How to use podcasts in neurology.

Virtual learning resources such as podcasts and social media are increasingly used in medical education. Podcasts are one example of virtual learning, where prerecorded audio files are available to stream or download from the internet, usually without a fee and at any time. This gives listeners flexibility in when and where they engage with the educational material, enabling learning to be better tailored to individual needs. Podcasts are often enjoyed for their relaxed and conversational style. However, listeners must be aware of the lack of external peer review and incomplete coverage of information. There are also risks inherent to distant learning, including depersonalisation of medical education. We describe the roles that podcasts now play in neurological education, exploring some of the ways that they can be used to enhance neurological training both as a learner and educator and giving our top tips, based on our own experiences, for anyone keen to add to the expanding field of available podcasts.

A reference genome for the Andean cavefish Trichomycterus rosablanca (Siluriformes, Trichomycteridae): Building genomic resources to study evolution in cave environments.

Animals living in caves are of broad relevance to evolutionary biologists interested in understanding the mechanisms underpinning convergent evolution. In the Eastern Andes of Colombia, populations from at least two distinct clades of Trichomycterus catfishes (Siluriformes) independently colonized cave environments and converged in phenotype by losing their eyes and pigmentation. We are pursuing several research questions using genomics to understand the evolutionary forces and molecular mechanisms responsible for repeated morphological changes in this system. As a foundation for such studies, here we describe a diploid, chromosome-scale, long-read reference genome for Trichomycterus rosablanca, a blind, depigmented species endemic to the karstic system of the department of Santander. The nuclear genome comprises 1 Gb in 27 chromosomes, with a 40.0× HiFi long-read genome coverage having an N50 scaffold of 40.4 Mb and N50 contig of 13.1 Mb, with 96.9% (Eukaryota) and 95.4% (Actinopterygii) universal single-copy orthologs (BUSCO). This assembly provides the first reference genome for the speciose genus Trichomycterus, serving as a key resource for research on the genomics of phenotypic evolution.

The genome sequence of Molossusnigricans (Chiroptera, Molossidae; Miller, 1902).

We present a genome assembly from an individual male Molossus nigricans (Chordata; Mammalia; Chiroptera; Molossidae). The genome sequence is 2.41 gigabases in span. The majority of the assembly is scaffolded into 24 chromosomal pseudomolecules, with the X sex chromosome assembled.

Scalable, accessible, and reproducible reference genome assembly and evaluation in Galaxy.

Improvements in genome sequencing and assembly are enabling high-quality reference genomes for all species. However, the assembly process is still laborious, computationally and technically demanding, lacks standards for reproducibility, and is not readily scalable. Here we present the latest Vertebrate Genomes Project assembly pipeline and demonstrate that it delivers high-quality reference genomes at scale across a set of vertebrate species arising over the last ~500 million years. The pipeline is versatile and combines PacBio HiFi long-reads and Hi-C-based haplotype phasing in a new graph-based paradigm. Standardized quality control is performed automatically to troubleshoot assembly issues and assess biological complexities. We make the pipeline freely accessible through Galaxy, accommodating researchers even without local computational resources and enhanced reproducibility by democratizing the training and assembly process. We demonstrate the flexibility and reliability of the pipeline by assembling reference genomes for 51 vertebrate species from major taxonomic groups (fish, amphibians, reptiles, birds, and mammals).

Early access schemes for innovative health technologies: the views of international stakeholders.

OBJECTIVES: Early access schemes (EASs) are approaches used by payers to balance and facilitate earlier patient access to innovative health technologies while evidence generation is ongoing. Schemes require investment from payers and are associated with significant risk since not all technologies will be routinely reimbursed. The purpose of this study was to gain the perspectives of policy experts about the key challenges for EASs and potential solutions for their optimal design and implementation. METHODS: Two virtual workshops were convened including (i) UK-based policy experts (England, Wales, and Scotland) and (ii) representatives from multiple healthcare systems (England, France, Sweden, Canada, Poland, and Norway). Participants were encouraged to share their experiences with EASs in their healthcare system and highlight key challenges for policy makers. Discussions were transcribed and analyzed using framework analysis. RESULTS: Participants agreed that EASs have value when targeted toward innovative technologies with the potential for significant clinical benefit in an area of high unmet need. Participants discussed potential solutions to the challenges faced by payers implementing EASs, including defining eligibility criteria, supporting evidence generation, and approaches to reimbursement. CONCLUSIONS: Participants agreed that EASs are one possible solution for their healthcare systems and have the potential to deliver significant clinical value to patients. However, widespread adoption of EASs is limited due to concerns about the risks for patients and healthcare budgets, further solutions are needed to deliver EASs for targeted therapies.

Advancing Posttraumatic Stress Disorder Diagnosis and the Treatment of Trauma in Humanitarian Emergencies via Mobile Health: Protocol for a Proof-of-Concept Nonrandomized Controlled Trial.

BACKGROUND: Decentralized health systems in low- and middle-income countries (LMICs) affected by humanitarian crises lack resources and a qualified workforce to attend to the overwhelming demand for mental health care in emergencies. Innovative approaches that are safe, cost-effective, and scalable are needed to address the burden of traumatic stress caused by emergencies. High mobile phone ownership rates combined with the precision of neural, cognitive, and biometric measures of trauma and their feasible integration with artificial intelligence makes digital app interventions a promising pathway to promote precision diagnosis and high-impact care. OBJECTIVE: This study aimed to advance methods for the objective diagnosis and treatment of trauma in emergencies across LMICs by examining neural, cognitive, and biometric markers and the efficacy of the eResilience app, a neuroscience-informed mobile health mental health app intervention, via changes in clinical symptomatology, cognitive performance, and brain activity. METHODS: Trauma-exposed African refugees residing in Australia were selected for this study. A research software version of the eResilience app with advanced monitoring capabilities was designed for this trial. Participants completed the eResilience app at home during a 7-day period. Clinical, cognitive, and electrophysiological data were collected at baseline, along with posttest measurements to examine biomarkers of trauma and the efficacy of the proposed digital intervention for the treatment of trauma and its potential outcomes, including depression, anxiety, physical symptoms, self-harm, substance misuse, and cognitive impairment. In addition, biofeedback, well-being, and subjective stress data points were collected via the app during the treatment week, followed by clinical interviews at 1, 3, 6, and 12 months after the intervention. RESULTS: Data collection was conducted between 2018 and 2020. A total of 100 participants exposed to war were screened; 75 (75%) were enrolled and assigned to a trauma-exposed control (38/75, 51%) or posttraumatic stress disorder condition (37/75, 49%); and 70 (70%) completed all baseline, treatment, and posttest assessments. A total of 89% (62/70) of those who completed the intervention opted to enroll in the 3-, 6-, and 12-month follow-ups. Data collection is complete. As of May 2022, the results of all proposed analyses are being prepared for publication. If proven efficacious, this proof-of-concept clinical trial will inform fully powered randomized clinical trials in LMICs to further develop artificial intelligence-powered, app-based diagnostic and prognostic features and determine the app's cross-cultural efficacy for the treatment of trauma in emergency settings. CONCLUSIONS: This protocol provides researchers with a comprehensive background of the study rationale, a detailed guideline for replication studies interested in examining the feasibility and efficacy of the eResilience app across varied demographics, and a robust framework for investigating low-cost objective diagnostic markers in mental health interventions. Methodological limitations and suggestions are also provided. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12616001205426; https://tinyurl.com/yckwc4d7. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/38223.

Intergenerational Transmission of Posttraumatic Stress Disorder in Australian Vietnam Veterans' Daughters and Sons: The Effect of Family Emotional Climate While Growing Up.

Posttraumatic stress disorder (PTSD) in military veterans increases the risk of PTSD in their offspring, a concept known as "intergenerational transmission;" however, the mechanism by which this transmission may occur is, as yet, undetermined. The present study included a nonclinical sample of 197 Australian Army veterans of the Vietnam War who were interviewed 17 years before in-person interviews of their adult daughters (n = 163) and sons (n = 120) were conducted. Veterans' PTSD symptoms were assessed using the Mississippi Scale for Combat-Related PTSD. Approximately 17 years later, offspring PTSD symptoms were assessed using the Clinician-Administered PTSD Scale for DSM-IV. In addition, offspring described the family emotional climate during their youth; responses were coded using the Family Affective Attitude Rating Scale (FAARS) to produce scale scores of veterans' negative, positive, and family relationship styles. A path analysis was conducted via structural equation modeling to test for significant path coefficients between veteran PTSD, family emotional climate, and offspring PTSD symptoms. For daughters, significant path coefficients were observed between veteran PTSD scores and FAARS scores, path coefficient = -.268; FAARS scores and offspring CAPS severity scores, path coefficient = -.223; and veteran PTSD scores and daughters' CAPS severity scores, path coefficient = .186. No satisfactory model could be found for sons. The results suggest that a positive emotional climate while growing up may be a significant protective factor against the development of PTSD in veterans' daughters, but other factors remain significant in veteran-to-offspring intergenerational transmission.

Family emotional climate in childhood and risk of PTSD in adult children of Australian Vietnam veterans.

The mechanisms of intergenerational transmission of posttraumatic stress disorder (PTSD) from parent to child are not yet known. We hypothesised that the mechanisms involved in trauma transmission may be dependent upon sex specific caregiver-child dyads and these dyads may have a differential impact on post-traumatic stress disorder (PTSD). A non-clinical sample of adult offspring (N = 306) of Australian Vietnam veterans was interviewed in-person to assess the relationship between family emotional climate and caregiver attachment with the offspring's adult experience of post-traumatic stress disorder (PTSD). Attachment to the veteran father was not associated with sons' PTSD, but was for daughters. Attachment to mother was associated with PTSD and depression for both sons and daughters, with positive and warm attachment related to reduced PTSD diagnosis and its symptom clusters. A less positive family emotional environment was related to increased PTSD symptoms in daughters, while for sons a negative relationship style with their mother was related to increased frequency and severity of numbing/avoidance behaviours and hyperarousal symptoms. The findings suggest that sex-related differences in caregiver-child dyads do have a differential impact on PTSD symptom domains and may be one environmental mechanism by which trauma is transmitted across generations.

Military Combat, Posttraumatic Stress Disorder, and the Course of Alcohol Use Disorders in a Cohort of Australian Vietnam War Veterans.

The present study examined the course of diagnosed alcohol use disorders (AUDs) in a cohort of Australian veterans of the Vietnam War (N = 388) who were assessed 22 and 36 years after returning home. Standardized interviews provided data on AUDs, posttraumatic stress disorder (PTSD), other psychiatric diagnoses, and combat exposure. Overall, 148 veterans (38.1%) had no history of alcohol-related diagnoses, 151 veterans (38.9%) had a past AUD diagnosis that was not current at the second assessment point, and 89 veterans (22.9%) had a current AUD diagnosis at the second assessment. Less education, lower intelligence test scores, and misconduct were individual risk factors for AUDs, as were first-interview diagnoses of PTSD, antisocial personality disorder, generalized anxiety, and dysthymia, but not depression; these variables were all nonsignificant after controlling for combat exposure and PTSD. Multinomial regression was used to assess the relative contributions of combat exposure and PTSD to the course of AUDs. Combat exposure and PTSD had different patterns of association with AUDs whereby combat exposure, but not PTSD, was associated with a history of AUDs, odds ratio (OR) = 1.02, but not with current AUDs, whereas PTSD, but not combat exposure, was associated with current AUDs, OR = 3.37. Current numbing and avoidance symptoms were associated with current AUDs, OR = 4.48. The results do not support a mutual maintenance model of PTSD and AUDs but are consistent with a self-medication model, which suggests treatment for PTSD may have beneficial effects on AUDs.

Growing up with a father with PTSD: The family emotional climate of the children of Australian Vietnam veterans.

A non-clinical sample of male Australian Vietnam veterans, their wives, and adult offspring were interviewed in-person in a national epidemiological study to assess the relationship between the mental ill-health of veterans and the emotional climate of the family while the children were growing up. Veterans were assessed 17 years before their children using standardised psychiatric diagnostic interviews. Family emotional climate was assessed using offspring ratings of parental attachment, and codings of positive and negative family relationship styles based on five minute speech samples provided by the offspring. Sons and daughters had different views of their mothers and fathers, and were less positive towards their fathers particularly if he had posttraumatic stress disorder (PTSD). Veteran PTSD and depression significantly negatively impacted the family emotional climate, while mothers' mental health was not related. Veteran PTSD symptoms were lowest in secure attachment to the veteran and highest in inconsistent attachment for both sons and daughters, but were not related to attachment to the mother. Veteran PTSD was related to daughters' but not sons' perceptions of family emotional climate. The impact of veterans' PTSD on their families' emotional climate is more marked for daughters than sons.

The mental health of sons and daughters of Australian Vietnam veterans.

Background: War service increases the risk of post-traumatic stress disorder (PTSD) to combatants, and has been shown to increase the risk of PTSD in their offspring. The extent to which there is an excess compared with the general population is not yet established, nor whether PTSD increases the risk of other psychiatric problems. Methods: A national sample of 133 sons and 182 daughters of a cohort of 179 Australian Vietnam veterans' families were assessed in person, using structured psychiatric interviews. The prevalence of trauma exposures, DSM-IV (Diagnostic and Statistical Manual of Mental Disorders Fourth Edition) diagnoses and suicidality were compared with the Australian Bureau of Statistics' 2007 National Survey of Mental Health and Wellbeing data matched for age and sex. The risk of mental health problems potentially attributable to PTSD was also assessed. Results: Sons and daughters were more likely than population expectations to report exposures to natural disasters, fire or explosions and transport accidents, and sons more likely to report exposure to toxic chemicals whereas daughters were more likely to report sexual assault. Sons and daughters had higher prevalences of alcohol and other substance dependence, depression and anxiety, and PTSD, and children's PTSD was associated with substance dependence, depression and suicidal ideation. There were strong associations between children's PTSD and comorbid conditions of substance use disorders, depression and anxiety. Conclusions: Higher rates of mental health problems in veterans' families, together with comorbidity with PTSD and the link between veterans' and children's PTSD, suggest that the effects of trauma may continue into subsequent generations.

Combat, Posttraumatic Stress Disorder, and Smoking Trajectory in a Cohort of Male Australian Army Vietnam Veterans.

Background: Whether trauma exposure itself or consequent posttraumatic stress disorder (PTSD) is primarily responsible for smoking and failure to quit remains unclear. Methods: A cohort of male Australian Vietnam veterans (N = 388) was interviewed twice, 22 and 36 years after their return to Australia using standardized psychiatric diagnostic and health interviews and assessment of combat exposure. The smoking trajectory over time revealed a spectrum of outcomes (never smoked, early quitters, late quitters, and continuing smokers). Analysis used multivariate statistics to assess the relative contributions of combat trauma exposure and PTSD while controlling for potential confounders. Results: The trajectory of smoking over time revealed that 21.9% of veterans had never smoked, 45.1% had quit smoking by the time of wave 1, 16.2% were current smokers at wave 1 who had quit by the time of wave 2, 2.8% were late adopters who were current smokers, and 13.9% were continuing smokers. Smoking was associated in single-predictor models with demographics, intelligence, combat exposure, PTSD symptom clusters and diagnosis, and alcohol disorders. Multivariate analysis revealed that PTSD, combat, and intelligence were related to the smoking spectrum but, after adding demographics and other Axis I psychiatric diagnoses, only combat remained significant. No PTSD symptom cluster uniquely predicted smoking status. Conclusions: The results suggest that trauma exposure in the form of military combat may be a more robust predictor of smoking status over time than PTSD. It may be stress itself, rather than poststress disorder, that is more germane to smoking and failure to quit. Implications: Exposure to traumatic stress and development of PTSD have been implicated separately in the maintenance of smoking. This longitudinal cohort study of smoking in war veterans up to three decades postwar enabled evaluation of traumatic stress exposure in combat and the course of PTSD in smoking and quitting while controlling for intelligence, background disadvantage, and other psychiatric conditions. Combat rather than PTSD emerged as more significant to smoking status, suggesting that it may be the traumatic stress itself rather than the development of a poststress disorder that is more germane to smoking in war veterans.

Raising the standard of care in the treatment of schizophrenia: Yes we can!

OBJECTIVE: In response to evidence of deteriorating outcomes of people with schizophrenia we recently published a critical review in the journal concerning why outcomes for schizophrenia are not improving. A published commentary on our review raised criticisms that we aim to address herein. METHOD: Published data related to four issues raised in the commentary were reviewed. RESULTS: There is a body of evidence that supports the possibility of dramatic improvements in treatment effectiveness, presented in our critical review, and these can be achieved within existing financial resources and present day understanding of the pathophysiology of schizophrenia. However, the commentary leads us to highlight four current obstacles to improving treatment effectiveness: (1) the belief of many psychiatrists that long-term antipsychotic medication raises the cardiovascular mortality rate in schizophrenia when the opposite is almost certainly the case; (2) the need to improve psychiatrist training in diagnostic and communication skills, especially with first episode presentations; (3) the requirement for comprehensive and structured assessment of the highly prevalent deficits in insight and decision making capacity associated with schizophrenia; and (4) the need for improved intervention design to minimise the impact of these deficits on treatment choice and refusal. CONCLUSION: With a sense of professional urgency, a genuinely respectful and caring partnership between clinicians, affected individuals and their families, and researchers, with relative little innovation, we conclude that the standard of care can definitely be raised now in the treatment of schizophrenia.

The Course and Correlates of Combat-Related PTSD in Australian Vietnam Veterans in the Three Decades After the War.

Australian male Vietnam veterans (N = 388) were assessed 22 and 36 years after their return to Australia using standardized diagnostic interviews, with added data from Army records and self-report questionnaires. Among veterans who ever had posttraumatic stress disorder (PTSD), 50.3% had a current diagnosis at the second assessment; of those who had a current diagnosis at Wave 1, 46.9% were also current at Wave 2. Late onset occurred for 19.0% of veterans, of whom 60.8% were current at Wave 2. Multivariate analysis compared veterans with no history of PTSD (n = 231) with veterans who had ever had PTSD (n = 157) to assess risk factors for PTSD incidence; and veterans with a history, but not current PTSD (n = 78) with veterans who had current PTSD at the second assessment (n = 79) to assess risk factors for failure to remit. Incidence was associated with lower education, shorter Army training predeployment, higher combat, excess drinking, and help-seeking after return to Australia. Prevalence was associated with having a father who saw combat in World War II, being injured in battle, having a lower intelligence test score, experiencing higher combat, and having a diagnosis of phobia at the first assessment. Only combat was common to incidence and prevalence.

The treatment of schizophrenia: Can we raise the standard of care?

OBJECTIVE: There is evidence that over time health outcomes of people with schizophrenia are deteriorating rather than improving both in terms of mortality rate and levels of morbidity, even in Australia where service resourcing is substantial. Our objective was to examine the evidence of whether poor outcomes reflect decreases in treatment effectiveness and, if so, what are the barriers to improving standards of care. This review will argue that the confidence of clinicians to diagnose schizophrenia early, and provide assertive and long-term care, may be being undermined by a series of controversies in the published literature and discrepancies in clinical practice guidelines. METHOD: A critical review was conducted of the evidence regarding six issues of high clinical relevance to the treatment of schizophrenia formulated as questions: (1) Is schizophrenia a progressive disease? (2) Does relapse contribute to disease progression and treatment resistance? (3) When should the diagnosis of schizophrenia be made? (4) Should maintenance antipsychotic medication be discontinued in fully remitted first-episode patients? (5) Do antipsychotic medications cause deleterious reductions in cortical grey matter volumes? and (6) Are long-acting injectable antipsychotics more effective in reducing relapse rate compared to oral formulations? RESULTS: There is reliable evidence for schizophrenia being a progressive disease with emergent treatment resistance in most cases, that relapse contributes to this treatment resistance, that maintenance antipsychotic medication should not be discontinued in remitted first-episode patients, that antipsychotic medication does not appear to cause deleterious grey matter volume changes, that maintenance antipsychotic medication reduces the mortality rate in schizophrenia and that long-acting injectable antipsychotics are more effective in preventing relapse than oral formulations. CONCLUSION: There is an urgent need to re-engineer the early management of schizophrenia and to routinely evaluate this type of innovation within practice-based research networks. A proposal for an assertive treatment algorithm is included.

Suicidality in Australian Vietnam veterans and their partners.

Lifetime suicidality was assessed in a cohort of 448 ageing Australian Vietnam veterans and 237 female partners during in-person structured psychiatric interviews that permitted direct comparison with age-sex matched Australian population statistics. Relative risks for suicidal ideation, planning and attempts were 7.9, 9.7 and 13.8 times higher for veterans compared with the Australian population and for partners were 6.2, 3.5 and 6.0 times higher. Odds ratios between psychiatric diagnoses and suicidality were computed using multivariate logistic regression, and suicidality severity scores were assigned from ideation, planning and attempt, and analysed using ordinal regression. PTSD, depression alcohol disorders, phobia and agoraphobia were prominent predictors of ideation, attempts and suicidal severity among veterans, while depression, PTSD, social phobia and panic disorder were prominent predictors among partners. For veterans and their partners, PTSD is a risk factor for suicidality even in the presence of other psychiatric disorders, and is stronger in Vietnam veterans than their partners.

Best practice in early psychosis intervention for Australian indigenous communities: indigenous worker consultation and service model description.

OBJECTIVE: The aim of this study was to identify promising elements of best practice relevant to mainstream mental health service (MHS) delivery of early psychosis intervention (EPI) to Indigenous communities. In a companion paper, a comprehensive literature review identified a promising service model with potential for delivering EPI: an Indigenous sub-team embedded within a mainstream health service. METHOD: This paper describes a consultation process with Indigenous Mental Health Workers (IMHWs) in south eastern Queensland. A case study of the Sunshine Coast Cultural Healing Program (CHP-SC) was carried out during the consultation process. RESULTS: IMHWs agreed that the Australian clinical guidelines for early psychosis were relevant to improving outcomes for Indigenous patients. IMHWs unanimously identified the CHP-SC as a best practice mainstream MHS for delivering EPI. The CHP-SC, which represented an Indigenous sub-team model, was found to be associated with substantially improved engagement of Indigenous young people. CONCLUSIONS: We provisionally conclude that specialist EPI could be delivered by specialist Indigenous sub-teams (rather than specialist EPI teams) embedded in mainstream MHSs that incorporate culturally safe practice and are fully integrated with Indigenous primary care services, and recommend that the model be formally evaluated.

The ecology of antibiotic use in the ICU: homogeneous prescribing of cefepime but not tazocin selects for antibiotic resistant infection.

BACKGROUND: Antibiotic homogeneity is thought to drive resistance but in vivo data are lacking. In this study, we determined the impact of antibiotic homogeneity per se, and of cefepime versus antipseudomonal penicillin/ß-lactamase inhibitor combinations (APP-ß), on the likelihood of infection or colonisation with antibiotic resistant bacteria and/or two commonly resistant nosocomial pathogens (methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa). A secondary question was whether antibiotic cycling was associated with adverse outcomes including mortality, length of stay, and antibiotic resistance. METHODS: We evaluated clinical and microbiological outcomes in two similar metropolitan ICUs, which both alternated cefepime with APP-ß in four-month cycles. All microbiological isolates and commensal samples were analysed for the presence of antibiotic-resistant bacteria including MRSA and P. aeruginosa. RESULTS: Length of stay, mortality and overall antibiotic resistance were unchanged after sixteen months. However, increased colonisation and infection by antibiotic-resistant bacteria were observed in cefepime cycles, returning to baseline in APP-ß cycles. Cefepime was the strongest risk factor for acquisition of antibiotic-resistant infection. CONCLUSIONS: Ecological effects of different ß-lactam antibiotics may be more important than specific activity against the causative agents or the effect of antibiotic homogeneity in selection for antibiotic resistance. This has important implications for antibiotic policy.