From the Cover: Proton transfers are key elementary steps in ethylene polymerization on isolated chromium(III) silicates

Mononuclear Cr(III) surface sites were synthesized from grafting [Cr(OSi(O^tBu)₃)₃(tetrahydrofurano)₂] on silica partially dehydroxylated at 700 °C, followed by a thermal treatment under vacuum, and characterized by infrared, ultraviolet-visible, electron paramagnetic resonance (EPR), and X-ray absorption spectroscopy (XAS). These sites are highly active in ethylene polymerization to yield polyethylene with a broad molecular weight distribution, similar to that typically obtained from the Phillips catalyst. CO binding, EPR spectroscopy, and poisoning studies indicate that two different types of Cr(III) sites are present on the surface, one of which is active in polymerization. Density functional theory (DFT) calculations using cluster models show that active sites are tricoordinated Cr(III) centers and that the presence of an additional siloxane bridge coordinated to Cr leads to inactive species. From IR spectroscopy and DFT calculations, these tricoordinated Cr(III) sites initiate and regulate the polymer chain length via unique proton transfer steps in polymerization catalysis.Almost half of the world’s high-density polyethylene is produced by the Phillips catalyst, a silica-supported chromium oxide (CrO_x/SiO₂) (1). This catalyst is prepared by incipient wetness impregnation of a chromium salt on silica, followed by high temperature calcination. Contacting this material with ethylene forms the active reduced species in situ that polymerizes ethylene. The Phillips catalyst is active in the absence of activators that are typically required for polymerization catalysts (2). Despite 50 y of research, the catalytically active site and the initiation mechanism, particularly the formation of the first Cr–C bond, remain controversial. Numerous spectroscopic techniques [infrared (IR), ultraviolet-visible (UV-Vis), electron paramagnetic resonance (EPR), X-ray absorption spectroscopy (XAS), etc.] established that the Phillips catalyst contains a complex mixture of surface Cr species, of which only ∼10% are active in polymerization (3, 4). The low number of active sites is one of the main limiting factors in using spectroscopic methods to study this material because the spectroscopic signature mainly belongs to inactive species.Previous molecular approaches to determine the Phillips catalyst ethylene polymerization mechanism focused on systems containing preformed Cr–C bonds (5–7). We recently reported the preparation of well-defined silica-supported Cr(II) and Cr(III) dinuclear sites (8), where Cr(III) species are active polymerization sites, in contrast to Cr(II), which is consistent with extensive research on homogeneous chromium complexes (9–11). We proposed that these well-defined Cr(III) silicates initiate polymerization by the heterolytic cleavage of a C–H bond of ethylene on a Cr–O bond to form a Cr–vinyl species that is capable of inserting ethylene by a Cossee–Arlman mechanism (8). However, extensive studies on Phillips catalyst invoke mononuclear polymerization sites (12–18). Furthermore, direct evidence of the active site structure and the polymerization mechanism is critically needed. Here we investigate the preparation and the detailed characterization of isolated Cr(III) sites supported on silica, prepared by grafting [Cr^III(OSi(O^tBu)₃)₃(tetrahydrofurano; THF)₂] (19) on dehydroxylated silica and a subsequent thermal treatment under vacuum. These isolated Cr(III) sites are highly active in ethylene polymerization in the absence of coactivator. Computational investigations in combination with IR spectroscopy indicate that polymerization occurs on tricoordinate Cr(III) sites and involves two key proton transfer steps: (i) formation of the first Cr–C bond through the C–H activation of ethylene across a Cr–O bond and (ii) termination by the microreverse of the initiation step while chain growth occurs by classical Cossee–Arlman insertion polymerization (20, 21).     

Colorectal cancer incidence and screening in US Medicaid patients with and without HIV infection

Non-AIDS defining malignancies, particularly colorectal cancer (CRC), may be more prevalent among persons living with HIV (PLWH). Further, PLWH may be less likely to receive CRC screening (CRCS). We studied the epidemiology of CRC and CRCS patterns in PLWH and HIV-uninfected persons in a large US Medicaid population. We performed a matched cohort study examining CRC incidence in 2006 and CRCS between 1999 and 2007. Study participants were continuously enrolled in the Medicaid programs of California, Florida, New York, Ohio, and Pennsylvania. All PLWH enrollees were matched to five randomly sampled HIV-uninfected enrollees on 5-year age group, gender, and state. Adjusted odds ratios (AORs) for incident CRC (adjusted for comorbidity index) and the presence of CRCS (adjusted for comorbidity index and years in the data-set) among PLWH compared to HIV-uninfected enrollees were calculated. PLWH were not more likely to be diagnosed with CRC after adjusting for comorbidity index (unadjusted OR: 1.73, 95% confidence interval [CI]: 1.37–2.19; AOR 1.29; 95% CI: 0.98–1.70). While CRCS rates were low overall, PLWH were more likely to have received CRCS in unadjusted analyses (35.8% vs. 33.7%; OR 1.10, 95% CI: 1.07–1.13). This relationship was reversed after adjusting for comorbidity index and years in the data-set (AOR: 0.80, 95% CI: 0.77–0.83). Limitations of the study include a focus on the Medicaid population, an inability to detect fecal occult blood tests (FOBT), and having half of patients between 50 and 55 years of age. In conclusion, PLWH were not more likely to be diagnosed with CRC, but in adjusted analyses, were less likely to have received CRCS. As we showed a low rate of CRCS overall in this Medicaid population, researchers, clinicians, and policy-makers should improve access to and uptake of CRCS among all Medicaid patients, and particularly among PLWH.     

Shortening the acquisition time of whole-body MRI: 3D T1 gradient echo Dixon vs fast spin echo for metastatic screening in prostate cancer

European Radiology - To compare 3D T1-weighted fast spin echo (FSE) and 3D T1-weighted gradient echo (GE) mDixon as morphologic sequences to complement diffusion-weighted imaging (DWI) for the...     

Embedded Pragmatic Trials in Dementia Care: Realizing the Vision of the NIA IMPACT Collaboratory

Close to 6 million Americans have Alzheimer's disease (AD) or Alzheimer's disease and related dementia (AD/ADRD). These high-need, high-cost patients are vulnerable to receiving poor quality uncoordinated care, ultimately leading to adverse health outcomes, poor quality of life, and misuse of resources. Improving the care of persons living with dementia (PLWD) and their caregivers is an urgent public health challenge that must be informed by high-quality evidence. Although prior research has elucidated opportunities to improve AD/ADRD care, the adoption of promising interventions has been stymied by the lack of research evaluating their effectiveness when implemented under real-world conditions. Embedded pragmatic clinical trials (ePCTs) in healthcare systems have the potential to accelerate the translation of evidence-based interventions into clinical practice. Building from the foundation of the National Institutes of Healthcare Systems Collaboratory, in September 2019 the National Institute on Aging Imbedded Pragmatic AD/ADRD Clinical Trials (IMPACT) Collaboratory was launched. Its mission is to build the nation's capacity to conduct ePCTs within healthcare systems for PLWD and their caregivers by (1) developing and disseminating best practice research methods, (2) supporting the design and conduct of ePCTs including pilot studies, (3) building investigator capacity through training and knowledge generation, (4) catalyzing collaboration among stakeholders, and (5) ensuring the research includes culturally tailored interventions for people from diverse backgrounds. This report presents the rationale, structure, key activities, and markers of success for the overall NIA IMPACT Collaboratory. The articles that follow in this special Issue describe the specific work of its 10 core working groups and teams. J Am Geriatr Soc 68:S1–S7, 2020 .     

Precise evaluation of liver histology by computerized morphometry shows that steatosis influences liver stiffness measured by transient elastography in chronic hepatitis C

Background

Liver stiffness evaluation (LSE) by Fibroscan is now widely used to assess liver fibrosis in chronic hepatitis C. Liver steatosis is a common lesion in chronic hepatitis C as in other chronic liver diseases, but its influence on LSE remains unclear. We aimed to precisely determine the influence of steatosis on LSE by using quantitative and precise morphometric measurements of liver histology.

Methods

650 patients with chronic hepatitis C, liver biopsy, and LSE were included. Liver specimens were evaluated by optical analysis (Metavir F and A, steatosis grading) and by computerized morphometry to determine the area (%, reflecting quantity) and fractal dimension (FD, reflecting architecture) of liver fibrosis and steatosis.

Results

The relationships between LSE and liver histology were better described using morphometry. LSE median was independently linked to fibrosis (area or FD), steatosis (area or FD), activity (serum AST), and IQR/LSE median. Steatosis area ≥4.0 % induced a 50 % increase in LSE result in patients with fibrosis area <9 %. In patients with IQR/LSE median ≤0.30, the rate of F0/1 patients misclassified as F ≥ 2 by Fibroscan was, respectively for steatosis area <4.0 and ≥4.0 %: 12.6 vs 32.4 % (p = 0.003). Steatosis level did not influence LSE median when fibrosis area was ≥9 %, and consequently did not increase the rate of F ≤ 3 patients misclassified as cirrhotic.

Conclusion

A precise evaluation of liver histology by computerized morphometry shows that liver stiffness measured by Fibroscan is linked to liver fibrosis, activity, and also steatosis. High level of steatosis induces misevaluation of liver fibrosis by Fibroscan.