Examining the benefits and harms of Alzheimer's disease screening for family members of older adults: study protocol for a randomized controlled trial

BACKGROUND: Multiple national expert panels have identified early detection of Alzheimer's disease and related dementias (ADRD) as a national priority. However, the United States Preventive Services Task Force (USPSTF) does not currently support screening for ADRD in primary care given that the risks and benefits are unknown. The USPSTF stresses the need for research examining the impact of ADRD screening on family caregiver outcomes. METHODS: The Caregiver Outcomes of Alzheimer's Disease Screening (COADS) is a randomized controlled trial that will examine the potential benefits or harms of ADRD screening on family caregivers. It will also compare the effectiveness of two strategies for diagnostic evaluation and management after ADRD screening. COADS will enroll 1800 dyads who will be randomized into three groups (n = 600/group): the 'Screening Only' group will receive ADRD screening at baseline and disclosure of the screening results, with positive-screen participants receiving a list of local resources for diagnostic follow-up; the 'Screening Plus' group will receive ADRD screening at baseline coupled with disclosure of the screening results, with positive-screen participants referred to a dementia collaborative care program for diagnostic evaluation and potential care; and the control group will receive no screening. The COADS trial will measure the quality of life of the family member (the primary outcome) and family member mood, anxiety, preparedness and self-efficacy (the secondary outcomes) at baseline and at 6, 12, 18 and 24 months. Additionally, the trial will examine the congruence of depressive and anxiety symptoms between older adults and family members at 6, 12, 18 and 24 months and compare the effectiveness of two strategies for diagnostic evaluation and management after ADRD screening between the two groups randomized to screening (Screening Only versus Screening Plus). DISCUSSION: We hypothesize that caregivers in the screening arms will express higher levels of health-related quality of life, lower depressive and anxiety symptoms, and better preparation for caregiving with higher self-efficacy at 24 months. Results from this study will directly inform the National Plan to Address Alzheimer's Disease, the USPSTF and other organizations regarding ADRD screening and early detection policies

Adherence and Tolerability of Alzheimer's Disease Medications: A Pragmatic Randomized Trial

BACKGROUND/OBJECTIVES: Post-marketing comparative trials describe medication use patterns in diverse, real-world populations. Our objective was to determine if differences in rates of adherence and tolerability exist among new users to acetylcholinesterase inhibitors (AChEI's). DESIGN: Pragmatic randomized, open label comparative trial of AChEI's currently available in the United States. SETTING: Four memory care practices within four healthcare systems in the greater Indianapolis area. PARTICIPANTS: Eligibility criteria included older adults with a diagnosis of possible or probable Alzheimer's disease (AD) who were initiating treatment with an AChEI. Participants were required to have a caregiver to complete assessments, access to a telephone, and be able to understand English. Exclusion criteria consisted of a prior severe adverse event from AChEIs. INTERVENTION: Participants were randomized to one of three AChEIs in a 1:1:1 ratio and followed for 18 weeks. MEASUREMENTS: Caregiver-reported adherence, defined as taking or not taking study medication, and caregiver-reported adverse events, defined as the presence of an adverse event. RESULTS: 196 participants were included with 74.0% female, 30.6% African Americans, and 72.9% who completed at least twelfth grade. Discontinuation rates after 18 weeks were 38.8% for donepezil, 53.0% for galantamine, and 58.7% for rivastigmine (P = .063) in the intent to treat analysis. Adverse events and cost explained 73.1% and 25.4% of discontinuation. No participants discontinued donepezil due to cost. Adverse events were reported by 81.2% of all participants; no between-group differences in total adverse events were statistically significant. CONCLUSIONS: This pragmatic comparative trial showed high rates of adverse events and cost-related non-adherence with AChEIs. Interventions improving adherence and persistence to AChEIs may improve AD management. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01362686 (https://clinicaltrials.gov/ct2/show/NCT01362686)

On the influence of tree size on the climate–growth relationship of New Zealand kauri (Agathis australis): insights from annual, monthly and daily growth patterns

Many tree-ring-based climate reconstructions are based on the assumption that the climate reaction of trees is independent of their size. Here, we test this assumption for New Zealand kauri (Agathis australis), one of the longest tree ring-based proxies for the El Niño-Southern Oscillation (ENSO). The most recent kauri chronology contains a large amount of archaeological material, e.g. timber for which the original tree size is often unknown. We analyzed the climate–growth relationship of different-sized kauri in a pristine forest using different temporal scales, i.e. annually, monthly and daily data on tree growth and climate conditions. Trees of different life stages exhibited approximately the same seasonal growth peaks during austral spring (October and November). The dormancy period overlaps with the period where weekly air temperature maxima are below ca. 17–18 °C, and where the corresponding daily minima are below ca. 8 °C. However, both correlation functions between annual growth and seasonal climate as well as Kalman filter regressions between daily growth and climate conditions suggest an influence of tree size on the climate–growth relationship for kauri. Smaller trees (DBH < 40 cm) contain weaker climate signals than larger trees. Therefore, the precautionary stripping of near-pith material (first 20 cm) from kauri chronologies may result in more uniform responses to climate forcing and thus enhance the reliability of long-term climate reconstructions

Hydrolases in GtoPdb v.2023.1

Listed in this section are hydrolases not accumulated in other parts of the Concise Guide, such as monoacylglycerol lipase and acetylcholinesterase. Pancreatic lipase is the predominant mechanism of fat digestion in the alimentary system; its inhibition is associated with decreased fat absorption. CES1 is present at lower levels in the gut than CES2 (P23141), but predominates in the liver, where it is responsible for the hydrolysis of many aliphatic, aromatic and steroid esters. Hormone-sensitive lipase is also a relatively non-selective esterase associated with steroid ester hydrolysis and triglyceride metabolism, particularly in adipose tissue. Endothelial lipase is secreted from endothelial cells and regulates circulating cholesterol in high density lipoproteins

Hydrolases (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

Listed in this section are hydrolases not accumulated in other parts of the Concise Guide, such as monoacylglycerol lipase and acetylcholinesterase. Pancreatic lipase is the predominant mechanism of fat digestion in the alimentary system; its inhibition is associated with decreased fat absorption. CES1 is present at lower levels in the gut than CES2 (P23141), but predominates in the liver, where it is responsible for the hydrolysis of many aliphatic, aromatic and steroid esters. Hormone-sensitive lipase is also a relatively non-selective esterase associated with steroid ester hydrolysis and triglyceride metabolism, particularly in adipose tissue. Endothelial lipase is secreted from endothelial cells and regulates circulating cholesterol in high density lipoproteins

Manganese tricarbonyl complexes with asymmetric 2 2‑iminopyridine ligands: toward decoupling steric and electronic 3 factors in electrocatalytic CO2 reduction

Manganese tricarbonyl bromide complexes incorporating IP (2-(phenylimino)pyridine) derivatives, [MnBr(CO)3(IP)], are demonstrated as a new group of catalysts for CO2 reduction, which represent the first example of utilization of (phenylimino)pyridine ligands on manganese centers for this purpose. The key feature is the asymmetric structure of the redox-noninnocent ligand that permits independent tuning of its steric and electronic properties. The α-diimine ligands and five new Mn(I) compounds have been synthesized, isolated in high yields, and fully characterized, including X-ray crystallography. Their electrochemical and electrocatalytic behavior was investigated using cyclic voltammetry and UV−vis−IR spectroelectrochemistry within an OTTLE cell. Mechanistic investigations under an inert atmosphere have revealed differences in the nature of the reduction products as a function of steric bulk of the ligand. The direct ECE (electrochemical−chemical−electrochemical) formation of a five-coordinate anion [Mn(CO)3(IP)]−, a product of two-electron reduction of the parent complex, is observed in the case of the bulky DIPIMP (2-[((2,6-diisopropylphenyl)imino)methyl]pyridine), TBIMP (2-[((2-tert-butylphenyl)imino)methyl]-pyridine), and TBIEP (2-[((2-tert-butylphenyl)imino)ethyl]pyridine) derivatives. This process is replaced for the least sterically demanding IP ligand in [MnBr(CO)3(IMP)] (2-[(phenylimino)methyl]pyridine) by the stepwise formation of such a monoanion via an ECEC(E) mechanism involving also the intermediate Mn−Mn dimer [Mn(CO)3(IMP)]2. The complex [MnBr(CO)3(IPIMP)] (2-[((2-diisopropylphenyl)imino)methyl]pyridine), which carries a moderately electron donating, moderately bulky IP ligand, shows an intermediate behavior where both the five-coordinate anion and its dimeric precursor are jointly detected on the time scale of the spectroelectrochemical experiments. Under an atmosphere of CO2 the studied complexes, except for the DIPIMP derivative, rapidly coordinate CO2, forming stable bicarbonate intermediates, with no dimer being observed. Such behavior indicates that the CO2 binding is outcompeting another pathway: viz., the dimerization reaction between the five-coordinate anion and the neutral parent complex. The bicarbonate intermediate species undergo reduction at more negative potentials (ca. −2.2 V vs Fc/Fc+ ), recovering [Mn(CO)3(IP)]− and triggering the catalytic production of CO

Bremsstrahlung Suppression due to the LPM and Dielectric Effects in a Variety of Materials

The cross section for bremsstrahlung from highly relativistic particles is suppressed due to interference caused by multiple scattering in dense media, and due to photon interactions with the electrons in all materials. We present here a detailed study of bremsstrahlung production of 200 keV to 500 MeV photons from 8 and 25 GeV electrons traversing a variety of target materials. For most targets, we observe the expected suppressions to a good accuracy. We observe that finite thickness effects are important for thin targets.Comment: 52 pages, 13 figures (incorporated in the revtex LaTeX file

An assessment of the use of sediment traps for estimating upper ocean particle fluxes

Author Posting. © Sears Foundation for Marine Research, 2007. This article is posted here by permission of Sears Foundation for Marine Research for personal use, not for redistribution. The definitive version was published in Journal of Marine Research 65 (2007): 345–416, doi: 10.1357/002224007781567621This review provides an assessment of sediment trap accuracy issues by gathering data to address trap hydrodynamics, the problem of zooplankton "swimmers," and the solubilization of material after collection. For each topic, the problem is identified, its magnitude and causes reviewed using selected examples, and an update on methods to correct for the potential bias or minimize the problem using new technologies is presented. To minimize hydrodynamic biases due to flow over the trap mouth, the use of neutrally buoyant sediment traps is encouraged. The influence of swimmers is best minimized using traps that limit zooplankton access to the sample collection chamber. New data on the impact of different swimmer removal protocols at the US time-series sites HOT and BATS are compared and shown to be important. Recent data on solubilization are compiled and assessed suggesting selective losses from sinking particles to the trap supernatant after collection, which may alter both fluxes and ratios of elements in long term and typically deeper trap deployments. Different methods are needed to assess shallow and short- term trap solubilization effects, but thus far new incubation experiments suggest these impacts to be small for most elements. A discussion of trap calibration methods reviews independent assessments of flux, including elemental budgets, particle abundance and flux modeling, and emphasizes the utility of U-Th radionuclide calibration methods.WG meetings and production of this report was partially supported by the U.S. National Science Foundation via grants to the SCOR. Individuals and science efforts discussed herein were supported by many national science programs, including the U.S. National Science Foundation, Swedish Research Council, the International Atomic Energy Agency through its support of the Marine Environmental Laboratory that also receives support from the Government of the Principality of Monaco, and the Australian Antarctic Science Program. K.B. was supported in part by a WHOI Ocean Life Institute Fellowship