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Many states are enacting restrictions on insurers' prior authorization policies, but these laws may increase costs and lead to other undesirable consequences.Many states are enacting restrictions on insurers' prior authorization policies, but these laws may increase costs and lead to other undesirable consequences.

The low gain avalanche detectors (LGADs) are thin sensors with fast charge collection which in combination with internal gain deliver an outstanding time resolution of about 30 ps. High collision rates and consequent large particle rates crossing the detectors at the upgraded Large Hadron Collider (LHC) in 2028 will lead to radiation damage and deteriorated performance of the LGADs. The main consequence of radiation damage is loss of gain layer doping (acceptor removal) which requires an increase of bias voltage to compensate for the loss of charge collection efficiency and consequently time resolution. The Institute of High Energy Physics (IHEP), Chinese Academy of Sciences (CAS) has developed a process based on the Institute of Microelectronics (IME), CAS capability to enrich the gain layer with carbon to reduce the acceptor removal effect by radiation. After 1 MeV neutron equivalent fluence of 2.5\\(\\times\\)10\\(^{15}\\) n\\(_{eq}\\)/cm\\(^{2}\\), which is the maximum fluence to which sensors will be exposed at ATLAS High Granularity Timing Detector (HGTD), the IHEP-IME second version (IHEP-IMEv2) 50 \\(\\mu\\)m LGAD sensors already deliver adequate charge collection > 4 fC and time resolution < 50 ps at voltages < 400 V. The operation voltages of these 50 \\(\\mu\\)m devices are well below those at which single event burnout may occur.

Motivated by the need for fast timing detectors to withstand up to 2 MGy of ionizing dose at the High Luminosity Large Hadron Collider, prototype low gain avalanche detectors (LGADs) have been fabricated in single pad configuration, 2x2 arrays, and related p-i-n diodes, and exposed to Co- 60 sources for study. Devices were fabricated with a range of dopant layer concentrations and, for the arrays, a variety of inter-pad distances and distances from the active area to the edge. Measurements of capacitance versus voltage and leakage current versus voltage have been made to compare pre- and post-irradiation characteristics in gain layer depletion voltage, full bulk depletion voltage, and breakdown voltage. Conclusions are drawn regarding the effects of the gammas both on surface and interface states and on their contribution to acceptor removal through non-ionizing energy loss from Compton electrons or photoelectrons. Comparison of the performances of members of the set of devices can be used to optimize gain layer parameters.

The performances of Low Gain Avalanche diode (LGAD) sensors from a neutron irradiation campaign with fluences of 0.8 x 10^15, 15 x 10^15 and 2.5 x 10^15 neq/cm2 are reported in this article. These LGAD sensors are developed by the Institute of High Energy Physics, Chinese Academy of Sciences and the Novel Device Laboratory for the High Granularity Timing Detector of the High Luminosity Large Hadron Collider. The timing resolution and collected charge of the LGAD sensors were measured with electrons from a beta source. After irradiation with a fluence of 2.5 x 10^15 neq/cm2, the collected charge decreases from 40 fC to 7 fC, the signal-to-noise ratio deteriorates from 48 to 12, and the timing resolution increases from 29 ps to 39 ps.

Low Gain Avalanche Diode (LGAD) is applied for the High-Granularity Timing Detector (HGTD), and it will be used to upgrade the ATLAS experiment. The first batch IHEP-IME LGAD sensors were designed by the Institute of High Energy Physics (IHEP) and fabricated by the Institute of Microelectronics (IME). Three IHEP-IME sensors (W1, W7 and W8) were irradiated by the neutrons up to the fluence of 2.5 x 10^15 n_eq/cm^2 to study the effect of the shallow carbon and deep N++ layer on the irradiation hardness. Taking W7 as a reference, W1 has an extra shallow carbon applied, and W8 has a deeper N++ layer.

Objectives. To develop a method leveraging hospital-based surveillance to estimate influenza-related hospitalizations by state, age, and month as a means of enhancing current US influenza burden estimation efforts. Methods. Using data from the Influenza Hospitalization Surveillance Network (FluSurv-NET), we extrapolated monthly FluSurv-NET hospitalization rates after adjusting for testing practices and diagnostic test sensitivities to non-FluSurv-NET states. We used a Poisson zero-inflated model with an overdispersion parameter within the Bayesian hierarchical framework and accounted for uncertainty and variability between states and across time. Model validation included checking the sensitivity of results to input data, as well as model convergence diagnostics and comparing the results with independent data sources. Results. We estimated 379 300 (90% credible interval [CrI] = 305 400, 479 300) influenza-related hospitalizations in the United States for the 2022–2023 season. Median cumulative state rates ranged widely from 23.2 to 249.0 per 100 000 people. Conclusions. Our estimates were comparable to national burden estimates incorporating other approaches while accounting for variations in the timing and geography of disease activity and changes in detection and reporting. Our results provide a complementary framework to calculate estimates at finer geographic scales. ( Am J Public Health. 2025;115(4):546–554. https://doi.org/10.2105/AJPH.2024.307928 )

The pathophysiological mechanisms of postoperative delirium (POD) are still not clear, and no reliable biomarker is available to differentiate those with and without POD. Pre- and post-surgery blood from epilepsy subjects undergoing neurosurgery were collected. DNA methylation (DNAm) levels of the TNF gene, IL1B gene, and IL6 gene by the Illumina EPIC array method, and DNAm levels of the TNF gene by pyrosequencing, were analyzed. Blood from 37 subjects were analyzed by the EPIC array method, and blood from 27 subjects were analyzed by pyrosequencing. Several CpGs in the TNF gene in preoperative blood showed a negative correlation between their DNAm and age both in the POD group and in the non-POD group. However, these negative correlations were observed only in the POD group after neurosurgery. Neurosurgery significantly altered DNAm levels at 17 out of 24 CpG sites on the TNF gene, 8 out of 14 CpG sites on the IL1B gene, and 4 out of 14 CpG sites on the IL6 gene. Furthermore, it was found that the Inflammatory Methylation Index (IMI), which was based on the post-surgery DNAm levels at the selected five CpG sites, can be a potential detection tool for delirium with moderate accuracy; area under the curve (AUC) value was 0.84. The moderate accuracy of this IMI was replicated using another cohort from our previous study, in which the AUC was 0.79. Our findings provide further evidence of the potential role of epigenetics and inflammation in the pathophysiology of delirium.

Tau aggregation is a hallmark feature in a subset of patients with frontotemporal dementia (FTD). Early and selective loss of von Economo neurons (VENs) and fork cells within the frontoinsular (FI) and anterior cingulate cortices (ACC) is observed in patients with sporadic behavioral variant FTD (bvFTD) due to frontotemporal lobar degeneration (FTLD), including FTLD with tau inclusions (FTLD-tau). Recently, we further showed that these specialized neurons show preferential aggregation of TDP-43 in FTLD-TDP. Whether VENs and fork cells are prone to tau accumulation in FTLD-tau remains unclear, and no previous studies of these neurons have focused on patients with pathogenic variants in the gene encoding microtubule-associated protein tau (FTLD-tau/ MAPT ). Here, we examined regional profiles of tau aggregation and neurodegeneration in 40 brain regions in 8 patients with FTLD-tau/ MAPT and 7 with Pick’s disease (PiD), a sporadic form of FTLD-tau that often presents with bvFTD. We further qualitatively assessed the cellular patterns of frontoinsular tau aggregation in FTLD-tau/ MAPT using antibodies specific for tau hyperphosphorylation, acetylation, or conformational change. ACC and mid-insula were among the regions most affected by neurodegeneration and tau aggregation in FTLD-tau/ MAPT and PiD. In these two forms of FTLD-tau, severity of regional neurodegeneration and tau protein aggregation were highly correlated across regions. In FTLD-tau/ MAPT , VENs and fork cells showed disproportionate tau protein aggregation in patients with V337 M, A152T, and IVS10 + 16 variants, but not in patients with the P301L variant. As seen in FTLD-TDP, our data suggest that VENs and fork cells represent preferentially vulnerable neuron types in most, but not all of the MAPT variants we studied.

Common neurodegenerative diseases feature progressive accumulation of disease-specific protein aggregates in selectively vulnerable brain regions. Increasing experimental evidence suggests that misfolded disease proteins exhibit prion-like properties, including the ability to seed corruptive templating and self-propagation along axons. Direct evidence for transneuronal spread in patients, however, remains limited. To test predictions made by the transneuronal spread hypothesis in human tissues, we asked whether tau deposition within axons of the corticospinal and corticopontine pathways can be predicted based on clinical syndromes and cortical atrophy patterns seen in frontotemporal lobar degeneration (FTLD). Sixteen patients with Pick’s disease, 21 with corticobasal degeneration, and 3 with FTLD- MAPT were included, spanning a range of clinical syndromes across the frontotemporal dementia (FTD) spectrum. Cortical involvement was measured using a neurodegeneration score, a tau score, and a composite score based on semiquantitative ratings and complemented by an MRI-based cortical atrophy W-map based on antemortem imaging. Midbrain cerebral peduncle and pontine base descending fibers were divided into three subregions, representing prefrontopontine, corticospinal, and parieto-temporo-occipital fiber pathways. Tau area fraction was calculated in each subregion and related to clinical syndrome and cortical measures. Within each clinical syndrome, there were predicted relationships between cortical atrophy patterns and axonal tau deposition in midbrain cerebral peduncle and pontine base. Between syndromes, contrasting and predictable patterns of brainstem axonal tau deposition emerged, with, for example, greater tau in prefrontopontine fibers in behavioral variant FTD and in corticospinal fibers in corticobasal syndrome. Finally, semiquantitative and quantitative cortical degeneration scores predicted brainstem axonal tau deposition based on anatomical principles. Taken together, these findings provide important human evidence in support of axonal tau spreading in patients with specific forms of tau-related neurodegeneration.

Coronavirus disease 2019 (COVID-19), the respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first identified in Wuhan, China and has since become pandemic. In response to the first cases identified in the United States, close contacts of confirmed COVID-19 cases were investigated to enable early identification and isolation of additional cases and to learn more about risk factors for transmission. Close contacts of nine early travel-related cases in the United States were identified and monitored daily for development of symptoms (active monitoring). Selected close contacts (including those with exposures categorized as higher risk) were targeted for collection of additional exposure information and respiratory samples. Respiratory samples were tested for SARS-CoV-2 by real-time reverse transcription polymerase chain reaction at the Centers for Disease Control and Prevention. Four hundred four close contacts were actively monitored in the jurisdictions that managed the travel-related cases. Three hundred thirty-eight of the 404 close contacts provided at least basic exposure information, of whom 159 close contacts had ≥1 set of respiratory samples collected and tested. Across all actively monitored close contacts, two additional symptomatic COVID-19 cases (i.e., secondary cases) were identified; both secondary cases were in spouses of travel-associated case patients. When considering only household members, all of whom had ≥1 respiratory sample tested for SARS-CoV-2, the secondary attack rate (i.e., the number of secondary cases as a proportion of total close contacts) was 13% (95% CI: 4-38%). The results from these contact tracing investigations suggest that household members, especially significant others, of COVID-19 cases are at highest risk of becoming infected. The importance of personal protective equipment for healthcare workers is also underlined. Isolation of persons with COVID-19, in combination with quarantine of exposed close contacts and practice of everyday preventive behaviors, is important to mitigate spread of COVID-19.