Spatial prioritization for widespread invasive species control: Trade-offs between current impact and future spread.

Spatially explicit prioritization of invasive species control is a complex issue, requiring consideration of trade-offs between immediate and future benefits. This study aimed to prioritize management efforts to account for current and future threats from widespread invasions and examine the strength of the trade-off between these different management goals. As a case study, we identified spatially explicit management priorities for the widespread invasion of introduced willow into riparian and wetland habitats across a 102,145-km2 region in eastern Australia. In addition to targeting places where willow threatens biodiversity now, a second set of management goals was to limit reinfestation and further spread that could occur via two different mechanisms (downstream and by wind). A model of likely willow distribution across the region was combined with spatial data for biodiversity (native vegetation, threatened species and communities), ecological conditions, management costs, and two potential dispersal layers. We used systematic conservation planning software (Zonation) to prioritize where willow management should be focussed across more than 100,000 catchments for a range of different scenarios that reflected different weights between management goals. For willow invasion, we found that we could prioritize willow management to reduce the future threat of dispersal downstream with little reduction in the protection of biodiversity. However, accounting for future threats from wind dispersal resulted in a stronger trade-off with protection of threatened biodiversity. The strongest trade-off was observed when both dispersal mechanisms were considered together. This study shows that considering current and future goals together offers the potential to substantially improve conservation outcomes for invasive species management. Our approach also informs land managers about the relative trade-offs among different management goals under different control scenarios, helping to make management decisions more transparent. This approach can be used for other widespread invasive species to help improve invasive species management decisions.

SoxY gene family expansion underpins adaptation to diverse hosts and environments in symbiotic sulfide oxidizers.

Sulfur-oxidizing bacteria (SOB) have developed distinct ecological strategies to obtain reduced sulfur compounds for growth. These range from specialists that can only use a limited range of reduced sulfur compounds to generalists that can use many different forms as electron donors. Forming intimate symbioses with animal hosts is another highly successful ecological strategy for SOB, as animals, through their behavior and physiology, can enable access to sulfur compounds. Symbioses have evolved multiple times in a range of animal hosts and from several lineages of SOB. They have successfully colonized a wide range of habitats, from seagrass beds to hydrothermal vents, with varying availability of symbiont energy sources. Our extensive analyses of sulfur transformation pathways in 234 genomes of symbiotic and free-living SOB revealed widespread conservation in metabolic pathways for sulfur oxidation in symbionts from different host species and environments, raising the question of how they have adapted to such a wide range of distinct habitats. We discovered a gene family expansion of soxY in these genomes, with up to five distinct copies per genome. Symbionts harboring only the "canonical" soxY were typically ecological "specialists" that are associated with specific host subfamilies or environments (e.g., hydrothermal vents, mangroves). Conversely, symbionts with multiple divergent soxY genes formed versatile associations across diverse hosts in various marine environments. We hypothesize that expansion and diversification of the soxY gene family could be one genomic mechanism supporting the metabolic flexibility of symbiotic SOB enabling them and their hosts to thrive in a range of different and dynamic environments.IMPORTANCESulfur metabolism is thought to be one of the most ancient mechanisms for energy generation in microorganisms. A diverse range of microorganisms today rely on sulfur oxidation for their metabolism. They can be free-living, or they can live in symbiosis with animal hosts, where they power entire ecosystems in the absence of light, such as in the deep sea. In the millions of years since they evolved, sulfur-oxidizing bacteria have adopted several highly successful strategies; some are ecological "specialists," and some are "generalists," but which genetic features underpin these ecological strategies are not well understood. We discovered a gene family that has become expanded in those species that also seem to be "generalists," revealing that duplication, repurposing, and reshuffling existing genes can be a powerful mechanism driving ecological lifestyle shifts.

A comparison of frailty measures in population-based data for patients with colorectal cancer.

BACKGROUND: Numerous studies have revealed age-related inequalities in colorectal cancer care. Increasing levels of frailty in an ageing population may be contributing to this, but quantifying frailty in population-based studies is challenging. OBJECTIVE: To assess the feasibility, validity and reliability of the Hospital Frailty Risk Score (HFRS), the Secondary Care Administrative Records Frailty (SCARF) index and the frailty syndromes (FS) measures in a national colorectal cancer cohort. DESIGN: Retrospective population-based study using 136,008 patients with colorectal cancer treated within the English National Health Service. METHODS: Each measure was generated in the dataset to assess their feasibility. The diagnostic codes used in each measure were compared with those in the Charlson Comorbidity Index (CCI). Validity was assessed using the prevalence of frailty and relationship with 1-year survival. The Brier score and the c-statistic were used to assess performance and discriminative ability of models with included each measure. RESULTS: All measures demonstrated feasibility, validity and reliability. Diagnostic codes used in SCARF and CCI have considerable overlap. Prevalence of frailty determined by each differed; SCARF allocating 55.4% of the population to the lowest risk group compared with 85.1% (HFRS) and 81.2% (FS). HFRS and FS demonstrated the greatest difference in 1-year overall survival between those with the lowest and highest measured levels of frailty. Differences in model performance were marginal. CONCLUSIONS: HFRS, SCARF and FS all have value in quantifying frailty in routine administrative health care datasets. The most suitable measure will depend on the context and requirements of each individual epidemiological study.

Impact of freshwater rearing history on Atlantic salmon gill response to viral stimulation post seawater transfer.

Land-based recirculating aquaculture systems (RAS) have risen in prevalence in recent years for Atlantic salmon production, enabling intensive production which allows increased growth and environmental control, but also having the potential for reducing water use and eutrophication. The Atlantic salmon has an anadromous life history with juvenile stages in freshwater (FW) and on-growing in seawater (SW), enabled by a transformational process known as smoltification. The timing of smoltification and transfer of smolts from FW to SW is critical under commercial production with high mortalities during this period. The impact of FW rearing system on immune function following seawater transfer (SWT) is not well understood. In this study parr were raised in either RAS or a traditional open-LOCH system until smolting and then transferred to a common marine environment. Two-weeks post-SWT fish were immune stimulated with a viral mimic (poly I:C) for 24 h to assess the ability to mount an antiviral immune response, assessed by whole transcriptome analysis of gill tissue, an important immune organ in fish. We show that unstimulated smolts reared in the LOCH had higher immune gene expression than those reared in RAS as determined by functional analysis. However, following stimulation, smolts reared in the RAS mounted a greater magnitude of response with a suite of immune genes displaying higher fold induction of transcription compared to LOCH reared smolts. We suggest RAS smolts have a lower steady state immune-associated transcriptome likely due to an unvarying environment, in terms of environmental factors and lack of exposure to pathogens, which shows a compensatory mechanism following stimulation allowing immune 'catch-up' with those reared in the LOCH. Alternatively, the RAS fish are experiencing an excessive response to the immune stimulation.

Neuropathy target esterase activity defines phenotypes among PNPLA6 disorders.

Biallelic pathogenic variants in the PNPLA6 gene cause a broad spectrum of disorders leading to gait disturbance, visual impairment, anterior hypopituitarism and hair anomalies. PNPLA6 encodes neuropathy target esterase (NTE), yet the role of NTE dysfunction on affected tissues in the large spectrum of associated disease remains unclear. We present a systematic evidence-based review of a novel cohort of 23 new patients along with 95 reported individuals with PNPLA6 variants that implicate missense variants as a driver of disease pathogenesis. Measuring esterase activity of 46 disease-associated and 20 common variants observed across PNPLA6-associated clinical diagnoses unambiguously reclassified 36 variants as pathogenic and 10 variants as likely pathogenic, establishing a robust functional assay for classifying PNPLA6 variants of unknown significance. Estimating the overall NTE activity of affected individuals revealed a striking inverse relationship between NTE activity and the presence of retinopathy and endocrinopathy. This phenomenon was recaptured in vivo in an allelic mouse series, where a similar NTE threshold for retinopathy exists. Thus, PNPLA6 disorders, previously considered allelic, are a continuous spectrum of pleiotropic phenotypes defined by an NTE genotype:activity:phenotype relationship. This relationship, and the generation of a preclinical animal model, pave the way for therapeutic trials, using NTE as a biomarker.

The impact of inversions across 33,924 families with rare disease from a national genome sequencing project.

Detection of structural variants (SVs) is currently biased toward those that alter copy number. The relative contribution of inversions toward genetic disease is unclear. In this study, we analyzed genome sequencing data for 33,924 families with rare disease from the 100,000 Genomes Project. From a database hosting >500 million SVs, we focused on 351 genes where haploinsufficiency is a confirmed disease mechanism and identified 47 ultra-rare rearrangements that included an inversion (24 bp to 36.4 Mb, 20/47 de novo). Validation utilized a number of orthogonal approaches, including retrospective exome analysis. RNA-seq data supported the respective diagnoses for six participants. Phenotypic blending was apparent in four probands. Diagnostic odysseys were a common theme (>50 years for one individual), and targeted analysis for the specific gene had already been performed for 30% of these individuals but with no findings. We provide formal confirmation of a European founder origin for an intragenic MSH2 inversion. For two individuals with complex SVs involving the MECP2 mutational hotspot, ambiguous SV structures were resolved using long-read sequencing, influencing clinical interpretation. A de novo inversion of HOXD11-13 was uncovered in a family with Kantaputra-type mesomelic dysplasia. Lastly, a complex translocation disrupting APC and involving nine rearranged segments confirmed a clinical diagnosis for three family members and resolved a conundrum for a sibling with a single polyp. Overall, inversions play a small but notable role in rare disease, likely explaining the etiology in around 1/750 families across heterogeneous clinical cohorts.

Subjective hearing loss is not associated with an increased risk of Alzheimer's disease dementia.

Hearing loss is a risk-factor for dementia but the reasons for this are unclear. Subjective hearing loss is related to increased future dementia risk, however, this metric has not been previously examined with cognitive, neuroimaging and biochemical measures that are relevant to Alzheimer's disease. We assessed Cognitively Normal and Mild Cognitively Impaired participants from the Alzheimer's Disease Neuroimaging Initiative with subjective hearing loss to examine if they had faster decline in episodic memory scores, hippocampal volume and greater pTau positivity. The likelihood of a dementia diagnosis in hearing impaired participants over a 5-year period was also assessed. There were no statistically significant differences between the hearing subgroups over a 5-year period nor were there in conversions to a dementia diagnosis. Objective hearing loss metrics may provide a more reliable link between hearing loss and dementia risk.

Preclinical models of bladder cancer: BBN and beyond.

Preclinical modelling is a crucial component of advancing the understanding of cancer biology and therapeutic development. Several models exist for understanding the pathobiology of bladder cancer and evaluating therapeutics. N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)-induced bladder cancer is a commonly used model that recapitulates many of the features of human disease. Particularly in mice, BBN is a preferred laboratory model owing to a high level of reproducibility, high genetic fidelity to the human condition, and its relative ease of use. However, important aspects of the model are often overlooked in laboratory studies. Moreover, the advent of new models has yielded a variety of methodologies that complement the use of BBN. Toxicokinetics, histopathology, molecular genetics and sex can differ between available models and are important factors to consider in bladder cancer modelling.

A profile of urban agricultural growers, organizations, their needs, and challenges in the Northeastern United States.

Urban agriculture is increasingly valued as a strategy for improving quality of life in cities, but urban growers face challenges and often lack coordinated support from governments and the agricultural industry. We surveyed urban growers through an online survey, primarily in the Northeastern United States, to develop a profile of growers and associated organizations, assess the current state of urban agriculture, and determine how universities could help meet their needs. A total of 394 respondents completed the survey and most urban growers were white (non-Hispanic) and younger than 45 years old. Women and men were in almost equal proportion. Urban growers were well-educated, but most did not receive a degree in agriculture. Urban agriculture in our study area was dominated by relatively small non-profit organizations and home and community gardens were the most common types of organizations. Urban agricultural organizations want to improve environmental sustainability and socio-cultural conditions through food access and security, regardless of their tax status. Urban growers face diverse barriers and challenges and the most ubiquitous barriers and challenges reported by respondents were related to availability of land and long-term access in urban areas. Many respondents received low revenue or were operating at a net loss even though they reported diverse income streams. Respondents need a wide range of training, including in traditional agricultural topics as well as financial management and business trainings. Universities can play a key role in promoting urban agriculture by offering training and research. Workforce development is a large priority among universities, so urban growers should regularly be consulted, and the results shared with career and workforce development professionals and researchers in urban areas to identify training and research that meets the needs of stakeholders.

Assessing and forecasting collective urban heat exposure with smart city digital twins.

Due to population growth, climate change, and the urban heat island effect, heat exposure is becoming an important issue faced by urban built environments. Heat exposure assessment is a prerequisite for mitigation measures to reduce the impact of heat exposure. However, there is limited research on urban heat exposure assessment approaches that provides fine-scale spatiotemporal heat exposure information, integrated with meteorological status and human collective exposure as they move about in cities, to enable proactive heat exposure mitigation measures. Smart city digital twins (SCDTs) provide a new potential avenue for addressing this gap, enabling fine spatiotemporal scales, human-infrastructure interaction modeling, and predictive and decision support capabilities. This study aims to develop and test an SCDT for collective urban heat exposure assessment and forecasting. Meteorological sensors and computer vision techniques were implemented in Columbus, Georgia, to acquire temperature, humidity, and passersby count data. These data were then integrated into a collective temperature humidity index. A time-series prediction model and a crowd simulation were employed to predict future short-term heat exposures based on the data accumulated by this SCDT and to support heat exposure mitigation efforts. The results demonstrate the potential of SCDT to enhance public safety by providing city officials with a tool for discovering, predicting, and, ultimately, mitigating community exposure to extreme heat.

Trajectories of health-related quality of life following road trauma: Latent growth mixture modeling across a 12-month cohort study.

INTRODUCTION: Health-related quality of life (HRQoL) should be considered when evaluating the burden of road trauma (RT) injuries. This study aimed to identify distinct HRQoL trajectories following minor to severe RT injury and determine characteristics of trajectory membership. METHODS: This prospective inception cohort study recruited 1480 RT survivors from three emergency departments in British Columbia, Canada (July 2018 - March 2020). HRQoL outcome was measured with the Short Form 12 survey (SF-12) and the 5-level version of the EuroQol instrument (EQ-5D-5L) at baseline (pre-injury) and at 2, 4, 6, and 12 months post-injury. Potential predictors of outcome trajectory included sociodemographic, psychological, medical, crash, and injury factors collected at baseline. We used a latent growth mixture model to identify distinct recovery trajectories and multinomial logistic regression to determine predictors of trajectory membership. RESULTS: Three distinct HRQoL trajectories were identified for SF-12 subscales and EQ-5D-5L measures: Low/Moderate-Stable, High-Large decline, and High-Slight decline. Participants in the Low/Moderate-Stable trajectory had persistent low to moderate HRQoL before and after the injury. Those in the High-Large decline trajectory had good pre-injury HRQoL followed by persistently decreased HRQoL afterwards. The High-Slight decline trajectory was characterized by good pre-injury HRQoL and only a slight decline afterwards. Participants in the Low/Moderate-Stable and High-Large decline trajectories were considered at risk of permanently poor HRQoL following RT injury given their low HRQoL over a long period of time. Characteristics that placed participants in the Low/Moderate-Stable trajectory were older age, female gender, poor pre-injury health (medical comorbidity, prescribed medication use, complaints in the injured body area(s)), pre-injury somatic symptoms, pain catastrophizing or psychological distress, injury severity (ISS) and injury pain. Patients with head injury were less likely to be in the Low/Moderate-Stable trajectory. Risk factors for membership in the High-Large decline trajectory included older age (for physical HRQoL), younger age (for mental HRQoL), female gender, living alone, pre-injury psychological distress, ISS, injury pain, no expectations for a fast recovery, as well as head injuries, spine/back injuries or lower extremity injuries. CONCLUSIONS: This study highlighted the heterogeneity of HRQoL trajectories following RT injury and the importance of considering differences between characteristics of survivors. In addition to injury type and severity, outcome is related to demographic factors, pre-injury health and pre-injury psychological factors.

Associations between multimorbidity and neuropathology in dementia: consideration of functional cognitive disorders, psychiatric illness and dementia mimics.

BACKGROUND: Multimorbidity, the presence of two or more health conditions, has been identified as a possible risk factor for clinical dementia. It is unclear whether this is due to worsening brain health and underlying neuropathology, or other factors. In some cases, conditions may reflect the same disease process as dementia (e.g. Parkinson's disease, vascular disease), in others, conditions may reflect a prodromal stage of dementia (e.g. depression, anxiety and psychosis). AIMS: To assess whether multimorbidity in later life was associated with more severe dementia-related neuropathology at autopsy. METHOD: We examined ante-mortem and autopsy data from 767 brain tissue donors from the UK, identifying physical multimorbidity in later life and specific brain-related conditions. We assessed associations between these purported risk factors and dementia-related neuropathological changes at autopsy (Alzheimer's-disease related neuropathology, Lewy body pathology, cerebrovascular disease and limbic-predominant age-related TDP-43 encephalopathy) with logistic models. RESULTS: Physical multimorbidity was not associated with greater dementia-related neuropathological changes. In the presence of physical multimorbidity, clinical dementia was less likely to be associated with Alzheimer's disease pathology. Conversely, conditions which may be clinical or prodromal manifestations of dementia-related neuropathology (Parkinson's disease, cerebrovascular disease, depression and other psychiatric conditions) were associated with dementia and neuropathological changes. CONCLUSIONS: Physical multimorbidity alone is not associated with greater dementia-related neuropathological change; inappropriate inclusion of brain-related conditions in multimorbidity measures and misdiagnosis of neurodegenerative dementia may better explain increased rates of clinical dementia in multimorbidity.

Racial Differences in the Detection Rate of Bladder Cancer Using Blue Light Cystoscopy: Insights from a Multicenter Registry.

The use of blue light cystoscopy (BLC) has been shown to improve bladder tumor detection. However, data demonstrating the efficacy of BLC across different races are limited. Herein, we aim to evaluate heterogeneity in the characteristics of BLC for the detection of malignant lesions among various races. Clinicopathologic information was collected from patients enrolled in the multi-institutional Cysview® registry (2014-2021) who underwent transurethral resection or biopsy of bladder tumors. Outcome variables included sensitivity and negative and positive predictive values of BLC and white light cystoscopy (WLC) for the detection of malignant lesions among various races. Overall, 2379 separate lesions/tumors were identified from 1292 patients, of whom 1095 (85%) were Caucasian, 96 (7%) were African American, 51 (4%) were Asian, and 50 (4%) were Hispanic. The sensitivity of BLC was higher than that of WLC in the total cohort, as well as in the Caucasian and Asian subgroups. The addition of BLC to WLC increased the detection rate by 10% for any malignant lesion in the total cohort, with the greatest increase in Asian patients (18%). Additionally, the positive predictive value of BLC was highest in Asian patients (94%), while Hispanic patients had the highest negative predictive value (86%). Our study showed that regardless of race, BLC increases the detection of bladder cancer when combined with WLC.

Delirium is more common and associated with worse outcomes in Parkinson's disease compared to older adult controls: results of two prospective longitudinal cohort studies.

BACKGROUND: Inpatient prevalence of Parkinson's disease (PD) delirium varies widely across the literature. Delirium in general older populations is associated with adverse outcomes, such as increased mortality, dementia, and institutionalisation. However, to date there are no comprehensive prospective studies in PD delirium. This study aimed to determine delirium prevalence in hospitalised PD participants and the association with adverse outcomes, compared to a control group of older adults without PD. METHODS: Participants were hospitalised inpatients from the 'Defining Delirium and its Impact in Parkinson's Disease' and the 'Delirium and Cognitive Impact in Dementia' studies comprising 121 PD participants and 199 older adult controls. Delirium was diagnosed prospectively using the Diagnostic and Statistical Manual of Mental Disorders 5th Edition criteria. Outcomes were determined by medical note reviews and/or home visits 12 months post hospital discharge. RESULTS: Delirium was identified in 66.9% of PD participants compared to 38.7% of controls (p < 0.001). In PD participants only, delirium was associated with a significantly higher risk of mortality (HR = 3.3 (95% confidence interval [CI] = 1.3-8.6), p = 0.014) and institutionalisation (OR = 10.7 (95% CI = 2.1-54.6), p = 0.004) 12 months post-discharge, compared to older adult controls. However, delirium was associated with an increased risk of developing dementia 12 months post-discharge in both PD participants (OR = 6.1 (95% CI = 1.3-29.5), p = 0.024) and in controls (OR = 13.4 (95% CI = 2.5-72.6), p = 0.003). CONCLUSION: Delirium is common in hospitalised PD patients, affecting two thirds of patients, and is associated with increased mortality, institutionalisation, and dementia. Further research is essential to understand how to accurately identify, prevent and manage delirium in people with PD who are in hospital.

Twelve-month recovery following road trauma: Results from an inception cohort in Vancouver, Canada.

BACKGROUND: Injury-related disability following road trauma is a major public health concern. Unfortunately, outcome following road trauma and risk factors for poor recovery are inadequately studied, especially for road trauma survivors with minor injuries that do not require hospitalization. OBJECTIVES: This manuscript reports 12-month recovery outcomes for a large cohort of road trauma survivors. METHODS: This was a prospective, observational inception cohort study of 1,480 road trauma survivors recruited between July 2018 and March 2020 from 3 trauma centres in British Columbia, Canada. Participants were aged ≥16 years and arrived in a participating emergency department within 24 h of a motor vehicle collision. Data on baseline health and injury severity were collected from structured interviews and medical records. Outcome measures, including the SF-12, were collected during follow-up interviews at 2, 4, 6 and 12 months. Predictors of recovery outcomes were identified using Cox proportional hazards models and summarized using hazard ratios. RESULTS: Only 42 % of participants self-reported full recovery and only 66 % reported a return to usual daily activities. Females, older individuals, pedestrians, and those who required hospital admission had a poorer recovery than other groups. Similar patterns were observed for the SF-12 physical component. For the SF-12 mental component, no significant differences were observed between participants admitted to hospital and those discharged home from the ED. Return to work was reported by 77 % of participants who had a paying job at baseline, with no significant differences between sex and age groups. CONCLUSIONS: In a large cohort of road trauma survivors, under half self-reported full recovery one year after the injury. Poor mental health recovery was observed in both participants admitted to hospital and those discharged home from the ED. This finding may indicate a need for early intervention and continued mental health monitoring for all injured individuals, including for those with less serious injuries.

Health-related quality of life in the year following road trauma: Longitudinal analysis using piecewise latent curve modeling.

BACKGROUND: Road trauma (RT) survivors have reduced health-related quality of life (HRQoL). We identified phases and predictors of HRQoL change following RT injury. METHODS: In a prospective cohort study of 1480 Canadian RT survivors aged 16 to 103 years (July 2018 - March 2020), physical component (PCS) and mental component (MCS) summary scores from the SF-12v2 were measured pre-injury and 2, 4, 6, and 12 months post-injury and their trajectories were analyzed with piecewise latent growth curve modeling. Potential predictors of HRQoL changes included sociodemographic, psychological, medical, and trauma-related factors. RESULTS: PCS and MCS scores worsened from pre-injury to 2-months (phase 1) and then improved (phase 2), but never regained baseline values. Older age, somatic symptoms and pain catastrophizing were associated with lower preinjury PCS and MCS scores. Psychological distress was associated with lower preinjury MCS scores and higher preinjury PCS scores. Phase 1 PCS scores decreased most in females, participants with fewer pre-injury somatic symptoms and those without expectations for fast recovery. Phase 1 MCS decreases were associated with younger age, female sex, living alone, lower psychological distress, lack of expectation for fast recovery and higher injury pain. In phase 2, MCS improved most in participants not using recreational drugs; PCS improved most in participants with higher education and longer recovery expectations. LIMITATIONS: There may be recall bias with reporting pre-injury HRQoL. Selection bias is possible. CONCLUSIONS: Many factors influence HRQoL following RT. These findings may inform measures to minimize HRQoL reduction following RT and speed up subsequent recovery.

Cholinergic changes in Lewy body disease: implications for presentation, progression and subtypes.

Cholinergic degeneration is significant in Lewy body disease, including Parkinson's disease, dementia with Lewy bodies, and isolated REM sleep behavior disorder. Extensive research has demonstrated cholinergic alterations in the central nervous system of these disorders. More recently, studies have revealed cholinergic denervation in organs that receive parasympathetic denervation. This enables a comprehensive review of cholinergic changes in Lewy body disease, encompassing both central and peripheral regions, various disease stages, and diagnostic categories. Across studies, brain regions affected in Lewy body dementia show equal or greater levels of cholinergic impairment compared to the brain regions affected in Lewy body disease without dementia. This observation suggests a continuum of cholinergic alterations between these disorders. Patients without dementia exhibit relative sparing of limbic regions, whereas occipital and superior temporal regions appear to be affected to a similar extent in patients with and without dementia. This implies that posterior cholinergic cell groups in the basal forebrain are affected in the early stages of Lewy body disorders, while more anterior regions are typically affected later in the disease progression. The topographical changes observed in patients affected by comorbid Alzheimer pathology may reflect a combination of changes seen in pure forms of Lewy body disease and those seen in Alzheimer's disease. This suggests that Alzheimer co-pathology is important to understand cholinergic degeneration in Lewy body disease. Thalamic cholinergic innervation is more affected in Lewy body patients with dementia compared to those without dementia, and this may contribute to the distinct clinical presentations observed in these groups. In patients with Alzheimer's disease, the thalamus is variably affected, suggesting a different sequential involvement of cholinergic cell groups in Alzheimer's disease compared to Lewy body disease. Patients with isolated REM sleep behavior disorder demonstrate cholinergic denervation in abdominal organs that receive parasympathetic innervation from the dorsal motor nucleus of the vagus, similar to patients who experienced this sleep disorder in their prodrome. This implies that REM sleep behavior disorder is important for understanding peripheral cholinergic changes in both prodromal and manifest phases of Lewy body disease. In conclusion, cholinergic changes in Lewy body disease carry implications for understanding phenotypes and the influence of Alzheimer co-pathology, delineating subtypes and pathological spreading routes, and for developing tailored treatments targeting the cholinergic system.

Taxonomy and stratigraphic distribution of Lotagnostus (Agnostida: Agnostidae) and associated trilobites and conodonts in the Upper Cambrian (Furongian) of Laurentia.

Two Lotagnostus-dominated faunas from the Windfall Formation at Ninemile Canyon in the Antelope Range of Nevada, USA, are described: an older Lotagnostus nolani Fauna and younger L. rushtoni Fauna. The former is dominated by two morphs of Lotagnostus, one strongly scrobiculate and the other smooth to weakly scrobiculate. Both morphs fall within the broad concept advocated for L. americanus by Peng et al. (2015). The numerous (>1400 sclerites) specimens of Lotaganostus in collections of the L. nolani Fauna confirm that the two morphs do not intergrade and remain distinct throughout ontogeny. Both display multiple traits that distinguish them from the type material of L. americanus, justifying treatment as separate species. Similarly unique, diagnostic features were identified to restore the Asian species L. punctatus and L. asiaticus to full species status, whereas deficiencies in the type material for L. americanus warrant restriction of the name to the holotype. New species described from the Windfall include five agnostoids (Lotagnostus nolani, L. clarki, L. morrisoni, L. rushtoni, and Neoagnostus parki) and one trilobite (Bienvillia eurekensis). Plicatolina nyensis Taylor is reassigned to Mendoparabolina on the form of its pygidium. Conodonts from the Catlin Member of the Windfall Formation and overlying informal Caryocaris shale member of the Goodwin Formation at Ninemile Canyon provide a late Sunwaptan (Eoconodontus Zone) age for the Lotagnostus rushtoni Fauna and assign the entire Caryocaris shale to the early Ordovician Rossodus manitouensis Zone. Combined with published data on trilobite faunas, the conodont faunas confirm strong diachroneity for the top of the Catlin, and a lack of overlap in age between the Caryocaris shale and Bullwhacker Member of the Windfall in ranges to the north and east. Co-occurrence of Lotagnostus nolani and Mendoparabolina nyensis establishes age equivalence of the L. nolani Fauna with the Hedinaspis-Charchaqia (HC) Fauna at the base of the Hales Limestone in the Hot Creek Range, and earlier correlations of the latter with the L. punctatus Zone in Asia are supported. However, isolation of the HC Fauna in starved-basin deposits above a major sequence boundary at the base of the Hales, and ecologic restriction of Lotagnostus to lower slope and basinal environments that prevented association with endemic shallow marine taxa, renders correlation into the biostratigraphy of Laurentian upper slope and platform imprecise on the order of 10s, if not 100s of meters.

Extending section 12 approval under the Mental Health Act to professions other than medicine.

Applications for detention under civil sections of the England and Wales Mental Health Act 1983 require at least one recommendation from a registered medical practitioner who is approved under section 12 of the Act. The Mental Health Act 2007 introduced multi-professional approved clinicians who may act as a patient's responsible clinician with responsibilities that include renewal of detention for treatment. Approved clinicians who are medical practitioners are automatically approved for section 12 purposes, whereas other approved clinicians are not. It is argued in this paper that this inconsistency is illogical, has implications for patient care and needs to be remedied.

Adopting Optimal Statistical Practices: Graduate Programs.

In 2024, the Methodology Corner will briefly look at how we might foster enduring commitments from nurse education researchers to remain up-to-date on their statistical expertise and to use optimal statistical methods. The first column of the year specifically looks at how graduate programs might enrich their statistics curriculum in a manner that could foster an increasingly valid science of nursing education. [J Nurs Educ. 2024;63(3):197-198.].