Ongoing genome doubling shapes evolvability and immunity in ovarian cancer.

Whole-genome doubling (WGD) is a common feature of human cancers and is linked to tumour progression, drug resistance, and metastasis. Here we examine the impact of WGD on somatic evolution and immune evasion at single-cell resolution in patient tumours. Using single-cell whole-genome sequencing, we analysed 70 high-grade serous ovarian cancer samples from 41 patients (30,260 tumour genomes) and observed near-ubiquitous evidence that WGD is an ongoing mutational process.

Inferring active mutational processes in cancer using single cell sequencing and evolutionary constraints.

Ongoing mutagenesis in cancer drives genetic diversity throughout the natural history of cancers. As the activities of mutational processes are dynamic throughout evolution, distinguishing the mutational signatures of 'active' and 'historical' processes has important implications for studying how tumors evolve. This can aid in understanding mutagenic states at the time of presentation, and in associating active mutational process with therapeutic resistance.

Tracking clonal evolution of drug resistance in ovarian cancer patients by exploiting structural variants in cfDNA.

Drug resistance is the major cause of therapeutic failure in high-grade serous ovarian cancer (HGSOC). Yet, the mechanisms by which tumors evolve to drug resistant states remains largely unknown. To address this, we aimed to exploit clone-specific genomic structural variations by combining scaled single-cell whole genome sequencing with longitudinally collected cell-free DNA (cfDNA), enabling clonal tracking before, during and after treatment.

Ongoing genome doubling promotes evolvability and immune dysregulation in ovarian cancer.

Whole-genome doubling (WGD) is a critical driver of tumor development and is linked to drug resistance and metastasis in solid malignancies. Here, we demonstrate that WGD is an ongoing mutational process in tumor evolution. Using single-cell whole-genome sequencing, we measured and modeled how WGD events are distributed across cellular populations within tumors and associated WGD dynamics with properties of genome diversification and phenotypic consequences of innate immunity.

HATCHet2: clone- and haplotype-specific copy number inference from bulk tumor sequencing data.

Bulk DNA sequencing of multiple samples from the same tumor is becoming common, yet most methods to infer copy-number aberrations (CNAs) from this data analyze individual samples independently. We introduce HATCHet2, an algorithm to identify haplotype- and clone-specific CNAs simultaneously from multiple bulk samples. HATCHet2 extends the earlier HATCHet method by improving identification of focal CNAs and introducing a novel statistic, the minor haplotype B-allele frequency (mhBAF), that enables identification of mirrored-subclonal CNAs.

HATCHet2: clone- and haplotype-specific copy number inference from bulk tumor sequencing data.

Multi-region DNA sequencing of primary tumors and metastases from individual patients helps identify somatic aberrations driving cancer development. However, most methods to infer copy-number aberrations (CNAs) analyze individual samples. We introduce HATCHet2 to identify haplotype- and clone-specific CNAs simultaneously from multiple bulk samples.

Spinal Fractures Incurred by Sports-Related Injuries.

Background: Sports-related injuries are the third commonest cause of spine fractures. Spinal fractures incurred as a result of partaking in sport by their nature are different from those associated with frailty and road traffic accidents. The patient demographics and nature of fractures associated with sports activities are not well documented.

Multiple-Choice versus Open-Ended Questions in Advanced Clinical Neuroanatomy: Using a National Neuroanatomy Assessment to Investigate Variability in Performance Using Different Question Types.

Methods of assessment in anatomy vary across medical schools in the United Kingdom (UK) and beyond; common methods include written, spotter, and oral assessment. However, there is limited research evaluating these methods in regards to student performance and perception. The National Undergraduate Neuroanatomy Competition (NUNC) is held annually for medical students throughout the UK.

Identifying tumor clones in sparse single-cell mutation data.

Motivation: Recent single-cell DNA sequencing technologies enable whole-genome sequencing of hundreds to thousands of individual cells. However, these technologies have ultra-low sequencing coverage (<0.5× per cell) which has limited their use to the analysis of large copy-number aberrations (CNAs) in individual cells.

The Career Impact of the National Undergraduate Neuroanatomy Competition.

Background: Neurosurgery is a notoriously difficult career to enter and requires medical students to engage in extracurricular activities to demonstrate their commitment to the specialty. The National Undergraduate Neuroanatomy Competition (NUNC) was established in 2013 as a means for students to display this commitment as well as academic ability.

Methods: A bespoke 22-item questionnaire was designed to determine career outcomes and the role of competition attendance in job applications.

Reviewing the Role of Instagram in Education: Can a Photo Sharing Application Deliver Benefits to Medical and Dental Anatomy Education?

Instagram is an increasingly popular social media site tailored towards sharing photos and videos. An audit investigating current Instagram accounts focusing on anatomy education found a variety of successful teaching styles, including clinical images, descriptive videos, multiple-choice questions, and cartoons. Utilising Instagram for educational purposes, benefits such as ease of use, hashtags, and its effectiveness in conveying visual topics should be weighed against limitations such as passive learning and the requirement of committed staff to oversee its use.

CALDER: Inferring Phylogenetic Trees from Longitudinal Tumor Samples.

Longitudinal DNA sequencing of cancer patients yields insight into how tumors evolve over time or in response to treatment. However, sequencing data from bulk tumor samples often have considerable ambiguity in clonal composition, complicating the inference of ancestral relationships between clones. We introduce Cancer Analysis of Longitudinal Data through Evolutionary Reconstruction (CALDER), an algorithm to infer phylogenetic trees from longitudinal bulk DNA sequencing data.

Spinal fractures incurred by a fall from standing height.

Objective: Falls from standing are common, particularly amongst the aging population, due to declining mobility, proprioception and vision. They are often complicated by fragility fractures, including vertebral fractures, that are associated with significant morbidity and may represent a pre-terminal condition with high one-year mortality rates.

Patients And Methods: A retrospective review of the Trauma Audit and Research Network database for a major trauma centre was conducted for all patients admitted between January 2011 and December 2016.

Rat behavior and dopamine release are modulated by conspecific distress.

Rats exhibit 'empathy' making them a model to understand the neural underpinnings of such behavior. We show data consistent with these findings, but also that behavior and dopamine (DA) release reflects subjective rather than objective evaluation of appetitive and aversive events that occur to another. We recorded DA release in two paradigms: one that involved cues predictive of unavoidable shock to the conspecific and another that allowed the rat to refrain from reward when there were harmful consequences to the conspecific.

The Efficacy of Frontline Near-Peer Teaching in a Modern Medical Curriculum.

Within medical education a reduction in curriculum time for subjects, such as anatomy puts pressure on educators to ensure the same learning outcomes are conveyed in less time. This has the potential to impact negatively on student experience. Near-peer teaching (NPT) is often praised as an effective revision tool, but its use as a frontline teaching resource remains unreported.

The Wessex modified Richmond Sedation Scale as a novel tool for monitoring patients at risk of malignant MCA syndrome.

Background: The Wessex Modified Richmond Sedation Scale (WMRSS) has been developed with the aim of improving the early identification of patients requiring decompressive hemicraniectomy for malignant middle cerebral artery syndrome (MMS). The objective of this study was to evaluate the WMRSS against the Glasgow Coma Scale (GCS).

Methods: A retrospective study was conducted of patients admitted to our unit for observation of MMS.

The benefits of being a near-peer teacher.

Background: Near-peer teaching is used in anatomy education because of its benefits to the learner, teacher and faculty members. Despite the range of reports focusing on the learner, the advantages for the teacher, which are thought to include communication skills, subject knowledge and employability, are only beginning to be explored.

Method: A questionnaire was distributed to the teachers involved in anatomy near-peer teaching at the University of Southampton and Brighton and Sussex Medical School (BSMS).