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Background: TERT promoter mutation (TPM) is an established biomarker in meningiomas associated with aberrant TERT expression and reduced progression-free survival (PFS). TERT expression, however, has also been observed even in tumours with wildtype TERT promoters (TP-WT). This study aimed to examine TERT expression and clinical outcomes in meningiomas. Methods: TERT expression, TPM status, and TERT promoter methylation of a multi-institutional cohort of meningiomas (n=1241) was assessed through nulk RNA sequencing (n=604), Sanger sequencing of the promoter (n=1095), and methylation profiling (n=1218). 380 Toronto meningiomas were used for discovery, and 861 external institution samples were compiled as a validation cohort. Results: Both TPMs and TERTpromoter methylation were associated with increased TERT expression and may represent independent mechanisms of TERT reactivation. TERT expression was detected in 30.4% of meningiomas that lacked TPMs, was associated with higher WHO grades, and corresponded to shorter PFS, independent of grade and even among TP-WT tumours. TERT expression was associated with a shorter PFS equivalent to those of TERT-negative meningiomas of one higher grade. Conclusions: Our findings highlight the prognostic significance of TERT expression in meningiomas, even in the absence of TPMs. Its presence may identify patients who may progress earlier and should be considered in risk stratification models.
Despite the increased awareness and action towards Equality, Diversity and Inclusion (EDI), the glaciological community still experiences and perpetuates examples of exclusionary and discriminatory behavior. We here discuss the challenges and visions from a group predominantly composed of early-career researchers from the 2023 edition of the Karthaus Summer School on Ice Sheets and Glaciers in the Climate System. This paper presents the results of an EDI-focused workshop that the 36 students and 12 lecturers who attended the summer school actively participated in. We identify common threads from participant responses and distill them into collective visions for the future of the glaciological research community, built on actionable steps toward change. In this paper, we address the following questions that guided the workshop: What do we see as current EDI challenges in the glaciology research community and which improvements would we like to see in the next fifty years? Contributions have been sorted into three main challenges we want and need to face: making glaciology (1) more accessible, (2) more equitable and (3) more responsible.
The current food system is not only unsustainable but also increasingly inequitable, resulting in food insecurity for many people in the United Kingdom and globally(1). The health impacts of the current food system on disadvantaged communities warrants examination to improve ecological public health nutrition strategies(2). Community gardens and kitchens are frequently established by volunteers in the hope that they will serve as alternatives to the current food environment, building healthy food capacity in the community as well as outdoor physical and social activities for urban residents(3). This remains to be explored in deprived communities in Dorset, UK.
This pilot research was conducted in fourteen adults living in disadvantaged areas in Dorset (Hamworthy-Poole). Inclusion criteria were individuals over 18 years old living in low-income households, who were users of community food garden and kitchen initiatives. The individuals usually attend with their family members in the food growing and cooking activities, including young children and older adults in the programmes. Three semi-structured interviews and three focus groups (total n = 14) were undertaken to uncover views on the importance and roles of these community food initiatives in relation to healthy eating and access to locally grown fresh produce. All discussions were digitally recorded, and data were transcribed verbatim. Qualitative data analysis, using Clarke and Braun’s(4)six steps of thematic analysis, was performed via NVivo software.
Four main themes emerged: Tackling food insecurity & sustainability, Utilization of climate friendly & organic Food, Bridging intergenerational gap and Promoting healthy lifestyle. These food initiatives help in addressing food insecurity from the perspective of the participants. The role of community gardens together with cooking sessions can be further recognised as contributors to community development, access to healthy food such as fresh fruits and vegetables and nurturing skills related to nutritious food preparation.
In conclusion, this research provided insights into the perceptions on how we can design a health promotion initiative that is inclusive and sustainable to tackle food insecurity effectively.
This editorial considers the value and nature of academic psychiatry by asking what defines the specialty and psychiatrists as academics. We frame academic psychiatry as a way of thinking that benefits clinical services and discuss how to inspire the next generation of academics.
Background: Meningiomas are the most common intracranial tumor with surgery, dural margin treatment, and radiotherapy as cornerstones of therapy. Response to treatment continues to be highly heterogeneous even across tumors of the same grade. Methods: Using a cohort of 2490 meningiomas in addition to 100 cases from the prospective RTOG-0539 phase II clinical trial, we define molecular biomarkers of response across multiple different, recently defined molecular classifications and use propensity score matching to mimic a randomized controlled trial to evaluate the role of extent of resection, dural marginal resection, and adjuvant radiotherapy on clinical outcome. Results: Gross tumor resection led to improved progression-free-survival (PFS) across all molecular groups (MG) and improved overall survival in proliferative meningiomas (HR 0.52, 95%CI 0.30-0.93). Dural margin treatment (Simpson grade 1/2) improved PFS versus complete tumor removal alone (Simpson 3). MG reliably predicted response to radiotherapy, including in the RTOG-0539 cohort. A molecular model developed using clinical trial cases discriminated response to radiotherapy better than standard of care grading in multiple cohorts (ΔAUC 0.12, 95%CI 0.10-0.14). Conclusions: We elucidate biological and molecular classifications of meningioma that influence response to surgery and radiotherapy in addition to introducing a novel molecular-based prediction model of response to radiation to guide treatment decisions.
Clinical outcomes of repetitive transcranial magnetic stimulation (rTMS) for treatment of treatment-resistant depression (TRD) vary widely and there is no mood rating scale that is standard for assessing rTMS outcome. It remains unclear whether TMS is as efficacious in older adults with late-life depression (LLD) compared to younger adults with major depressive disorder (MDD). This study examined the effect of age on outcomes of rTMS treatment of adults with TRD. Self-report and observer mood ratings were measured weekly in 687 subjects ages 16–100 years undergoing rTMS treatment using the Inventory of Depressive Symptomatology 30-item Self-Report (IDS-SR), Patient Health Questionnaire 9-item (PHQ), Profile of Mood States 30-item, and Hamilton Depression Rating Scale 17-item (HDRS). All rating scales detected significant improvement with treatment; response and remission rates varied by scale but not by age (response/remission ≥ 60: 38%–57%/25%–33%; <60: 32%–49%/18%–25%). Proportional hazards models showed early improvement predicted later improvement across ages, though early improvements in PHQ and HDRS were more predictive of remission in those < 60 years (relative to those ≥ 60) and greater baseline IDS burden was more predictive of non-remission in those ≥ 60 years (relative to those < 60). These results indicate there is no significant effect of age on treatment outcomes in rTMS for TRD, though rating instruments may differ in assessment of symptom burden between younger and older adults during treatment.
This quality improvement project was a collaboration between an adult, inpatient female psychiatric intensive care unit (PICU) in South London and the Sexual and Reproductive Health Rights, Inclusion and Empowerment (SHRINE) programme. SHRINE is a London-based programme delivering SRH care to any individual with serious mental illness, substance misuse and/or learning disability.
Objectives
The primary aim of this quality improvement project was to assess patients’ sexual and reproductive (SRH) needs, and the acceptability of providing SRH assessments in a female PICU setting. Secondary aims were to explore the barriers to access and the feasibility of providing SRH assessments and SHRINE interventions in the PICU.
Methods
A bi-monthly SRH in-reach clinic and a nurse led SRH referral pathway were implemented on the PICU over a seven-month period. Within a quality improvement framework, a staff training needs assessment was performed, training delivered, a protocol developed, staff attitudes explored, and patient and carer engagement sought.
Results
30% of women were identified as having unmet SRH needs and proceeded to a specialist appointment, representing a 2.5-fold increase in unmet need detection. 42% of women were assessed, representing a 3.5-fold increase in uptake. 21% of women initiated SRH interventions of which 14% had all their SRH needs met.
Conclusions
Results identified SRH needs for PICU admissions are greater than realised. Staff highlighted the acceptability and importance of SRH care, if interventions are appropriately timed and the patient’s individual risk profile considered. Providing a nurse-led referral pathway for an SRH in-reach clinic is acceptable, feasible and beneficial for PICU patients.
The Hierarchical Taxonomy of Psychopathology (HiTOP) has emerged out of the quantitative approach to psychiatric nosology. This approach identifies psychopathology constructs based on patterns of co-variation among signs and symptoms. The initial HiTOP model, which was published in 2017, is based on a large literature that spans decades of research. HiTOP is a living model that undergoes revision as new data become available. Here we discuss advantages and practical considerations of using this system in psychiatric practice and research. We especially highlight limitations of HiTOP and ongoing efforts to address them. We describe differences and similarities between HiTOP and existing diagnostic systems. Next, we review the types of evidence that informed development of HiTOP, including populations in which it has been studied and data on its validity. The paper also describes how HiTOP can facilitate research on genetic and environmental causes of psychopathology as well as the search for neurobiologic mechanisms and novel treatments. Furthermore, we consider implications for public health programs and prevention of mental disorders. We also review data on clinical utility and illustrate clinical application of HiTOP. Importantly, the model is based on measures and practices that are already used widely in clinical settings. HiTOP offers a way to organize and formalize these techniques. This model already can contribute to progress in psychiatry and complement traditional nosologies. Moreover, HiTOP seeks to facilitate research on linkages between phenotypes and biological processes, which may enable construction of a system that encompasses both biomarkers and precise clinical description.
PICU inpatients are likely to be at increased risk of having unmet SRH needs due to barriers to accessing services. Since May 2018, an in-reach SRH assessment has been available to all psychiatric inpatients on ES1 ward, if referred. Analysis of referrals over 15 months identified only 24 had been made during this time.
Objectives
To assess the SRH needs of women admitted to ES1 PICU, the feasibility of providing a SRH in-reach clinic, and the acceptability of delivering a nurse lead referral programme.
Methods
A bi-monthly SRH in-reach clinic and a nurse led SRH referral pathway were implemented on ES1 over a seven-month period. A staff training needs assessment was performed followed by training, a protocol was developed, staff attitudes were explored, and patient engagement was sought.
Results
A total of 41% (32/77) of patients were referred, which was a 29% increase. 53.1% (17/32) of the total referrals had a true SRH need, equating to a 10% increase and 22% (17/77) of all PICU admissions. 90% of referrals were made by nursing staff. A staff focus group (n15) highlighted the acceptability and perceived importance of offering SRH care in PICU, if interventions were appropriately timed and the patient’s individual risk profile was considered.
Conclusions
Results identify that SRH needs for PICU admissions are greater than previously realised. Providing a nurse led referral pathway for an SRH in-reach clinic is acceptable, feasible and beneficial for PICU patients. This project has resulted in service improvements including offering asymptomatic STI testing to all PICU admissions.
Multiple hospitalisations towards the end of life is an indicator of poor-quality care. Understanding the characteristics of patients who experience hospitalisations at the end-of-life and how they vary is important for improved care planning.
Objectives
To describe socio-demographic and clinical characteristics of patients diagnosed with serious mental illness who experienced multiple hospitalisations in the last 90 days of life.
Methods
Data for all adult patients with a diagnosis of serious mental illness who died in 2018-2019 in England, UK were extracted from the National Mental Health Services Data Set linked with Hospital Episode Statistics and death registry data. Variables of interest included age, gender, marital status, underlying and contributory cause of death, ethnicity, place of death, deprivation status, urban-rural indicator, and patient’s region of residence. The number of hospitalisations and patient’s sociodemographic & clinical were described using descriptive statistics and percentages, respectively.
Results
Of the 45924 patients, 38.1% (n=17505, Male=42.9%, Female=57.1%, Mean age:78.4) had at least one hospitalisation in the last 90 days of life. The median number of hospitalisations was 2(StdDev:1.64, Minimum=1,Maximum=23). Most of those hospitalised (n=11808, 67.5%), died in a health care establishment (e.g. Hospital or hospice). There were marked geographic differences in the proportions of hospitalisations.The North West region of England recorded the most hospitalisations (n= 2906,16.6%), compared to other regions.
Conclusions
Further analysis is needed to understand factors independently associated with hospitalisations in people with serious mental illness. Funding: This project is supported by the National Institute for Health Research (NIHR) Applied Research Collaborations (ARC) South London.
At Guy's King's and St Thomas’ School of Medicine, a unique initiative is the Psychiatry Early Experience Programme (PEEP), which allows students to shadow psychiatry trainees at work several times a year. The students’ attitudes towards psychiatry and the scheme are regularly assessed and initial results are already available.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Introduction: Acute aortic syndrome (AAS) is a time sensitive aortic catastrophe that is often misdiagnosed. There are currently no Canadian guidelines to aid in diagnosis. Our goal was to adapt the existing American Heart Association (AHA) and European Society of Cardiology (ESC) diagnostic algorithms for AAS into a Canadian evidence based best practices algorithm targeted for emergency medicine physicians. Methods: We chose to adapt existing high-quality clinical practice guidelines (CPG) previously developed by the AHA/ESC using the GRADE ADOLOPMENT approach. We created a National Advisory Committee consisting of 21 members from across Canada including academic, community and remote/rural emergency physicians/nurses, cardiothoracic and cardiovascular surgeons, cardiac anesthesiologists, critical care physicians, cardiologist, radiologists and patient representatives. The Advisory Committee communicated through multiple teleconference meetings, emails and a one-day in person meeting. The panel prioritized questions and outcomes, using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess evidence and make recommendations. The algorithm was prepared and revised through feedback and discussions and through an iterative process until consensus was achieved. Results: The diagnostic algorithm is comprised of an updated pre test probability assessment tool with further testing recommendations based on risk level. The updated tool incorporates likelihood of an alternative diagnosis and point of care ultrasound. The final best practice diagnostic algorithm defined risk levels as Low (0.5% no further testing), Moderate (0.6-5% further testing required) and High ( >5% computed tomography, magnetic resonance imaging, trans esophageal echocardiography). During the consensus and feedback processes, we addressed a number of issues and concerns. D-dimer can be used to reduce probability of AAS in an intermediate risk group, but should not be used in a low or high-risk group. Ultrasound was incorporated as a bedside clinical examination option in pre test probability assessment for aortic insufficiency, abdominal/thoracic aortic aneurysms. Conclusion: We have created the first Canadian best practice diagnostic algorithm for AAS. We hope this diagnostic algorithm will standardize and improve diagnosis of AAS in all emergency departments across Canada.
The dominant source of oxalate-soluble Al in the B horizon of a brown podzolic soil developed on andesite appears to be hydroxyaluminium interlayers in a dioctahedral vermiculite in the clay and silt fractions, of which the latter contributes most to the total extractable Al and fluoride reactivity of the whole soil. Cold sodium carbonate solutions extract as much interlayer Al as does oxalate, indicating that this fraction of the interlayer material is highly reactive, and sharply distinguished from more resistant interlayers which are also present.
Chemistry of six white micas from the high-pressure garnet granulites of Jijal is presented, together with trace elements, refractive indices, and 2Vα for one. The micas are rich in the paragonite component (over 93%), with one analysis having the highest 100 Na/(Na + K) ratio (98.5) so far reported. The paragonite is not a stable mineral of the granulites but was overprinted on the granulites at about 505–540°C and 8–9 kbar (suggesting a depth of 30 km).
The mineral in bones and teeth is an impure form of hydroxylapatite (HAP), the principal impurity being 2—5 wt.% carbonate. This mineral dissolves during remodelling of bone and also in dental caries as a result of the action of acids produced by osteoclasts and by bacteria, respectively. In enamel, demineralization proceeds with preferential loss of carbonate relative to phosphate. Surprisingly, in the early stages, the demineralization is subsurface. In order to facilitate the understanding of physical chemical aspects of these processes, we have undertaken studies of demineralization in model systems. We give three examples here. The first two used scanning microradiography in which the specimen is stepped across a 10—30 μm diameter X-ray beam. Intensity measurements allow calculation of the mineral mass per unit area in the X-ray path through the specimen. In the first experiment, porous HAP sections were separated from a reservoir of acidic buffer by a column initially filled with water (the diffusion length) and scanned with the X-ray beam perpendicular to the axis of the diffusion length. The rate of total loss of mineral along each profile was calculated from the scans. The rate of demineralization fell as the diffusion length increased. We believe the explanation is that the rate-controlling step is the diffusion of dissolved HAP away from the solid to the buffer reservoir. In the second experiment, demineralizing solution and water were pumped alternately, for equal lengths of time, past blocks of porous HAP or enamel. The X-ray beam was perpendicular to the exposed surface. As the rate of switching between solutions decreased, the mean rate of demineralization also fell. We propose that this effect is due to retention of acid in the pores of the HAP during the time when water flows, allowing further demineralization to take place during this time. The third study used X-ray microtomography, a form of 3D microscopy, to study the loss of mineral in compacted carbonate apatite powders. The powders were packed in six 10 mm internal diameter acrylic cylinders to a depth of 4 mm (after pressing). One end was covered with a porous polyethylene disc and each tube placed in acidic buffer for 70 days. Periodic examination by microtomography showed the development of subsurface demineralization. Infrared spectroscopy of the dissected-out surface layers showed preferential loss of carbonate over phosphate by comparison with deeper layers. Rietveld analysis of X-ray powder diffraction data showed changes in the crystallographic structures of the apatites between the initial and dissected-out apatite.
The Molonglo Observatory Synthesis Telescope (MOST) is an 18000 m2 radio telescope located 40 km from Canberra, Australia. Its operating band (820–851 MHz) is partly allocated to telecommunications, making radio astronomy challenging. We describe how the deployment of new digital receivers, Field Programmable Gate Array-based filterbanks, and server-class computers equipped with 43 Graphics Processing Units, has transformed the telescope into a versatile new instrument (UTMOST) for studying the radio sky on millisecond timescales. UTMOST has 10 times the bandwidth and double the field of view compared to the MOST, and voltage record and playback capability has facilitated rapid implementaton of many new observing modes, most of which operate commensally. UTMOST can simultaneously excise interference, make maps, coherently dedisperse pulsars, and perform real-time searches of coherent fan-beams for dispersed single pulses. UTMOST operates as a robotic facility, deciding how to efficiently target pulsars and how long to stay on source via real-time pulsar folding, while searching for single pulse events. Regular timing of over 300 pulsars has yielded seven pulsar glitches and three Fast Radio Bursts during commissioning. UTMOST demonstrates that if sufficient signal processing is applied to voltage streams, innovative science remains possible even in hostile radio frequency environments.
The class of radio transients called Fast Radio Bursts (FRBs) encompasses enigmatic single pulses, each unique in its own way, hindering a consensus for their origin. The key to demystifying FRBs lies in discovering many of them in order to identity commonalities – and in real time, in order to find potential counterparts at other wavelengths. The recently upgraded UTMOST in Australia, is undergoing a backend transformation to rise as a fast transient detection machine. The first interferometric detections of FRBs with UTMOST, place their origin beyond the near-field region of the telescope thus ruling out local sources of interference as a possible origin. We have localised these bursts to much better than the ones discovered at the Parkes radio telescope and have plans to upgrade UTMOST to be capable of much better localisation still.
Purple nutsedge (Cyperus rotundus L.) and yellow nutsedge (C. esculentus L.) appeared to be equally acceptable for oviposition by caged Bactra verutana Zeller, but purple nutsedge was significantly more suitable as a host: 90% of the larvae survived to maturity on purple nutsedge compared with 65% on yellow nutsedge. Responses of the plant species to both larval feeding injury and plant density were similar but purple nutsedge tended to be injured more than yellow nutsedge. At a high shoot density (nine shoots per pot), production of tubers by purple nutsedge was more adversely affected by feeding of five larvae per shoot than was production by yellow nutsedge: tuber dry weights were reduced 93 and 80% and numbers of tubers per pot were reduced 77 and 62%, respectively. Production of inflorescences was greatly reduced in both species. The effect of B. verutana on inflorescences may be more important for yellow nutsedge, which is generally considered to reproduce freely by seeds. Both species of nutsedge probably would be about equally affected by augmentation of B. verutana populations as a method of biological control.
For effective biological control through augmentation, Bactra verutana Zeller, would have to be released against purple nutsedge (Cyperus rotundus L.) in May and June when temperatures are cooler than they are from late July through September when maximal natural populations of this biological control agent occur. Bactra larvae exposed to simulated mid-May (24/13 C) and mid-June (29/18 C) temperature regimes developed more slowly than larvae exposed to the mid-July (32/26 C) temperature regime, but nutsedge plant growth was also slower. Thus, the relative amounts of feeding injury were similar at all three regimes. Larval feeding generally increased the number of shoots slightly, but not significantly, reduced significantly the production of inflorescences, and reduced the weight of total dry matter produced between 28 and 49%.