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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.
Quality improvement programmes (QIPs) are designed to enhance patient outcomes by systematically introducing evidence-based clinical practices. The CONQUEST QIP focuses on improving the identification and management of patients with COPD in primary care. The process of developing CONQUEST, recruiting, preparing systems for participation, and implementing the QIP across three integrated healthcare systems (IHSs) is examined to identify and share lessons learned.
Approach and development:
This review is organized into three stages: 1) development, 2) preparing IHSs for implementation, and 3) implementation. In each stage, key steps are described with the lessons learned and how they can inform others interested in developing QIPs designed to improve the care of patients with chronic conditions in primary care.
Stage 1 was establishing and working with steering committees to develop the QIP Quality Standards, define the target patient population, assess current management practices, and create a global operational protocol. Additionally, potential IHSs were assessed for feasibility of QIP integration into primary care practices. Factors assessed included a review of technological infrastructure, QI experience, and capacity for effective implementation.
Stage 2 was preparation for implementation. Key was enlisting clinical champions to advocate for the QIP, secure participation in primary care, and establish effective communication channels. Preparation for implementation required obtaining IHS approvals, ensuring Health Insurance Portability and Accountability Act compliance, and devising operational strategies for patient outreach and clinical decision support delivery.
Stage 3 was developing three IHS implementation models. With insight into the local context from local clinicians, implementation models were adapted to work with the resources and capacity of the IHSs while ensuring the delivery of essential elements of the programme.
Conclusion:
Developing and launching a QIP programme across primary care practices requires extensive groundwork, preparation, and committed local champions to assist in building an adaptable environment that encourages open communication and is receptive to feedback.
We provide an assessment of the Infinity Two fusion pilot plant (FPP) baseline plasma physics design. Infinity Two is a four-field period, aspect ratio $A = 10$, quasi-isodynamic stellarator with improved confinement appealing to a max-$J$ approach, elevated plasma density and high magnetic fields ($ \langle B\rangle = 9$ T). Here $J$ denotes the second adiabatic invariant. At the envisioned operating point ($800$ MW deuterium-tritium (DT) fusion), the configuration has robust magnetic surfaces based on magnetohydrodynamic (MHD) equilibrium calculations and is stable to both local and global MHD instabilities. The configuration has excellent confinement properties with small neoclassical transport and low bootstrap current ($|I_{bootstrap}| \sim 2$ kA). Calculations of collisional alpha-particle confinement in a DT FPP scenario show small energy losses to the first wall (${\lt}1.5 \,\%$) and stable energetic particle/Alfvén eigenmodes at high ion density. Low turbulent transport is produced using a combination of density profile control consistent with pellet fueling and reduced stiffness to turbulent transport via three-dimensional shaping. Transport simulations with the T3D-GX-SFINCS code suite with self-consistent turbulent and neoclassical transport predict that the DT fusion power$P_{{fus}}=800$ MW operating point is attainable with high fusion gain ($Q=40$) at volume-averaged electron densities $n_e\approx 2 \times 10^{20}$ m$^{-3}$, below the Sudo density limit. Additional transport calculations show that an ignited ($Q=\infty$) solution is available at slightly higher density ($2.2 \times 10^{20}$ m$^{-3}$) with $P_{{fus}}=1.5$ GW. The magnetic configuration is defined by a magnetic coil set with sufficient room for an island divertor, shielding and blanket solutions with tritium breeding ratios (TBR) above unity. An optimistic estimate for the gas-cooled solid breeder designed helium-cooled pebble bed is TBR $\sim 1.3$. Infinity Two satisfies the physics requirements of a stellarator fusion pilot plant.
Although cognitive remediation (CR) improves cognition and functioning, the key features that promote or inhibit its effectiveness, especially between cognitive domains, remain unknown. Discovering these key features will help to develop CR for more impact.
Aim
To identify interrelations between cognition, symptoms, and functioning, using a novel network analysis approach and how CR affects these recovery outcomes.
Methods
A secondary analysis of randomized controlled trial data (N = 165) of CR in early psychosis. Regularized partial correlation networks were estimated, including symptoms, cognition, and functioning, for pre-, post-treatment, and change over time. Pre- and post-CR networks were compared on global strength, structure, edge invariance, and centrality invariance.
Results
Cognition, negative, and positive symptoms were separable constructs, with symptoms showing independent relationships with cognition. Negative symptoms were central to the CR networks and most strongly associated with change in functioning. Verbal and visual learning improvement showed independent relationships to improved social functioning and negative symptoms. Only visual learning improvement was positively associated with personal goal achievement. Pre- and post-CR networks did not differ in structure (M = 0.20, p = 0.45) but differed in global strength, reflecting greater overall connectivity in the post-CR network (S = 0.91, p = 0.03).
Conclusions
Negative symptoms influenced network changes following therapy, and their reduction was linked to improvement in verbal and visual learning following CR. Independent relationships between visual and verbal learning and functioning suggest that they may be key intervention targets to enhance social and occupational functioning.
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.
The clay minerals formed in a deeply weathered boulder conglomerate of Middle Old Red Sandstone (Devonian) age in north-east Scotland have been studied by a variety of physical and chemical techniques. The granite and granulite boulders in this deposit are completely weathered. With the exception of microcline, all the feldspars in these rocks—orthoclase feldspar, orthoclase-microperthite, albite, and oligoclase—weather to a Cheto-type montmorillonite, poor in iron. Electron and optical microscopy indicate that the weathering transformation is a direct one, without the intervention of any intermediate crystalline or well-defined amorphous phase. Structural control of the primary mineral over the formation of the montmorillonite seems to have been a minimal factor and the evidence suggests that the clay mineral crystallized from the soluble or colloidal products arising from the decomposed feldspars. Smaller amounts of kaolinite also formed during weathering but largely from the weathering of muscovite. The environment in which these changes occurred seems to have been alkaline in a relatively closed system. Chemical analyses of related cores and weathered shells of granite and granulite bounders show only a slight decrease of silica and an increase in magnesia. Judging from the extent of alteration to secondary clay minerals, the order of resistance towards weathering of the primary minerals in these rocks is plagioclase = orthoclase < muscovite < biotite < microcline < quartz.
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.
Decreasing the time to contact precautions (CP) is critical to carbapenem-resistant Enterobacterales (CRE) prevention. Identifying factors associated with delayed CP can decrease the spread from patients with CRE. In this study, a shorter length of stay was associated with being placed in CP within 3 days.
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 US National Action Plan for Combating Antibiotic-Resistant Bacteria established a goal to decrease unnecessary outpatient antibiotic use by 50%. However, data to inform this goal have been limited to medical settings and have not included dental prescribing. Thus, we sought to identify the proportion of antibiotics prescribed inappropriately by dentists to inform outpatient stewardship efforts.
Methods:
Cross-sectional analysis of 2019 Veterans’ Affairs (VA) national electronic health record data. Antibiotics prescribed by dentists were evaluated for appropriateness based on 2 definitions: one derived from current guidelines (consensus-based recommendations) and the other based on relevant clinical literature (nonconsensus). A clustered binomial logistic regression model determined factors associated with discordant prescribing.
Results:
In total, 92,224 antibiotic prescriptions (63% amoxicillin; mean supply, 8.0 days) were associated with 88,539 dental visits. Prophylaxis for complications in medically compromised patients was associated with the most (30.9%) antibiotic prescriptions, followed by prevention of postsurgical complications (20.1%) and infective endocarditis (18.0%). At the visit level, 15,476 (17.5%) met the consensus-based definition for appropriate antibiotic usage and 56,946 (64.3%) met the nonconsensus definition.
Conclusions:
More than half of antibiotics prescribed by dentists do not have guidelines supporting their use. Regardless of definition applied, antibiotics prescribed by dentists were commonly unnecessary. Improving prescribing by dentists is critical to reach the national goal to decrease unnecessary antibiotic use.
Aviation passenger screening has been used worldwide to mitigate the translocation risk of SARS-CoV-2. We present a model that evaluates factors in screening strategies used in air travel and assess their relative sensitivity and importance in identifying infectious passengers. We use adapted Monte Carlo simulations to produce hypothetical disease timelines for the Omicron variant of SARS-CoV-2 for travelling passengers. Screening strategy factors assessed include having one or two RT-PCR and/or antigen tests prior to departure and/or post-arrival, and quarantine length and compliance upon arrival. One or more post-arrival tests and high quarantine compliance were the most important factors in reducing pathogen translocation. Screening that combines quarantine and post-arrival testing can shorten the length of quarantine for travelers, and variability and mean testing sensitivity in post-arrival RT-PCR and antigen tests decrease and increase with the greater time between the first and second post-arrival test, respectively. This study provides insight into the role various screening strategy factors have in preventing the translocation of infectious diseases and a flexible framework adaptable to other existing or emerging diseases. Such findings may help in public health policy and decision-making in present and future evidence-based practices for passenger screening and pandemic preparedness.