914 research outputs found

    Layered architecture for quantum computing

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    We develop a layered quantum computer architecture, which is a systematic framework for tackling the individual challenges of developing a quantum computer while constructing a cohesive device design. We discuss many of the prominent techniques for implementing circuit-model quantum computing and introduce several new methods, with an emphasis on employing surface code quantum error correction. In doing so, we propose a new quantum computer architecture based on optical control of quantum dots. The timescales of physical hardware operations and logical, error-corrected quantum gates differ by several orders of magnitude. By dividing functionality into layers, we can design and analyze subsystems independently, demonstrating the value of our layered architectural approach. Using this concrete hardware platform, we provide resource analysis for executing fault-tolerant quantum algorithms for integer factoring and quantum simulation, finding that the quantum dot architecture we study could solve such problems on the timescale of days.Comment: 27 pages, 20 figure

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

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    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

    Hydrolases in GtoPdb v.2023.1

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    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

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    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

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

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    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)

    Long-haul northeast travel disrupts sleep and induces perceived fatigue in endurance athletes

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    Introduction: Long-haul transmeridian travel is known to cause disruptions to sleep and immune status, which may increase the risk of illness. Aim: This study aimed to determine the effects of long-haul northeast travel for competition on sleep, illness and preparedness in endurance athletes. Methods: Twelve trained (13.8 ± 3.2 training h/week) masters (age: 48 ± 14 years) triathletes were monitored for sleep (quantity via actigraphy and quality via self-report), mucosal immunity (salivary immunoglobulin-A) and stress (salivary cortisol) as well as self-reported illness, fatigue, recovery and preparedness. Baseline measures were recorded for 2 weeks prior to travel for all variables except for the saliva samples, which were collected on three separate days upon waking. Participants completed normal training during the baseline period. Measures were subsequently recorded before, during and after long-haul northeast travel from the Australian winter to the Hawaiian summer, and in the lead up to an Ironman 70.3 triathlon. Results: All comparisons are to baseline. There was a most likely decrease in sleep duration on the over-night flight (-4.8 ± 1.2 h; effect size; ±90% confidence limits = 3.06; ±1.26) and a very likely increase in sleep duration on the first night after arrival (0.7 ± 1.0 h; 1.15; ±0.92). After this time, sleep duration returned to baseline for several days until it was very likely decreased on the night prior to competition (-1.2 ± 1.0 h; 1.18; ±0.93). Nap duration was likely increased on the first day after arrival (36 ± 65 min; 3.90; ±3.70). There was also a likely increase in self-reported fatigue upon waking after the first night in the new destination (1.1 ± 1.6 AU; 0.54; ±0.41) and there were three athletes (25%) who developed symptoms of illness 3-5 days after arrival. There were no changes in sleep quality or mucosal measures across study. Discussion: Long-haul northeast travel from a cool to a hot environment had substantial influences on sleep and self-reported fatigue, but these alterations had returned to pre-departure baseline 48 h after arrival. Endurance athletes undertaking similar journeys may benefit from optimizing sleep hygiene, especially on the first 2 days after arrival, or until sleep duration and fatigue levels return to normal

    The value of high-resolution Met Office regional climate models in the simulation of multi-hourly precipitation extremes

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    Open access articleExtreme value theory is used as a diagnostic for two high-resolution (12-km parameterized convection and 1.5-km explicit convection) Met Office regional climate model (RCM) simulations. On subdaily time scales, the 12-km simulation has weaker June–August (JJA) short-return-period return levels than the 1.5-km RCM, yet the 12-km RCM has overly large high return levels. Comparisons with observations indicate that the 1.5-km RCM is more successful than the 12-km RCM in representing (multi)hourly JJA very extreme events. As accumulation periods increase toward daily time scales, the erroneous 12-km precipitation extremes become more comparable with the observations and the 1.5-km RCM. The 12-km RCM fails to capture the observed low sensitivity of the growth rate to accumulation period changes, which is successfully captured by the 1.5-km RCM. Both simulations have comparable December–February (DJF) extremes, but the DJF extremes are generally weaker than in JJA at daily or shorter time scales. Case studies indicate that “gridpoint storms” are one of the causes of unrealistic very extreme events in the 12-km RCM. Caution is needed in interpreting the realism of 12-km RCM JJA extremes, including short-return-period events, which have return values closer to observations. There is clear evidence that the 1.5-km RCM has a higher degree of realism than the 12-km RCM in the simulation of JJA extremes.Natural Environment Research Council (NERC)UKMONewcastle Universit
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