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High grade serous ovarian carcinoma (HGSOC) is characterised by poor outcome and extreme chromosome instability (CIN). Therapies targeting centrosome amplification (CA), a key mediator of chromosome missegregation and CIN, may have significant clinical utility in HGSOC. However, the prevalence of CA in HGSOC, its relationship to genomic biomarkers of CIN and its potential impact on therapeutic response have not been defined. Using high-throughput multi-regional microscopy on 287 clinical HGSOC tumour tissues and 73 ovarian cancer cell lines, we show that CA through centriole overduplication is a highly recurrent and heterogeneous feature of HGSOC and is strongly associated with CIN and genome subclonality. Cell-based studies showed that high prevalence CA is phenocopied in ovarian cancer cell lines, and that high CA is associated with increased multi-treatment resistance; most notably to paclitaxel which is the most common treatment used in HGSOC. CA in HGSOC may therefore present a potential driver of tumour evolution and a powerful biomarker for response to standard-of-care treatment.

Background One in six five 16-year-olds have a probable mental health difficulty. Of these, almost half of older teenagers and a quarter of 11–16-year-olds report having self-harmed or attempted suicide. Currently, there is little research into mental health crisis services for young people, with little understanding of what services exist, who uses them, or what works best. Question ‘How are mental health crisis responses for children and young people up to the age of 25 sustained, experienced and integrated within their local systems of services’? Objectives To describe National Health Service (NHS), local authority, education and third sector approaches to the implementation and organisation of crisis care for children and young people across England and Wales.To identify eight contrasting case studies in which to evaluate how crisis services have developed and are currently organised, sustained, experienced and integrated within the context of their local systems of services.To compare and contrast these services in the context of the available international evidence, drawing out and disseminating clear implications for the design and delivery of future crisis responses for children and young people and their families. Methods A sequential mixed methods approach, underpinned by normalisation process theory will be employed. A survey will create a detailed record of how crisis responses across England and Wales are organised, implemented and used. Subsequently, eight contrasting services in relation to geographic and socioeconomic setting, populations served, and service configuration will be identified as case studies. Interviews will be conducted with children, young people and parents/carers who have used the service, as well as commissioners, managers and practitioners. Operational policies and service usage data will also be examined. Analysis of how each service is provided, experienced, implemented and sustained will be conducted both inductively and deductively, reflecting normalisation process theory constructs.

This study describes the best hybrid energy system in terms of emissions, cost, and other factors. All the computations performed by HOMER Pro. A standalone hybrid power system model is suggested in this study. The suggested concept combines diesel generation with PV and Wind energy sources. The National Aeronautics and Space Administration (NASA) provided the data for simulation in HOMER to determine system performance. To reduce dependency on either conventional energy or renewable energy sources, a hybrid renewable energy system may be employed. Studies have shown that the suggested approach and the optimization technique for sizing standalone hybrid power systems both settle really well. The study aim is to optimize the size and expense of a renewable energy system at the chosen location in order to satisfy the electrical demand. The evaluation of the hybrid systems is based on the net present cost (NPC), levelized cost of energy (COE), initial cost, operating cost, and renewable fraction. The results support the use of RES at the chosen location, with the PV-Wind-Diesel generator system emerging as the most cost-effective RES with a COE of 0.2424 $/kWh. The outcomes are in favor of using a hybrid renewable system.

We report transport studies through Nb-based superconducting meander wires fabricated by focused ion beam (FIB) milling technique. The effect of meandering on quantum transport has been probed experimentally by a direct comparison with the pristine thin-film device before meandering. The normal metal (NM) to superconductor (SC) phase transition becomes a wide and multi-step transition by meandering. Below the transition temperature (Tc), the resistance-versus-temperature measurements reveal resistive tailing which is explained by the thermally activated phase slip (TAPS) mechanism. The TAPS fit indicates a selective region of the meander to be responsible for the resistive tailing. Besides, the phase slip (PS) mechanism in the meander is evident in its current-voltage characteristics that feature the stair-case type intermediate resistive steps during the SC-NM transition. The modulation of the intermediate resistive steps is investigated with respect to temperature and external magnetic field. It is observed that the PS events are facilitated by magnetic fields up to about 250 mT. Further, the critical current varies strongly on the temperature and magnetic field for T less than 0.5Tc and H less tahn 100 mT where it fluctuates in an oscillatory manner. Finally, Nb based meander structures can be promising candidates for future PS based studies and applications., Accepted for publication in Superconductor Science and Technology

Aging is an inevitable Biological phenomenon determined by genetic and epigenetic processes. Various studies have indicated aging is associated with progressive changes in epigenetics. Epigenetics is a dynamic process like aging and is affected by DNA methylation, histone acetylation, post translational modifications of histone proteins and varied non-coding RNA expression. These can turn on or off the genetic expression of a particular set of DNA and defects in them lead to aberrant gene expression and genomic instability. Growing number of studies have found out that these epigenomes can be modified by environmental influences, like dietary supplements, exposure to pollutants, caloric intake and biological stress. These epigenetic processes which are transgenerationally inheritable make the cellular organisms prone to aging and senescence. As these epigenetic markers are potentially modifiable, these new studies have opened up innovative therapeutic interventions in aging and other geriatric associated diseases such as Diabetes mellitus type 2, cancer, etc. The aim of this literature review is to give a brief summary of the relation between aging and modifiable factors affecting epigenetics. In the end, we highlight the different measures which are preventive and curative to arrest or modify or reverse the aging.