Proposed clinical management of pregnancies after combined screening for pre-eclampsia at 30-34 weeks' gestation

Objective: To estimate the patient-specific risk of preeclampsia (PE) at 30-34 weeks’ gestation by a combination of maternal characteristics and medical history with multiple of the median (MoM) values of mean arterial pressure, uterine artery pulsatility index, serum the median (MoM) values of mean arterial pressure, uterine artery pulsatility index, serum placental growth factor and serum soluble fmsm-like tyrosine kinase-1 and stratify women into high-, intermediate- and low-risk management groups. Methods: This was a prospective observational study in women attending for a third-trimester ultrasound scan at 30-34 weeks as part of routine pregnancy care. Patient-specific risks of delivery with PE at <4 weeks from assessment and at <40 weeks’ of delivery with PE at <4 weeks from assessment and at <40 weeks’ gestation were calculated using the competing risks model to combine the prior risk from maternal characteristics and medical history with MoM values of MAP, UTPI, PLGF and sFLT-1. On the basis of these risks the population was stratified into high-, intermediate- and low-risk groups. Different risk cut-offs were used to vary the proportion of the population stratified into each risk category and the performance of screening for delivery with PE at <4 weeks and delivery with PE from four weeks after assessment and up to 40 weeks’ gestation (PE 4w-40GW) was estimated. Results: The study population of 8,128 singleton pregnancies included 234 (2.9%) that subsequently developed PE. Using a risk cut-off for PE at <4 weeks of 1 in 50 and a risk cut-off of 1 in 150 for PE at <40 weeks’ gestation the proportion of the population stratified into high-, intermediate- and low-risk was about 3%, 26% and 71%, respectively. The high-risk group contained 90% of pregnancies with PE at at <4 weeks and 40% of those with PE at 4w-40GW. The intermediate-risk group contained a further 49% of women with PE at 4w-40GW. In the low-risk group, none of the women developed PE at <4 weeks and only 0.3% developed PE at 4w-40GW. Conclusion: The study presents risk stratification of PE by the combined test at 30-34 weeks aiming to identify a high-risk group in need of intensive monitoring from the time of the initial assessment and up to 40 weeks’ gestation and an intermediate-risk group, in need of monitoring starting from four weeks after the initial assessment and up to 40 weeks’ gestation. All pregnancies would need to be reassessed at 40 weeks’ gestation

New Suggestions for the Mechanical Control of Bone Remodeling

Bone is constantly renewed over our lifetime through the process of bone (re)modeling. This process is important for bone to allow it to adapt to its mechanical environment and to repair damage from everyday life. Adaptation is thought to occur through the mechanosensitive response controlling the bone-forming and -resorbing cells. This report shows a way to extract quantitative information about the way remodeling is controlled using computer simulations. Bone resorption and deposition are described as two separate stochastic processes, during which a discrete bone packet is removed or deposited from the bone surface. The responses of the bone-forming and -resorbing cells to local mechanical stimuli are described by phenomenological remodeling rules. Our strategy was to test different remodeling rules and to evaluate the time evolution of the trabecular architecture in comparison to what is known from μ-CT measurements of real bone. In particular, we tested the reaction of virtual bone to standard therapeutic strategies for the prevention of bone deterioration, i.e., physical activity and medications to reduce bone resorption. Insensitivity of the bone volume fraction to reductions in bone resorption was observed in the simulations only for a remodeling rule including an activation barrier for the mechanical stimulus above which bone deposition is switched on. This is in disagreement with the commonly used rules having a so-called lazy zone

Nuclear localisation of Aurora-A: its regulation and significance for Aurora-A functions in cancer.

The Aurora-A kinase regulates cell division, by controlling centrosome biology and spindle assembly. Cancer cells often display elevated levels of the kinase, due to amplification of the gene locus, increased transcription or post-translational modifications. Several inhibitors of Aurora-A activity have been developed as anti-cancer agents and are under evaluation in clinical trials. Although the well-known mitotic roles of Aurora-A point at chromosomal instability, a hallmark of cancer, as a major link between Aurora-A overexpression and disease, recent evidence highlights the existence of non-mitotic functions of potential relevance. Here we focus on a nuclear-localised fraction of Aurora-A with oncogenic roles. Interestingly, this pool would identify not only non-mitotic, but also kinase-independent functions of the kinase. We review existing data in the literature and databases, examining potential links between Aurora-A stabilisation and localisation, and discuss them in the perspective of a more effective targeting of Aurora-A in cancer therapy

Chickpea

The narrow genetic base of cultivated chickpea warrants systematic collection, documentation and evaluation of chickpea germplasm and particularly wild Cicer species for effective and efficient use in chickpea breeding programmes. Limiting factors to crop production, possible solutions and ways to overcome them, importance of wild relatives and barriers to alien gene introgression and strategies to overcome them and traits for base broadening have been discussed. It has been clearly demonstrated that resistance to major biotic and abiotic stresses can be successfully introgressed from the primary gene pool comprising progenitor species. However, many desirable traits including high degree of resistance to multiple stresses that are present in the species belonging to secondary and tertiary gene pools can also be introgressed by using special techniques to overcome pre- and post-fertilization barriers. Besides resistance to various biotic and abiotic stresses, the yield QTLs have also been introgressed from wild Cicer species to cultivated varieties. Status and importance of molecular markers, genome mapping and genomic tools for chickpea improvement are elaborated. Because of major genes for various biotic and abiotic stresses, the transfer of agronomically important traits into elite cultivars has been made easy and practical through marker-assisted selection and marker-assisted backcross. The usefulness of molecular markers such as SSR and SNP for the construction of high-density genetic maps of chickpea and for the identification of genes/QTLs for stress resistance, quality and yield contributing traits has also been discussed

Development of an intravaginal ring for the topical delivery of Aurora kinase A inhibitor, MLN8237.

Human papilloma virus (HPV) is the main culprit in cervical cancers. Although the HPV vaccine is now available, the slow and gradual process for HPV cancers to form means little will change, even for vaccinated individuals. This warrants the development of new therapeutic strategies in both the newly diagnosed and recurrent patients. We have previously shown that Alisertib (MLN8237), an Aurora A kinase inhibitor, potently and selectively kills HPV-positive cervical cancer cells. However, Alisertib is known for its unfavorable side effects when administered systemically. A targeted delivery approach is therefore warranted. The topical delivery of drugs to the cervix for the treatment of cervical cancer is an underexplored area of research that has the potential to significantly improve therapeutic outcome. Here, we design a novel topical drug delivery system for localized delivery in the vaginal tract using intravaginal silicone rings loaded with Alisertib. We assessed the suitability of the drug for the application and delivery method and develop a high-performance liquid chromatography method, then show that the vaginal rings were effective at releasing Alisertib over an extended period of time. Furthermore, we showed that Alisertib-loaded vaginal rings did not induce overt inflammation in the mouse vaginal tract. Our work has major translational implications for the future development of vaginal ring devices for the topical treatment of cervical cancer

An exploratory analysis of business intelligence practices in two travel agencies in Ankara, Turkey

This paper reviews dimensions of business intelligence applications for the travel sector and explores their use in two sample travel agencies in Turkey. Areas of business intelligence identified and elaborated on are: market intelligence, customer relationship management, yield management, employee scheduling, over/ under booking, tour management, and security management. While the literature review yielded a multitude of business intelligence tools for potential use, in-depth interviews of two travel agencies in Turkey showed that business intelligence tools were limited to booking and hotel reservation applications, and on-line accounting of transactions. These preliminary findings indicate that small to medium-sized travel operators may gain from a more comprehensive implementation of business intelligence tools in the industry, prompting a more comprehensive empirical study throughout Australia\ud about business intelligence practices in the travel sector, which is currently in progress. Such study will provide further insight into the current adoption rate of business intelligence applications across the travel industry in Australia

CogNLP-Sheffield at CMCL 2021 Shared Task: Blending cognitively inspired features with transformer-based language models for predicting eye tracking patterns

The CogNLP-Sheffield submissions to the CMCL 2021 Shared Task examine the value of a variety of cognitively and linguistically inspired features for predicting eye tracking patterns, as both standalone model inputs and as supplements to contextual word embeddings (XLNet). Surprisingly, the smaller pre-trained model (XLNet-base) outperforms the larger (XLNet-large), and despite evidence that multi-word expressions (MWEs) provide cognitive processing advantages, MWE features provide little benefit to either model