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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.
Background: Degenerative Cervical Myelopathy (DCM) is a progressive condition causing cervical spinal cord injury. Disease severity is commonly assessed using the modified Japanese Orthopedic Association (mJOA) score, yet clinical guidelines do not integrate pain—a key symptom—in evaluations. This meta-analysis examines the relationship between pain scores and quality of life outcomes (QOL) in surgical DCM patients. Methods: A comprehensive literature search using MEDLINE, Web of Science, and Embase identified 73 studies. Data regarding pain scores (VAS/NRS) and QOL outcomes (SF-12, SF-36) were extracted by 2 independent reviewers and all conflicts were resolved by the senior author. The number of patients analyzed in the studies included was 929. Results: Meta-regression identified no significant relationship between pain and SF-36 preoperatively but found a significant negative correlation at 3 months (r = -0.67, p<0.05), 6 months (r = -0.65, p<0.05), 1 year (-0.63, p<0.05), and 2 years (r = -0.62, p<0.05). Conclusions: Our results indicate a strong relationship between postoperative pain and QOL among patients with DCM. Surgeons and care teams should prioritize optimal pain management postoperatively for patients with DCM.
Fifty-three tests designed to measure aspects of creative thinking were administered to 410 air cadets and student officers. The scores were intercorrelated and 16 factors were extracted. Orthogonal rotations resulted in 14 identifiable factors, a doublet, and a residual. Nine previously identified factors were: verbal comprehension, numerical facility, perceptual speed, visualization, general reasoning, word fluency, associational fluency, ideational fluency, and a factor combining Thurstone's closure I and II. Five new factors were identified as originality, redefinition, adaptive flexibility, spontaneous flexibility, and sensitivity to problems.
Next generation high-power laser facilities are expected to generate hundreds-of-MeV proton beams and operate at multi-Hz repetition rates, presenting opportunities for medical, industrial and scientific applications requiring bright pulses of energetic ions. Characterizing the spectro-spatial profile of these ions at high repetition rates in the harsh radiation environments created by laser–plasma interactions remains challenging but is paramount for further source development. To address this, we present a compact scintillating fiber imaging spectrometer based on the tomographic reconstruction of proton energy deposition in a layered fiber array. Modeling indicates that spatial resolution of approximately 1 mm and energy resolution of less than 10% at proton energies of more than 20 MeV are readily achievable with existing 100 μm diameter fibers. Measurements with a prototype beam-profile monitor using 500 μm fibers demonstrate active readouts with invulnerability to electromagnetic pulses, and less than 100 Gy sensitivity. The performance of the full instrument concept is explored with Monte Carlo simulations, accurately reconstructing a proton beam with a multiple-component spectro-spatial profile.
The incubation period for Clostridioides difficile infection (CDI) is generally considered to be less than 1 week, but some recent studies suggest that prolonged carriage prior to disease onset may be common.
Objective:
To estimate the incubation period for patients developing CDI after initial negative cultures.
Methods:
In 3 tertiary care medical centers, we conducted a cohort study to identify hospitalized patients and long-term care facility residents with negative initial cultures for C. difficile followed by a diagnosis of CDI with or without prior detection of carriage. Cases were classified as healthcare facility-onset, community-onset, healthcare facility-associated, or community-associated and were further classified as probable, possible, or unlikely CDI. A parametric accelerated failure time model was used to estimate the distribution of the incubation period.
Results:
Of 4,179 patients with negative enrollment cultures and no prior CDI diagnosis within 56 days, 107 (2.6%) were diagnosed as having CDI, including 19 (17.8%) with and 88 (82.2%) without prior detection of carriage. When the data were censored to only include participants with negative cultures collected within 14 days, the estimated median incubation period was 6 days with 25% and 75% of estimated incubation periods occurring within 3 and 12 days, respectively. The observed estimated incubation period did not differ significantly for patients classified as probable, possible, or unlikely CDI.
Conclusion:
Our findings are consistent with the previous studies that suggested the incubation period for CDI is typically less than 1 week and is less than 2 weeks in most cases.
The Asian tapir Tapirus indicus is the only tapir species in Southeast Asia. It is declining across its range and is categorized as Endangered on the IUCN Red List. The forests of Sumatra are critical to Asian tapir conservation as they contain some of the last remaining populations of the species, yet conservation efforts are hindered by a lack of information on habitat suitability. We collated camera-trap data from nine landscapes across 69,500 km2 of Sumatran rainforest to help predict suitable habitat for Asian tapirs on the island. Predictions from Bayesian occupancy models demonstrated that tapir occupancy was greatest in forests below 600 m elevation and exclusively in forests with high aboveground biomass. Forests around the Barisan Mountains on the west of Sumatra provide the most suitable habitat for the species. Only 36% of the most critical habitat (i.e. 80th percentile of predicted occupancy values, or above) for tapirs is formally protected for conservation, with much of the remainder found in forests allocated to watershed protection (35%) or logging (23%). We highlight several key areas in Sumatra where tapir conservation could be bolstered, such as by leveraging existing conservation efforts for other charismatic flagships species on the island.
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.
Sperlingite, (H2O)K(Mn2+Fe3+)(Al2Ti)(PO4)4[O(OH)][(H2O)9(OH)]⋅4H2O, is a new monoclinic member of the paulkerrite group, from the Hagendorf-Süd pegmatite, Oberpfalz, Bavaria, Germany. It was found in corrosion pits of altered zwieselite, in association with columbite, hopeite, leucophosphite, mitridatite, scholzite, orange–brown zincoberaunite sprays and tiny green crystals of zincolibethenite. Sperlingite forms colourless prisms with pyramidal terminations, which are predominantly only 5 to 20 μm in size, rarely to 60 μm and frequently are multiply intergrown and are overgrown with smaller crystals. The crystals are flattened on {010} and slightly elongated along [100] with forms {010}, {001} and {111}. Twinning occurs by rotation about c. The calculated density is 2.40 g⋅cm–3. Optically, sperlingite crystals are biaxial (+), α = 1.600(est), β = 1.615(5), γ = 1.635(5) (white light) and 2V (calc.) = 82.7°. The optical orientation is X = b, Y = c and Z = a. Neither dispersion nor pleochroism were observed. The empirical formula from electron microprobe analyses and structure refinement is A1[(H2O)0.96K0.04]Σ1.00A2(K0.52□0.48)Σ1.00M1(Mn2+0.60Mg0.33Zn0.29Fe3+0.77)Σ1.99M2+M3(Al1.05Ti4+1.33Fe3+0.62)Σ3.00(PO4)4X[F0.19(OH)0.94O0.87]Σ2.00[(H2O)9.23(OH)0.77]Σ10.00⋅3.96H2O. Sperlingite has monoclinic symmetry with space group P21/c and unit-cell parameters a = 10.428(2) Å, b = 20.281(4) Å, c = 12.223(2) Å, β = 90.10(3)°, V = 2585.0(8) Å3 and Z = 4. The crystal structure was refined using synchrotron single-crystal data to wRobs = 0.058 for 5608 reflections with I > 3σ(I). Sperlingite is the first paulkerrite-group mineral to have co-dominant divalent and trivalent cations at the M1 sites; All other reported members have Mn2+ or Mg dominant at M1. Local charge balance for Fe3+ at M1 is achieved by H2O → OH– at H2O coordinated to M1.
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.
A kaolin clay occurring in Carboniferous mudstone near the Jiangshan-Shaoxing deep fault in Zhejiang Province, eastern China was characterized by XRD and IR. Although the dominant mineral appeared to be kaolinite, IR also suggested the possible occurrence of nacrite. This was confirmed by forming intercalation complexes with potassium acetate and with hydrazine hydrate, both water complexes having the same characteristic spacing at 8.35 Â. Different particle size fractions of the kaolin clay were studied and the results indicated that nacrite content increased with increasing particle size. This occurrence of nacrite is consistent with previous findings of the polytype in high temperature and pressure environments.
The optimum parameters for the generation of synchrotron radiation in ultraintense laser pulse interactions with planar foils are investigated with the application of Bayesian optimization, via Gaussian process regression, to 2D particle-in-cell simulations. Individual properties of the synchrotron emission, such as the yield, are maximized, and simultaneous mitigation of bremsstrahlung emission is achieved with multi-variate objective functions. The angle-of-incidence of the laser pulse onto the target is shown to strongly influence the synchrotron yield and angular profile, with oblique incidence producing the optimal results. This is further explored in 3D simulations, in which additional control of the spatial profile of synchrotron emission is demonstrated by varying the polarization of the laser light. The results demonstrate the utility of applying a machine learning-based optimization approach and provide new insights into the physics of radiation generation in laser–foil interactions, which will inform the design of experiments in the quantum electrodynamics (QED)-plasma regime.
Strain, temperature and strain rate are crucial factors governing the development of crystallographic preferred orientations (CPO) in ice. To better understand how CPO patterns change in response to these variables, we performed quantitative analyses on neutron diffraction data between 2010 and 2019, collected in situ during uniaxial compression experiments on deuterium ice. At strains >10% and temperatures <−10°C, the c-axis pattern switches from a single maximum (‘cluster’) to small circle (‘cone’), both oriented parallel to shortening. The diameter and mean width of the cone pattern decrease as strain and/or strain rate increases. Prismatic axis (a and m) patterns are characterised by great circles parallel to the pole figure margin and may be distinguishable from the patterns in ice deformed under simple shear. While strain has the main influence on the degree of preferred orientation (or CPO ‘strength’), both temperature and strain rate have minor influences, which limits the extent to which CPOs can be used to measure strain. As cluster patterns can be observed in the c-axes of ice deformed under both pure and simple shear settings, this may complicate interpretations of flow geometry in terrestrial ice unless the prismatic axis patterns are also considered.
The updated vancomycin guideline for treatment of serious methicillin-resistant Staphylococcus aureus infections prompted institutions to convert from trough to area-under-the-curve monitoring. The physician perception of the transition, coupled with that of pharmacists, was measured by pre- and postimplementation surveys. Both groups believed safety would be increased without efficacy changes.
Monitoring the prevalence and abundance of parasites over time is important for addressing their potential impact on host life histories, immunological profiles and their influence as a selective force. Only long-term ecological studies have the potential to shed light on both the temporal trends in infection prevalence and abundance and the drivers of such trends, because of their ability to dissect drivers that may be confounded over shorter time scales. Despite this, only a relatively small number of such studies exist. Here, we analysed changes in the prevalence and abundance of gastrointestinal parasites in the wild Soay sheep population of St. Kilda across 31 years. The host population density (PD) has increased across the study, and PD is known to increase parasite transmission, but we found that PD and year explained temporal variation in parasite prevalence and abundance independently. Prevalence of both strongyle nematodes and coccidian microparasites increased during the study, and this effect varied between lambs, yearlings and adults. Meanwhile, abundance of strongyles was more strongly linked to host PD than to temporal (yearly) dynamics, while abundance of coccidia showed a strong temporal trend without any influence of PD. Strikingly, coccidian abundance increased 3-fold across the course of the study in lambs, while increases in yearlings and adults were negligible. Our decades-long, intensive, individual-based study will enable the role of environmental change and selection pressures in driving these dynamics to be determined, potentially providing unparalleled insight into the drivers of temporal variation in parasite dynamics in the wild.
Borderline personality disorder (BPD) is a mental health condition characterized by emotion dysregulation, interpersonal impairment, and high suicidality. Dialectical behaviour therapy (DBT) is the most widely studied psychotherapeutic treatment for BPD. To date, the vast majority of DBT research has focused on cisgender women, with a notable lack of systematic investigation of sex and/or gender differences in treatment response. In order to encourage effective, equitable treatment of BPD, further investigation into treatment targets in this population is critical. Here, we employed a systematic strategy to delineate gaps in the DBT literature pertaining to sex and gender differences and propose directions for future research. Findings demonstrate a significant discrepancy in measurement of sex and gender, particularly among gender-diverse individuals. Exploring DBT treatment response across the full spectrum of genders will facilitate the provision of more tailored, impactful care to all individuals who suffer from BPD.
Key learning aims
(1) To date, DBT treatment literature has focused almost exclusively on cisgender women, with only two of 253 DBT studies in current literature accounting for transgender and gender diverse (TGD) individuals.
(2) Recognize how gender minority stress may impact the prevalence of BPD among TGD individuals.
(3) Learn how future research initiatives can be employed to rectify this gap in the DBT literature.