Causal Attributions of Low Sexual Desire in Women Partnered with Men.

Low sexual desire in women partnered with men has been the subject of controversy and research over the past decades, including both as construct and diagnosis. Despite discussion surrounding the causes of low desire, there is a gap in research about how women themselves understand the causes of their low desire and the potential consequences of these causal attributions. In the current study, we investigated this by asking 130 women who had low desire and were partnered with men about their attributions for low desire. Through content analysis, we identified five attribution categories: psychological/individual, relational, biological, sociocultural, and/or sexual orientation/identity/status. Many participants chose more than one category, indicating a multifaceted nature of women's causes of low desire. We then quantitatively assessed women's feelings of responsibility for, and emotions surrounding, their low desire. Our findings indicate that the majority-but not all-of women have negative feelings about their low desire. However, the specific emotions they experience are related to their attribution patterns. This underscores the significance of investigating various facets of women's attributions regarding low desire in order to gain a more comprehensive understanding of their emotional experiences and desire overall.

TMEM67, TMEM237, and Embigin in Complex With Monocarboxylate Transporter MCT1 Are Unique Components of the Photoreceptor Outer Segment Plasma Membrane.

The outer segment (OS) organelle of vertebrate photoreceptors is a highly specialized cilium evolved to capture light and initiate light response. The plasma membrane which envelopes the OS plays vital and diverse roles in supporting photoreceptor function and health. However, little is known about the identity of its protein constituents, as this membrane cannot be purified to homogeneity. In this study, we used the technique of protein correlation profiling to identify unique OS plasma membrane proteins. To achieve this, we used label-free quantitative MS to compare relative protein abundances in an enriched preparation of the OS plasma membrane with a preparation of total OS membranes. We have found that only five proteins were enriched at the same level as previously validated OS plasma membrane markers. Two of these proteins, TMEM67 and TMEM237, had not been previously assigned to this membrane, and one, embigin, had not been identified in photoreceptors. We further showed that embigin associates with monocarboxylate transporter MCT1 in the OS plasma membrane, facilitating lactate transport through this cellular compartment.

Efficacy of Single-Dose Primaquine With Artemisinin Combination Therapy on Plasmodium falciparum Gametocytes and Transmission: An Individual Patient Meta-Analysis.

BACKGROUND: Since the World Health Organization recommended single low-dose (0.25 mg/kg) primaquine (PQ) in combination with artemisinin-based combination therapies (ACTs) in areas of low transmission or artemisinin-resistant Plasmodium falciparum, several single-site studies have been conducted to assess efficacy. METHODS: An individual patient meta-analysis to assess gametocytocidal and transmission-blocking efficacy of PQ in combination with different ACTs was conducted. Random effects logistic regression was used to quantify PQ effect on (1) gametocyte carriage in the first 2 weeks post treatment; and (2) the probability of infecting at least 1 mosquito or of a mosquito becoming infected. RESULTS: In 2574 participants from 14 studies, PQ reduced PCR-determined gametocyte carriage on days 7 and 14, most apparently in patients presenting with gametocytemia on day 0 (odds ratio [OR], 0.22; 95% confidence interval [CI], .17-.28 and OR, 0.12; 95% CI, .08-.16, respectively). Rate of decline in gametocyte carriage was faster when PQ was combined with artemether-lumefantrine (AL) compared to dihydroartemisinin-piperaquine (DP) (P = .010 for day 7). Addition of 0.25 mg/kg PQ was associated with near complete prevention of transmission to mosquitoes. CONCLUSIONS: Transmission blocking is achieved with 0.25 mg/kg PQ. Gametocyte persistence and infectivity are lower when PQ is combined with AL compared to DP.

Safety of single-dose primaquine as a Plasmodium falciparum gametocytocide: a systematic review and meta-analysis of individual patient data.

BACKGROUND: In 2012, the World Health Organization (WHO) recommended single low-dose (SLD, 0.25 mg/kg) primaquine to be added as a Plasmodium (P.) falciparum gametocytocide to artemisinin-based combination therapy (ACT) without glucose-6-phosphate dehydrogenase (G6PD) testing, to accelerate malaria elimination efforts and avoid the spread of artemisinin resistance. Uptake of this recommendation has been relatively slow primarily due to safety concerns. METHODS: A systematic review and individual patient data (IPD) meta-analysis of single-dose (SD) primaquine studies for P. falciparum malaria were performed. Absolute and fractional changes in haemoglobin concentration within a week and adverse effects within 28 days of treatment initiation were characterised and compared between primaquine and no primaquine arms using random intercept models. RESULTS: Data comprised 20 studies that enrolled 6406 participants, of whom 5129 (80.1%) had received a single target dose of primaquine ranging between 0.0625 and 0.75 mg/kg. There was no effect of primaquine in G6PD-normal participants on haemoglobin concentrations. However, among 194 G6PD-deficient African participants, a 0.25 mg/kg primaquine target dose resulted in an additional 0.53 g/dL (95% CI 0.17-0.89) reduction in haemoglobin concentration by day 7, with a 0.27 (95% CI 0.19-0.34) g/dL haemoglobin drop estimated for every 0.1 mg/kg increase in primaquine dose. Baseline haemoglobin, young age, and hyperparasitaemia were the main determinants of becoming anaemic (Hb < 10 g/dL), with the nadir observed on ACT day 2 or 3, regardless of G6PD status and exposure to primaquine. Time to recovery from anaemia took longer in young children and those with baseline anaemia or hyperparasitaemia. Serious adverse haematological events after primaquine were few (9/3, 113, 0.3%) and transitory. One blood transfusion was reported in the primaquine arms, and there were no primaquine-related deaths. In controlled studies, the proportions with either haematological or any serious adverse event were similar between primaquine and no primaquine arms. CONCLUSIONS: Our results support the WHO recommendation to use 0.25 mg/kg of primaquine as a P. falciparum gametocytocide, including in G6PD-deficient individuals. Although primaquine is associated with a transient reduction in haemoglobin levels in G6PD-deficient individuals, haemoglobin levels at clinical presentation are the major determinants of anaemia in these patients. TRIAL REGISTRATION: PROSPERO, CRD42019128185.

Persistence of Plasmodium falciparum HRP-2 antigenaemia after artemisinin combination therapy is not associated with gametocytes.

BACKGROUND: In some settings, sensitive field diagnostic tools may be needed to achieve elimination of falciparum malaria. To this end, rapid diagnostic tests (RDTs) based on the detection of the Plasmodium falciparum protein HRP-2 are being developed with increasingly lower limits of detection. However, it is currently unclear how parasite stages that are unaffected by standard drug treatments may contribute to HRP-2 detectability and potentially confound RDT results even after clearance of blood stage infection. This study assessed the detectability of HRP-2 in periods of post-treatment residual gametocytaemia. METHODS: A cohort of 100 P. falciparum infected, gametocyte positive individuals were treated with or without the gametocytocidal drug primaquine (PQ), alongside standard artemisinin-based combination therapy (ACT), in the context of a randomised clinical trial in Ouelessebougou, Mali. A quantitative ELISA was used to measure levels of HRP-2, and compared time to test negativity using a standard and ultra-sensitive RDT (uRDT) between residual gametocyte positive and negative groups. RESULTS: Time to test negativity was longest by uRDT, followed by ELISA and then standard RDT. No significant difference in time to negativity was found between the treatment groups with and without residual gametocytes: uRDT (HR 0.79 [95% CI 0.52-1.21], p = 0.28), RDT (HR 0.77 [95% CI 0.51-1.15], p = 0.20) or ELISA (HR 0.88 [95% CI 0.59-1.32], p = 0.53). Similarly, no difference was observed when adjusting for baseline asexual parasite density. Quantified levels of HRP-2 over time were similar between groups, with differences attributable to asexual parasite densities. Furthermore, no difference in levels of HRP-2 was found between individuals who were or were not infectious to mosquitoes (OR 1.19 [95% CI 0.98-1.46], p = 0.077). CONCLUSIONS: Surviving sexual stage parasites after standard ACT treatment do not contribute to the persistence of HRP-2 antigenaemia, and appear to have little impact on RDT results.

Genetic variation in reproductive timing in a long-lived herbaceous perennial.

PREMISE: Reproductive fitness of individual plants depends on the timing of flowering, especially in mate-limited populations, such as those in fragmented habitats. When flowering time traits are associated with differential reproductive success, the narrow-sense heritability (h2 ) of traits will determine how rapidly trait means evolve in response to selection. Heritability of flowering time is documented in many annual plants. However, estimating h2 of flowering time in perennials presents additional methodological challenges, often including paternity assignment and trait expression over multiple years. METHODS: We evaluated the h2 of onset and duration of flowering using offspring-midparent regressions and restricted maximum likelihood methods in an experimental population of an iterocarpic, perennial, herbaceous plant, Echinacea angustifolia, growing in natural conditions. We assessed the flowering time of the parental cohort in 2005 and 2006; the offspring in 2014 through 2017. We also examined the effects of the paternity assignment from Cervus and MasterBayes on estimates of h2 . RESULTS: We found substantial h2 for onset and duration of flowering. We also observed variation in estimates among years. The most reliable estimates for both traits fell in the range of 0.1-0.17. We found evidence of a genotype by year interaction for onset of flowering and strong evidence that genotypes are consistent in their duration of flowering across years. CONCLUSIONS: Substantial heritabilities in this population imply the capacity for a response to natural selection, while also suggesting the potential for differential contributions to adaptive evolution among seasons.

Impact of woodland agri-environment management on woodland structure and target bird species.

Agri-environment incentives form a central mechanism supporting changes to land management to provide public benefits. This study assesses the medium-term effects of woodland management on 13 target, specialist woodland bird species, as well as other woodland birds in a single region of the UK. The abundance of breeding birds (using two methods: point counts and territory mapping) and metrics of woodland structure were recorded on sites with Woodland Improvement Grants (improvement sites) and nearby comparison sites (control sites). Initial measurements were made prior to management and repeated 7-9 years later. A separate comparison of changes in bird abundance was made between the managed woodland sites and woodland from similar landscapes surveyed as part of the national Breeding Bird Survey (BBS). There was an increase in abundance of target species on improvement sites compared to a decrease on both control sites and BBS sites, although this was only evident from point count data. The effects on target species were stronger than for other woodland specialists and there was no apparent effect on woodland generalists, suggesting that the management interventions were appropriate for the target species. Changes in woodland structure were generally consistent with the expected effect of management, with lower tree density and greater Bramble (Rubus sp.) cover. However, contrary to the aim of increasing understorey cover, a reduction was recorded within the 2-10 m height category in improvement sites. This contrast is due to the removal of young trees during thinning affecting this height band and the short time period since management to allow regrowth. Our findings show that bespoke management supported through government agri-environment incentives can have a positive impact on target woodland birds. For managed forests, identifying species requirements and how management can be adapted to improve their habitats can be an effective way of delivering biodiversity gains when financial incentives are provided to achieve policy goals.

Automated calculation of the right ventricle to left ventricle ratio on CT for the risk stratification of patients with acute pulmonary embolism.

OBJECTIVES: To assess the feasibility and reliability of the use of artificial intelligence post-processing to calculate the RV:LV diameter ratio on computed tomography pulmonary angiography (CTPA) and to investigate its prognostic value in patients with acute PE. METHODS: Single-centre, retrospective study of 101 consecutive patients with CTPA-proven acute PE. RV and LV volumes were segmented on 1-mm contrast-enhanced axial slices and maximal ventricular diameters were derived for RV:LV ratio using automated post-processing software (IMBIO LLC, USA) and compared to manual analysis in two observers, via intraclass coefficient correlation analysis. Each CTPA report was analysed for mention of the RV:LV ratio and compared to the automated RV:LV ratio. Thirty-day all-cause mortality post-CTPA was recorded. RESULTS: Automated RV:LV analysis was feasible in 87% (n = 88). RV:LV ratios ranged from 0.67 to 2.43, with 64% (n = 65) > 1.0. There was very strong agreement between manual and automated RV:LV ratios (ICC = 0.83, 0.77-0.88). The use of automated analysis led to a change in risk stratification in 45% of patients (n = 40). The AUC of the automated measurement for the prediction of all-cause 30-day mortality was 0.77 (95% CI: 0.62-0.99). CONCLUSION: The RV:LV ratio on CTPA can be reliably measured automatically in the majority of real-world cases of acute PE, with perfect reproducibility. The routine use of this automated analysis in clinical practice would add important prognostic information in patients with acute PE. KEY POINTS: • Automated calculation of the right ventricle to left ventricle ratio was feasible in the majority of patients and demonstrated perfect intraobserver variability. • Automated analysis would have added important prognostic information and altered risk stratification in the majority of patients. • The optimal cut-off value for the automated right ventricle to left ventricle ratio was 1.18, with a sensitivity of 100% and specificity of 54% for the prediction of 30-day mortality.

Translating Knowledge of Sexual Configurations Theory via Instructional Videos.

Gender/sex and sexual diversity are increasingly understood by the public as complex. But, scientific frameworks that address the complexity of gender/sex and sexual diversity are few and not well situated for the public. Sexual configurations theory (SCT; van Anders, 2015) is one approach that provides a visual framework for understanding and measuring gender/sex and sexual diversity. But how might knowledge users and creators actually use it? To make SCT more accessible to researchers, educators, clinicians, and the general public, we created three instructional videos (individual gender/sex, gender/sex sexuality, and partner number sexuality) that explained SCT and demonstrated how to use its diagrams. Participants (N = 242) of diverse gender/sex and sexual identities, including professionals who work in gender/sex- and sexuality-related fields, watched one of the three videos, filled out the diagrams, and evaluated the video and diagrams via scaled and open-ended questions. Results demonstrated that the SCT videos were sufficient for most participants to fill out the diagrams. Participants evaluated the video generally positively, with some variation by condition, identity group, and professional status. These results indicate that instructional videos are able to translate SCT, potentially facilitating uptake of SCT by clinicians, researchers, and educators as well as increasing awareness of gender/sex and sexual diversity more broadly within the public.

Identifying potentially invasive non-native marine and brackish water species for the Arabian Gulf and Sea of Oman.

Invasive non-native species (NNS) are internationally recognized as posing a serious threat to global biodiversity, economies and human health. The identification of invasive NNS is already established, those that may arrive in the future, their vectors and pathways of introduction and spread, and hotspots of invasion are important for a targeted approach to managing introductions and impacts at local, regional and global scales. The aim of this study was to identify which marine and brackish NNS are already present in marine systems of the northeastern Arabia area (Arabian Gulf and Sea of Oman) and of these which ones are potentially invasive, and which species have a high likelihood of being introduced in the future and negatively affect biodiversity. Overall, 136 NNS were identified, of which 56 are already present in the region and a further 80 were identified as likely to arrive in the future, including fish, tunicates, invertebrates, plants and protists. The Aquatic Species Invasiveness Screening Kit (AS-ISK) was used to identify the risk of NNS being (or becoming) invasive within the region. Based on the AS-ISK basic risk assessment (BRA) thresholds, 36 extant and 37 horizon species (53.7% of all species) were identified as high risk. When the impact of climate change on the overall assessment was considered, the combined risk score (BRA+CCA) increased for 38.2% of all species, suggesting higher risk under warmer conditions, including the highest-risk horizon NNS the green crab Carcinus maenas, and the extant macro-alga Hypnea musciformis. This is the first horizon-scanning exercise for NNS in the region, thus providing a vital baseline for future management. The outcome of this study is the prioritization of NNS to inform decision-making for the targeted monitoring and management in the region to prevent new bio-invasions and to control existing species, including their potential for spread.

Testing Low-Redshift Cosmic Acceleration with Large-Scale Structure.

We examine the cosmological implications of measurements of the void-galaxy cross-correlation at redshift z=0.57 combined with baryon acoustic oscillation (BAO) data at 0.110σ significance from these data alone, independent of the cosmic microwave background (CMB) and supernovae. Using a nucleosynthesis prior on Ω_{b}h^{2}, we measure the Hubble constant to be H_{0}=72.3±1.9 km s^{-1} Mpc^{-1} from BAO+voids at z<2, and H_{0}=69.0±1.2 km s^{-1} Mpc^{-1} when adding Lyman-α BAO at z=2.34, both independent of the CMB. Adding voids to CMB, BAO, and supernova data greatly improves measurement of the dark energy equation of state, increasing the figure of merit by >40%, but remaining consistent with flat Λ cold dark matter.

Shear Modulus Measurement by Quantitative Phase Imaging and Correlation with Atomic Force Microscopy.

Many approaches have been developed to characterize cell elasticity. Among these, atomic force microscopy (AFM) combined with modeling has been widely used to characterize cellular compliance. However, such approaches are often limited by the difficulties associated with using a specific instrument and by the complexity of analyzing the measured data. More recently, quantitative phase imaging (QPI) has been applied to characterize cellular stiffness by using an effective spring constant. This metric was further correlated to mass distribution (disorder strength) within the cell. However, these measurements are difficult to compare to AFM-derived measurements of Young's modulus. Here, we describe, to our knowledge, a new way of analyzing QPI data to directly retrieve the shear modulus. Our approach enables label-free measurement of cellular mechanical properties that can be directly compared to values obtained from other rheological methods. To demonstrate the technique, we measured shear modulus and phase disorder strength using QPI, as well as Young's modulus using AFM, across two breast cancer cell-line populations dosed with three different concentrations of cytochalasin D, an actin-depolymerizing toxin. Comparison of QPI-derived and AFM moduli shows good agreement between the two measures and further agrees with theory. Our results suggest that QPI is a powerful tool for cellular biophysics because it allows for optical quantitative measurements of cell mechanical properties.

Distinct capacity for differentiation to inner ear cell types by progenitor cells of the cochlea and vestibular organs.

Disorders of hearing and balance are most commonly associated with damage to cochlear and vestibular hair cells or neurons. Although these cells are not capable of spontaneous regeneration, progenitor cells in the hearing and balance organs of the neonatal mammalian inner ear have the capacity to generate new hair cells after damage. To investigate whether these cells are restricted in their differentiation capacity, we assessed the phenotypes of differentiated progenitor cells isolated from three compartments of the mouse inner ear - the vestibular and cochlear sensory epithelia and the spiral ganglion - by measuring electrophysiological properties and gene expression. Lgr5+ progenitor cells from the sensory epithelia gave rise to hair cell-like cells, but not neurons or glial cells. Newly created hair cell-like cells had hair bundle proteins, synaptic proteins and membrane proteins characteristic of the compartment of origin. PLP1+ glial cells from the spiral ganglion were identified as neural progenitors, which gave rise to neurons, astrocytes and oligodendrocytes, but not hair cells. Thus, distinct progenitor populations from the neonatal inner ear differentiate to cell types associated with their organ of origin.

Bird conservation and the land sharing-sparing continuum in farmland-dominated landscapes of lowland England.

Empirical evidence from many regions suggests that most species would be least negatively affected if human food demand were met through high-yield agricultural production and conservation of nonfarm ecosystems (land sparing), rather than through wildlife-friendly farming over a larger area (land sharing). However, repeated glaciation and a long history of agriculture may lead to different results in regions such as western Europe. We compared the consequences of land sparing and land sharing on breeding bird species in 2 lowland regions of England, The Fens, with 101 species, and Salisbury Plain, with 83. We derived density-yield responses for each species and then estimated regional population size under regional food production strategies, including land sharing and land sparing, a range of intermediate strategies, and a novel mixed strategy. In both regions, more species achieved maximum regional population size under land sparing than land sharing. In The Fens, the majority of birds were loser species (estimated to have smaller populations under all food production strategies than in the preagricultural baseline scenario), whereas in Salisbury Plain the majority were winners (smaller populations in the preagricultural baseline scenario). Loser species overwhelmingly achieved maximum regional population size under land sparing, whereas winner species achieved maximum regional population size under either land sharing or an intermediate strategy, highlighting the importance of defining which groups of species are the target of conservation. A novel 3-compartment strategy (combining high-yield farming, natural habitat, and low-yield farming) often performed better than either land sharing or land sparing. Our results support intermediate or 3-compartment land-sparing strategies to maximize bird populations across lowland agricultural landscapes. To deliver conservation outcomes, any shift toward land sparing must, however, ensure yield increases are sustainable in the long term, do not entail increased negative effects on surrounding areas, and are linked to allocation of land for nature.

Conservación de Aves y el Continuo de Suelo Compartido-Reservado en Paisajes Dominados por Tierras de Cultivo en las Tierras Bajas de Inglaterra Resumen La evidencia empírica proveniente de muchas regiones sugiere que la mayoría de las especies se verían menos afectadas negativamente si se cumpliera con la demanda humana de alimentos por medio de una producción agrícola de alto rendimiento y la conservación de ecosistemas no agrícolas (dosificación de suelo) en lugar de hacerlo a través de la agricultura amigable con la fauna en un área mayor (partición de suelo). Sin embargo, la glaciación repetitiva y una larga historia agrícola podrían brindar diferentes resultados en regiones como Europa occidental. Comparamos las consecuencias de la dosificación y la partición de suelo sobre especies de aves en reproducción en dos regiones de tierras bajas en Inglaterra: Los Fens, con 101 especies, y la Planicie Salisbury, con 83 especies. Derivamos las respuestas con densidad de rendimiento para cada especie y después estimamos el tamaño poblacional regional bajo estrategias regionales de producción de alimentos, incluyendo la dosificación y la partición de suelo, una gama de estrategias intermedias y una novedosa estrategia mixta. En ambas regiones, más especies alcanzaron el tamaño poblacional máximo para la región bajo la dosificación del suelo que bajo la partición del suelo. En Los Fens, la mayoría de las aves fueron especies perdedoras (se estimó que tendrían tamaños poblacionales menores bajo todas las estrategias de producción de alimento que en el escenario pre-agrícola de la línea base) mientras que en la Planicie Salisbury, la mayoría de las especies fueron ganadoras (con poblaciones más pequeñas en el escenario pre-agrícola de la línea base). Las especies perdedoras tuvieron abrumadoramente un tamaño poblacional máximo para la región bajo la dosificación de suelo, mientras que las especies ganadoras tuvieron este máximo poblacional bajo la partición de suelo o alguna estrategia intermedia, lo que resalta la importancia de la definición de cuáles grupos de especies son el objetivo de conservación. Una estrategia novedosa de tres compartimentos (combina la agricultura de alto rendimiento, el hábitat natural y la agricultura de bajo rendimiento) muchas veces tuvo un mejor desempeño que la dosificación o la partición del suelo. Nuestros resultados respaldan a las estrategias de dosificación de suelo intermedias o de tres compartimentos para maximizar las poblaciones de aves en todos los paisajes agrícolas de las tierras bajas. Para brindar resultados de conservación, cualquier cambio hacia la dosificación del suelo, sin embargo, debe asegurar que los incrementos en el rendimiento son sustentables a largo plazo, no conllevan un incremento de efectos negativos en las áreas circundantes, y que están vinculados a la asignación de suelo para la naturaleza.

Single and double hole quantum dots in strained Ge/SiGe quantum wells.

Even as today's most prominent spin-based qubit technologies are maturing in terms of capability and sophistication, there is growing interest in exploring alternate material platforms that may provide advantages, such as enhanced qubit control, longer coherence times, and improved extensibility. Recent advances in heterostructure material growth have opened new possibilities for employing hole spins in semiconductors for qubit applications. Undoped, strained Ge/SiGe quantum wells are promising candidate hosts for hole spin-based qubits due to their low disorder, large intrinsic spin-orbit coupling strength, and absence of valley states. Here, we use a simple one-layer gated device structure to demonstrate both a single quantum dot as well as coupling between two adjacent quantum dots. The hole effective mass in these undoped structures, m* âˆ¼ 0.08 m 0, is significantly lower than for electrons in Si/SiGe, pointing to the possibility of enhanced tunnel couplings in quantum dots and favorable qubit-qubit interactions in an industry-compatible semiconductor platform.

Sexual and Gender Diversity Among Sexual and Gender/Sex Majorities: Insights via Sexual Configurations Theory.

Recent research on gender and sexual majority individuals suggests that their attractions, identities, and experiences may not be as homogenous or easily generalizable as is often assumed. Sexual configurations theory (SCT; van Anders, 2015) is a framework for conceptualizing individuals' partnered sexualities and gender/sexes with a focus on gender/sex and sexual diversity. SCT has been successfully used in recent empirical work with gender and sexual minority individuals (Schudson, Manley, Diamond, & van Anders, 2018), but it has not yet been tested with heterosexual, cisgender individuals. In the present study, we tested the use of SCT in qualitative interviews with 26 gender and sexual majority participants to address the following research questions: What are the strengths and weaknesses of SCT for representing heterosexual, cisgender individuals' gender/sexes and partnered sexualities? How do gender and sexual majority individuals use SCT to express their gender/sexes and partnered sexualities? And, what insights about sexual and gender diversity can be gained from using SCT with a gender and sexual majority sample? Using thematic analysis, we evaluated how participants interacted with SCT and the SCT diagrams. Results showed that our participants used components of SCT to convey comprehensive and nuanced interests, which included gender/sex and sexual diversity outside of what is typically expected in research on heterosexual, cisgender individuals. We discuss findings and challenges specific to working with majority participants and offer implications for future work on gender/sex and sexual majorities and on gender/sex and sexual diversity in general.

Germline BRCA mutation and outcome in young-onset breast cancer (POSH): a prospective cohort study.

BACKGROUND: Retrospective studies provide conflicting interpretations of the effect of inherited genetic factors on the prognosis of patients with breast cancer. The primary aim of this study was to determine the effect of a germline BRCA1 or BRCA2 mutation on breast cancer outcomes in patients with young-onset breast cancer. METHODS: We did a prospective cohort study of female patients recruited from 127 hospitals in the UK aged 40 years or younger at first diagnosis (by histological confirmation) of invasive breast cancer. Patients with a previous invasive malignancy (except non-melanomatous skin cancer) were excluded. Patients were identified within 12 months of initial diagnosis. BRCA1 and BRCA2 mutations were identified using blood DNA collected at recruitment. Clinicopathological data, and data regarding treatment and long-term outcomes, including date and site of disease recurrence, were collected from routine medical records at 6 months, 12 months, and then annually until death or loss to follow-up. The primary outcome was overall survival for all BRCA1 or BRCA2 mutation carriers (BRCA-positive) versus all non-carriers (BRCA-negative) at 2 years, 5 years, and 10 years after diagnosis. A prespecified subgroup analysis of overall survival was done in patients with triple-negative breast cancer. Recruitment was completed in 2008, and long-term follow-up is continuing. FINDINGS: Between Jan 24, 2000, and Jan 24, 2008, we recruited 2733 women. Genotyping detected a pathogenic BRCA mutation in 338 (12%) patients (201 with BRCA1, 137 with BRCA2). After a median follow-up of 8·2 years (IQR 6·0-9·9), 651 (96%) of 678 deaths were due to breast cancer. There was no significant difference in overall survival between BRCA-positive and BRCA-negative patients in multivariable analyses at any timepoint (at 2 years: 97·0% [95% CI 94·5-98·4] vs 96·6% [95·8-97·3]; at 5 years: 83·8% [79·3-87·5] vs 85·0% [83·5-86·4]; at 10 years: 73·4% [67·4-78·5] vs 70·1% [67·7-72·3]; hazard ratio [HR] 0·96 [95% CI 0·76-1·22]; p=0·76). Of 558 patients with triple-negative breast cancer, BRCA mutation carriers had better overall survival than non-carriers at 2 years (95% [95% CI 89-97] vs 91% [88-94]; HR 0·59 [95% CI 0·35-0·99]; p=0·047) but not 5 years (81% [73-87] vs 74% [70-78]; HR 1·13 [0·70-1·84]; p=0·62) or 10 years (72% [62-80] vs 69% [63-74]; HR 2·12 [0·82-5·49]; p= 0·12). INTERPRETATION: Patients with young-onset breast cancer who carry a BRCA mutation have similar survival as non-carriers. However, BRCA mutation carriers with triple-negative breast cancer might have a survival advantage during the first few years after diagnosis compared with non-carriers. Decisions about timing of additional surgery aimed at reducing future second primary-cancer risks should take into account patient prognosis associated with the first malignancy and patient preferences. FUNDING: Cancer Research UK, the UK National Cancer Research Network, the Wessex Cancer Trust, Breast Cancer Now, and the PPP Healthcare Medical Trust Grant.

Cellular shear stiffness reflects progression of arsenic-induced transformation during G1.

Cancer cells consistently exhibit decreased stiffness; however, the onset and progression of this change have not been characterized. To study the development of cell stiffness changes, we evaluated the shear stiffness of populations of cells during transformation to a carcinogenic state. Bronchial epithelial cells were exposed to sodium arsenite to initiate early stages of transformation. Exposed cells were cultured in soft agar to further transformation and select for clonal populations exhibiting anchorage-independent growth. Shear stiffness of various cell populations in G1 was assessed using a novel non-invasive assay that applies shear stress with fluid flow and evaluates nanoscale deformation using quantitative phase imaging (QPI). Arsenic-treated cells exhibited reduced stiffness relative to control cells, while arsenic clonal lines, selected by growth in soft agar, were found to have reduced stiffness relative to control clonal lines, which were cultured in soft agar but did not receive arsenic treatment. The relative standard deviation (RSD) of the stiffness of Arsenic clones was reduced compared with control clones, as well as to the arsenic-exposed cell population. Cell stiffness at the population level exhibits potential to be a novel and sensitive framework for identifying the development of cancerous cells.

Flexible sample cell for real-time GISAXS, GIWAXS and XRR: design and construction.

Since the properties of functional materials are highly dependent on their specific structure, and since the structural changes, for example during crystallization, induced by coating and annealing processes are significant, the study of structure and its formation is of interest for fundamental and applied science. However, structure analysis is often limited to ex situ determination of final states due to the lack of specialized sample cells that enable real-time investigations. The lack of such cells is mainly due to their fairly complex design and geometrical restrictions defined by the beamline setups. To overcome this obstacle, an advanced sample cell has been designed and constructed; it combines automated doctor blading, solvent vapor annealing and sample hydration with real-time grazing-incidence wide- and small-angle scattering (GIWAXS/GISAXS) and X-ray reflectivity (XRR). The sample cell has limited spatial requirements and is therefore widely usable at beamlines and laboratory-scale instruments. The cell is fully automatized and remains portable, including the necessary electronics. In addition, the cell can be used by interested scientists in cooperation with the Institute for Crystallography and Structural Physics and is expandable with regard to optical secondary probes. Exemplary research studies are presented, in the form of coating of P3HT:PC61PM thin films, solvent vapor annealing of DRCN5T:PC71BM thin films, and hydration of supported phospholipid multilayers, to demonstrate the capabilities of the in situ cell.

Assessing Plasmodium falciparum transmission in mosquito-feeding assays using quantitative PCR.

BACKGROUND: Evaluating the efficacy of transmission-blocking interventions relies on mosquito-feeding assays, with transmission typically assessed by microscopic identification of oocysts in mosquito midguts; however, microscopy has limited throughput, sensitivity and specificity. Where low prevalence and intensity mosquito infections occur, as observed during controlled human malaria infection studies or natural transmission, a reliable method for detection and quantification of low-level midgut infection is required. Here, a semi-automated, Taqman quantitative PCR (qPCR) assay sufficiently sensitive to detect a single-oocyst midgut infection is described. RESULTS: Extraction of genomic DNA from Anopheles stephensi midguts using a semi-automated extraction process was shown to have equivalent extraction efficiency to manual DNA extraction. An 18S Plasmodium falciparum qPCR assay was adapted for quantitative detection of P. falciparum midgut oocyst infection using synthetic DNA standards. The assay was validated for sensitivity and specificity, and the limit of detection was 0.7 genomes/µL (95% CI 0.4-1.6 genomes/µL). All microscopy-confirmed oocyst infected midgut samples were detected by qPCR, including all single-oocyst positive midguts. The genome number per oocyst was assessed 8-9 days after feeding assay using both qPCR and droplet digital PCR and was 3722 (IQR: 2951-5453) and 3490 (IQR: 2720-4182), respectively. CONCLUSIONS: This semi-automated qPCR method enables accurate detection of low-level P. falciparum oocyst infections in mosquito midguts, and may improve the sensitivity, specificity and throughput of assays used to evaluate candidate transmission-blocking interventions.