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In response to the COVID-19 pandemic, we rapidly implemented a plasma coordination center, within two months, to support transfusion for two outpatient randomized controlled trials. The center design was based on an investigational drug services model and a Food and Drug Administration-compliant database to manage blood product inventory and trial safety.
Methods:
A core investigational team adapted a cloud-based platform to randomize patient assignments and track inventory distribution of control plasma and high-titer COVID-19 convalescent plasma of different blood groups from 29 donor collection centers directly to blood banks serving 26 transfusion sites.
Results:
We performed 1,351 transfusions in 16 months. The transparency of the digital inventory at each site was critical to facilitate qualification, randomization, and overnight shipments of blood group-compatible plasma for transfusions into trial participants. While inventory challenges were heightened with COVID-19 convalescent plasma, the cloud-based system, and the flexible approach of the plasma coordination center staff across the blood bank network enabled decentralized procurement and distribution of investigational products to maintain inventory thresholds and overcome local supply chain restraints at the sites.
Conclusion:
The rapid creation of a plasma coordination center for outpatient transfusions is infrequent in the academic setting. Distributing more than 3,100 plasma units to blood banks charged with managing investigational inventory across the U.S. in a decentralized manner posed operational and regulatory challenges while providing opportunities for the plasma coordination center to contribute to research of global importance. This program can serve as a template in subsequent public health emergencies.
Mixed-layer clays composed of randomly interstratified kerolite/stevensite occur as lake and/or spring deposits of probable Pliocene and Pleistocene age in the Amargosa Desert of southern Nevada, U.S.A. The percentage of expandable layers of these clays, determined from computer-simulated X-ray diffractograms, ranges from almost 0 to about 80%. This range in expandabilities most likely results from differences in solution chemistry and/or temperature at the time of formation. An average structural formula for the purest clay (sample P-7), a clay with about 70% expandable layers, is:
Deposits of sepiolite, trioctahedral smectite (mixed-layer kerolite/stevensite), calcite, and dolomite, found in the Amargosa Flat and Ash Meadows areas of the Amargosa Desert were formed by precipitation from nonsaline solutions. This mode of origin is indicated by crystal growth patterns, by the low Al content for the deposits, and by the absence of volcanoclastic textures. Evidence for low salinity is found in the isotopic compositions for the minerals, in the lack of abundant soluble salts in the deposits, and in the crystal habits of the dolomite. In addition, calculations show that modern spring water in the area can precipitate sepiolite, dolomite, and calcite following only minor evaporative concentration and equilibration with atmospheric CO2. However, precipitation of mixed-layer kerolite/stevensite may require a more saline environment. Mineral precipitation probably occurred during a pluvial period in shallow lakes or swamps fed by spring water from Paleozoic carbonate aquifers.
Digenetic trematodes are important parasites of humans and animals. They have complex life cycles and typically infect a gastropod as the first intermediate host. Bithynia siamensis goniomphalos, the first intermediate host of the liver fluke, Opisthorchis viverrini, harbours a wide variety of other trematode species. Morphological details of cercariae of 20 trematode taxa from B. s. goniomphalos, collected mainly in Thailand from 2009 to 2014, were provided in an earlier paper. Correct identification to the species or genus level based on morphology of these cercariae is generally not possible. Therefore, we used molecular data to improve identification and to investigate the diversity of the species of trematodes infecting B. s. goniomphalos. We were successful in extracting, amplifying and sequencing portions of the 28S ribosomal RNA (rRNA) gene for 19 of these 20 types of cercaria, and the internal transcribed spacer 2 region for 18 types. BLAST searches in GenBank and phylogenetic trees inferred from the 28S rRNA sequences identified members of at least nine superfamilies and 12 families. Only a few cercariae could be assigned confidently to genus or species on the basis of the sequence data. Matching sequence data from named adult trematodes will be required for definitive identification. There is clearly a great diversity of trematode species utilizing B. s. goniomphalos in Thailand.
Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.
Objectives: Despite changes to brain integrity with aging, some functions like basic language processes remain remarkably preserved. One theory for the maintenance of function in light of age-related brain atrophy is the engagement of compensatory brain networks. This study examined age-related changes in the neural networks recruited for simple language comprehension. Methods: Sixty-five adults (native English-speaking, right-handed, and cognitively normal) aged 17–85 years underwent a functional magnetic resonance imaging (fMRI) reading paradigm and structural scanning. The fMRI data were analyzed using independent component analysis to derive brain networks associated with reading comprehension. Results: Two typical frontotemporal language networks were identified, and these networks remained relatively stable across the wide age range. In contrast, three attention-related networks showed increased activation with increasing age. Furthermore, the increased recruitment of a dorsal attention network was negatively correlated to gray matter thickness in temporal regions, whereas an anterior frontoparietal network was positively correlated to gray matter thickness in insular regions. Conclusions: We found evidence that older adults can exert increased effort and recruit additional attentional resources to maintain their reading abilities in light of increased cortical atrophy.
Psychotropic medication use and psychiatric symptoms during pregnancy each are associated with adverse neurodevelopmental outcomes in offspring. Commonly, studies considering medication effects do not adequately assess symptoms, nor evaluate children when the effects are believed to occur, the fetal period. This study examined maternal serotonin reuptake inhibitor and polypharmacy use in relation to serial assessments of five indices of fetal neurobehavior and Bayley Scales of Infant Development at 12 months in N = 161 socioeconomically advantaged, non-Hispanic White women with a shared risk phenotype, diagnosed major depressive disorder. On average fetuses showed the expected development over gestation. In contrast, infant average Bayley psychomotor and mental development scores were low (M = 84.10 and M = 89.92, range of normal limits 85–114) with rates of delay more than 2–3 times what would be expected based on this measure's normative data. Controlling for prenatal and postnatal depressive symptoms, prenatal medication effects on neurobehavioral development were largely undetected in the fetus and infant. Mental health care directed primarily at symptoms may not address the additional psychosocial needs of women parenting infants. Speculatively, prenatal serotonin reuptake inhibitor exposure may act as a plasticity rather than risk factor, potentially enhancing receptivity to a nonoptimal postnatal environment in some mother–infant dyads.
Introduction: The optimal diagnostic strategy for children presenting to the Emergency Department (ED) with suspected appendicitis (SA), the most common non-traumatic surgical emergency in children, remains unclear. This study aims to identify which investigations and management priorities are preferred by Canadian surgeons prior to consultation from the ED. Methods: An internet survey was extended to practicing surgeons who are members of the Canadian Association of Pediatric Surgeons and Canadian Association of General Surgeons. Three case-based scenarios evaluated surgeons expected ED investigations and management for SA with varying severity of disease (simple - SA vs perforated - PA) and sex (male vs female). Differences across scenarios were determined by ANOVA and direct comparisons were reported using proportions and odds ratios with 95% confidence intervals. Results: Surveys were completed by 82 surgeons. Across the 3 cases, CBC (227/246, 92.3%) and urinalysis (188/246, 76.4%) were the sole investigations expected in >75% of responses. Expectations differed across cases for use of blood cultures (p<0.001), electrolytes (p<0.001), sexually transmitted infection testing (0.015) and ultrasound (US) (p<0.001). Blood cultures (26/82, 31.7% vs 4/82, 4.9%; OR 9.05 95%CI 2.88-37.33) and electrolytes (58/82, 70.7% vs 33/82, 40.2%; OR 3.59 95%CI 1.79-7.24) were expected more often in severe disease. US was expected more often in females (58/82,70.7% vs 25/82, 30.5%; OR 5.51, 95% CI 2.68-11.38). Expected management differed across cases for fluid boluses (p=0.01), intravenous (IV) analgesia (p<0.001) and antibiotics (p<0.001), with all differences attributed to severity of illness (fluids 73/82, 89.0% vs 59/82, 72.0% OR 3.16 95%CI 1.28-8.33; IV analgesia 66/82, 80.5% vs 42/82, 51.2% OR 3.93 95%CI 1.86-8.45; antibiotics 44/82, 53.7% vs 10/82, 12.2% OR 8.34 95%CI 3.59-20.44). Conclusion: Severity of illness and sex of the child impact the ED investigations and management expected by surgeons consulted for suspected appendicitis. Further research focusing on how these expectations influence patient outcomes should be conducted. Collaborative ED-surgery protocols for the diagnosis and management of acute appendicitis in children should be established.
The foetal mammary gland is sensitive to maternal weight and nutrition during gestation, which could affect offspring milk production. It has previously been shown that ewes born to dams offered maintenance nutrition during pregnancy (day 21 to 140 of gestation) produced greater milk, lactose and CP yields in their first lactation when compared with ewes born to dams offered ad libitum nutrition. In addition, ewes born to heavier dams produced greater milk and lactose yields when compared with ewes born to lighter dams. The objective of this study was to analyse and compare the 5-year lactation performance of the previously mentioned ewes, born to heavy or light dams that were offered maintenance or ad libitum pregnancy nutrition. Ewes were milked once per week, for the first 6 weeks of their lactation, for 5 years. Using milk yield and composition data, accumulated yields were calculated over a 42-day period for each year for milk, milk fat, CP, true protein, casein and lactose using a Legendre orthogonal polynomial model. Over the 5-year period, ewes born to heavy dams produced greater average milk (P=0.04), lactose (P=0.01) and CP (P=0.04) yields than offspring born to light dams. In contrast, over the 5-year period dam nutrition during pregnancy did not affect average (P>0.05) offspring milk yields or composition, but did increase milk and lactose accumulated yield (P=0.03 and 0.01, respectively) in the first lactation. These results indicate that maternal gestational nutrition appears to only affect the first lactational performance of ewe offspring. Neither dam nutrition nor size affected grand-offspring live weight gain to, or live weight at weaning (P>0.05). Combined these data indicate that under the conditions of the present study, manipulating dam weight or nutrition in pregnancy can have some effects of offspring lactational performance, however, these effects are not large enough to alter grand-offspring growth to weaning. Therefore, such manipulations are not a viable management tool for farmers to influence lamb growth to weaning.
Social anxiety disorder involves fear of social objects or situations. Social referencing may play an important role in the acquisition of this fear and could be a key determinant in future biomarkers and treatment pathways. However, the neural underpinnings mediating such learning in social anxiety are unknown. Using event-related functional magnetic resonance imaging, we examined social reference learning in social anxiety disorder. Specifically, would patients with the disorder show increased amygdala activity during social reference learning, and further, following social reference learning, show particularly increased response to objects associated with other people's negative reactions?
Method
A total of 32 unmedicated patients with social anxiety disorder and 22 age-, intelligence quotient- and gender-matched healthy individuals responded to objects that had become associated with others’ fearful, angry, happy or neutral reactions.
Results
During the social reference learning phase, a significant group × social context interaction revealed that, relative to the comparison group, the social anxiety group showed a significantly greater response in the amygdala, as well as rostral, dorsomedial and lateral frontal and parietal cortices during the social, relative to non-social, referencing trials. In addition, during the object test phase, relative to the comparison group, the social anxiety group showed increased bilateral amygdala activation to objects associated with others’ fearful reactions, and a trend towards decreased amygdala activation to objects associated with others’ happy and neutral reactions.
Conclusions
These results suggest perturbed observational learning in social anxiety disorder. In addition, they further implicate the amygdala and dorsomedial prefrontal cortex in the disorder, and underscore their importance in future biomarker developments.
Paragonimus westermani is one of the most medically important lung flukes and is widely distributed in Asia. It exhibits considerable variation in morphological, genetic and biological features. In central provinces of Vietnam, a high prevalence of metacercariae of this species has been reported from the crab intermediate host, Vietopotamon aluoiense. In this study, we detected P. westermani metacercariae in two additional crab hosts, Donopotamon haii in Quang Tri Province, central Vietnam and Indochinamon tannanti in Yen Bai Province in the north. The latter is a new locality for P. westermani in a northern region of Vietnam where P. heterotremus is the only species currently known to cause human paragonimiasis. Paragonimus westermani metacercariae found in Vietnam showed considerable morphological variation but slight genetic variation based on DNA sequences from the nuclear ribosomal ITS2 region and the mitochondrial 16S gene. Co-infection of the same individual crabs with P. westermani and P. heterotremus and/or some other Paragonimus species was found frequently, suggesting potential for co-infection in humans. The findings of the present study emphasize the need for highly specific molecular and immunodiagnostic methods to differentially diagnose between P. westermani and P. heterotremus infections.
This paper describes a system utilising a sapphire-loaded superconductor cavity to provide a high-stability oscillator signal for use in VLBI observations.
Both physical activity (PA) and diet are important contributors to health and well-being; however, there is limited information on the association of these behaviours and whether observed associations differ by weight. The present study aimed to evaluate whether nutrient intake is associated with PA and if this association varies by weight in young adults.
Design
Cross-sectional study to analyse the association between PA and nutrient intake.
Setting
Participants were stratified as normal weight (18·5 kg/m2 <BMI <25·0 kg/m2) and overweight/obese (BMI≥25·0 kg/m2). PA level (PAL) was calculated (PAL=total daily energy expenditure/RMR) and used to stratify groups (PAL<1·6, 1·6≤PAL<1·9, PAL≥1·9).
Subjects
Adults (n 407; age 27·6 (sd 3·8) years, 48 % male), with BMI between 20 and 35 kg/m2, having at least two 24 h diet recalls and at least 5 d (including two weekend days) of valid, objectively measured PA data were included in the analysis.
Results
In normal-weight participants, higher PAL was associated with higher intakes of minerals (except Ca, Fe and Zn), B-vitamins and choline (P for trend <0·05). In the overweight/obese group, higher PAL was associated with higher intakes of fibre, K, Na and Cu (P for trend <0·05). These differences, however, were no longer significant after additionally controlling for total energy intake.
Conclusions
More active young adults have higher intakes of essential micronutrients. The benefits of PA may be predominantly due to a higher overall food intake while maintaining energy balance rather than a healthier diet.
Here, we report the feasibility and long-term efficacy of a granulomatous slack skin disease (GSSD) treatment with combined high-energy photon and proton beams.
Patient and methods
A GSSD patient with abdominal disease volume 25×15×2–4 cm deep was recommended for treatment at this institution. In addition to photons and electrons, high-energy protons delivered with advanced planning techniques and patient positioning were used. The patient was irradiated to a total dose of 40 Gy by using 20 Gy matched photon and electrons followed by 20 Gy equivalent protons delivered by using innovative range compensation and patient positioning.
Results
The test patient tolerated the treatment well and is now a 10-year survivor of the disease.
Conclusions
Treatment of GSSD with protons is feasible. The range and narrow penumbra properties of the proton beam provided an ideal capability to match fields accurately to cover large volumes while also sparing underlying normal tissues.
This chapter reviews evidence concerning the vital role that temporal dynamics can have in the ecology of trees and other long-lived species in the assembly and maintenance of natural communities. The research synthesised here was stimulated by a desire to determine the action of temporal dynamics in nature, and its implications for the nature of competition, community structure and assembly on multiple scales and across a range of climatic conditions. For the most part, the results discussed concern tropical forests, but we think they provide strong support for a more general view that can be applied across biomes. Finally, we ask if there may be a potential role for temporal dynamics in speciation, in light of what we have learned from the tropical trees.
A field programme begun in the late ’90s in the tropical dry forest of México was consciously designed to study the coexistence of closely related species in a very speciose community, but the role of temporal dynamics had not been suspected and its finding was serendipitous. With centuries-long lifespans, decades-long juvenile stages and low population turnover rates, trees are problematic candidates for demographic analyses, either observational or experimental. Unless instant death is involved, the particular hurdle with trees, as with any long-lived organism, is directly connecting any specific response in the early life of the individual with the long-term individual persistence or character of the standing population. However, trees differ from many long-lived organisms in carrying their history in their structure at both the individual and population levels. Thus, a tree population itself documents individual success over the history of the population (Parker et al. 1997, Cole et al. 2011). The distribution of a population with regard to physical conditions, size and age structure and relative to other woody species all contain information on the ecology and interactions of species (e.g. Veblen 1989, 1992, Villalba and Veblen 1998, Kelly et al. 2001) and it was the age structure of populations that revealed the action of temporal dynamics at Chamela Biological Station.