Evaluating the genetic consequences of population subdivision as it unfolds and how to best mitigate them: A rare story about koalas.

The genetic consequences of the subdivision of populations are regarded as significant to long-term evolution, and research has shown that the scale and speed at which this is now occurring is critically reducing the adaptive potential of most species which inhabit human-impacted landscapes. Here, we provide a rare and, to our knowledge, the first analysis of this process while it is happening and demonstrate a method of evaluating the effect of mitigation measures such as fauna crossings. We did this by using an extensive genetic data set collected from a koala population which was intensely monitored during the construction of linear transport infrastructure which resulted in the subdivision of their population. First, we found that both allelic richness and effective population size decreased through the process of population subdivision. Second, we predicted the extent to which genetic drift could impact genetic diversity over time and showed that after only 10 generations the resulting two subdivided populations could experience between 12% and 69% loss in genetic diversity. Lastly, using forward simulations we estimated that a minimum of eight koalas would need to disperse from each side of the subdivision per generation to maintain genetic connectivity close to zero but that 16 koalas would ensure that both genetic connectivity and diversity remained unchanged. These results have important consequences for the genetic management of species in human-impacted landscapes by showing which genetic metrics are best to identify immediate loss in genetic diversity and how to evaluate the effectiveness of any mitigation measures.

Early Release Science of the exoplanet WASP-39b with JWST NIRSpec PRISM.

Transmission spectroscopy1-3 of exoplanets has revealed signatures of water vapour, aerosols and alkali metals in a few dozen exoplanet atmospheres4,5. However, these previous inferences with the Hubble and Spitzer Space Telescopes were hindered by the observations' relatively narrow wavelength range and spectral resolving power, which precluded the unambiguous identification of other chemical species-in particular the primary carbon-bearing molecules6,7. Here we report a broad-wavelength 0.5-5.5 µm atmospheric transmission spectrum of WASP-39b8, a 1,200 K, roughly Saturn-mass, Jupiter-radius exoplanet, measured with the JWST NIRSpec's PRISM mode9 as part of the JWST Transiting Exoplanet Community Early Release Science Team Program10-12. We robustly detect several chemical species at high significance, including Na (19σ), H2O (33σ), CO2 (28σ) and CO (7σ). The non-detection of CH4, combined with a strong CO2 feature, favours atmospheric models with a super-solar atmospheric metallicity. An unanticipated absorption feature at 4 µm is best explained by SO2 (2.7σ), which could be a tracer of atmospheric photochemistry. These observations demonstrate JWST's sensitivity to a rich diversity of exoplanet compositions and chemical processes.

A preliminary study of cerebral blood flow, aging and dementia in people with Down syndrome.

BACKGROUND: People with Down syndrome (DS) develop Alzheimer's disease (AD) at an earlier age of onset than those with sporadic AD. AD neuropathology is typically present in DS by 40 years of age with an onset of dementia approximately 10 years later. This early onset is due to the overexpression of amyloid precursor protein from the third copy of chromosome 21. Cerebrovascular neuropathology is thought to contribute in 40-60% of cases sporadic AD. However, the vascular contribution to dementia in people with DS has been relatively unexplored. We hypothesised that vascular perfusion is compromised in older adults with DS relative to younger individuals and is further exacerbated in those with dementia. METHOD: Cerebral blood flow (CBF) was measured using pulsed arterial spin labelling in 35 cognitively characterised adults with DS (26-65 years). DS participants were also compared with 15 control subjects without DS or dementia (26-65 years). Linear regression evaluated the difference in CBF across groups and diagnosis along with assessing the association between CBF and cognitive measures within the DS cohort. RESULTS: Cerebral blood flow was significantly lower among DS participants with probable AD compared with controls (P = 0.02) and DS participants with no dementia (P = 0.01). Within the DS cohort, CBF was significantly associated with the Severe Impairment Battery (SIB) measure and the Dementia Questionnaire for People with Learning Disabilities (DLD) rating (F3,25  = 5.13; P = 0.007). Both the SIB (ß = 0.74; t = 2.71; P = 0.01) and DLD (ß = -0.96; t = -3.87; P < 0.001) indicated greater impairment as global CBF decreased. Age was significantly associated with CBF among participants with DS. There was a non-linear effect of age, whereby CBF declined more rapidly after 45 years of age. CONCLUSIONS: This preliminary study of CBF in DS indicates that cerebrovascular pathology may be a significant contributor to dementia in DS. CBF was associated with diagnosis, cognition and age. Notably, CBF decreases at a greater rate after age 45 and may represent a significant prodromal event in AD progression.

Publisher Correction: A dynamically cold disk galaxy in the early Universe.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A dynamically cold disk galaxy in the early Universe.

The extreme astrophysical processes and conditions that characterize the early Universe are expected to result in young galaxies that are dynamically different from those observed today1-5. This is because the strong effects associated with galaxy mergers and supernova explosions would lead to most young star-forming galaxies being dynamically hot, chaotic and strongly unstable1,2. Here we report the presence of a dynamically cold, but highly star-forming, rotating disk in a galaxy at redshift6 z = 4.2, when the Universe was just 1.4 billion years old. Galaxy SPT-S J041839-4751.9 is strongly gravitationally lensed by a foreground galaxy at z = 0.263, and it is a typical dusty starburst, with global star-forming7 and dust properties8 that are in agreement with current numerical simulations9 and observations10. Interferometric imaging at a spatial resolution of about 60 parsecs reveals a ratio of rotational to random motions of 9.7 ± 0.4, which is at least four times larger than that expected from any galaxy evolution model at this epoch1-5 but similar to the ratios of spiral galaxies in the local Universe11. We derive a rotation curve with the typical shape of nearby massive spiral galaxies, which demonstrates that at least some young galaxies are dynamically akin to those observed in the local Universe, and only weakly affected by extreme physical processes.

We are what we (think we) eat: The effect of expected satiety on subsequent calorie consumption.

Varying expected satiety (ES) for equi-calorie portions of different foods can affect subsequent feelings of hunger and fullness and alter consumption. To our knowledge, no study has manipulated ES for an equal portion of the same solid food, subsequent appetite has not been measured >3 h and studies have not consistently measured later consumption. Further, it is not clear whether any changes in hunger, fullness or later consumption that stem from differing ES are the result of a psychological or physiological response. The aims of this study were to manipulate ES for the same solid food on two occasions in order to compare participants' appetitive responses over a 4-h inter-meal period, to measure later consumption, and to assess whether any effect of ES on these measures was related to a physiological (i.e. total ghrelin) response. Using a within-subjects design, 26 healthy participants had their ES for omelettes manipulated experimentally, believing that a 3-egg omelette contained either 2 (small condition) or 4 (large condition) eggs. When ES was higher (large condition) participants ate significantly fewer calories at a lunchtime test meal (mean difference = 69 kcal [± 95% CI 4-136]) and consumed significantly fewer calories throughout the day (mean difference = 167 kcal [± 95% CI 26-309]). The results show that there was a significant main effect of time on hunger and fullness, but no main effect of 'portion size' (p > .05). There was also a significant interaction between time and portion size for hunger. There was no evidence for any significant differences in appetite or consumtpion resulting from changes in total ghrelin. Overall, the data suggest that ES for a solid food can be manipulated and that, when given at breakfast, having a higher ES for a meal significantly reduces lunchtime and whole day caloric consumption.

Concussion history associated with increased postural control deficits after subsequent injury.

OBJECTIVE: Postural control deficits have been extensively reported following sport-related concussions. Concussed athletes demonstrate these deficits as early as 24 h post-concussion and may persist for up to six months. Many of these prior studies have included mixed samples with prior injury history that may affect the postural control data. The purpose of this investigation was to evaluate the effect of concussion history on postural control 24-48 h following sport-related concussion in Division I athletes. APPROACH: Twenty-eight Division I athletes (seven athlete controls (CON), seven no history (SRC0), seven with a previous concussion (SRC1), and seven with 2-3 concussions (SRC3) participated in this study. All participants were assessed within 24-48 h post-subsequent SRC and performed three trials of quiet stance in the eyes closed (EC) conditions for 30 s each on a force platform (1000 Hz). The data were analyzed with root mean square (RMS) and mean excursion velocity (MEV) in the anteroposterior (AP) and mediolateral (ML) directions. Two 3 × 2 MANOVAs were run by direction for group comparisons. MAIN RESULTS: SRC2 had significantly greater RMS than CON, SRC0, and SRC1 in the AP direction and ML direction. SRC2 exhibited significantly greater AP and ML MEV than CON, SRC0, and SRC1. SIGNIFICANCE: These results demonstrate that having 2-3 prior concussions negatively affects the postural system after a subsequent head injury. Sports medicine staff should approach the recovery process with caution with those that have a prior history of concussion, due to the negative effects that history of concussion has on postural control strategies.

A qualitative study of the processes by which carers of people with dementia derive meaning from caring.

BACKGROUND: Most individuals with dementia live in the community, receiving care from family or lay carers. Carers' wellbeing, and the quality of the care they provide, partly depends on their ability to derive meaning from caring for someone with dementia. Both carers' previous relationship with their relative and the caregiving process itself contribute to this sense of meaning. However, it remains unclear why some carers derive meaning from these sources, whereas others do not. OBJECTIVE: To further explore the processes by which carers derive a sense of meaning from caring. METHODS: Representative case sampling was used to recruit a purposive sample of 20 carers for individuals living with dementia. In-depth semi-structured interviews were audio-recorded and transcribed, and analysed using pluralist qualitative methodology. RESULTS: A framework of three sources from which carers derived meaning from caring was identified, encompassing: carers' perceptions of how 'right' or 'symmetrical' caring felt in light of their current and previous relationship with the person with dementia; maintenance of a 'protected' sense of self within the care relationship; and carers' perceptions of their 'social connectedness' outside the relationships. CONCLUSION: Holistic assessment based on this framework could help to tailor individualised provision of support, foster resilience and safeguard carers' well-being.

Putative chemosensory receptors are differentially expressed in the sensory organs of male and female crown-of-thorns starfish, Acanthaster planci.

BACKGROUND: Chemosensation is a critical signalling process for all organisms and is achieved through the interaction between chemosensory receptors and their ligands. The Crown-of-thorns starfish, Acanthaster planci species complex (COTS), is a predator of coral polyps and Acanthaster cf. solaris is currently considered to be one of the main drivers of coral loss on the Great Barrier Reef in Queensland, Australia. RESULTS: This study reveals the presence of putative variant Ionotropic Receptors (IRs) which are differentially expressed in the olfactory organs of COTS. Several other types of G protein-coupled receptors such as adrenergic, metabotropic glutamate, cholecystokinin, trace-amine associated, GRL101 and GPCR52 receptors have also been identified. Several receptors display male-biased expression within the sensory tentacles, indicating possible reproductive significance. CONCLUSIONS: Many of the receptors identified in this study may have a role in reproduction and are therefore key targets for further investigation. Based on their differential expression within the olfactory organs and presence in multiple tissues, it is possible that several of these receptor types have expanded within the Echinoderm lineage. Many are likely to be species-specific with novel ligand-binding affinity and a diverse range of functions. This study is the first to describe the presence of variant Ionotropic Glutamate Receptors in any Echinoderm, and is only the second study to investigate chemosensory receptors in any starfish or marine pest. These results represent a significant step forward in understanding the chemosensory abilities of COTS.

Peeking into the Black Box of Coregistration in Clinical fMRI: Which Registration Methods Are Used and How Well Do They Perform?

BACKGROUND AND PURPOSE: Interpretation of fMRI depends on accurate functional-to-structural alignment. This study explores registration methods used by FDA-approved software for clinical fMRI and aims to answer the following question: What is the degree of misalignment when registration is not performed, and how well do current registration methods perform? MATERIALS AND METHODS: This retrospective study of presurgical fMRI for brain tumors compares nonregistered images and 5 registration cost functions: Hellinger, mutual information, normalized mutual information, correlation ratio, and local Pearson correlation. To adjudicate the accuracy of coregistration, we edge-enhanced echo-planar maps and rated them for alignment with structural anatomy. Lesion-to-activation distances were measured to evaluate the effects of different cost functions. RESULTS: Transformation parameters were congruent among Hellinger, mutual information, normalized mutual information, and the correlation ratio but divergent from the local Pearson correlation. Edge-enhanced images validated the local Pearson correlation as the most accurate. Hellinger worsened misalignment in 59% of cases, primarily exaggerating the inferior translation; no cases were worsened by the local Pearson correlation. Three hundred twenty lesion-to-activation distances from 25 patients were analyzed among nonregistered images, Hellinger, and the local Pearson correlation. ANOVA analysis revealed significant differences in the coronal (P < .001) and sagittal (P = .04) planes. If registration is not performed, 8% of cases may have a >3-mm discrepancy and up to a 5.6-mm lesion-to-activation distance difference. If a poor registration method is used, 23% of cases may have a >3-mm discrepancy and up to a 6.9-mm difference. CONCLUSIONS: The local Pearson correlation is a special-purpose cost function specifically designed for T2*-T1 coregistration and should be more widely incorporated into software tools as a better method for coregistration in clinical fMRI.

Galactic Cosmic Radiation Induces Persistent Epigenome Alterations Relevant to Human Lung Cancer.

Human deep space and planetary travel is limited by uncertainties regarding the health risks associated with exposure to galactic cosmic radiation (GCR), and in particular the high linear energy transfer (LET), heavy ion component. Here we assessed the impact of two high-LET ions 56Fe and 28Si, and low-LET X rays on genome-wide methylation patterns in human bronchial epithelial cells. We found that all three radiation types induced rapid and stable changes in DNA methylation but at distinct subsets of CpG sites affecting different chromatin compartments. The 56Fe ions induced mostly hypermethylation, and primarily affected sites in open chromatin regions including enhancers, promoters and the edges ("shores") of CpG islands. The 28Si ion-exposure had mixed effects, inducing both hyper and hypomethylation and affecting sites in more repressed heterochromatic environments, whereas X rays induced mostly hypomethylation, primarily at sites in gene bodies and intergenic regions. Significantly, the methylation status of 56Fe ion sensitive sites, but not those affected by X ray or 28Si ions, discriminated tumor from normal tissue for human lung adenocarcinomas and squamous cell carcinomas. Thus, high-LET radiation exposure leaves a lasting imprint on the epigenome, and affects sites relevant to human lung cancer. These methylation signatures may prove useful in monitoring the cumulative biological impact and associated cancer risks encountered by astronauts in deep space.

The impact of fatigue on the non-technical skills performance of critical care air ambulance clinicians.

BACKGROUND: The relationship between fatigue-related risk and impaired clinical performance is not entirely clear. Non-technical factors represent an important component of clinical performance and may be sensitive to the effects of fatigue. The hypothesis was that the sum score of overall non-technical performance is degraded by fatigue. METHODS: Nineteen physicians undertook two different simulated air ambulance missions, once when rested, and once when fatigued (randomised crossover design). Trained assessors blinded to participants' fatigue status performed detailed structured assessments based on expected behaviours in four non-technical skills domains: teamwork, situational awareness, task management, and decision making. Participants also provided self-ratings of their performance. The primary endpoint was the sum score of overall non-technical performance. RESULTS: The main finding, the overall non-technical skills performance rating of the clinicians, was better in rested than fatigued states (mean difference with 95% CI, 2.8 [2.2-3.4]). The findings remained consistent across individual non-technical skills domains; also when controlling for an order effect and examining the impact of a number of possible covariates. There was no difference in self-ratings of clinical performance between rested and fatigued states. CONCLUSION: Non-technical performance of critical care air transfer clinicians is degraded when they are fatigued. Fatigued clinicians may fail to recognise the degree to which their performance is compromised. These findings represent risk to clinical care quality and patient safety in the dynamic and isolated environment of air ambulance transfer.

The Second Victim: a Review.

Amongst the lay and media population there is a perception that pregnancy, labour and delivery is always physiological, morbidity and mortality should be "never events" and that error is the only cause of adverse events. Those working in maternity care know that it is an imperfect art, where adverse outcomes and errors will occur. When errors do occur, there is a domino effect with three groups being involved - the patient (first victim), the staff (second victims) and the organization (third victims). If the perceived expectation of patients on all clinicians is that of perfection, then clinicians may suffer the consequences of adverse outcomes in isolation and silence. More recently identification and discussion on the phenomenon of the second victim has become a popular research topic. This review aimed to study not only the phenomenon of second victim in general medical care but to also concentrate on maternity care where the expectation of perfection may be argued to be greater. Risk factors, prevalence and effect of second victims were identified from a thorough search of the literature on the topic. The review focuses on the recent research of the effect on maternity staff of adverse outcomes and discusses topical issues of resilience, disclosure, support systems as well as Learning from Excellence. It is now well documented that when staff members are supported in their disclosure of errors this domino effect is less traumatic. It is the responsibility of everyone working in healthcare to support all the victims of an error, as an ethical duty and to have a supportive culture of disclosure. In addition, balance can be provided by developing a culture of learning from excellence as well as from errors.

Over or under: hydride attack at the metal versus the coordinated nitrosyl ligand in ferric nitrosyl porphyrins.

Hydride attack at a ferric heme-NO to give an Fe-HNO intermediate is a key step in the global N-cycle. We demonstrate differential reactivity when six- and five-coordinate ferric heme-NO models react with hydride. Although Fe-HNO formation is thermodynamically favored from this reaction, Fe-H formation is kinetically favored for the 5C case.

(1)H-MRS metabolites in adults with Down syndrome: Effects of dementia.

To determine if proton magnetic resonance spectroscopy ((1)H-MRS) detect differences in dementia status in adults with Down syndrome (DS), we used (1)H-MRS to measure neuronal and glial metabolites in the posterior cingulate cortex in 22 adults with DS and in 15 age- and gender-matched healthy controls. We evaluated associations between (1)H-MRS results and cognition among DS participants. Neuronal biomarkers, including N-acetylaspartate (NAA) and glutamate-glutamine complex (Glx), were significantly lower in DS patients with Alzheimer's should probably be changed to Alzheimer (without ' or s) through ms as per the new naming standard disease (DSAD) when compared to non-demented DS (DS) and healthy controls (CTL). Neuronal biomarkers therefore appear to reflect dementia status in DS. In contrast, all DS participants had significantly higher myo-inositol (MI), a putative glial biomarker, compared to CTL. Our data indicate that there may be an overall higher glial inflammatory component in DS compared to CTL prior to and possibly independent of developing dementia. When computing the NAA to MI ratio, we found that presence or absence of dementia could be distinguished in DS. NAA, Glx, and NAA/MI in all DS participants were correlated with scores from the Brief Praxis Test and the Severe Impairment Battery. (1)H-MRS may be a useful diagnostic tool in future longitudinal studies to measure AD progression in persons with DS. In particular, NAA and the NAA/MI ratio is sensitive to the functional status of adults with DS, including prior to dementia.