The rate and spectrum of new mutations in mice inferred by long-read sequencing.

All forms of genetic variation originate from new mutations, making it crucial to understand their rates and mechanisms. Here, we use long-read sequencing from Pacific Biosciences (PacBio) to investigate de novo mutations that accumulated in 12 inbred mouse lines derived from three commonly used inbred strains (C3H, C57BL/6, and FVB) maintained for 8 to 15 generations in a mutation accumulation (MA) experiment. We built chromosome-level genome assemblies based on the MA line founders' genomes and then employed a combination of read and assembly-based methods to call the complete spectrum of new mutations.

Variation in the Spectrum of New Mutations among Inbred Strains of Mice.

The mouse serves as a mammalian model for understanding the nature of variation from new mutations, a question that has both evolutionary and medical significance. Previous studies suggest that the rate of single-nucleotide mutations (SNMs) in mice is ∼50% of that in humans. However, information largely comes from studies involving the C57BL/6 strain, and there is little information from other mouse strains.

The Transitioning From Pediatric to Adult Inflammatory Bowel Disease Services: A Qualitative Study of Adolescents and Their Parents.

Background: Inflammatory bowel disease (IBD) often has its onset during late childhood and adolescence, a time of significant change. Young people may be required to transition from a pediatric to an adult IBD service during this time. The transition from pediatric to adult services can be a high-risk period for poor outcomes for emerging adults with IBD.

Online medical student OSCE examinations during the first three years of the COVID-19 pandemic compared to three years pre-pandemic: An Australian experience in psychiatry and addiction medicine.

Purpose: We have evaluated the final-year Psychiatry and Addiction Medicine (PAM) summative Objective Structured Clinical Examination (OSCE) examinations in a four-year graduate medical degree program, for the previous three years as a baseline comparator, and during three years of the COVID-19 pandemic (2020-2022).

Methods: A de-identified analysis of medical student summative OSCE examination performance, and comparative review for the 3 years before, and for each year of the pandemic.

Results: Internal reliability in test scores as measured by -squared remained the same or increased following the start of the pandemic.

Aripiprazole, brexpiprazole, and cariprazine can affect milk supply: Advice to breastfeeding mothers.

Objective: We sought to review the effects of Dopamine Receptor Partial Agonist (DRPA) antipsychotic medications on milk supply and breastfeeding.

Method: Narrative review of selected literature including animal and human data.

Results: Scant case study evidence suggests that DRPAs may lead to reduced milk supply for some.

Commentary on alignment of medical student assessment and vocational training in psychiatry and addiction medicine.

Objective: To comment upon the potential for alignment of medical student assessment and vocational specialist training through the RANZCP-CanMEDS model of Entrustable Professional Activities (EPAs) and Workplace-Based Assessments (WBAs). We discuss a specific example of such an alignment in an Australian graduate medical school in Psychiatry and Addiction Medicine.

Conclusions: Vocational training models of assessment, such as the RANZCP specialist training program for psychiatrists, can potentially be mapped to medical student education in formative and summative assessment through CanMEDs-based EPAs and WBAs, to assist in transition to specialist training.

Rates and spectra of de novo structural mutations in .

Genetic variation originates from several types of spontaneous mutation, including single-nucleotide substitutions, short insertions and deletions (indels), and larger structural changes. Structural mutations (SMs) drive genome evolution and are thought to play major roles in evolutionary adaptation, speciation, and genetic disease, including cancers. Sequencing of mutation accumulation (MA) lines has provided estimates of rates and spectra of single-nucleotide and indel mutations in many species, yet the rate of new SMs is largely unknown.

The distribution of fitness effects of spontaneous mutations in Chlamydomonas reinhardtii inferred using frequency changes under experimental evolution.

The distribution of fitness effects (DFE) for new mutations is fundamental for many aspects of population and quantitative genetics. In this study, we have inferred the DFE in the single-celled alga Chlamydomonas reinhardtii by estimating changes in the frequencies of 254 spontaneous mutations under experimental evolution and equating the frequency changes of linked mutations with their selection coefficients. We generated seven populations of recombinant haplotypes by crossing seven independently derived mutation accumulation lines carrying an average of 36 mutations in the haploid state to a mutation-free strain of the same genotype.

Recommendations for improving statistical inference in population genomics.

The field of population genomics has grown rapidly in response to the recent advent of affordable, large-scale sequencing technologies. As opposed to the situation during the majority of the 20th century, in which the development of theoretical and statistical population genetic insights outpaced the generation of data to which they could be applied, genomic data are now being produced at a far greater rate than they can be meaningfully analyzed and interpreted. With this wealth of data has come a tendency to focus on fitting specific (and often rather idiosyncratic) models to data, at the expense of a careful exploration of the range of possible underlying evolutionary processes.

Final-year medical student Psychiatry and Addiction Medicine synchronous summative tele-assessments during a COVID-19 Delta-variant stay-at-home lockdown.

Objective: We describe the planning, process and evaluation of final-year Psychiatry and Addiction Medicine summative assessments in a four-year graduate medical degree program, during a COVID-19 Delta-variant public health stay-at-home lockdown.

Conclusions: We conducted separate written and clinical synchronous (real-time simultaneous) tele-assessments. We used online assessment technology with students, examiners and simulated patients, all in different physical locations.

Seeing it clearly: How to use graphics to guide collaborative consultation in pregnancy.

Objective: This study aims to examine the use of decision aids which may improve shared decision making through an exploration of risk apprehension and modes of collaborative communication.

Conclusions: Decision aids such as graphics have a key role in facilitating shared treatment decision making, perhaps particularly in perinatal mental health care. They are most useful within a trusting, two-way conversation.

Criminal and financial penalties for clinicians in the ACT Mental Health Act weigh more heavily on senior doctors.

Objective: We sought to assess the attitudes of ACT public psychiatry doctors towards the financial and criminal penalties in the ACT Mental Health Act 2015.

Method: Baseline attitude was surveyed with an 11-item 5-point Likert scale. Education was then provided about the offences outlined in the Act and the associated penalties.

Cis-regulatory evolution spotlights species differences in the adaptive potential of gene expression plasticity.

Phenotypic plasticity is the variation in phenotype that a single genotype can produce in different environments and, as such, is an important component of individual fitness. However, whether the effect of new mutations, and hence evolution, depends on the direction of plasticity remains controversial. Here, we identify the cis-acting modifications that have reshaped gene expression in response to dehydration stress in three Arabidopsis species.

Conduct and evaluation of final-year medical student summative assessments in Psychiatry and Addiction Medicine during COVID-19: an Australian University Medical School experience.

Objective: To describe and share with the medical education community, the conduct and evaluation of summative graduate medical student assessments in Psychiatry and Addiction Medicine during COVID-19 at an Australian university.

Methods: Summative assessments were redesigned as follows: written assessments were administered via an online platform (WATTLE), while the Objective Structured Clinical Examinations (OSCE) were conducted via a secure video-conferencing software (Zoom).

Results: Our preliminary analysis of the summative assessments indicated that both examiners and students adapted to the format, with overall performance of the students showing no variation due to timing of the assessment (earlier versus later in the day) and performances similar to face-to-face assessments in previous years.

De Novo Mutation Rate Variation and Its Determinants in Chlamydomonas.

De novo mutations are central for evolution, since they provide the raw material for natural selection by regenerating genetic variation. However, studying de novo mutations is challenging and is generally restricted to model species, so we have a limited understanding of the evolution of the mutation rate and spectrum between closely related species. Here, we present a mutation accumulation (MA) experiment to study de novo mutation in the unicellular green alga Chlamydomonas incerta and perform comparative analyses with its closest known relative, Chlamydomonas reinhardtii.

Comparative genomics of Chlamydomonas.

Despite its role as a reference organism in the plant sciences, the green alga Chlamydomonas reinhardtii entirely lacks genomic resources from closely related species. We present highly contiguous and well-annotated genome assemblies for three unicellular C. reinhardtii relatives: Chlamydomonas incerta, Chlamydomonas schloesseri, and the more distantly related Edaphochlamys debaryana.

Inbred lab mice are not isogenic: genetic variation within inbred strains used to infer the mutation rate per nucleotide site.

For over a century, inbred mice have been used in many areas of genetics research to gain insight into the genetic variation underlying traits of interest. The generalizability of any genetic research study in inbred mice is dependent upon all individual mice being genetically identical, which in turn is dependent on the breeding designs of companies that supply inbred mice to researchers. Here, we compare whole-genome sequences from individuals of four commonly used inbred strains that were procured from either the colony nucleus or from a production colony (which can be as many as ten generations removed from the nucleus) of a large commercial breeder, in order to investigate the extent and nature of genetic variation within and between individuals.

Flattening the curve of COVID-19 for medical education in psychiatry and addiction medicine.

Objective: To describe the context, challenges and responses to COVID-19 public health measures for medical education in psychiatry, with an emphasis on sharing strategies for ongoing COVID-19 challenges.

Conclusion: The rapidity of COVID-19 public health measures instituted in Australia required swift action for medical education to address lockdowns of student clinical placements. The responses included a transition to interim online learning followed by a return to truncated clinical placements renegotiated to conform to public health measures.

Telehealth mental health services during COVID-19: summary of evidence and clinical practice.

Objective: To provide a rapid clinical update on the evidence for telehealth in mental healthcare in the context of the COVID-19 pandemic public health measures.

Conclusions: Telehealth has been rapidly implemented in metropolitan and rural settings and the existing evidence base demonstrates that it represents an effective mode of service delivery.