Perceptions of mental health providers of the barriers and facilitators of using and engaging youth in digital mental-health-enabled measurement based care.

Objectives: Increased rates of mental health disorders and substance use among youth and young adults have increased globally, furthering the strain on an already burdened mental health system. Digital solutions have been proposed as a potential option for the provision of timely mental health services for youth, with little research exploring mental health professional views about using such innovative tools. In Alberta, Canada, we are evaluating the implementation and integration of a digital mental health (dMH) platform into existing service pathways. Within this paper we seek to explore mental health professionals' perceptions of the barriers and facilitators that may influence their utilization of digital MH-enabled measurement-based care (MBC) with the youth who access their services. Methods: A qualitative, descriptive methodology was used to inductively generate themes from focus groups conducted with mental health professionals from specialized mental health services and primary care networks in Alberta. Results: As mental health professionals considered the barriers and facilitators of using dMH with youth, they referenced individual and family barriers and facilitators to consider. Providers highlighted perceived barriers, including: first, cultural stigma, family apprehension about mental health care, and parental access to dMH and MBC as deterrents to providers adopting digital platforms in routine care; second, perceptions of increased responsibility and liability for youth in crisis; third, perception that some psychiatric and neurodevelopmental disorders in youth are not amenable to dMH; fourth, professionals contemplated youth readiness to engage with dMH-enabled MBC. Participants also highlighted pertinent facilitators to dMH use, noting: first, the suitability of dMH for youth with mild mental health concerns; second, youth motivated to report their changes in mental health symptoms; and lastly, youth proficiency and preference for dMH options. Conclusions: By identifying professionals' perceptions of barriers and facilitators for youth users, we may better understand how to address misconceptions about who is eligible and appropriate for dMH through training and education.

Acidithiobacillia class members originating at sites within the Pacific Ring of Fire and other tectonically active locations and description of the novel genus 'Igneacidithiobacillus'.

Recent studies have expanded the genomic contours of the Acidithiobacillia, highlighting important lacunae in our comprehension of the phylogenetic space occupied by certain lineages of the class. One such lineage is 'Igneacidithiobacillus', a novel genus-level taxon, represented by 'Igneacidithiobacillus copahuensis' VAN18-1T as its type species, along with two other uncultivated metagenome-assembled genomes (MAGs) originating from geothermally active sites across the Pacific Ring of Fire. In this study, we investigate the genetic and genomic diversity, and the distribution patterns of several uncharacterized Acidithiobacillia class strains and sequence clones, which are ascribed to the same 16S rRNA gene sequence clade. By digging deeper into this data and contributing to novel MAGs emerging from environmental studies in tectonically active locations, the description of this novel genus has been consolidated. Using state-of-the-art genomic taxonomy methods, we added to already recognized taxa, an additional four novel Candidate (Ca.) species, including 'Ca. Igneacidithiobacillus chanchocoensis' (mCHCt20-1TS), 'Igneacidithiobacillus siniensis' (S30A2T), 'Ca. Igneacidithiobacillus taupoensis' (TVZ-G3 TS), and 'Ca. Igneacidithiobacillus waiarikiensis' (TVZ-G4 TS). Analysis of published data on the isolation, enrichment, cultivation, and preliminary microbiological characterization of several of these unassigned or misassigned strains, along with the type species of the genus, plus the recoverable environmental data from metagenomic studies, allowed us to identify habitat preferences of these taxa. Commonalities and lineage-specific adaptations of the seven species of the genus were derived from pangenome analysis and comparative genomic metabolic reconstruction. The findings emerging from this study lay the groundwork for further research on the ecology, evolution, and biotechnological potential of the novel genus 'Igneacidithiobacillus'.

Culture, conditions and care support mental health of healthcare workers during crises.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has presented immense challenges to health systems worldwide and significantly impacted the mental health of frontline healthcare workers. AIMS: This study drew on the experiences of frontline healthcare workers to examine organizational strategies needed to support the mental health and well-being of healthcare workers during times of crisis. METHODS: Semi-structured focus groups or individual interviews were conducted with healthcare workers to examine their perspectives on organizational strategies for enhancing staff mental health and well-being during crises. Data were analysed thematically. Following this, evidence for the identified strategies was reviewed to assess alignment with participant views and recommendations. RESULTS: Thirty-two healthcare workers from diverse disciplines (10 allied health, 11 nursing, 11 medical) participated in the study. Data analysis identified three broad themes contributing to supporting mental health and well-being. These themes can be encapsulated as the 'Three Cs'-culture (building an organizational culture that prioritizes mental health); conditions (implementing proactive organizational strategies during crises) and care (ensuring fit-for-purpose strategies to support mental health and well-being). CONCLUSIONS: Study findings underscore the necessity of an integrated and systemic organizational approach to address mental health and well-being in the healthcare workplace. This approach must be long term with the components of the 'Three Cs', particularly cultural change and conditions, viewed as a part of a suite of strategies to ensure crisis preparedness. It is imperative that organizations collaborate with their staff, providing support and fostering a safe and inclusive work environment that ultimately benefits patients, their care and staff well-being.

Land management shapes drought responses of dominant soil microbial taxa across grasslands.

Soil microbial communities are dominated by a relatively small number of taxa that may play outsized roles in ecosystem functioning, yet little is known about their capacities to resist and recover from climate extremes such as drought, or how environmental context mediates those responses. Here, we imposed an in situ experimental drought across 30 diverse UK grassland sites with contrasting management intensities and found that: (1) the majority of dominant bacterial (85%) and fungal (89%) taxa exhibit resistant or opportunistic drought strategies, possibly contributing to their ubiquity and dominance across sites; and (2) intensive grassland management decreases the proportion of drought-sensitive and non-resilient dominant bacteria-likely via alleviation of nutrient limitation and pH-related stress under fertilisation and liming-but has the opposite impact on dominant fungi. Our results suggest a potential mechanism by which intensive management promotes bacteria over fungi under drought with implications for soil functioning.

Utility of BRAF V600E immunohistochemistry in the diagnosis of mandibular ameloblastomas.

Ameloblastoma, odontogenic keratocyst (OKC), and dentigerous cyst (DC) can have similar radiographic and histological appearances. The purpose of this study was to determine the utility of BRAF immunohistochemistry in discerning mandibular ameloblastomas from OKCs and DCs. This retrospective cohort study included patients treated between 1998 and 2018. Inclusion criteria include incisional biopsy-proven mandibular ameloblastoma, OKC, or DC, and sufficient tissue for immunohistochemistry. The primary predictor variable was the type of lesion. The primary outcome variable was the presence/absence of BRAF V600E immunoreactivity. The cohort consisted of 43 patients (19 female, 24 male; mean age 48 ± 17 years). There were 22 ameloblastomas, 11 OKCs, and 10 DCs. Among ameloblastomas, 68.2% (15/22) stained positive for BRAF V600E; no OKC or DC was positive (P < 0.001). By subtype, the majority of the follicular (83.3%), unicystic (83.3%), desmoplastic (66.7%), and acanthomatous (100%) subtypes were positive, but only 33.3% of the plexiform subtype were positive. BRAF immunohistochemistry may be a useful adjunct in the differentiation of ameloblastoma from OKCs and DCs on incisional biopsies. It may be particularly useful for small samples with a prominent cystic component or equivocal histopathology. Mandibular lesions that are BRAF immunohistochemistry positive are unlikely to be DCs or OKCs.

Development of an in vivo murine model of perineural invasion and spread of cutaneous squamous cell carcinoma of the head and neck.

Introduction: Cutaneous squamous cell carcinoma of the head and neck (cSCCHN) can metastasize by invading nerves and spread toward the central nervous system. This metastatic process is called perineural invasion (PNI) and spread (PNS). An in vivo sciatic nerve mouse model is used for cSCCHN PNI/PNS. Here we describe a complementary whisker pad model which allows for molecular studies investigating drivers of PNI/PNS in the head and neck environment. Methods: A431 cells were injected into the whisker pads of BALB/c Foxn1nu and NSG-A2 mice. Tumor progression was monitored by bioluminescence imaging and primary tumor resection was performed. PNI was detected by H&E and IHC. Tumor growth and PNI were assessed with inducible ablation of LOXL2. Results: The rate of PNI development in mice was 10%-28.6%. Tumors exhibited PNI/PNS reminiscent of the morphology seen in the human disease. Our model's utility was demonstrated with inducible ablation of LOXL2 reducing primary tumor growth and PNI. Discussion: This model consists in a feasible way to test molecular characteristics and potential therapies, offers to close a gap in the described in vivo methods for PNI/PNS of cSCCHN and has uses in concert with the established sciatic nerve model.

Love Is Good, but Does It Have Teeth?

This letter responds to the article "Love Your Patient as Yourself: On Reviving the Broken Heart of American Medical Ethics," by Tyler Tate and Joseph Clair, in the March-April 2023 issue of the Hastings Center Report.

Benign Enhancing Foramen Magnum Lesions.

Benign enhancing foramen magnum lesions have been previously described as T2-hyperintense small, enhancing lesions located posterior to the intradural vertebral artery. We present the first case with pathologic correlation. These lesions are fibrotic nodules adhering to the spinal accessory nerve. While they can enlarge with time on subsequent examinations, on the basis of the imaging characteristics and location, they do not necessitate surgical resection.

Influence of mobile genetic elements and insertion sequences in long- and short-term adaptive processes of Acidithiobacillus ferrooxidans strains.

The recent revision of the Acidithiobacillia class using genomic taxonomy methods has shown that, in addition to the existence of previously unrecognized genera and species, some species of the class harbor levels of divergence that are congruent with ongoing differentiation processes. In this study, we have performed a subspecies-level analysis of sequenced strains of Acidithiobacillus ferrooxidans to prove the existence of distinct sublineages and identify the discriminant genomic/genetic characteristics linked to these sublineages, and to shed light on the processes driving such differentiation. Differences in the genomic relatedness metrics, levels of synteny, gene content, and both integrated and episomal mobile genetic elements (MGE) repertoires support the existence of two subspecies-level taxa within A. ferrooxidans. While sublineage 2A harbors a small plasmid related to pTF5, this episomal MGE is absent in sublineage 2B strains. Likewise, clear differences in the occurrence, coverage and conservation of integrated MGEs are apparent between sublineages. Differential MGE-associated gene cargo pertained to the functional categories of energy metabolism, ion transport, cell surface modification, and defense mechanisms. Inferred functional differences have the potential to impact long-term adaptive processes and may underpin the basis of the subspecies-level differentiation uncovered within A. ferrooxidans. Genome resequencing of iron- and sulfur-adapted cultures of a selected 2A sublineage strain (CCM 4253) showed that both episomal and large integrated MGEs are conserved over twenty generations in either growth condition. In turn, active insertion sequences profoundly impact short-term adaptive processes. The ISAfe1 element was found to be highly active in sublineage 2A strain CCM 4253. Phenotypic mutations caused by the transposition of ISAfe1 into the pstC2 encoding phosphate-transport system permease protein were detected in sulfur-adapted cultures and shown to impair growth on ferrous iron upon the switch of electron donor. The phenotypic manifestation of the △pstC2 mutation, such as a loss of the ability to oxidize ferrous iron, is likely related to the inability of the mutant to secure the phosphorous availability for electron transport-linked phosphorylation coupled to iron oxidation. Depletion of the transpositional △pstC2 mutation occurred concomitantly with a shortening of the iron-oxidation lag phase at later transfers on a ferrous iron-containing medium. Therefore, the pstII operon appears to play an essential role in A. ferrooxidans when cells oxidize ferrous iron. Results highlight the influence of insertion sequences and both integrated and episomal mobile genetic elements in the short- and long-term adaptive processes of A. ferrooxidans strains under changing growth conditions.

Validation of Immunotherapy Response Score as Predictive of Pan-solid Tumor Anti-PD-1/PD-L1 Benefit.

Immunotherapy response score (IRS) integrates tumor mutation burden (TMB) and quantitative expression biomarkers to predict anti-PD-1/PD-L1 [PD-(L)1] monotherapy benefit. Here, we evaluated IRS in additional cohorts. Patients from an observational trial (NCT03061305) treated with anti-PD-(L)1 monotherapy were included and assigned to IRS-High (-H) versus -Low (-L) groups. Associations with real-world progression-free survival (rwPFS) and overall survival (OS) were determined by Cox proportional hazards (CPH) modeling. Those with available PD-L1 IHC treated with anti-PD-(L)1 with or without chemotherapy were separately assessed. Patients treated with PD-(L)1 and/or chemotherapy (five relevant tumor types) were assigned to three IRS groups [IRS-L divided into IRS-Ultra-Low (-UL) and Intermediate-Low (-IL), and similarly assessed]. In the 352 patient anti-PD-(L)1 monotherapy validation cohort (31 tumor types), IRS-H versus IRS-L patients had significantly longer rwPFS and OS. IRS significantly improved CPH associations with rwPFS and OS beyond microsatellite instability (MSI)/TMB alone. In a 189 patient (10 tumor types) PD-L1 IHC comparison cohort, IRS, but not PD-L1 IHC nor TMB, was significantly associated with anti-PD-L1 rwPFS. In a 1,103-patient cohort (from five relevant tumor types), rwPFS did not significantly differ in IRS-UL patients treated with chemotherapy versus chemotherapy plus anti-PD-(L)1, nor in IRS-H patients treated with anti-PD-(L)1 versus anti-PD-(L)1 + chemotherapy. IRS associations were consistent across subgroups, including both Europeans and non-Europeans. These results confirm the utility of IRS utility for predicting pan-solid tumor PD-(L)1 monotherapy benefit beyond available biomarkers and demonstrate utility for informing on anti-PD-(L)1 and/or chemotherapy treatment. Significance: This study confirms the utility of the integrative IRS biomarker for predicting anti-PD-L1/PD-1 benefit. IRS significantly improved upon currently available biomarkers, including PD-L1 IHC, TMB, and MSI status. Additional utility for informing on chemotherapy, anti-PD-L1/PD-1, and anti-PD-L1/PD-1 plus chemotherapy treatments decisions is shown.

Non-oral manifestations in adults with a clinical and molecularly confirmed diagnosis of periodontal Ehlers-Danlos syndrome.

Introduction: Periodontal Ehlers-Danlos Syndrome (pEDS) is a rare autosomal dominant type of EDS characterised by severe early-onset periodontitis, lack of attached gingiva, pretibial plaques, joint hypermobility and skin hyperextensibility as per the 2017 International EDS Classification. In 2016, deleterious pathogenic heterozygous variants were identified in C1R and C1S, which encode components of the complement system. Materials and Methods: Individuals with a clinical suspicion of pEDS were clinically and molecularly assessed through the National EDS Service in London and Sheffield and in genetic services in Austria, Sweden and Australia. Transmission electron microscopy and fibroblast studies were performed in a small subset of patients. Results: A total of 21 adults from 12 families were clinically and molecularly diagnosed with pEDS, with C1R variants in all families. The age at molecular diagnosis ranged from 21-73 years (mean 45 years), male: female ratio 5:16. Features of easy bruising (90%), pretibial plaques (81%), skin fragility (71%), joint hypermobility (24%) and vocal changes (38%) were identified as well as leukodystrophy in 89% of those imaged. Discussion: This cohort highlights the clinical features of pEDS in adults and contributes several important additional clinical features as well as novel deleterious variants to current knowledge. Hypothetical pathogenic mechanisms which may help to progress understanding and management of pEDS are also discussed.

Study protocol for The GOAL Trial: comprehensive geriatric assessment for frail older people with chronic kidney disease to increase attainment of patient-identified goals-a cluster randomised controlled trial.

BACKGROUND: An increasing number of older people are living with chronic kidney disease (CKD). Many have complex healthcare needs and are at risk of deteriorating health and functional status, which can adversely affect their quality of life. Comprehensive geriatric assessment (CGA) is an effective intervention to improve survival and independence of older people, but its clinical utility and cost-effectiveness in frail older people living with CKD is unknown. METHODS: The GOAL Trial is a pragmatic, multi-centre, open-label, superiority, cluster randomised controlled trial developed by consumers, clinicians, and researchers. It has a two-arm design, CGA compared with standard care, with 1:1 allocation of a total of 16 clusters. Within each cluster, study participants ≥ 65 years of age (or ≥ 55 years if Aboriginal or Torres Strait Islander (First Nations Australians)) with CKD stage 3-5/5D who are frail, measured by a Frailty Index (FI) of > 0.25, are recruited. Participants in intervention clusters receive a CGA by a geriatrician to identify medical, social, and functional needs, optimise medication prescribing, and arrange multidisciplinary referral if required. Those in standard care clusters receive usual care. The primary outcome is attainment of self-identified goals assessed by standardised Goal Attainment Scaling (GAS) at 3 months. Secondary outcomes include GAS at 6 and 12 months, quality of life (EQ-5D-5L), frailty (Frailty Index - Short Form), transfer to residential aged care facilities, cost-effectiveness, and safety (cause-specific hospitalisations, mortality). A process evaluation will be conducted in parallel with the trial including whether the intervention was delivered as intended, any issue or local barriers to intervention delivery, and perceptions of the intervention by participants. The trial has 90% power to detect a clinically meaningful mean difference in GAS of 10 units. DISCUSSION: This trial addresses patient-prioritised outcomes. It will be conducted, disseminated and implemented by clinicians and researchers in partnership with consumers. If CGA is found to have clinical and cost-effectiveness for frail older people with CKD, the intervention framework could be embedded into routine clinical practice. The implementation of the trial's findings will be supported by presentations at conferences and forums with clinicians and consumers at specifically convened workshops, to enable rapid adoption into practice and policy for both nephrology and geriatric disciplines. It has potential to materially advance patient-centred care and improve clinical and patient-reported outcomes (including quality of life) for frail older people living with CKD. TRIAL REGISTRATION: ClinicalTrials.gov NCT04538157. Registered on 3 September 2020.

Development and validation of an integrative pan-solid tumor predictor of PD-1/PD-L1 blockade benefit.

BACKGROUND: Anti-PD-1 and PD-L1 (collectively PD-[L]1) therapies are approved for many advanced solid tumors. Biomarkers beyond PD-L1 immunohistochemistry, microsatellite instability, and tumor mutation burden (TMB) may improve benefit prediction. METHODS: Using treatment data and genomic and transcriptomic tumor tissue profiling from an observational trial (NCT03061305), we developed Immunotherapy Response Score (IRS), a pan-tumor predictive model of PD-(L)1 benefit. IRS real-world progression free survival (rwPFS) and overall survival (OS) prediction was validated in an independent cohort of trial patients. RESULTS: Here, by Cox modeling, we develop IRS-which combines TMB with CD274, PDCD1, ADAM12 and TOP2A quantitative expression-to predict pembrolizumab rwPFS (648 patients; 26 tumor types; IRS-High or -Low groups). In the 248 patient validation cohort (248 patients; 24 tumor types; non-pembrolizumab PD-[L]1 monotherapy treatment), median rwPFS and OS are significantly longer in IRS-High vs. IRS-Low patients (rwPFS adjusted hazard ratio [aHR] 0.52, p = 0.003; OS aHR 0.49, p = 0.005); TMB alone does not significantly predict PD-(L)1 rwPFS nor OS. In 146 patients treated with systemic therapy prior to pembrolizumab monotherapy, pembrolizumab rwPFS is only significantly longer than immediately preceding therapy rwPFS in IRS-High patients (interaction test p = 0.001). In propensity matched lung cancer patients treated with first-line pembrolizumab monotherapy or pembrolizumab+chemotherapy, monotherapy rwPFS is significantly shorter in IRS-Low patients, but is not significantly different in IRS-High patients. Across 24,463 molecularly-evaluable trial patients, 7.6% of patients outside of monotherapy PD-(L)1 approved tumor types are IRS-High/TMB-Low. CONCLUSIONS: The validated, predictive, pan-tumor IRS model can expand PD-(L)1 monotherapy benefit outside currently approved indications.

Therapies activating the immune system (checkpoint inhibitors) have revolutionized the treatment of patients with advanced cancer, however new molecular tests may better identify patients who could benefit. Using treatment data and clinical molecular test results, we report the development and validation of Immunotherapy Response Score (IRS) to predict checkpoint inhibitor benefit. Across patients with more than 20 advanced cancer types, IRS better predicted checkpoint inhibitor benefit than currently available tests. Data from >20,000 patients showed that IRS identifies ~8% of patients with advanced cancer who may dramatically benefit from checkpoint inhibitors but would not receive them today based on currently available tests. Our approach may help clinicians to decide which patients should receive checkpoint inhibitors to treat their disease.

Severe hyponatraemia with cerebral oedema after Pfizer BNT162b2 mRNA vaccination against COVID-19.

Background: Severe hyponatraemia can lead to serious neurological complications including coma, seizure and death. Hyponatraemia and the Syndrome of Inappropriate Antidiuretic Hormone (SIADH) has been previously described in cases of COVID-19, however there have been few reports post vaccination. We describe a case of severe hyponatraemia post second Pfizer BNT162b2 mRNA vaccination against COVID-19. Case presentation: A 48-year-old previously well woman presented to the emergency department with severe headaches and confusion one day after she received her second Pfizer COVID-19 vaccination. She reported no more than 2.5 L fluid intake. Vital signs were normal. Laboratory investigation revealed serum sodium 113 mmol/L, potassium 3.4 mmol/L, urea 3.5 mmol/L and serum osmolality 266 mmol/kg. TSH, random cortisol and C-reactive protein levels were normal. She was found to be in urinary retention and developed marked polyuria post in dwelling catheter insertion. Following this she underwent spontaneous and rapid correction of serum sodium without intervention. Retrospective analysis showed an inappropriately high copeptin of 4.4 pmol/L. Conclusions: It is important to be cautioned and aware of hyponatraemia as an immediate side effect of COVID-19 vaccination. The exact mechanism is unknown and further research is required to understand the acute endocrine effects which may arise in response to COVID-19 vaccination.

Implementing post-normal science with or for EU policy actors: using quantitative story-telling.

There is increasing recognition of the wicked nature of the intertwined climate, biodiversity and economic crises, and the need for adaptive, multi-scale approaches to understanding the complexity of both the problems and potential responses. Most science underpinning policy responses to sustainability issues, however, remains overtly apolitical and focussed on technical innovation; at odds with a critical body of literatures insisting on the recognition of systemic problem framing when supporting policy processes. This paper documents the experience of implementing a mixed method approach called quantitative story-telling (QST) to policy analysis that explicitly recognises this normative dimension, as the methodology is part of a post-normal science (PNS) toolkit. The authors reflect on what was learnt when considering how QST fared as a tool for science-policy interaction, working with European Union (EU) level policy actors interested in sustainable agriculture and sustainable development goal 2. These goals-also known as UN Agenda 2030-are the latest institutionalisation of the pursuit of sustainable development and the EU has positioned itself as taking a lead in its implementation. Thus, the paper illustrates our experience of using PNS as an approach to science policy interfaces in a strategic policy context; and illustrates how the challenges identified in the science-policy literature are amplified when working across multiple policy domains and taking a complex systems approach. Our discussion on lessons learnt may be of interest to researchers seeking to work with policy-makers on complex sustainability issues.

Mineralogy affects prokaryotic community composition in an acidic metal mine.

The microbial ecology of acidic mine and sulfide cave ecosystems is well characterised with respect to aquatic communities, typically revealing low taxonomic complexity and dominance by a relatively limited number of cosmopolitan acidophilic bacterial and archaeal taxa. Whilst pH, temperature, and geochemistry are recognised drivers of diversity in these ecosystems, the specific question of a possible influence of substratum mineralogy on microbial community composition remains unanswered. Here we address this void, using 81 subterranean mineral samples from a low temperature abandoned, acidic, sulfide ore mine system at Mynydd Parys (Parys Mountain in English), Wales, UK. Four primary and 15 secondary minerals were identified via x-ray diffraction, each sample containing a maximum of five and an average of two minerals. The mineralogy of primary (e.g. pyrite and quartz) and secondary (e.g. melanterite and pisanite) minerals was significantly correlated with prokaryotic community structure at multiple taxonomic levels, implying that the mineralosphere effect reported in less extreme terrestrial environments is also implicated in driving prokaryotic community composition in extremely acidic, base metal-bearing sulfide mineralisation at Mynydd Parys. Twenty phyla were identified, nine of which were abundant (mean relative abundance >1%). While taxa characteristic of acidic mines were detected, for example Leptospirillum (phylum Nitrospirae), Acidithiobacillus (phylum Proteobacteria), Sulfobacillus (phylum Firmicutes) and Ferroplasma (phylum Euryarchaeota), their abundance in individual samples was highly variable. Indeed, in the majority of the 81 samples investigated the abundance of these and other typical acidic mine taxa was low, with 25% of samples devoid of sequences from recognised acidic mine taxa. Most notable amongst the bacterial taxa not previously reported in such environments were the recently cultivated Muribaculaceae family (phylum Bacteroidetes), which often dominated Mynydd Parys samples regardless of their mineralogical content. Our results pose further questions regarding the mechanisms by which taxa not previously reported in such extreme environments appear to survive in Mynydd Parys, opening up research pathways for exploring the biodiversity drivers underlying microbial community composition and function in extremely acidic mine environments.

Sulfoacidibacillus ferrooxidans, gen. nov., sp. nov., Sulfoacidibacillus thermotolerans, gen. nov., sp. nov., and Ferroacidibacillus organovorans, gen. nov., sp. nov.: Extremely acidophilic chemolitho-heterotrophic Firmicutes.

Ten strains of extremely acidophilic bacteria, isolated from different environments form a distinct monophyletic clade within the phylum Firmicutes. Comparison of complete genomes of the proposed type strains confirm that they comprise two genera (proposed names Sulfoacidibacillus and Ferroacidibacillus), and at least three species (Sulfoacidibacillus ferrooxidans, Sulfoacidibacillus thermotolerans and Ferroacidibacillus organovorans). The bacterial strains share some physiological traits, including catalysing the dissimilatory oxidation and reduction of iron, and in being obligately heterotrophic. Both species of Sulfoacidibacillus are also able to oxidise elemental sulfur and tetrathionate. Both S. ferrooxidans and Ferroacidibacillus spp. are mesophilic, while S. thermotolerans isolates are moderate thermophiles. The isolates display different degrees of acid-tolerance: Ferroacidibacillus spp. are the most acid-sensitive while the type strain of S. ferrooxidans grows at pH 0.9. MK7 was detected as the sole menaquinone present in all three nominated type strains, and their peptidoglycans all contain meso-2,6 diaminopimelic acid type A1γ. The chromosomal DNA of the strains examined contain between 44 and 52 mol% G + C. The nominated type strains of the new species are S. ferrooxidans S0ABT (= DSM 105355T = JCM 33225T); S. thermotolerans Y002T (= ATCC TSD-104T = JCM 31946T); F. organovorans SLC66T (= ATCC TSD-103T = JCM 31945T).

The Monro-Kellie Doctrine: A Review and Call for Revision.

The Monro-Kellie doctrine is a well-accepted principle of intracranial hemodynamics. It has undergone few consequential revisions since it was established. Its principle is straightforward: The combined volume of neuronal tissue, blood, and CSF is constant. To maintain homeostatic intracranial pressure, any increase or decrease in one of these elements leads to a reciprocal and opposite change in the others. The Monro-Kellie doctrine assumes a rigid, unadaptable calvaria. Recent studies have disproven this assumption. The skull expands and grows in response to pathologic changes in intracranial pressure. In this review, we outline what is known about calvarial changes in the setting of pressure dysregulation and suggest a revision to the Monro-Kellie doctrine that includes an adaptable skull as a fourth component.