Understanding tissue structure and function requires tools that quantify the expression of multiple proteins while preserving spatial information. Here, we describe MIBI-TOF (multiplexed ion beam ...imaging by time of flight), an instrument that uses bright ion sources and orthogonal time-of-flight mass spectrometry to image metal-tagged antibodies at subcellular resolution in clinical tissue sections. We demonstrate quantitative, full periodic table coverage across a five-log dynamic range, imaging 36 labeled antibodies simultaneously with histochemical stains and endogenous elements. We image fields of view up to 800 μm × 800 μm at resolutions down to 260 nm with sensitivities approaching single-molecule detection. We leverage these properties to interrogate intrapatient heterogeneity in tumor organization in triple-negative breast cancer, revealing regional variability in tumor cell phenotypes in contrast to a structured immune response. Given its versatility and sample back-compatibility, MIBI-TOF is positioned to leverage existing annotated, archival tissue cohorts to explore emerging questions in cancer, immunology, and neurobiology.
Abstract
Background
Functional decline is common following acute hospitalization and is associated with hospital readmission, institutionalization, and mortality. People with functional decline may ...have difficulty accessing post-discharge medical care, even though early physician follow-up has the potential to prevent poor outcomes and is integral to high-quality transitional care. We sought to determine whether recent functional decline was associated with lower rates of post-discharge physician follow-up, and whether this association changed during the COVID-19 pandemic, given that both functional decline and COVID-19 may affect access to post-discharge care.
Method
We conducted a retrospective cohort study using health administrative data from Ontario, Canada. We included patients over 65 who were discharged from an acute care facility during March 1st, 2019 – January 31st, 2020 (pre-COVID-19 period), and March 1st, 2020 – January 31st, 2021 (COVID-19 period), and who were assessed for home care while in hospital. Patients with and without functional decline were compared. Our primary outcome was any physician follow-up visit within 7 days of discharge. We used propensity score weighting to compare outcomes between those with and without functional decline.
Results
Our study included 21,771 (pre-COVID) and 17,248 (COVID) hospitalized patients, of whom 15,637 (71.8%) and 12,965 (75.2%) had recent functional decline. Pre-COVID, there was no difference in physician follow-up within 7 days of discharge (Functional decline 45.0% vs. No functional decline 44.0%; RR = 1.02, 95% CI 0.98–1.06). These results did not change in the COVID-19 period (Functional decline 51.1% vs. No functional decline 49.4%; RR = 1.03, 95% CI 0.99–1.08, Z-test for interaction p = 0.72). In the COVID-19 cohort, functional decline was associated with having a 7-day physician virtual visit (RR 1.15; 95% CI 1.08–1.24) and a 7-day physician home visit (RR 1.64; 95% CI 1.10–2.43).
Conclusions
Functional decline was not associated with reduced 7-day post-discharge physician follow-up in either the pre-COVID-19 or COVID-19 periods. In the COVID-19 period, functional decline was positively associated with 7-day virtual and home-visit follow-up.
Population-based chronic disease surveillance systems were likely disrupted by the COVID-19 pandemic. The objective of this study was to examine the immediate and ongoing impact of the COVID-19 ...pandemic on the claims-based incidence of dementia.
We conducted a population-based time series analysis from January 2015 to December 2021 in Ontario, Canada. We calculated the monthly claims-based incidence of dementia using a validated case ascertainment algorithm drawing from routinely collected health administrative data. We used autoregressive linear models to compare the claims-based incidence of dementia during the COVID-19 period (2020-2021) to the expected incidence had the pandemic not occurred, controlling for seasonality and secular trends. We examined incidence by source of ascertainment and across strata of sex, age, community size and number of health conditions.
The monthly claims-based incidence of dementia dropped from a 2019 average of 11.9 per 10 000 to 8.5 per 10 000 in April 2020 (32.6% lower than expected). The incidence returned to expected levels by late 2020. Across the COVID-19 period there were a cumulative 2990 (95% CI 2109 to 3704) fewer cases of dementia observed than expected, equivalent to 1.05 months of new cases. Despite the overall recovery, ascertainment rates continued to be lower than expected among individuals aged 65-74 years and in large urban areas. Ascertainment rates were higher than expected in hospital and among individuals with 11 or more health conditions.
The claims-based incidence of dementia recovered to expected levels by late 2020, suggesting minimal long-term changes to population-based dementia surveillance. Continued monitoring of claims-based incidence is necessary to determine whether the lower than expected incidence among individuals aged 65-74 and in large urban areas, and higher than expected incidence among individuals with 11 or more health conditions, is transitory.
Electrochemical deposition of materials with hard magnetic properties in the as-deposited state is essential for the efficient integration of micro-magnetic components into MEMS devices. Here we ...discuss the growth process and the microstructure-magnetic properties correlation for two Co-rich alloys, Co–Ni–P and Co–Pt. Under suitable synthesis conditions, these materials exhibit perpendicular anisotropy and hard magnetic properties in the as-deposited state; in addition, such properties are maintained up to several micrometer film thickness through close control of the film microstructure. In the case of Co–Ni–P films we achieved a saturation magnetization of 1.21
T (963
emu/cm
3), perpendicular coercivity up to 188
kA/m (2.36
kOe) at a thickness of 10
μm, and energy products up to 4.2
kJ/m
3. Co-rich Co–Pt films were grown on several substrates – Cr, Cu(0
0
1), Cu(1
1
1), and Ru(0
0
0
1) – in order to control magnetic anisotropy and achieve optimum hard magnetic properties. Cu(1
1
1) contributes to stabilize the hexagonal hcp phase at high current density yielding excellent hard magnetic properties, although only in films thicker than 100
nm; saturation magnetization in these films was about 1.04
T (828
emu/cm
3). Perpendicular coercivities up to 485.6
kA/m (6.1
kOe) were obtained in 1
μm thick film deposited at 50
mA/cm
2. Ru(0
0
0
1) seed layers provide an appropriate interface structure to further facilitate the epitaxial growth of hcp films, yielding hard magnetic properties and perpendicular coercivity with a squareness ∼1 in films as thin as 10
nm. The hard magnetic properties were only marginally compromised at large film thickness. Deposition at higher current density (50
mA/cm
2) favored markedly improved hard magnetic properties. The Co–Pt films on Ru exhibited perpendicular anisotropy with anisotropy constant up to 1.2
MJ/m
3. The electrodeposition process was further extended to fill lithographically patterned hole arrays (850
nm diameter, center-to-center distance 2550
nm and about 700
nm thick resist), yielding arrays of micron-sized hard magnetic cylinders with perpendicular coercivity of 361
kA/m (4.54
kOe) and high squareness.
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