on the surgical management of adenomyosis.

PURPOSE OF REVIEW: Adenomyosis is a benign gynaecological condition associated with menstrual symptoms and pelvic pain in premenopausal women, it has also been linked to subfertility. Improvement in ultrasound and MRI imaging has allowed accurate diagnosis of this condition prior to histological confirmation. Patients opting for surgical management need to be counselled regarding the surgical options available. This review summarizes the surgical management of adenomyosis and reviews the recent surgical developments. RECENT FINDINGS: For patients who wish to preserve their fertility, cytoreductive surgery is an option in centres with surgical expertise. Recently, modified surgical procedures to remove extensive adenomyosis known as an adenomyomectomy have been described. These operations may enhance subsequent fertility. SUMMARY: Access to accurate imaging modalities such as MRI and transvaginal ultrasound allows for adequate patient counselling preoperatively. Depending on the fertility requirements and the extent of adenomyosis, patients can be offered various surgical treatment options including laparoscopic hysterectomy or adenomyomectomy.

Developing a universal model of reading necessitates cracking the orthographic code.

I argue, contra Frost, that when prime lexicality and target density are considered, it is not clear that there are fundamental differences between form priming effects in Semitic and European languages. Furthermore, identifying and naming printed words in these languages raises common theoretical problems. Solving these problems and developing a universal model of reading necessitates "cracking" the orthographic input code.

Efficacy information influences intention to take COVID-19 vaccine.

OBJECTIVES: A successful response to the COVID-19 pandemic requires achieving high levels of vaccine uptake. We tested whether directly contrasting the high efficacy of COVID-19 vaccines with the lower efficacy of the annual flu vaccine would increase intentions to take a COVID-19 vaccine. DESIGN: A pre-registered online study of 481 participants compared four information conditions: (1) no information; (2) COVID-19 Vaccine Information Only; and COVID-19 Vaccine Information combined with flu vaccine information suggesting either (3) 60% efficacy or (4) 40% efficacy; we measured COVID-19 and flu vaccine intentions along with several other vaccine-related variables. METHODS: The Prolific platform was used to recruit 481 UK participants (64% female; aged between 18 and 85 years) who had been pre-screened to have intermediate levels of vaccine hesitancy. After reading a short text (~200 words) about COVID-19 vaccines, participants were asked about their vaccination intentions. RESULTS: Providing information about the safety and efficacy of the new COVID-19 vaccines resulted in vaccination intentions that were, on average, 0.39 standard deviations (SDs) higher than those in the no information condition; providing the same COVID vaccine efficacy information in the context of information about flu vaccine efficacy resulted in a further significant increase in vaccination intentions that were 0.68 SD higher than those in the no information condition. This positive contrast effect for the COVID-19 vaccine was not associated with reduced flu vaccine intentions. CONCLUSIONS: Vaccination intentions can be strengthened through a simple messaging intervention that utilizes context effects to increase perceived response efficacy.