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Yuval Peres and Perla Sousi showed that the mixing times and average mixing times of reversible Markov chains on finite state spaces are equal up to some universal multiplicative constant. We use tools from nonstandard analysis to extend this result to reversible Markov chains on compact state spaces that satisfy the strong Feller property.
Spinal muscular atrophy (SMA) is a devastating rare disease that affects individuals regardless of ethnicity, gender, and age. The first-approved disease-modifying therapy for SMA, nusinursen, was approved by Health Canada, as well as by American and European regulatory agencies following positive clinical trial outcomes. The trials were conducted in a narrow pediatric population defined by age, severity, and genotype. Broad approval of therapy necessitates close follow-up of potential rare adverse events and effectiveness in the larger real-world population.
The Canadian Neuromuscular Disease Registry (CNDR) undertook an iterative multi-stakeholder process to expand the existing SMA dataset to capture items relevant to patient outcomes in a post-marketing environment. The CNDR SMA expanded registry is a longitudinal, prospective, observational study of patients with SMA in Canada designed to evaluate the safety and effectiveness of novel therapies and provide practical information unattainable in trials.
The consensus expanded dataset includes items that address therapy effectiveness and safety and is collected in a multicenter, prospective, observational study, including SMA patients regardless of therapeutic status. The expanded dataset is aligned with global datasets to facilitate collaboration. Additionally, consensus dataset development aimed to standardize appropriate outcome measures across the network and broader Canadian community. Prospective outcome studies, data use, and analyses are independent of the funding partner.
Prospective outcome data collected will provide results on safety and effectiveness in a post-therapy approval era. These data are essential to inform improvements in care and access to therapy for all SMA patients.
Morning coffee is a common remedy following disrupted sleep, yet each factor can independently impair glucose tolerance and insulin sensitivity in healthy adults. Remarkably, the combined effects of sleep fragmentation and coffee on glucose control upon waking per se have never been investigated. In a randomised crossover design, twenty-nine adults (mean age: 21 (sd 1) years, BMI: 24·4 (sd 3·3) kg/m2) underwent three oral glucose tolerance tests (OGTT). One following a habitual night of sleep (Control; in bed, lights-off trying to sleep approximately 23.00–07.00 hours), the others following a night of sleep fragmentation (as Control but waking hourly for 5 min), with and without morning coffee approximately 1 h after waking (approximately 300 mg caffeine as black coffee 30 min prior to OGTT). Individualised peak plasma glucose and insulin concentrations were unaffected by sleep quality but were higher following coffee consumption (mean (normalised CI) for Control, Fragmented and Fragmented + Coffee, respectively; glucose: 8·20 (normalised CI 7·93, 8·47) mmol/l v. 8·23 (normalised CI 7·96, 8·50) mmol/l v. 8·96 (normalised CI 8·70, 9·22) mmol/l; insulin: 265 (normalised CI 247, 283) pmol/l; and 235 (normalised CI 218, 253) pmol/l; and 310 (normalised CI 284, 337) pmol/l). Likewise, incremental AUC for plasma glucose was higher in the Fragmented + Coffee trial compared with Fragmented. Whilst sleep fragmentation did not alter glycaemic or insulinaemic responses to morning glucose ingestion, if a strong caffeinated coffee is consumed, then a reduction in glucose tolerance can be expected.
Scaling laws for the thrust production and energetics of self-propelled or fixed-velocity three-dimensional rigid propulsors undergoing pitching motions are presented. The scaling relations extend the two-dimensional scaling laws presented in Moored & Quinn (AIAA J., 2018, pp. 1–15) by accounting for the added mass of a finite-span propulsor, the downwash/upwash effects from the trailing vortex system of a propulsor and the elliptical topology of shedding trailing-edge vortices. The novel three-dimensional scaling laws are validated with self-propelled inviscid simulations and fixed-velocity experiments over a range of reduced frequencies, Strouhal numbers and aspect ratios relevant to bio-inspired propulsion. The scaling laws elucidate the dominant flow physics behind the thrust production and energetics of pitching bio-propulsors, and they provide guidance for the design of bio-inspired propulsive systems.
De-industrialization and the rise of the service sector have formed the basis of recent attempts to develop a new metanarrative of economic change in twentieth-century Britain. Their effects have been taken as writ through labour market statistics or aggregate measures of gross domestic product. However, by focusing on particular micro-economic spaces, a different story emerges. Using the inner areas of Liverpool as a case-study, this article shows how the city's social and economic problems were underwritten by the decline of the service sector, located around the port. By reading the effects of social and economic change through accounts of the physical environment, it demonstrates how urban decay and dereliction provided material resonance to Liverpool's economic decline. The city's landscape of urban decay and dereliction encompassed the infrastructure of everyday life – housing, roads and even trees – as well as that of economic activity, including the docks and warehouses. Taken together, this article shows how this landscape of urban decay and dereliction came to be constituted as an agent within Liverpool's continued economic decline in the 1970s rather than simply being a reflection of it.
Prevented planting provision in crop insurance protects producers from failure to plant attributable to natural causes. We determined the impact of this provision at various crop insurance coverage levels on prevented planting claims and ex post moral hazard. The moral hazard incentive in the prevented planting provision is stronger for corn than soybeans. Reducing the prevented planting coverage factor for corn could likely reduce moral hazard, but the degree of the reduction will likely depend on the revenue protection coverage level. Conversely, we found moral hazard is unlikely to occur for soybean production regardless of the revenue protection coverage level.
Our ALMA observations of HCO+ and HCN show such redshifted absorption toward an isolated core, BHR 71. Both lines show a similar redshifted absorption profile. We also found emissions of complex organic molecules (COMs) around 345 GHz from a compact region centered on the continuum source, which is barely resolved with a beam of 0″27, corresponding to ∼50 AU.
Near-field communication (NFC) readers, ubiquitously embedded in smartphones and other infrastructures can wirelessly deliver mW-level power to NFC tags. Our previous work NFC-wireless identification and sensing platform (WISP) proves that the generated NFC signal from an NFC enabled phone can power a tag (NFC-WISP) with display and sensing capabilities in addition to identification. However, accurately aligning and placing the NFC tag's antenna to ensure the high power delivery efficiency and communication performance is very challenging for the users. In addition, the performance of the NFC tag is not only range and alignment sensitive but also is a function of its run-time load impedance. This makes the execution of power-hungry tasks on an NFC tag (like the NFC-WISP) very challenging. Therefore, we explore a low-cost tag antenna design to achieve higher power delivered to the load (PDL) by utilizing two different antenna configurations (2-coil/3-coil). The two types of antenna configurations can be used to dynamically adapt to the requirements of varied range, alignment and load impedance in real-time, therefore, we achieve continuous high PDL and reliable communication. With the proposed method, we can, for example, turn a semi-passive NFC-WISP into a passive display tag in which an embedded 2.7″ E-ink screen can be updated robustly by a tapped NFC reader (e.g. an NFC-enable cell-phone) over a 3 seconds and within 1.5cm range.
The SKA and its pathfinders will enable studies of H i emission at higher redshifts than ever before. In moving beyond the local Universe, this will require the use of cosmologically appropriate formulae that have traditionally been simplified to their low-redshift approximations. In this paper, we summarise some of the most important relations for tracing H i emission in the SKA era, and present an online calculator to assist in the planning and analysis of observations (http://hifi.icrar.org).
Archaeological investigations of the age and origins of marine shell beads are important for understanding the emergence and maintenance of long-distance trade networks in prehistory. In this paper we expand upon and re-examine the incremental carbon (14C and δ13C) and oxygen (δ18O) isotope data from two Olivella biplicata shell beads from the LSP-1 Rockshelter, Oregon, USA, to address two common problems in dating marine shell trade goods: (1) the source region is large, adding to uncertainty regarding the appropriate specification of ΔR; and (2) the 14C activity within individual specimens is variable. Although this combination of factors severely limits the dating precision that is possible, we recommend a sampling and calibration approach that accounts for these added sources of uncertainty and minimizes the loss of precision. We recommend (1) sequential sampling in order to quantify the range of variability in 14C within shells; (2) a Bayesian calibration procedure that models the 14C dates as an ontogenetic sequence, in this case constrained by stable isotope sclerochronology; and (3) specifying ΔR in a manner that accounts for the full range of possible reservoir offsets in the source region.
Mild behavioral impairment (MBI) describes later life acquired, sustained neuropsychiatric symptoms (NPS) in cognitively normal individuals or those with mild cognitive impairment (MCI), as an at-risk state for incident cognitive decline and dementia. We developed an operational definition of MBI and tested whether the presence of MBI was related to caregiver burden in patients with subjective cognitive decline (SCD) or MCI assessed at a memory clinic.
MBI was assessed in 282 consecutive memory clinic patients with SCD (n = 119) or MCI (n = 163) in accordance with the International Society to Advance Alzheimer's Research and Treatment – Alzheimer's Association (ISTAART–AA) research diagnostic criteria. We operationalized a definition of MBI using the Neuropsychiatric Inventory Questionnaire (NPI-Q). Caregiver burden was assessed using the Zarit caregiver burden scale. Generalized linear regression was used to model the effect of MBI domains on caregiver burden.
While MBI was more prevalent in MCI (85.3%) than in SCD (76.5%), this difference was not statistically significant (p = 0.06). Prevalence estimates across MBI domains were affective dysregulation (77.8%); impulse control (64.4%); decreased motivation (51.7%); social inappropriateness (27.8%); and abnormal perception or thought content (8.7%). Affective dysregulation (p = 0.03) and decreased motivation (p=0.01) were more prevalent in MCI than SCD patients. Caregiver burden was 3.35 times higher when MBI was present after controlling for age, education, sex, and MCI (p < 0.0001).
MBI was common in memory clinic patients without dementia and was associated with greater caregiver burden. These data show that MBI is a common and clinically relevant syndrome.
Oral glucose tolerance and insulin sensitivity are common measures, but are determined using various blood sampling methods, employed under many different experimental conditions. This study established whether measures of oral glucose tolerance and oral glucose-derived insulin sensitivity (insulin sensitivity indices; ISI) differ when calculated from venous v. arterialised blood. Critically, we also established whether any differences between sampling methods are consistent across distinct metabolic conditions (after rest v. after exercise). A total of ten healthy men completed two trials in a randomised order, each consisting of a 120-min oral glucose tolerance test (OGTT), either at rest or post-exercise. Blood was sampled simultaneously from a heated hand (arterialised) and an antecubital vein of the contralateral arm (venous). Under both conditions, glucose time-averaged AUC was greater from arterialised compared with venous plasma but importantly, this difference was larger after rest relative to after exercise (0·99 (sd 0·46) v. 0·56 (sd 0·24) mmol/l, respectively; P<0·01). OGTT-derived ISIMatsuda and ISICederholm were lower when calculated from arterialised relative to venous plasma and the arterialised–venous difference was greater after rest v. after exercise (ISIMatsuda: 1·97 (sd 0·81) v. 1·35 (sd 0·57) arbitrary units (au), respectively; ISICederholm : 14·76 (sd 7·83) v. 8·70 (sd 3·95) au, respectively; both P<0·01). Venous blood provides lower postprandial glucose concentrations and higher estimates of insulin sensitivity, compared with arterialised blood. Most importantly, these differences between blood sampling methods are not consistent after rest v. post-exercise, preventing standardised venous-to-arterialised corrections from being readily applied.
Last Supper Cave, located in northwestern Nevada, was excavated in the 1960s and 1970s. It contained a rich record of human occupation spanning the Holocene, but many artifacts from the site, including a large basketry collection, remain unstudied. We report the results of our technological analysis and radiocarbon dating of 14 fiber sandals from Last Supper Cave, which include examples of Fort Rock, Multiple Warp, and Spiral Weft types found at other sites in the northwestern Great Basin. Radiocarbon dates on the sandals correspond well with previous dates from Last Supper Cave and suggest that it was visited episodically for over 10 millennia; however, when considered together with the growing list of dates from the site, the sandal dates suggest that Last Supper Cave saw a prolonged hiatus in occupation during the Middle Holocene—a pattern common at other sandal-bearing sites in the northwestern Great Basin.
This article reports on a case study of a decade-long organizing forms response to the need for groundbreaking innovation while maintaining existing operational performance – the explore–exploit conundrum. Employing ‘grounded research,’ data were collected on the experiences of the Asia-Pacific arm of a multinational professional service firm’s key decision-makers, innovators and entrepreneurs. The findings reveal a three-tiered organizing forms response to the explore–exploit paradox, characterized by a novel combination of heavy exploitation-driven actions alongside deep exploration projects. This case suggests that one successful approach to delivering on both explore and exploit focuses on a productive tension that emerges by enacting innovative organizing forms with contextual awareness. This productive tension was sufficiently powerful to impel individuals to innovate, but also sufficiently contained to avoid interfering with commercial outcomes. An explore–exploit framework conceptualizes organizational changes incorporating complexity and contradiction, without the implicit emphasis on removing or denying the existing tension.
Beads manufactured from marine shells originating along the Pacific Coast have been found at numerous sites in the western United States. Because they were conveyed across substantial distances and widely exchanged during ethnographic times, researchers generally assume that shell beads were also traded prehistorically. By examining the spatial and temporal distribution of beads, researchers have reconstructed prehistoric exchange networks. In this article, we present stable isotope data and accelerator mass spectrometer (AMS) radiocarbon dates for six Callianax (previously Olivella) biplicata beads from the LSP-1 rockshelter in southcentral Oregon. Most of the beads were deposited during the early Holocene during a series of short-term occupations and the shells used to manufacture them were procured along the northern California, Oregon, or Washington coasts.
We determined the profitability and risk for spring- and fall-calving beef cows in Tennessee. Simulation models were developed using 19 years of data and considered the seasonality of cattle prices and feed prices for least-cost feed rations to find a distribution of net returns for spring- and fall-calving seasons for two weaning months. Fall calving was more profitable than the spring calving for all feed rations and weaning months. Fall calving was also risk preferred over spring calving for all levels of risk aversion. Higher calf prices at weaning were the primary factor influencing the risk efficiency of fall calving.
Since cow-calf operations are large contributors of agricultural greenhouse gas (GHG) emissions in North America, consequences of pasture species composition, weaning age, and stocking rate decisions were examined by operation size, calving season, and pasture fertility. Fixed resource use and seasonal prices affected the mix of forage and beef production. Overall, adding fertilizer to pasture was unprofitable, resulting in increased stocking rates and greater emissions. Calving season and attendant breeding failure rates influenced the relative profitability of the analyzed beef-production strategies, which in turn affected farm GHG emissions. More-efficient practices led to greater amounts of beef sold per bred cow.
Little is known about the impact of corn and energy prices on the profitability of irrigating corn in Tennessee. We evaluated the probability of a positive net present value (NPV) for center-pivot irrigation in Tennessee corn production. Three corn price series were employed to evaluate the effects of the shift in corn prices on the feasibility of irrigation. The recent rise in corn prices increased the probability of NPV being positive for irrigation investment. Future corn prices will need to remain high for investment in center-pivot irrigation to remain profitable under Tennessee growing conditions.