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The Coronavirus Disease 2019 (COVID-19) pandemic has had substantial global morbidity and mortality. Clinical research related to prevention, diagnosis, and treatment of COVID-19 is a top priority. Effective and efficient recruitment is challenging even without added constraints of a global pandemic. Recruitment registries offer a potential solution to slow or difficult recruitment.
Objectives:
The purpose of this paper is to describe the design and implementation of a digital research recruitment registry to optimize awareness and participant enrollment for COVID-19-related research in Baltimore and to report preliminary results.
Methods:
Planning began in March 2020, and the registry launched in July 2020. The primary recruitment mechanisms include electronic medical record data, postcards distributed at testing sites, and digital advertising campaigns. Following consent in a Research Electronic Data Capture survey, participants answer questions related to COVID-19 exposure, testing, and willingness to participate in research. Branching logic presents participants with studies they might be eligible for.
Results:
As of March 24, 2021, 9010 participants have enrolled, and 64.2% are female, 80.6% are White, 9.4% are Black or African American, and 6% are Hispanic or Latino. Phone outreach has had the highest response rate (13.1%), followed by email (11.9%), text (11.4%), and patient portal message (9.4%). Eleven study teams have utilized the registry, and 4596 matches have been made between study teams and interested volunteers.
Conclusion:
Effective and efficient recruitment strategies are more important now than ever due to the time-limited nature of COVID-19 research. Pilot efforts have been successful in connecting interested participants with recruiting study teams.
Innovation Concept: Global health fieldwork is valuable for Canadian residents, but is often trainee-organized, short-term, unsupervised, and lacking in preparation and debriefing. In contrast, we have developed a Certificate Program which will be offered to University of Toronto (UofT) emergency medicine (EM) trainees in their final year of residency. This 6-month Program will complement the Transition to Practice stage for residents interested in becoming leaders in GHEM. Methods: We completed a multi-phase needs assessment to inform the structure and content of a GHEM Certificate Program. Phase 1 consisted of 9 interviews with Program Directors (PDs), Assistant PDs, and past fellows from existing GH fellowships in Canada and USA to understand program structure, curriculum, fieldwork and funding. In Phase 2 we interviewed 4 PDs and fellows from UofT fellowship programs to understand local administrative structures. In Phase 3 we collected feedback from 5 UofT residents and 7 faculty with experience in global health to assess interest in a local GHEM Program. All interview data was reviewed and best practices and lessons learned from key stakeholders were summarized into a proposed outline for a 6-month GHEM Certificate Program. Curriculum, Tool, or Material: The Program will comprise of 1) 3 months of preparatory work in Toronto followed by 2) 3 months of fieldwork in Addis Ababa, Ethiopia. Fieldwork will coincide with activities under the Toronto-Addis Ababa Academic Collaboration in Emergency Medicine (TAAAC-EM). The GHEM trainee's work will support TAAAC-EM activities. Preparatory months will include training in specific competencies (POCUS, teaching, tropical medicine, QI) and meetings between the trainee and a UofT mentor to design an academic project. During fieldwork, the trainee will do EM teaching (75% of time) and complete their academic project (25% of time). A UofT supervisor will accompany, orient and supervise the trainee for their first 2 weeks in Addis. Throughout fieldwork, the trainee will be required to debrief with their UofT mentor weekly for academic and clinical mentoring. One AAU faculty member will be identified as a local supervisor and will participate in all evaluations of the trainee during fieldwork. Conclusion: This Program will launch with a call for applications in July 2021, expecting the first trainee to complete the Program in 2022-23. We anticipate that this Program will increase the number of Canadian EM trainees committed to global health projects and partnerships throughout their career.
This pilot study tested the feasibility, acceptability, and effect-sizes of a multimodal, individual intervention designed to optimize antipsychotic medication use in patients ≥40 years of age with schizophrenia or schizoaffective disorder.
Methods:
We randomized 40 patients into two groups: usual care (UC) or a nine-session, manualized, antipsychotic adherence intervention (AAI). the AAI attempted to improve adherence by combining three psychosocial techniques:
a. education,
b. skills training, and
c. alliance building.
Sessions employed a semi-structured format to facilitate open communication. the primary outcome was antipsychotic adherence at study end. We obtained qualitative data regarding patient preferences for the duration and modality for receiving the adherence intervention.
Results:
Compared to the UC group, a greater proportion of the AAI group was adherent post-intervention based on medication possession ratio, a commonly used measure of medication adherence (85% vs. 66.6%; OR=2.64), a difference that was statistically not significant. the entire AAI group reported that they intended to take medications, and 75% were satisfied with the intervention.
Conclusions:
The AAI was feasible and acceptable. Preliminary data on its effectiveness warrant a larger study. Qualitative data shows that patients prefer brief adherence interventions and accept telephone strategies.
Although various epidemiologic studies have found that chronic back pain is comorbid with psychiatric disorders, little is known about the temporal relationship between the two. In this study, the relationship between chronic back pain and psychiatric disorders was disentangled both cross-sectionally and longitudinally. Data are from the Netherlands Mental Health Survey and Incidence Study (NEMESIS), a prospective survey conducted among adults in the Netherlands. Anxiety, mood and substance use disorders were diagnosed with the Composite International Diagnostic Interview (CIDI). Self-report was used to ascertain chronic back pain. The key findings are that persons with chronic back pain are more likely to have anxiety, mood and substance use disorders. These results add to the growing body of knowledge that chronic back pain is associated not only with depression but also with anxiety and substance use disorder. Secondly, this study provides support for both the consequence (chronic back pain precedes the development of anxiety disorders) and the antecedent hypothesis (anxiety disorders precede the development of chronic back pain). Regarding the consequence hypothesis, it was found that pre-existing chronic back pain not only elevates the risk of developing a mood disorder, but also of anxiety disorders. Regarding the antecedent hypothesis, it was found that anxiety disorders predict new onset chronic back pain. It is concluded that care providers should be aware of the co-occurrence of chronic back pain and psychiatric disorders. Screening tools for psychiatric disorders and guidelines should be made available for the treatment of both chronic back pain and psychiatric disorders.
The Centre for Isotope Research (CIO) at the University of Groningen has operated a radiocarbon (14C) dating laboratory for almost 70 years. In 2017, the CIO received a major upgrade, which involved the relocation of the laboratory to new purpose-built premises, and the installation of a MICADAS accelerator mass spectrometer. This period of transition provides an opportunity to update the laboratory’s routine procedures. This article addresses all of the processes and quality checks the CIO has in place for registering, tracking and pretreating samples for radiocarbon dating. Complementary updates relating to radioisotope measurement and uncertainty propagation will be provided in other forthcoming publications. Here, the intention is to relay all the practical information regarding the chemical preparation of samples, and to provide a concise explanation as to why each step is deemed necessary.
New and archival collections from the Chelsey Drive Group of the Avalon terrane of Cape Breton Island, Nova Scotia, Canada, yield late Cambrian trilobites and agnostoid arthropods with full convexity that contrast with compacted, often deformed material from shale and slate typical of Avalonian Britain. Four species of the agnostoid Lotagnostus form a stratigraphic succession in the upper Furongian (Ctenopyge tumida–Parabolina lobata zones). Two species, L. ponepunctus (Matthew, 1901) and L. germanus (Matthew, 1901) are previously named; L. salteri and L. matthewi are new. Lotagnostus trisectus (Salter, 1864), the type species of the genus, is restricted to compacted material from its type area in Malvern, England. Lotagnostus americanus (Billings, 1860) has been proposed as a globally appropriate index for the base of ‘Stage 10’ of the Cambrian. All four species from Avalonian Canada are differentiated clearly from L. americanus in its type area in Laurentian North America (i.e., from debris flow blocks in Taconian Quebec). In our view, putative occurrences of L. americanus from other Cambrian continents record very different species. Lotagnostus americanus cannot be recognized worldwide, and other taxa should be sought to define the base of Stage 10, such as the conodont Eoconodontus notchhpeakensis.
The common belief that organic-rich mudstones formed in quiescent, distal settings is further weakened by study of an upper Cambrian (Leptoplastus – lower Peltura superzones) succession in the Chesley Drive Group in Avalonian Cape Breton Island that is comparable to Alum Shale successions in Baltica. Dramatic sea-level (likely eustatic) changes are now recognized by punctuation of deposition of shallow, wave-influenced black mudstone with brachiopod (Orusia lenticularis) and olenid trilobite-bearing limestones by offlap and formation of a subaerially cemented calcrete-clast conglomerate. Subaerial exposure was followed by transgression and accumulation of clastic pyrite sand and phosphatic granules with Leptoplastus Superzone (L. ovatus Zone) trilobite sclerites. Dynamic processes are shown by wave ripples in the mudstone and limestone, sorting and winnowing of fossil rudstones, and pre-compactional fracture of the conglomerate and rudstones. Orusia rudstones in the succession below the conglomerate are regarded as analogues of Eoorthis and Billingsella rudstones in the ‘biomere’ extinction intervals of the Laurentian basal Sunwaptan. The lowest Orusia-rich beds are no older than the P. spinulosa Zone but, as elsewhere in Avalonia, they range into the higher Leptoplastus (Cape Breton) and even the Peltura (Britain, New Brunswick) superzones. Rare agnostoid sclerites in lower Peltura Superzone (Ctenopyge tumida Zone) olenid rudstone resemble those traditionally assigned to Lotagnostus trisectus in Avalonian Britain and Sweden, and are distinct from Laurentian L. americanus. An L. americanus Zone cannot be identified in Avalonia or Baltica, and the first appearance datum (FAD) of purported ‘L. americanus’ is not suitable as a standard for the base of the highest Cambrian stage.
This paper will discuss the structure-property model developed that correlates the tensile modulus to the elastic properties and angular distribution of constituent graphitic layers for carbon fiber derived from a polyethylene precursor. In addition, a high-temperature fiber tensile device was built to enable heating of carbon fiber bundles at a variable rate from 25 °C to greater than ∼2300 °C, while simultaneously applying a tensile stress. This capability combined with synchrotron wide-angle x-ray diffraction (WAXD), enabled observation in situ and in real time of the microstructural transformation from different carbon fiber precursors to high-modulus carbon fiber. Experiments conducted using PAN- and PE-derived fiber precursors reveal stark differences in their carbonization and high-temperature graphitization behavior.
An Early Cambrian caliche on the St Non's Formation (emended) is the base of the Caerfai Bay Formation (unit-term changed) at Caerfai Bay, South Wales. Subaerial exposure and the caliche mean the two formations were not genetically related units. The St Non's is an older sand sheet (likely tidalitic, not delta-related) referred to Avalonian depositional sequence (ADS) 2, and the Caerfai Bay is a shallow mud basin unit refered to ADS 4A. The similar Random Formation (upper ADS 2) in North American Avalonia has a basal age of c. 528 Ma and is unconformably overlain by red mudstones or sandstones in fault-bounded basins on the Avalonian inner platform. Coeval British sandstones (lower Hartshill, Wrekin, St Non's, Brand Hills?) are unconformably overlain by latest Terreneuvian (ADS 3) or Epoch 2 (ADS 4A) units. Dates of 519 Ma on Caerfai Bay ashes give an upper bracket on the late appearance of Avalonian trilobites and suggest an ADS 2–4A hiatus of several million years. Post-St Non's and post-Random basin reorganization led to abundant Caerfai Bay Formation volcanic ashes and sparse Brigus Formation ashes in Newfoundland. The broad extent of erosional sequence boundaries that bracket lithologically similar to identical units emphasize that ‘east’ and ‘west’ Avalonia formed one palaeocontinent. The inner platform in southern Britain was larger than the Midlands craton, a tectonically defined later Palaeozoic area unrelated to terminal Ediacaran – Early Palaeozoic depositional belts. The cool-water successions of Early Palaeozoic Avalonia were distant from coeval West Gondwanan carbonate platforms.
We have used times of maximum light for SX Phe, obtained by ourselves and other workers over 55 years to study the behaviour of the fundamental and first overtone radial pulsation modes of the star. We find (1/P0)dP0/dt to be (+2.53 ± 0.05) × 10−8 yr−1 and (1/P1)dP1/dt to be (−1.60 ± 0.03) × 10−7 yr−1, which differ significantly from the value +1.9 × 10−9 yr−1 expected if the changes are due to standard evolution of the star. The residuals in O–C from a quadratic fit cannot be explained by a light–time effect in a binary. There is some evidence that the amplitudes of the two modes change slowly with time.
F is an important trace element for bones and teeth. The protective effect of F against dental caries is well established. Urine is the prime vehicle for the excretion of F from the body; however, the relationship between F intake and excretion is complex: the derived fractional urinary F excretion (FUFE) aids understanding of this in different age groups. The present study aimed to investigate the relationships between (1) total daily F intake (TDFI) and daily urinary F excretion (DUFE), and (2) TDFI and FUFE in 6–7-year-olds, recruited in low-F and naturally fluoridated (natural-F) areas in north-east England. TDFI from diet and toothbrushing and DUFE were assessed through F analysis of duplicate dietary plate, toothbrushing expectorate and urine samples using a F-ion-selective electrode. FUFE was calculated as the ratio between DUFE and TDFI. Pearson's correlation and regression analysis were used to investigate the relationship between TDFI and FUFE. A group of thirty-three children completed the study; twenty-one receiving low-F water (0·30 mg F/l) and twelve receiving natural-F water (1·06 mg F/l) at school. The mean TDFI was 0·076 (sd 0·038) and 0·038 (sd 0·027) mg/kg per d for the natural-F and low-F groups, respectively. The mean DUFE was 0·017 (sd 0·007) and 0·012 (sd 0·006) mg/kg per d for the natural-F and low-F groups, respectively. FUFE was lower in the natural-F group (30 %) compared with the low-F group (40 %). Pearson's correlation coefficient for (1) TDFI and DUFE was +0·22 (P= 0·22) and for (2) TDFI and FUFE was − 0·63 (P< 0·001). In conclusion, there was no correlation between TDFI and DUFE. However, there was a statistically significant negative correlation between FUFE and TDFI.
Pregnancy and lactation are times of additional demand for Ca. Ca is transferred across the placenta for fetal skeletal mineralisation, and supplied to the mammary gland for secretion into breast milk. In theory, these additional maternal requirements could be met through mobilisation of Ca from the skeleton, increased intestinal Ca absorption efficiency, enhanced renal Ca retention or greater dietary Ca intake. The extent to which any or all of these apply, the underpinning biological mechanisms and the possible consequences for maternal and infant bone health in the short and long term are the focus of the present review. The complexities in the methodological aspects of interpreting the literature in this area are highlighted and the inter-individual variation in the response to pregnancy and lactation is reviewed. In summary, human pregnancy and lactation are associated with changes in Ca and bone metabolism that support the transfer of Ca between mother and child. The changes generally appear to be independent of maternal Ca supply in populations where Ca intakes are close to current recommendations. Evidence suggests that the processes are physiological in humans and that they provide sufficient Ca for fetal growth and breast-milk production, without relying on an increase in dietary Ca intake or compromising long-term maternal bone health. Further research is needed to determine the limitations of the maternal response to the Ca demands of pregnancy and lactation, especially among mothers with marginal and low dietary Ca intake, and to define vitamin D adequacy for reproductive women.
Slow subsidence and tectonic quiescence along the New York Promontory margin of Laurentia mean that the carbonate-dominated Tribes Hill and overlying Rochdale formations serve as proxies for the magnitude and timing of Tremadocian eustatic changes. Both formations are unconformity-bound, deepening–shoaling, depositional sequences that double in thickness from the craton into the parautochthonous, western Appalachian Mountains. A consistent, ‘layer cake’ succession of member-level units of the formations persists through this region. The Tribes Hill Formation (late early Tremadocian, late Skullrockian, late Fauna B–Rossodus manitouensis Chron) unconformably overlies the terminal Cambrian Little Falls Formation as the lowest Ordovician unit on the New York Promontory. It was deposited during the strong early Tremadocian, or Stonehenge, transgression that inundated Laurentia, brought dysoxic/anoxic (d/a) slope water onto the shelf and led to deposition of the Schaghticoke d/a interval (black mudstone and ‘ribbon limestone’) on the Laurentian continental slope. The uniform lithofacies succession of the Tribes Hill includes a lower sand-rich member; a middle, dark grey to black mudstone that records d/a in eastern exposures; and an upper, shoaling-up carbonate highstand facies. A widespread (12000+ km2) thrombolitic interval in the highstand carbonate suggests the New York Promontory was rimmed by thrombolites during deposition of the Tribes Hill. Offlap and erosion of the Tribes Hill was followed by the relatively feeble sea-level rise of the Rochdale transgression (new) in Laurentia, and deposition of the Rochdale Formation. The Rochdale transgression, correlated with the Kierograptus Drowning Interval in Baltica, marks a eustatic rise. The Rochdale Formation represents a short Early Ordovician interval (early late Tremadocian, middle–late Stairsian, Macerodus dianae Chron). It correlates with a depositional sequence that forms the middle Boat Harbour Formation in west Newfoundland and with the Rte 299 d/a interval on the east Laurentian slope. The Rochdale has a lower carbonate with abundant quartz silt (Comstock Member, new) and an upper, thrombolitic (Hawk Member, new) high-stand facies. Tribes Hill and Rochdale faunas are mollusc-rich, generally trilobite-poor, and have low diversity, Laurentian faunal province conodonts. Ulrichodina rutnika Landing n. sp. is rare in Rochdale conodont assemblages. Trilobites are also low in diversity, but locally form coquinas in the middle Tribes Hill. The poorly preserved Rochdale trilobites include the bathyurid Randaynia, at least two hystricurid species and Leiostegium.
It is well accepted that n-3 long-chain PUFA intake is positively associated with a range of health benefits. However, while benefits have been clearly shown, especially for CVD, the mechanisms for prevention/benefit are less understood. Analysis of plasma and erythrocyte phospholipids (PL) have been used to measure the status of the highly unsaturated fatty acids (HUFA), especially EPA (20 : 5n-3) and DHA (22 : 6n-3), although the time and complexity of the process places limitations on the sample numbers analysed. An assay has been developed using whole blood, collected by finger prick, and stored on absorbant paper, subjected to direct methylation and fatty acids quantified by automated GC. Tests on fatty acid stability show that blood samples are stable when stored at − 20°C for 1 month although some loss of HUFA was seen at 4°C. A total of fifty-one patients, including twenty-seven who consumed no fatty acid supplements, provided a blood sample for analysis. Concentrations of all major fatty acids were measured in erythrocyte PL and whole blood. The major HUFA, including EPA, DHA and arachidonic acid (ARA; 20 : 4n-6), as well as the ARA:EPA ratio and the percentage n-3 HUFA/total HUFA all showed good correlations, between erythrocyte PL and whole blood. Values of r2 ranged from 0·48 for ARA to 0·95 for the percentage of n-3 HUFA/total HUFA. This assay provides a non-invasive, rapid and reliable method of HUFA quantification with the percentage of n-3 HUFA value providing a potential blood biomarker for large-scale nutritional trials.
Two completely dissimilar faunal changes occur between the Sunwaptan and Skullrockian Stages (Ptychaspid and Symphysurid ‘Biomeres’) in the uppermost Cambrian on the east Laurentian craton. An undolomitized section in the Little Falls Formation in Washington County, New York, shows a typical ‘biomere’ extinction, with highest Sunwaptan trilobites followed by the abrupt appearance of Cordylodus proavus Zone conodonts and the lowest post-extinction trilobites (Parakoldinioidia Endo) 5.0 m higher. This stage boundary interval is very condensed by comparison with coeval Great Basin and Texas sections. Approximately 70 km southwest, typical pre-extinction taxa (the catillicephalid Acheilops Ulrich and several dikelocephalid species) are shown for the first time to persist well beyond the extinction as they occur with middle C. proavus Zone conodonts (Clavohamulus elongatus or, more likely, Hirsutodontus simplex Subzone). The Ritchie Limestone member of the uppermost Little Falls Formation yields a succession of conodont faunas that spans the C. elongatus–H. simplex–Clavohamulus hintzei Subzones (middle–upper C. proavus Zone). These data prove that the trilobites are a relict fauna that persisted into the Symphysurina Zone of the Skullrockian Stage. The massive (burrow-churned), mollusc-dominated Ritchie Limestone, with the second Upper Cambrian cephalopod locality in east Laurentia, represents an inner-shelf refugium for Sunwaptan trilobites that has not been previously encountered. Final extinction of typical Sunwaptan clades is at least locally diachronous, and a simple, genus-based approach to trilobite biostratigraphy in the Cambrian–Ordovician boundary interval is untenable. The relict fauna appears to be distinct at the species level, so it is likely that a viable, species-based biostratigraphy can be developed. Teridontus gallicus Serpagli et al. 2008 is a synonym of T. nakamurai (Nogami, 1967), and T.? francisi Landing sp. nov., with a large base and tiny cusp, is a lower C. proavus Zone form. New trilobites are Acheilops olbermanni Westrop sp. nov. and Parakoldinioidia maddowae Westrop sp. nov. The lowest Ordovician ‘Gailor Dolomite’ is a junior synonym of the Tribes Hill Formation, and the Ritchie Limestone is assigned to the top of the terminal Cambrian Little Falls Formation.
A computer model is developed that simulates Marker Assisted Selection (MAS) in a population produced by a cross between two inbred lines. Selection is based on an index that incorporates both phenotypic and molecular information. Molecular markers contributing to the index and their relative weights are determined by multiple regression of individual phenotype on the markers. The model is applied to investigate the efficiency of MAS as affected by several factors including total number of markers in the genome, number of markers contributing to the index, population size and heritability of the character. It is demonstrated that selection based on genetic markers can effectively utilize the linkage disequilibrium between genetic markers and QTLs created by crossing inbred lines. Selection is more efficient if markers contributing to the index are re-evaluated each generation than if they are evaluated only once. Increasing the total number of markers in the genome as well as the number of markers contributing to the index does not necessarily result in a higher efficiency of selection. Moreover, too many markers may result in a weaker response to selection. Population size is shown to be the most important factor affecting the efficiency of MAS.
The genetic and phenotypic regressions and correlations between ovulation rate and body weight were examined in a random bred strain (Q) of laboratory mice during the course of three experiments. These experiments were (1) a sib analysis; (2) selection for natural and induced primiparous ovulation rate; and (3) replicated selection for 6-week weight. The following results were obtained:
(a) The genetic correlations between body weight and natural and induced ovulation rate were positive, and approximately equal to 0·4 and 0·6 respectively.
(b) The genetic regressions of natural and of induced ovulation rate on body weight were approximately 0·4 and 0·9 eggs per gram respectively.
(c) The genetic regressions of body weight on natural and on induced ovulation rate were approximately 0·5 and 0·25 g per egg respectively.
(d) The phenotypic correlation between natural ovulation rate and body weight was approximately 0·4 and the corresponding regression of ovulation rate on body weight approximately 0·4 eggs per gram.
(e) The phenotypic correlation between induced ovulation rate and body weight declined from 0·4 at 6 weeks of age to zero at the time of scoring, the corresponding regressions of ovulation rate on body weight declining from 0·1 eggs per gram to zero.
It was concluded that natural ovulation rate itself, and both its components (FSH activity and ovarian sensitivity) are positively genetically correlated with body weight. Furthermore, the observation that large mice shed at least as many eggs as small ones in response to the same dose of PMS showed that the response was more closely related to the absolute dose than to the resultant concentration.
Selection was carried out in mice for concentration of thyroxine hormone (T4) in plasma of males at 11 weeks of age over seven generations. Selection was practised for high level in two replicate lines and for low level in two replicate lines, and there was an unselected control. There was a response in both directions, and the divergence of 12·4 ng/ml observed in generation seven was equivalent to about 20% of the base population mean or nearly one phenotypic standard deviation. The realised heritability was 9%.
Plasma thyroxine level had a repeatability of 0·54 when two measurements were made 24 h apart. The responses made at 11 weeks in males were also evident in both males and females at 5 weeks. Plasma tri-iodo thyronine (T3) concentrations showed a correlated response almost as large, relative to the mean level, as that in T4.
Positive correlated responses were observed in total weights of the litter at 12 days, and in individual weights at 3, 6 and 9 weeks, the responses in the early weights being greater relative to their mean. The results suggest that the correlated weight changes were due to genetic responses in maternal characteristics, probably milk production, rather than individual growth.