Advances in Atomic Data for Neutron-Capture Elements

Neutron(n)-capture elements (atomic number Z>30), which can be produced in planetary nebula (PN) progenitor stars via s-process nucleosynthesis, have been detected in nearly 100 PNe. This demonstrates that nebular spectroscopy is a potentially powerful tool for studying the production and chemical evolution of trans-iron elements. However, significant challenges must be addressed before this goal can be achieved. One of the most substantial hurdles is the lack of atomic data for n-capture elements, particularly that needed to solve for their ionization equilibrium (and hence to convert ionic abundances to elemental abundances). To address this need, we have computed photoionization cross sections and radiative and dielectronic recombination rate coefficients for the first six ions of Se and Kr. The calculations were benchmarked against experimental photoionization cross section measurements. In addition, we computed charge transfer (CT) rate coefficients for ions of six n-capture elements. These efforts will enable the accurate determination of nebular Se and Kr abundances, allowing robust investigations of s-process enrichments in PNe.Comment: To be published in IAU Symp. 283: Planetary Nebulae, an Eye to the Future; 2 page

Neutron-Capture elements in planetary nebulae: first detections of near-Infrared [Te III] and [Br V] emission lines

We have identified two new near-infrared emission lines in the spectra of planetary nebulae (PNe) arising from heavy elements produced by neutron capture reactions: [Te III] 2.1019 $\mu$m and [Br V] 1.6429 $\mu$m. [Te III] was detected in both NGC 7027 and IC 418, while [Br V] was seen in NGC 7027. The observations were obtained with the medium-resolution spectrograph EMIR on the 10.4m Gran Telescopio Canarias at La Palma, and with the high-resolution spectrograph IGRINS on the 2.7m Harlan J. Smith telescope at McDonald Observatory. New calculations of atomic data for these ions, specifically A-values and collision strengths, are presented and used to derive ionic abundances of Te$^{2+}$ and Br$^{4+}$. We also derive ionic abundances of other neutron-capture elements detected in the near-infrared spectra, and estimate total elemental abundances of Se, Br, Kr, Rb, and Te after correcting for unobserved ions. Comparison of our derived enrichments to theoretical predictions from AGB evolutionary models shows reasonable agreement for solar metallicity progenitor stars of $\sim$2 - 4 M$_{\odot}$. The spectrally-isolated [Br V] 1.6429 $\mu$m line has advantages for determining nebular Br abundances over optical [Br III] emission lines that can be blended with other features. Finally, measurements of Te are of special interest because this element lies beyond the first peak of the s-process, and thus provides new leverage on the abundance pattern of trans-iron species produced by AGB stars.Comment: 9 pages, 1 figure, 4 tables. Accepted for publication in ApJ Letter

Associations Between Performance on an Abbreviated CogState Battery, Other Measures of Cognitive Function, and Biomarkers in People at Risk for Alzheimer\u27s Disease

It is not known whether computerized cognitive assessments, like the CogState battery, are sensitive to preclinical cognitive changes or pathology in people at risk for Alzheimer\u27s disease(AD). In 469 late middle-aged participants from the Wisconsin Registry for Alzheimer\u27s Prevention(mean age 63.8±7 years at testing; 67% female; 39% APOE4+), we examined relationships between a CogState abbreviated battery(CAB) of seven tests and demographic characteristics, traditional paper-based neuropsychological tests as well as a composite cognitive impairment index, cognitive impairment status(determined by consensus review), and biomarkers for amyloid and tau(CSF phosphorylated-tau/Aβ42 and global PET-PiB burden) and neural injury(CSF neurofilament light protein). CSF and PET-PiB were collected in n = 71 and n = 91 participants, respectively, approximately four years prior to CAB testing. For comparison, we examined three traditional tests of delayed memory in parallel. Similar to studies in older samples, the CAB was less influenced by demographic factors than traditional tests. CAB tests were generally correlated with most paper-based cognitive tests examined and mapped onto the same cognitive domains. Greater composite cognitive impairment index was associated with worse performance on all CAB tests. Cognitively impaired participants performed significantly worse compared to normal controls on all but one CAB test. Poorer One Card Learning test performance was associated with higher levels of CSF phosphorylated-tau/Aβ42. These results support the use of the CogState battery as measures of early cognitive impairment in studies of people at risk for AD

Prediction of Longitudinal Cognitive Decline in Preclinical Alzheimer Disease Using Plasma Biomarkers

IMPORTANCE: Alzheimer disease (AD) pathology starts with a prolonged phase of β-amyloid (Aβ) accumulation without symptoms. The duration of this phase differs greatly among individuals. While this disease phase has high relevance for clinical trial designs, it is currently unclear how to best predict the onset of clinical progression. OBJECTIVE: To evaluate combinations of different plasma biomarkers for predicting cognitive decline in Aβ-positive cognitively unimpaired (CU) individuals. DESIGN, SETTING, AND PARTICIPANTS: This prospective population-based prognostic study evaluated data from 2 prospective longitudinal cohort studies (the Swedish BioFINDER-1 and the Wisconsin Registry for Alzheimer Prevention [WRAP]), with data collected from February 8, 2010, to October 21, 2020, for the BioFINDER-1 cohort and from August 11, 2011, to June 27, 2021, for the WRAP cohort. Participants were CU individuals recruited from memory clinics who had brain Aβ pathology defined by cerebrospinal fluid (CSF) Aβ42/40 in the BioFINDER-1 study and by Pittsburgh Compound B (PiB) positron emission tomography (PET) in the WRAP study. A total of 564 eligible Aβ-positive and Aβ-negative CU participants with available relevant data from the BioFINDER-1 and WRAP cohorts were included in the study; of those, 171 Aβ-positive participants were included in the main analyses. EXPOSURES: Baseline P-tau181, P-tau217, P-tau231, glial fibrillary filament protein, and neurofilament light measured in plasma; CSF biomarkers in the BioFINDER-1 cohort, and PiB PET uptake in the WRAP cohort. MAIN OUTCOMES AND MEASURES: The primary outcome was longitudinal measures of cognition (using the Mini-Mental State Examination [MMSE] and the modified Preclinical Alzheimer Cognitive Composite [mPACC]) over a median of 6 years (range, 2-10 years). The secondary outcome was conversion to AD dementia. Baseline biomarkers were used in linear regression models to predict rates of longitudinal cognitive change (calculated separately). Models were adjusted for age, sex, years of education, apolipoprotein E ε4 allele status, and baseline cognition. Multivariable models were compared based on model R2 coefficients and corrected Akaike information criterion. RESULTS: Among 171 Aβ-positive CU participants included in the main analyses, 119 (mean [SD] age, 73.0 [5.4] years; 60.5% female) were from the BioFINDER-1 study, and 52 (mean [SD] age, 64.4 [4.6] years; 65.4% female) were from the WRAP study. In the BioFINDER-1 cohort, plasma P-tau217 was the best marker to predict cognitive decline in the mPACC (model R2 = 0.41) and the MMSE (model R2 = 0.34) and was superior to the covariates-only models (mPACC: R2 = 0.23; MMSE: R2 = 0.04; P < .001 for both comparisons). Results were validated in the WRAP cohort; for example, plasma P-tau217 was associated with mPACC slopes (R2 = 0.13 vs 0.01 in the covariates-only model; P = .01) and MMSE slopes (R2 = 0.29 vs 0.24 in the covariates-only model; P = .046). Sparse models were identified with plasma P-tau217 as a predictor of cognitive decline. Power calculations for enrichment in hypothetical clinical trials revealed large relative reductions in sample sizes when using plasma P-tau217 to enrich for CU individuals likely to experience cognitive decline over time. CONCLUSIONS AND RELEVANCE: In this study, plasma P-tau217 predicted cognitive decline in patients with preclinical AD. These findings suggest that plasma P-tau217 may be used as a complement to CSF or PET for participant selection in clinical trials of novel disease-modifying treatments

Implementation of a novel stratified PAthway of CarE for common musculoskeletal (MSK) conditions in primary care: Protocol for a multicentre pragmatic randomised controlled trial (the PACE MSK trial)

Introduction Musculoskeletal (MSK) conditions constitute the highest burden of disease globally, with healthcare services often utilised inappropriately and overburdened. The aim of this trial is to evaluate the effectiveness of a novel clinical PAthway of CarE programme (PACE programme), where care is provided based on people's risk of poor outcome. Methods and analysis Multicentre randomised controlled trial. 716 people with MSK conditions (low back pain, neck pain or knee osteoarthritis) will be recruited in primary care. They will be stratified for risk of a poor outcome (low risk/high risk) using the Short Form Örebro Musculoskeletal Pain Screening Questionnaire (SF-ÖMSPQ) then randomised to usual care (n=358) or the PACE programme (n=358). Participants at low risk in the PACE programme will receive up to 3 sessions of guideline based care from their primary healthcare professional (HCP) supported by a custom designed website (mypainhub.com). Those at high risk will be referred to an allied health MSK specialist who will conduct a comprehensive patient-centred assessment then liaise with the primary HCP to determine further care. Primary outcome (SF 12-item PCS) and secondary outcomes (eg, pain self-efficacy, psychological health) will be collected at baseline, 3, 6 and 12 months. Cost-effectiveness will be measured as cost per quality-Adjusted life-year gained. Health economic analysis will include direct and indirect costs. Analyses will be conducted on an intention-To-Treat basis. Primary and secondary outcomes will be analysed independently, using generalised linear models. Qualitative and mixed-methods studies embedded within the trial will evaluate patient experience, health professional practice and interprofessional collaboration. Ethics and dissemination Ethics approval has been received from the following Human Research Ethics Committees: The University of Sydney (2018/926), The University of Queensland (2019000700/2018/926), University of Melbourne (1954239), Curtin University (HRE2019-0263) and Northern Sydney Local Health District (2019/ETH03632). Dissemination of findings will occur via peer-reviewed publications, conference presentations and social media. Trial registration number ACTRN12619000871145

Rationale and design of a multicenter Chronic Kidney Disease (CKD) and at-risk for CKD electronic health records-based registry: CURE-CKD.

BACKGROUND: Chronic kidney disease (CKD) is a global public health problem, exhibiting sharp increases in incidence, prevalence, and attributable morbidity and mortality. There is a critical need to better understand the demographics, clinical characteristics, and key risk factors for CKD; and to develop platforms for testing novel interventions to improve modifiable risk factors, particularly for the CKD patients with a rapid decline in kidney function. METHODS: We describe a novel collaboration between two large healthcare systems (Providence St. Joseph Health and University of California, Los Angeles Health) supported by leadership from both institutions, which was created to develop harmonized cohorts of patients with CKD or those at increased risk for CKD (hypertension/HTN, diabetes/DM, pre-diabetes) from electronic health record data. RESULTS: The combined repository of candidate records included more than 3.3 million patients with at least a single qualifying measure for CKD and/or at-risk for CKD. The CURE-CKD registry includes over 2.6 million patients with and/or at-risk for CKD identified by stricter guide-line based criteria using a combination of administrative encounter codes, physical examinations, laboratory values and medication use. Notably, data based on race/ethnicity and geography in part, will enable robust analyses to study traditionally disadvantaged or marginalized patients not typically included in clinical trials. DISCUSSION: CURE-CKD project is a unique multidisciplinary collaboration between nephrologists, endocrinologists, primary care physicians with health services research skills, health economists, and those with expertise in statistics, bio-informatics and machine learning. The CURE-CKD registry uses curated observations from real-world settings across two large healthcare systems and has great potential to provide important contributions for healthcare and for improving clinical outcomes in patients with and at-risk for CKD

Prevalence and Clinical Implications of a β-Amyloid–Negative, Tau-Positive Cerebrospinal Fluid Biomarker Profile in Alzheimer Disease

IMPORTANCE: Knowledge is lacking on the prevalence and prognosis of individuals with a β-amyloid-negative, tau-positive (A-T+) cerebrospinal fluid (CSF) biomarker profile. OBJECTIVE: To estimate the prevalence of a CSF A-T+ biomarker profile and investigate its clinical implications. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective cohort study of the cross-sectional multicenter University of Gothenburg (UGOT) cohort (November 2019-January 2021), the longitudinal multicenter Alzheimer Disease Neuroimaging Initiative (ADNI) cohort (individuals with mild cognitive impairment [MCI] and no cognitive impairment; September 2005-May 2022), and 2 Wisconsin cohorts, Wisconsin Alzheimer Disease Research Center and Wisconsin Registry for Alzheimer Prevention (WISC; individuals without cognitive impairment; February 2007-November 2020). This was a multicenter study, with data collected from referral centers in clinical routine (UGOT) and research settings (ADNI and WISC). Eligible individuals had 1 lumbar puncture (all cohorts), 2 or more cognitive assessments (ADNI and WISC), and imaging (ADNI only) performed on 2 separate occasions. Data were analyzed on August 2022 to April 2023. EXPOSURES: Baseline CSF Aβ42/40 and phosphorylated tau (p-tau)181; cognitive tests (ADNI: modified preclinical Alzheimer cognitive composite [mPACC]; WISC: modified 3-test PACC [PACC-3]). Exposures in the ADNI cohort included [18F]-florbetapir amyloid positron emission tomography (PET), magnetic resonance imaging (MRI), [18F]-fluorodeoxyglucose PET (FDG-PET), and cross-sectional tau-PET (ADNI: [18F]-flortaucipir, WISC: [18F]-MK6240). MAIN OUTCOMES AND MEASURES: Primary outcomes were the prevalence of CSF AT biomarker profiles and continuous longitudinal global cognitive outcome and imaging biomarker trajectories in A-T+ vs A-T- groups. Secondary outcomes included cross-sectional tau-PET. RESULTS: A total of 7679 individuals (mean [SD] age, 71.0 [8.4] years; 4101 male [53%]) were included in the UGOT cohort, 970 individuals (mean [SD] age, 73 [7.0] years; 526 male [54%]) were included in the ADNI cohort, and 519 individuals (mean [SD] age, 60 [7.3] years; 346 female [67%]) were included in the WISC cohort. The prevalence of an A-T+ profile in the UGOT cohort was 4.1% (95% CI, 3.7%-4.6%), being less common than the other patterns. Longitudinally, no significant differences in rates of worsening were observed between A-T+ and A-T- profiles for cognition or imaging biomarkers. Cross-sectionally, A-T+ had similar tau-PET uptake to individuals with an A-T- biomarker profile. CONCLUSION AND RELEVANCE: Results suggest that the CSF A-T+ biomarker profile was found in approximately 5% of lumbar punctures and was not associated with a higher rate of cognitive decline or biomarker signs of disease progression compared with biomarker-negative individuals

Readout of a quantum processor with high dynamic range Josephson parametric amplifiers

We demonstrate a high dynamic range Josephson parametric amplifier (JPA) in which the active nonlinear element is implemented using an array of rf-SQUIDs. The device is matched to the 50 $\Omega$ environment with a Klopfenstein-taper impedance transformer and achieves a bandwidth of 250-300 MHz, with input saturation powers up to -95 dBm at 20 dB gain. A 54-qubit Sycamore processor was used to benchmark these devices, providing a calibration for readout power, an estimate of amplifier added noise, and a platform for comparison against standard impedance matched parametric amplifiers with a single dc-SQUID. We find that the high power rf-SQUID array design has no adverse effect on system noise, readout fidelity, or qubit dephasing, and we estimate an upper bound on amplifier added noise at 1.6 times the quantum limit. Lastly, amplifiers with this design show no degradation in readout fidelity due to gain compression, which can occur in multi-tone multiplexed readout with traditional JPAs.Comment: 9 pages, 8 figure