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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.
Palmer amaranth resistant to dicamba, glufosinate, and protoporphyrinogen oxidase inhibitors has been documented in several southern states. With extensive use of these and other herbicides in South Carolina, a survey was initiated in the fall of 2020 and repeated in the fall of 2021 and 2022 to determine the relative response of Palmer amaranth accessions to selected preemergence (PRE) and postemergence (POST) herbicides. A greenhouse screening experiment was conducted where accessions were treated with three PRE (atrazine, s-metolachlor, and isoxaflutole) and six POST (glyphosate, thifensulfuron-methyl, fomesafen, glufosinate, dicamba, 2,4-D) herbicides at the 1× and 2× use rates. Herbicides were applied shortly after planting (PRE) or at the 2 to 4 leaf growth stage (POST). Percent survival was evaluated 5-14 days after application depending on herbicide activity. Sensitivity to atrazine PRE was lower for 49 and 33 accessions out of 115 to atrazine PRE at the 1× and 2× rate, respectively. Most of the accessions (90%) were controlled by isoxaflutole PRE at the 1× rate. Response to S-metolachlor PRE indicated 34% of the Palmer amaranth accessions survived the 1× rate (>60% survival). There were 11 accessions with reduced sensitivity to fomesafen POST; however, these percentages were not different from the 0% survivor group. Glyphosate POST at the 1× rate did not control most accessions (79%). Palmer amaranth response to thifensulfuron-methyl POST varied across the accessions, with only 36 and 28% controlled at the 1× and 2×rate, respectively. All accessions were controlled by 2,4-D, dicamba, or glufosinate POST. Palmer amaranth accessions from this survey exhibited reduced susceptibility to several herbicides commonly used in agronomic crops in South Carolina. Therefore, growers should continue to utilize multiple management tactics to minimize the evolution of herbicide resistance in Palmer amaranth in South Carolina.
Diagnostic criteria for major depressive disorder allow for heterogeneous symptom profiles but genetic analysis of major depressive symptoms has the potential to identify clinical and etiological subtypes. There are several challenges to integrating symptom data from genetically informative cohorts, such as sample size differences between clinical and community cohorts and various patterns of missing data.
Methods
We conducted genome-wide association studies of major depressive symptoms in three cohorts that were enriched for participants with a diagnosis of depression (Psychiatric Genomics Consortium, Australian Genetics of Depression Study, Generation Scotland) and three community cohorts who were not recruited on the basis of diagnosis (Avon Longitudinal Study of Parents and Children, Estonian Biobank, and UK Biobank). We fit a series of confirmatory factor models with factors that accounted for how symptom data was sampled and then compared alternative models with different symptom factors.
Results
The best fitting model had a distinct factor for Appetite/Weight symptoms and an additional measurement factor that accounted for the skip-structure in community cohorts (use of Depression and Anhedonia as gating symptoms).
Conclusion
The results show the importance of assessing the directionality of symptoms (such as hypersomnia versus insomnia) and of accounting for study and measurement design when meta-analyzing genetic association data.
The aim of this review is to identify, evaluate, and graphically display gaps in the literature related to scarce health resource allocation in humanitarian aid settings.
Methods
A systematic search strategy was utilized in MEDLINE (via Ovid), Scopus, EMBASE, CINAHL Complete, and ProQuest Central. Articles were reviewed by 2 reviewers with a third reviewer remedying any screening conflicts. Articles meeting inclusion criteria underwent data extraction to facilitate evaluation of the scope, nature, and quality of experience-based evidence for health resource allocation in humanitarian settings. Finally, articles were mapped on a matrix to display evidence graphically.
Results
The search strategy identified 6093 individual sources, leaving 4000 for screening after removal of duplicates. Following full-text screening, 12 sources were included. Mapping extracted data according to surge capacity domains demonstrated that all 4 domains were reflected most of all the staff domain. Much of the identified data was presented without adhering to a clear structure or nomenclature. Finally, the mapping suggested potential incompleteness of surge capacity constructs in humanitarian response settings.
Conclusions
Through this review, we identified a gap in evidence available to address challenges associated with scarce resource allocation in humanitarian settings. In addition to presenting the distribution of existing literature, the review demonstrated the relevance of surge capacity and resource allocation principles underpinning the developed framework.
5wPatients with end stage kidney disease (ESKD) who receive in-center hemodialysis are disproportionately vulnerable to extreme weather events, including hurricanes and heat waves, that may disrupt access to healthcare providers, and life-sustaining treatments. This current era of climate-driven compounding disasters is progressively elevating the level of threat to the health and well-being of patients with ESKD. This analysis brings together multi-disciplinary expertise to explore the contours of this increasingly complex risk landscape. Despite the challenges, important advances have been made for safeguarding this medically high-risk patient population. Hemodialysis services providers have devised innovative systems for preparing their patients and sustaining, or rapidly reestablishing, hemodialysis services in the aftermath of a disaster, and maintaining open lines of communication with their caseloads of ESKD patients throughout all phases of the event. A description of lessons learned along the path towards improved patient support in disasters, is provided. The article concludes with a detailed case example, describing dialysis providers’ effective response throughout Hurricane Ian’s passage across the State of Florida in 2022. Based on lessons learned, this analysis outlines strategies for protecting patients with ESKD that may be adapted for future climate-potentiated disaster scenarios.
A significant proportion of the forested production area in South Carolina is managed using aerial applications of imazapyr. Cotton injury from off-target movement of imazapyr has been observed in South Carolina. Field experiments were conducted twice at the Edisto Research and Education Center (EREC) in 2021 and 2022, and once at the Pee Dee Research and Education Center (PDREC) in 2022, to evaluate the response of cotton at two growth stages to imazapyr at 0.1×, 0.05×, 0.025×, 0.0125×, and 0.00625× of the normal use rate of 0.84 kg ae ha−1. Injury to cotton at the vegetative stage was 86% and 74% at 0.1× and 0.05× imazapyr rates 28 d after application (DAA). Cotton height ranged from 23 to 93 cm at all three locations. Yield at the EREC location in 2021 was reduced by 79%, 48%, and 31% at the 0.1×, 0.05×, and 0.025× rates of imazapyr, respectively. Similar reductions from imazapyr were observed at both EREC and PDREC in 2022. Injury to cotton at the reproductive stage based on visual estimates at 28 DAA ranged from 95% to 64% for the 0.1× to 0.0125× rates, respectively. Cotton height at the reproductive stage was reduced to 59% of the untreated control 28 DAA when the 0.1× rate of imazapyr was applied. Seed cotton (which included both seed and lint) yield ranged from 0 to 2,880 kg ha−1 at the three locations in both years. Seed cotton yield was lowest when imazapyr was applied at the 0.1× to 0.025× rates. Cotton exposure to imazapyr at the vegetative and reproductive growth stages resulted in plant injury, height, and yield reductions, especially at the higher rates of imazapyr. The greatest reduction in cotton growth and yield was observed after exposure at the reproductive growth stage regardless of imazapyr rate. In summary, the magnitude of cotton response to imazapyr depends on crop growth stage and imazapyr concentration at the time of exposure with the greatest impact occurring at the reproductive growth stage.
In times of health reform, fiscal restraint and population aging, it becomes increasingly imperative to understand what must be done to better link research and policy in the health area. In this paper, the major determinants of healthy aging are discussed in terms of current conceptual frameworks of health, measurement, methodologies, and data sources. In order to maximize the benefit for the health of current and future Canadian seniors, policy recommendations are made to Statistics Canada, Health Canada, and the Seniors Independence Research Program (SIRP) which cover a range of issues related to measurement and data sources, health services, health status, economic status, and education.
Subsidised or cost-offset community-supported agriculture (CO-CSA) connects farms directly to low-income households and can improve fruit and vegetable intake. This analysis identifies factors associated with participation in CO-CSA.
Design:
Farm Fresh Foods for Healthy Kids (F3HK) provided a half-price, summer CO-CSA plus healthy eating classes to low-income households with children. Community characteristics (population, socio-demographics and health statistics) and CO-CSA operational practices (share sizes, pick up sites, payment options and produce selection) are described and associations with participation levels are examined.
Setting:
Ten communities in New York (NY), North Carolina (NC), Vermont and Washington states in USA.
Participants:
Caregiver–child dyads enrolled in spring 2016 or 2017.
Results:
Residents of micropolitan communities had more education and less poverty than in small towns. The one rural location (NC2) had the fewest college graduates (10 %) and most poverty (23 %) and poor health statistics. Most F3HK participants were white, except in NC where 45·2 % were African American. CO-CSA participation varied significantly across communities from 33 % (NC2) to 89 % (NY1) of weeks picked up. Most CO-CSA farms offered multiple share sizes (69·2 %) and participation was higher than when not offered (76·8 % v. 57·7 % of weeks); whereas 53·8 % offered a community pick up location, and participation in these communities was lower than elsewhere (64·7 % v. 78·2 % of weeks).
Conclusion:
CO-CSA programmes should consider offering a choice of share sizes and innovate to address potential barriers such as rural location and limited education and income among residents. Future research is needed to better understand barriers to participation, particularly among participants utilising community pick up locations.
The remarkable archaeological record of Neolithic Orkney has ensured that these islands play a prominent role in narratives of European late prehistory, yet knowledge of the subsequent Bronze Age is comparatively poor. The Bronze Age settlement and cemetery at the Links of Noltland, on the island of Westray, offers new evidence, including aDNA, that points to a substantial population replacement between the Late Neolithic and Bronze Age. Focusing on funerary practice, the authors argue for interconnecting identities centred on household and community, patrilocality and inheritance. The findings prompt a reconsideration of the Orcadian Bronze Age, with wider implications for population movement and the uptake of cultural innovations more widely across prehistoric north-western Europe.
This study investigated how bilingual experience alters neural mechanisms supporting novel word learning. We hypothesised that novel words elicit increased semantic activation in the larger bilingual lexicon, potentially stimulating stronger memory integration than in monolinguals. English monolinguals and Spanish–English bilinguals were trained on two sets of written Swahili–English word pairs, one set on each of two consecutive days, and performed a recognition task in the MRI-scanner. Lexical integration was measured through visual primed lexical decision. Surprisingly, no group difference emerged in explicit word memory, and priming occurred only in the monolingual group. This difference in lexical integration may indicate an increased need for slow neocortical interleaving of old and new information in the denser bilingual lexicon. The fMRI data were consistent with increased use of cognitive control networks in monolinguals and of articulatory motor processes in bilinguals, providing further evidence for experience-induced neural changes: monolinguals and bilinguals reached largely comparable behavioural performance levels in novel word learning, but did so by recruiting partially overlapping but non-identical neural systems to acquire novel words.
We present continuous estimates of snow and firn density, layer depth and accumulation from a multi-channel, multi-offset, ground-penetrating radar traverse. Our method uses the electromagnetic velocity, estimated from waveform travel-times measured at common-midpoints between sources and receivers. Previously, common-midpoint radar experiments on ice sheets have been limited to point observations. We completed radar velocity analysis in the upper ~2 m to estimate the surface and average snow density of the Greenland Ice Sheet. We parameterized the Herron and Langway (1980) firn density and age model using the radar-derived snow density, radar-derived surface mass balance (2015–2017) and reanalysis-derived temperature data. We applied structure-oriented filtering to the radar image along constant age horizons and increased the depth at which horizons could be reliably interpreted. We reconstructed the historical instantaneous surface mass balance, which we averaged into annual and multidecadal products along a 78 km traverse for the period 1984–2017. We found good agreement between our physically constrained parameterization and a firn core collected from the dry snow accumulation zone, and gained insights into the spatial correlation of surface snow density.
New guidelines for peanut allergy prevention in high-risk infants recommend introducing peanut during infancy but do not address breastfeeding or maternal peanut consumption. We assessed the independent and combined association of these factors with peanut sensitization in the general population CHILD birth cohort (N = 2759 mother–child dyads). Mothers reported peanut consumption during pregnancy, timing of first infant peanut consumption, and length of breastfeeding duration. Child peanut sensitization was determined by skin prick testing at 1, 3, and 5 years. Overall, 69% of mothers regularly consumed peanuts and 36% of infants were fed peanut in the first year (20% while breastfeeding and 16% after breastfeeding cessation). Infants who were introduced to peanut early (before 1 year) after breastfeeding cessation had a 66% reduced risk of sensitization at 5 years compared to those who were not (1.9% vs. 5.8% sensitization; aOR 0.34, 95% CI 0.14–0.68). This risk was further reduced if mothers introduced peanut early while breastfeeding and regularly consumed peanut themselves (0.3% sensitization; aOR 0.07, 0.01–0.25). In longitudinal analyses, these associations were driven by a higher odds of outgrowing early sensitization and a lower odds of late-onset sensitization. There was no apparent benefit (or harm) from maternal peanut consumption without breastfeeding. Taken together, these results suggest the combination of maternal peanut consumption and breastfeeding at the time of peanut introduction during infancy may help to decrease the risk of peanut sensitization. Mechanistic and clinical intervention studies are needed to confirm and understand this “triple exposure” hypothesis.
Treatment resistance causes significant burden in psychosis. Clozapine is the only evidence-based pharmacologic intervention available for people with treatment-resistant schizophrenia; current guidelines recommend commencement after two unsuccessful trials of standard antipsychotics.
Aims
This paper aims to explore the prevalence of treatment resistance and pathways to commencement of clozapine in UK early intervention in psychosis (EIP) services.
Method
Data were taken from the National Evaluation of the Development and Impact of Early Intervention Services study (N = 1027) and included demographics, medication history and psychosis symptoms measured by the Positive and Negative Syndrome Scale (PANSS) at baseline, 6 months and 12 months. Prescribing patterns and pathways to clozapine were examined. We adopted a strict criterion for treatment resistance, defined as persistent elevated positive symptoms (a PANSS positive score ≥16, equating to at least two items of at least moderate severity), across three time points.
Results
A total of 143 (18.1%) participants met the definition of treatment resistance of having continuous positive symptoms over 12 months, despite treatment in EIP services. Sixty-one (7.7%) participants were treatment resistant and eligible for clozapine, having had two trials of standard antipsychotics; however, only 25 (2.4%) were prescribed clozapine over the 12-month study period. Treatment-resistant participants were more likely to be prescribed additional antipsychotic medication and polypharmacy, instead of clozapine.
Conclusions
Prevalent treatment resistance was observed in UK EIP services, but prescription of polypharmacy was much more common than clozapine. Significant delays in the commencement of clozapine may reflect a missed opportunity to promote recovery in this critical period.
Hurricane Sandy made landfall in New Jersey on October 29, 2012, resulting in widespread power outages and gasoline shortages. These events led to potentially toxic exposures and the need for information related to poisons/toxins in the environment. This report characterizes the New Jersey Poison Information and Education System (NJPIES) call patterns in the days immediately preceding, during, and after Hurricane Sandy to identify areas in need of public health education and prevention.
Methods:
We examined NJPIES case data from October through December 2012. Most Sandy-related calls had been coded as such by NJPIES staff. Additional Sandy-related cases were identified by performing a case narrative review. Descriptive analyses were performed for timing, case frequencies, exposure substances, gender, caller site, type of information requests, and other data.
Results:
The most frequent Sandy-related exposures were gasoline and carbon monoxide (CO). Gasoline exposure cases were predominantly males and CO exposure cases, females (P < 0.0001). Other leading reasons for Sandy-related calls were poison information, food poisoning/spoilage information, and water contamination.
Conclusions:
This analysis identified the need for enhanced public health education and intervention to improve the handling of gasoline and encourage the proper use of gasoline-powered generators and cleaning and cooking equipment, thus reducing toxic exposures.
Registry-based trials have emerged as a potentially cost-saving study methodology. Early estimates of cost savings, however, conflated the benefits associated with registry utilisation and those associated with other aspects of pragmatic trial designs, which might not all be as broadly applicable. In this study, we sought to build a practical tool that investigators could use across disciplines to estimate the ranges of potential cost differences associated with implementing registry-based trials versus standard clinical trials.
Methods:
We built simulation Markov models to compare unique costs associated with data acquisition, cleaning, and linkage under a registry-based trial design versus a standard clinical trial. We conducted one-way, two-way, and probabilistic sensitivity analyses, varying study characteristics over broad ranges, to determine thresholds at which investigators might optimally select each trial design.
Results:
Registry-based trials were more cost effective than standard clinical trials 98.6% of the time. Data-related cost savings ranged from $4300 to $600,000 with variation in study characteristics. Cost differences were most reactive to the number of patients in a study, the number of data elements per patient available in a registry, and the speed with which research coordinators could manually abstract data. Registry incorporation resulted in cost savings when as few as 3768 independent data elements were available and when manual data abstraction took as little as 3.4 seconds per data field.
Conclusions:
Registries offer important resources for investigators. When available, their broad incorporation may help the scientific community reduce the costs of clinical investigation. We offer here a practical tool for investigators to assess potential costs savings.
Heat stress is a global issue constraining pig productivity, and it is likely to intensify under future climate change. Technological advances in earth observation have made tools available that enable identification and mapping livestock species that are at risk of exposure to heat stress due to climate change. Here, we present a methodology to map the current and likely future heat stress risk in pigs using R software by combining the effects of temperature and relative humidity. We applied the method to growing-finishing pigs in Uganda. We mapped monthly heat stress risk and quantified the number of pigs exposed to heat stress using 18 global circulation models and projected impacts in the 2050s. Results show that more than 800 000 pigs in Uganda will be affected by heat stress in the future. The results can feed into evidence-based policy, planning and targeted resource allocation in the livestock sector.