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The COVID-19 pandemic accelerated the development of decentralized clinical trials (DCT). DCT’s are an important and pragmatic method for assessing health outcomes yet comprise only a minority of clinical trials, and few published methodologies exist. In this report, we detail the operational components of COVID-OUT, a decentralized, multicenter, quadruple-blinded, randomized trial that rapidly delivered study drugs nation-wide. The trial examined three medications (metformin, ivermectin, and fluvoxamine) as outpatient treatment of SARS-CoV-2 for their effectiveness in preventing severe or long COVID-19. Decentralized strategies included HIPAA-compliant electronic screening and consenting, prepacking investigational product to accelerate delivery after randomization, and remotely confirming participant-reported outcomes. Of the 1417 individuals with the intention-to-treat sample, the remote nature of the study caused an additional 94 participants to not take any doses of study drug. Therefore, 1323 participants were in the modified intention-to-treat sample, which was the a priori primary study sample. Only 1.4% of participants were lost to follow-up. Decentralized strategies facilitated the successful completion of the COVID-OUT trial without any in-person contact by expediting intervention delivery, expanding trial access geographically, limiting contagion exposure, and making it easy for participants to complete follow-up visits. Remotely completed consent and follow-up facilitated enrollment.
Archaeological dung pellets are time capsules of ancient herbivore diets and gut flora, informing on past agropastoral activity, ecology, and animal health. Improving multi-proxy approaches is key to maximizing this finite archaeological resource. Through experiments with standard pretreatments used in radiocarbon (14C) dating, we address a fundamental problem in maximal multi-proxy analysis: How to chronometrically date individual caprine pellets while conserving as much as possible for additional analyses? We applied acid-alkali-acid (AAA) or acid-only pretreatments to 37 samples of ancient and recent sheep/goat dung pellets from sites in the Negev desert, Israel, measuring weight-loss due to pretreatment. Shavings of outer surfaces and remaining inner pellets of four pairs were dated and compared. We found that (i) sample-specific factors affect pretreatment survivability, including preservation quality and initial sample size; (ii) given sufficient start weight, AAA can be used to pretreat sheep/goat coprolites; (iii) 100 mg appeared a desirable minimum sample weight before pretreatment; and (iv) shavings of coprolites’ outer surface produced 14C dates equivalent to dates obtained from inner coprolites. Whereas standard coprolite analysis protocols discard shavings removed from outer surfaces to avoid contamination, our findings indicate their efficacy for 14C dating. This offers an important addition to workflows for multi-proxy coprolite analysis.
Background: MRSA continues to spread in hospitals, despite modest recent success. Gaps exist regarding how hospital policies impact MRSA transmission in hospitals. Characterization of the policy environment has been useful in approaching other public health issues including control of alcohol, firearms, tobacco, and traffic safety. Objective: Our goal was to describe measurable and modifiable policy components designed to prevent MRSA in hospital settings. Methods: We examined 4 types of hospital policies from 5 metropolitan hospitals in Minnesota: hand hygiene, multidrug-resistant organism (MDRO) and isolation, healthcare personnel influenza vaccination, and whistleblower (corporate compliance). We developed a tool to systematically evaluate policies for each topic that included 19–23 instructional and implementation elements guided by regulatory and clinical practice guidelines: purpose, expectations, education and training, monitoring, enforcement, corrective actions, responsibilities, and corrective actions. Each policy element was evaluated for its presence (yes or no) and thoroughness (nonexistent = 0, cursory = 1, thorough = 2). Results: All hospitals had hand hygiene and MDRO and isolation policies; 3 of 5 had influenza and whistleblower policies. The policies varied in comprehensiveness and thoroughness across hospitals and topics. Most policies included purpose and policy statements with a statement of organizational rules (14 of 16 and 16 of 16, respectively) with mean thoroughness scores of 1.04 and 1.20, respectively. Most policies lacked consequences for noncompliance (6 of 16), accountability (6 of 16), and monitoring and enforcement of policy expectations (5 of 16). When included, the policy components scored low for thoroughness, and 50% of policies (8 of 16; range, 20% for hand hygiene and 100% for influenza vaccination) specified expectations for educating staff about the policy topic, with a mean thoroughness score of 0.75. Responsibilities for policy expectations were lacking: responsibilities for product needs and availability (3 of 13), training and education (1 of 16); and monitoring compliance with skills and techniques (4 of 16). Of the 4 policy types, influenza vaccination was the most complete. All influenza policies had 50% of categories completed versus hand hygiene (26%), MDRO (17%), and whistleblower (26%). The hand hygiene policies scored highest for thoroughness; 48% of policy elements scored >1.0 versus MDRO (22%), influenza (25%), and whistleblower (11%). Conclusions: We developed a systematic method to quantitatively evaluate hospital policies. Our review of hospital policies most commonly contained thorough instructional elements such as organizational requirements and protocols and procedures. Policies often lacked implementation elements such as expectations for monitoring, enforcement, responsibilities, accountabilities, and staff training and education. As we begin to characterize policy, endogenous in nature, as a potential exposure, it is important that we develop rigorous measurement. We have provided a first step in developing such an approach.
The majority of available US-published reports present populations with community spread in urban areas. The objective of this report is to describe a rural healthcare system's utilisation of therapeutic options available to treat Coronavirus Disease 2019 (COVID-19) and subsequent patient outcomes. A total of 150 patients were treated for COVID-19 at three hospitals in the Dakotas from 21 March 2020 to 30 April 2020. The most common pharmacological treatment regimens administered were zinc, hydroxychloroquine plus azithromycin and convalescent plasma. Adjunctive treatments included therapeutic anticoagulation, tocilizumab and corticosteroids. As of 1 June 2020, 127 patients have survived to hospital discharge, 12 patients remain hospitalised and 11 patients have expired. The efficacy of hydroxychloroquine and azithromycin use has yet to be determined but was not without risks of corrected QT interval prolongation and arrhythmias in our cohort. We did not appreciate any adverse effects that appeared related to tocilizumab or convalescent plasma administration in those patient subsets. These findings may provide insight into disease severity and treatment options in the rural setting with limited resources to participate in clinical trials and encourage larger comparative studies evaluating treatment efficacy.
Our objectives were to explore attitudes regarding food retail policy and government regulation among managers of small food stores and examine whether manager views changed due to the 2014 Minneapolis Staple Foods Ordinance, a city policy requiring retailers to stock specific healthy products.
Design:
Manager interviewer-administered surveys were used to assess views on food retail policy four times from 2014 to 2017. We examined baseline views across manager and store and neighbourhood characteristics using cross-sectional regression analyses and examined changes over time using mixed regression models. In 2017, open-ended survey questions asked about manager insights on the Minneapolis Staple Foods Ordinance.
Setting:
Minneapolis, MN, where the ordinance was enacted, and St. Paul, MN, a control community, USA.
Participants:
Managers from 147 small food retail stores.
Results:
At baseline, 48 % of managers were likely to support a policy requiring stores to stock healthy foods/beverages, 67·5 % of managers were likely to support voluntary programmes to help retailers stock healthy foods and 23·7 % agreed government regulation of business is good/necessary. There was a significant increase in overall support for food retail policies and voluntary programmes from 2014 to 2017 (P < 0·01); however, neither increase differed by city, suggesting no differential impact from the ordinance. Minneapolis store managers reported some challenges with ordinance compliance and offered suggestions for how local government could provide support.
Conclusions:
Findings suggest that managers of small food retail stores are becoming increasingly amenable to healthy food policies; yet, challenges need to be addressed to ensure healthy food is available to all customers.
The diet of most adults is low in fish and, therefore, provides limited quantities of the long-chain, omega-3 fatty acids (LCn-3FAs), eicosapentaenoic and docosahexaenoic acids (EPA, DHA). Since these compounds serve important roles in the brain, we sought to determine if healthy adults with low-LCn-3FA consumption would exhibit improvements in neuropsychological performance and parallel changes in brain morphology following repletion through fish oil supplementation.
Methods
In a randomized, controlled trial, 271 mid-life adults (30–54 years of age, 118 men, 153 women) consuming ⩽300 mg/day of LCn-3FAs received 18 weeks of supplementation with fish oil capsules (1400 mg/day of EPA and DHA) or matching placebo. All participants completed a neuropsychological test battery examining four cognitive domains: psychomotor speed, executive function, learning/episodic memory, and fluid intelligence. A subset of 122 underwent neuroimaging before and after supplementation to measure whole-brain and subcortical tissue volumes.
Results
Capsule adherence was over 95%, participant blinding was verified, and red blood cell EPA and DHA levels increased as expected. Supplementation did not affect performance in any of the four cognitive domains. Exploratory analyses revealed that, compared to placebo, fish oil supplementation improved executive function in participants with low-baseline DHA levels. No changes were observed in any indicator of brain morphology.
Conclusions
In healthy mid-life adults reporting low-dietary intake, supplementation with LCn-3FAs in moderate dose for moderate duration did not affect neuropsychological performance or brain morphology. Whether salutary effects occur in individuals with particularly low-DHA exposure requires further study.
We examined differences in consumer-level characteristics and structural resources and capabilities of small and non-traditional food retailers (i.e. corner stores, gas-marts, pharmacies, dollar stores) by racial segregation of store neighbourhood and corporate status (corporate/franchise- v. independently owned).
Design
Observational store assessments and manager surveys were used to examine availability-, affordability- and marketing-related characteristics experienced by consumers as well as store resources (e.g. access to distributors) and perceived capabilities for healthful changes (e.g. reduce pricing on healthy foods). Cross-sectional regression analyses of store and manager data based on neighbourhood segregation and store corporate status were conducted.
Setting
Small and non-traditional food stores in Minneapolis and St. Paul, MN, USA.
Participants
One hundred and thirty-nine stores; seventy-eight managers.
Results
Several consumer- and structural-level differences occurred by corporate status, independent of residential segregation. Compared with independently owned stores, corporate/franchise-owned stores were more likely to: not offer fresh produce; when offered, receive produce via direct delivery and charge higher prices; promote unhealthier consumer purchases; and have managers that perceived greater difficulty in making healthful changes (P≤0·05). Only two significant differences were identified by residential racial segregation. Stores in predominantly people of colour communities (<30 % non-Hispanic White) had less availability of fresh fruit and less promotion of unhealthy impulse buys relative to stores in predominantly White communities (P≤0·05).
Conclusions
Corporate status appears to be a relevant determinant of the consumer-level food environment of small and non-traditional stores. Policies and interventions aimed at making these settings healthier may need to consider multiple social determinants to enable successful implementation.
In midcontinent North America, the Fox Hills Formation (Upper Cretaceous, upper Maastrichtian) preserves the last marine faunas in the central Western Interior Seaway (WIS). Neritoptyx hogansoni new species, a small littoral snail, exhibited allometric change from smooth to corded ornament and rounded to shouldered shape during growth. Specimens preserve a zig-zag pigment pattern that changes to an axial pattern during growth. Neritoptyx hogansoni new species was preyed on by decapod crustaceans, and spent shells were occupied by pagurid crabs. Dead mollusk shells, particularly those of Crassostrea subtrigonalis (Evans and Shumard, 1857), provided a hard substrate to which they adhered on the Fox Hills tidal flats. This new neritimorph gastropod establishes a paleogeographic and chronostratigraphic proxy for intertidal conditions on the Dakota Isthmus during the late Maastrichtian. Presence of a neritid extends the marine tropical/temperate boundary in the WIS northward to ~44° late Maastrichtian paleolatitude. Late Maastrichtian closure of the isthmus subsequently altered marine heat transfer by interrupting northward flow of tropical currents from the Gulf Coast by as much as 1 to 1.5 million years before the Cretaceous ended.
Morphophysiological dormancy (MPD) is predominantly found in seeds of temperate regions and is uncommon in arid biomes. MPD has been reported in a number of Hibbertia (Dilleniaceae) species of temperate Australia, and in a single species of the arid zone, H. glaberrima. This study aimed to examine the dormancy and germination ecology of seeds of H. glaberrima. Seeds were subjected to temperature stratification treatments designed to mimic summer and autumn conditions in the Pilbara region of Western Australia. Seed germination and embryo growth were measured. We also tested the interaction between temperature stratification and cycles of drying and wetting designed to mimic sporadic rainfall events. All temperature and moisture treatments were tested in combination (+/–) with the smoke-derived chemical karrikinolide (KAR1). Exposing dormant seeds to temperatures suitable for warm stratification (35°C) for ≥ 8 weeks, followed by incubation at 25°C, resulted in significantly higher germination compared with non-stratified seeds. Exposing seeds to dry/wet cycling in conjunction with temperature stratification did not significantly increase germination. Exposure to KAR1 increased germination under most conditions. Once seeds are shed during October to December, they are exposed to hot and sporadically wet conditions over summer, allowing MPD to be overcome in a proportion of the seed population. Seeds may germinate in autumn (March to April), in conjunction with cooler temperatures. More deeply dormant individuals may require more than one summer to overcome dormancy. Similar to other species occurring in fire-prone ecosystems, fire also plays a crucial role in the germination ecology of H. glaberrima.
Little is known about customer purchases of foods and beverages from small and non-traditional food retailers (i.e. corner stores, gas-marts, dollar stores and pharmacies). The present study aimed to: (i) describe customer characteristics, shopping frequency and reasons for shopping at small and non-traditional food retailers; and (ii) describe food/beverage purchases and their nutritional quality, including differences across store type.
Design
Data were collected through customer intercept interviews. Nutritional quality of food/beverage purchases was analysed; a Healthy Eating Index-2010 (HEI-2010) score for purchases was created by aggregating participant purchases at each store.
Setting
Small and non-traditional food stores that were not WIC-authorized in Minneapolis and St. Paul, MN, USA.
Subjects
Customers (n 661) from 105 food retailers.
Results
Among participants, 29 % shopped at the store at least once daily; an additional 44 % shopped there at least once weekly. Most participants (74 %) cited convenient location as the primary draw to the store. Customers purchased a median of 2262 kJ (540 kcal), which varied by store type (P=0·04). The amount of added sugar far surpassed national dietary recommendations. At dollar stores, participants purchased a median of 5302 kJ (1266 kcal) for a median value of $US 2·89. Sugar-sweetened beverages were the most common purchase. The mean HEI-2010 score across all stores was 36·4.
Conclusions
Small and non-traditional food stores contribute to the urban food environment. Given the poor nutritional quality of purchases, findings support the need for interventions that address customer decision making in these stores.
During the Late Ordovician, arborescent and frondose trepostome, and cystoporate Bryozoa were frequently bored in a manner distinctly different from Trypanites, Palaeosabella, and Vermiforichnus, domichnia that are commonly associated with these organisms. Maysvillian and Richmondian bryozoan taxa on the Cincinnati Arch were particularly infested by an unidentified organism that used the interior of bryozoan branches as its domicile. The domichnial trace Sanctum laurentiensis is newly described. Dwelling openings range in size from 1.1 mm to 3.2 mm and are located singly on surfaces of colony branches, commonly in a somewhat protected position. The circular opening leads through the exozone into an elongate or saccate chamber representing a variably shaped excavation of the bryozoan endozone. Traces ranging from 3.0 mm to 8.8 mm wide and 9.7 mm to 53 mm long are documented. Thin sections demonstrate that chambers were unlined and had irregular interior walls resulting from organismal mining of zooecial tubes.
Cavity makers likely were multiple individuals of amphipod-like crustaceans (Arthropoda) that fed outside their domicile. Bryozoan colonies were occupied while upright, either entirely or partially live, or in some cases dead and overgrown by other bryozoans. Avoidance of predation and the ability to dwell and feed in a higher tier than that of infaunal tracemakers at the sediment-water interface were potential benefits of this domichnium. Presence of cavities reduced the strength of host branches, thus having a profound effect on colony morphology and growth over its lifetime. Unlike the many epizoans that used trepostomes as substrates with little long-term affect, Sanctum laurentiensis significantly impacted its bryozoan host.
A total of 18 radio sources selected on the basis of steep low-frequency radio spectra have been searched for the presence of millisecond pulsars using the Molonglo Observatory synthesis telescope. The search covered pulsar periods down to 2 ms with a limiting sensitivity of approximately 10 mJy. No pulsars were detected.
We have assembled a new sample of some of the most FIR-luminous galaxies in the Universe and have imaged them in 1.1 mm dust emission and measured their redshifts 1 < z < 4 via CO emission lines using the 32-m Large Millimeter Telescope / Gran Telescopio Milimétrico (LMT/GTM). Our sample of 31 submm galaxies (SMGs), culled from the Planck and Herschel all-sky surveys, includes 14 of the 21 most luminous galaxies known, with LFIR > 1014L⊙ and SFR > 104M⊙/yr. These extreme inferred luminosities – and multiple / extended 1.1 mm images – imply that most or all are strongly gravitationally lensed, with typical magnification μ ~ 10 × . The gravitational lensing provides two significant benefits: (1) it boosts the S/N, and (2) it allows investigation of star formation and gas processes on sub-kpc scales.
Little is known about the practices for stocking and procuring healthy food in non-traditional food retailers (e.g. gas-marts, pharmacies). The present study aimed to: (i) compare availability of healthy food items across small food store types; and (ii) examine owner/manager perceptions and stocking practices for healthy food across store types.
Design
Descriptive analyses were conducted among corner/small grocery stores, gas-marts, pharmacies and dollar stores. Data from store inventories were used to examine availability of twelve healthy food types and an overall healthy food supply score. Interviews with managers assessed stocking practices and profitability.
Setting
Small stores in Minneapolis and St. Paul, MN, USA, not participating in the Special Supplemental Nutrition Program for Women, Infants, and Children.
Subjects
One hundred and nineteen small food retailers and seventy-one store managers.
Results
Availability of specific items varied across store type. Only corner/small grocery stores commonly sold fresh vegetables (63 % v. 8 % of gas-marts, 0 % of dollar stores and 23 % of pharmacies). More than half of managers stocking produce relied on cash-and-carry practices to stock fresh fruit (53 %) and vegetables (55 %), instead of direct store delivery. Most healthy foods were perceived by managers to have at least average profitability.
Conclusions
Interventions to improve healthy food offerings in small stores should consider the diverse environments, stocking practices and supply mechanisms of small stores, particularly non-traditional food retailers. Improvements may require technical support, customer engagement and innovative distribution practices.
Seven fossil leaf species are described from impression fossils collected from the Upper Cretaceous (Maastrichtian) Fox Hills Formation in south-central North Dakota, USA. They are Marmarthia johnsonii n. sp., Nilssoniocladus yukonensis n. comb., Nilssoniocladus comtula n. comb., Mesocyparis borealis, Rhamnus salicifolius, Paloreodoxites plicatus, and Zingiberopsis magnifolia. These species represent some of the elements of the Fox Hills flora that have paleogeographic ranges to the northwest (N. yukonensis, N. comtula, and M. borealis) and to the southwest (M. johnsonii, R. salicifolius, P. plicatus, and Z. magnifolia) of the Fox Hills type area. The identification and reappraisal of these species represent an effort to understand the biogeographic relationships of Late Cretaceous floras across the Northern Hemisphere.
Using galvanostatic pulse deposition, we studied the factors influencing the quality of electroformed Bi1–xSbx nanowires with respect to composition, crystallinity, and preferred orientation for high thermoelectric performance. Two nonaqueous baths with different Sb salts were investigated. The Sb salts used played a major role in both crystalline quality and preferred orientations. Nanowire arrays electroformed using an SbI3-based chemistry were polycrystalline with no preferred orientation, whereas arrays electroformed from an SbCl3-based chemistry were strongly crystallographically textured with the desired trigonal orientation for optimal thermoelectric performance. From the SbCl3 bath, the electroformed nanowire arrays were optimized to have nanocompositional uniformity, with a nearly constant composition along the nanowire length. Nanowires harvested from the center of the array had an average composition of Bi0.75Sb0.25. However, the nanowire compositions were slightly enriched in Sb in a small region near the edges of the array, with the composition approaching Bi0.70Sb0.30.
Achieving control of crystalline quality is a key barrier to developing thermoelectric (TE) nanowires. We show that the structural properties of free-standing Bi2(Te.97Se.03)3 nanowire arrays on substrates can be improved by postdeposition annealing. Nanowires were electrochemically deposited into anodized aluminum oxide nanopore templates formed directly on metallized Si(100). The templates were chemically removed prior to annealing in a 3% H2/Ar environment to prevent microcrack formation that results from thermal stresses. Grain sizes grew exponentially with annealing temperature until reaching the full 75-nm diameter of the nanowires at 300 °C; growth was linear above this temperature since grains could grow further only in the axial directions. Crystalline quality, along with the development of the preferred (110) orientation for optimal TE properties, improved with increasing annealing temperature between 200 and 400 °C. However, continued loss of Te composition with annealing led to a mixed phase of Bi2Te3 and Bi4Te3 at 500 °C.
Significant new opportunities for astrophysics and cosmology have been identified at low radio frequencies. The Murchison Widefield Array is the first telescope in the southern hemisphere designed specifically to explore the low-frequency astronomical sky between 80 and 300 MHz with arcminute angular resolution and high survey efficiency. The telescope will enable new advances along four key science themes, including searching for redshifted 21-cm emission from the EoR in the early Universe; Galactic and extragalactic all-sky southern hemisphere surveys; time-domain astrophysics; and solar, heliospheric, and ionospheric science and space weather. The Murchison Widefield Array is located in Western Australia at the site of the planned Square Kilometre Array (SKA) low-band telescope and is the only low-frequency SKA precursor facility. In this paper, we review the performance properties of the Murchison Widefield Array and describe its primary scientific objectives.
This chapter presents several experimental approaches performed in the Laboratory of the Biology of Addictive Diseases to characterize the relationship of gene variations with heroin addiction and pharmacogenomics. Although opioid receptors often subserve similar physiological functions, activation of the kappa-opioid receptor (KOPr) by exogenous agonists produces dysphoria in humans and aversive effects in experimental animals, in contrast to activation of mu-opioid receptor (MOPr). Opiate addiction is a chronic relapsing disorder that is treated world-wide with methadone. The genes studied are usually those which have been shown to be involved in some aspects of development of addiction. In some studies, multiple genes, all hypothesized to be potentially involved in opioid addiction, have been studied. In other cases, genome-wide association studies (GWAS) have been performed to identify regions of chromosomes which may influence vulnerability to the development of addiction. These studies usually do not identify specific genes within chromosome regions.