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We read with interest the recent editorial, “The Hennepin Ketamine Study,” by Dr. Samuel Stratton commenting on the research ethics, methodology, and the current public controversy surrounding this study.1 As researchers and investigators of this study, we strongly agree that prospective clinical research in the prehospital environment is necessary to advance the science of Emergency Medical Services (EMS) and emergency medicine. We also agree that accomplishing this is challenging as the prehospital environment often encounters patient populations who cannot provide meaningful informed consent due to their emergent conditions. To ensure that fellow emergency medicine researchers understand the facts of our work so they may plan future studies, and to address some of the questions and concerns in Dr. Stratton’s editorial, the lay press, and in social media,2 we would like to call attention to some inaccuracies in Dr. Stratton’s editorial, and to the lay media stories on which it appears to be based.
Ho JD, Cole JB, Klein LR, Olives TD, Driver BE, Moore JC, Nystrom PC, Arens AM, Simpson NS, Hick JL, Chavez RA, Lynch WL, Miner JR. The Hennepin Ketamine Study investigators’ reply. Prehosp Disaster Med. 2019;34(2):111–113
We assessed whether paternal demographic, anthropometric and clinical factors influence the risk of an infant being born large-for-gestational-age (LGA). We examined the data on 3659 fathers of term offspring (including 662 LGA infants) born to primiparous women from Screening for Pregnancy Endpoints (SCOPE). LGA was defined as birth weight >90th centile as per INTERGROWTH 21st standards, with reference group being infants ⩽90th centile. Associations between paternal factors and likelihood of an LGA infant were examined using univariable and multivariable models. Men who fathered LGA babies were 180 g heavier at birth (P<0.001) and were more likely to have been born macrosomic (P<0.001) than those whose infants were not LGA. Fathers of LGA infants were 2.1 cm taller (P<0.001), 2.8 kg heavier (P<0.001) and had similar body mass index (BMI). In multivariable models, increasing paternal birth weight and height were independently associated with greater odds of having an LGA infant, irrespective of maternal factors. One unit increase in paternal BMI was associated with 2.9% greater odds of having an LGA boy but not girl; however, this association disappeared after adjustment for maternal BMI. There were no associations between paternal demographic factors or clinical history and infant LGA. In conclusion, fathers who were heavier at birth and were taller were more likely to have an LGA infant, but maternal BMI had a dominant influence on LGA.
The two major approaches to studying macroevolution in deep time are the fossil record and reconstructed relationships among extant taxa from molecular data. Results based on one approach sometimes conflict with those based on the other, with inconsistencies often attributed to inherent flaws of one (or the other) data source. Any contradiction between the molecular and fossil records represents a failure of our ability to understand the imperfections of our data, as both are limited reflections of the same evolutionary history. We therefore need to develop conceptual and mathematical models that jointly explain our observations in both records. Fortunately, the different limitations of each record provide an opportunity to test or calibrate the other, and new methodological developments leverage both records simultaneously. However, we must reckon with the distinct relationships between sampling and time in the fossil record and molecular phylogenies. These differences impact our recognition of baselines and the analytical incorporation of age estimate uncertainty.
SNP in the vitamin D receptor (VDR) gene is associated with risk of lower respiratory infections. The influence of genetic variation in the vitamin D pathway resulting in susceptibility to upper respiratory infections (URI) has not been investigated. We evaluated the influence of thirty-three SNP in eleven vitamin D pathway genes (DBP, DHCR7, RXRA, CYP2R1, CYP27B1, CYP24A1, CYP3A4, CYP27A1, LRP2, CUBN and VDR) resulting in URI risk in 725 adults in London, UK, using an additive model with adjustment for potential confounders and correction for multiple comparisons. Significant associations in this cohort were investigated in a validation cohort of 737 children in Manchester, UK. In all, three SNP in VDR (rs4334089, rs11568820 and rs7970314) and one SNP in CYP3A4 (rs2740574) were associated with risk of URI in the discovery cohort after adjusting for potential confounders and correcting for multiple comparisons (adjusted incidence rate ratio per additional minor allele ≥1·15, Pfor trend ≤0·030). This association was replicated for rs4334089 in the validation cohort (Pfor trend=0·048) but not for rs11568820, rs7970314 or rs2740574. Carriage of the minor allele of the rs4334089 SNP in VDR was associated with increased susceptibility to URI in children and adult cohorts in the United Kingdom.
After describing a newly assembled dataset consisting of almost 9,000 local appropriations made by the U.S. Congress between 1789 and 1882, we test competing accounts of the politics surrounding them before offering a more nuanced, historically contingent view of the emergence of the pork barrel. We demonstrate that for most of this historical period—despite contemporary accusations of crass electoral motives—the pattern of appropriations is largely inconsistent with accounts of distributive politics grounded in a logic of legislative credit-claiming. Instead, support for appropriations in the House mapped cleanly onto the partisan/ideological structure of Congress for most of this period, and only in the 1870s produced the universalistic coalitions commonly associated with pork-barrel spending. We trace this shift to two historical factors: the emergence of a solid Democratic South, and growth in the fraction of appropriations funding recurrent expenditures on extant projects rather than new starts.
Access to transition-related medical interventions (TRMIs) for transgender veterans has been the subject of substantial public interest and debate. To better inform these important conversations, the current study investigated whether undergoing hormone or surgical transition intervention(s) relates to the frequency of recent suicidal ideation (SI) and symptoms of depression in transgender veterans.
This study included a cross-sectional, national sample of 206 self-identified transgender veterans. They self-reported basic demographics, TRMI history, recent SI, and symptoms of depression through an online survey.
Significantly lower levels of SI experienced in the past year and 2-weeks were seen in veterans with a history of both hormone intervention and surgery on both the chest and genitals in comparison with those who endorsed a history of no medical intervention, history of hormone therapy but no surgical intervention, and those with a history of hormone therapy and surgery on either (but not both) the chest or genitals when controlling for sample demographics (e.g., gender identity and annual income). Indirect effect analyses indicated that lower depressive symptoms experienced in the last 2-weeks mediated the relationship between the history of surgery on both chest and genitals and SI in the last 2-weeks.
Results indicate the potential protective effect that TRMI may have on symptoms of depression and SI in transgender veterans, particularly when both genitals and chest are affirmed with one's gender identity. Implications for policymakers, providers, and researchers are discussed.
Ultrasound (US) detects synovitis more accurately than clinical examination (CE) in people with rheumatoid arthritis (RA). This review aimed to investigate the use of US, compared to CE alone, in treatment strategies for RA, and to estimate its potential to be cost-effective in making treatment decisions.
A systematic review was conducted of studies: investigating RA treatment response or strategies that compared US with CE-assessed synovitis; and of tapering RA treatment (1). A model was constructed to investigate the potential cost-effectiveness of US in (i) selecting patients suitable for treatment tapering; and (ii) avoiding treatment escalation (2).
Seven prospective cohort studies suggested US-detected synovitis was significantly associated with a treatment response or tapering failure, whereas in most cases clinical examination alone was not. Two randomized controlled trials (RCTs) identified suggested that US added to the Disease Activity Index (DAS)-based treatment strategies but did not significantly improve primary outcomes, but was associated with improved rate of DAS remission. The evidence showed that some patients (proportions varied widely) who had achieved low disease activity could have treatment tapered, with no, or little, short-term harm to the patient.
The model estimated that an average reduction of 2.5 percent in the costs of biological disease-modifying anti-rheumatic drug (bDMARDs) was sufficient to cover the costs of performing US every three months. This value increased to 4 percent and 13 percent for the costs of conventional disease-modifying anti-rheumatic drug (cDMARDs) depending on the assumed regimen.
Use of US to monitor synovitis could potentially be a cost-effective approach, given that low proportions of patients for whom clinicians consider amending treatment, would need to taper treatment, or remain on therapy without escalation. US could provide clinicians with more confidence in reducing the drug burden. However, there is considerable uncertainty in this conclusion due to lack of robust data relating to key parameters.
There is lack of evidence on the differential impact of maternal macronutrient consumption: carbohydrates (CHO), fats and protein on birth weight. We investigated the association between maternal dietary macronutrient intakes and their sub-components such as saccharides and fatty acids and birth weight. This analyses included 1,196 women with singleton pregnancies who were part of the CAffeine and REproductive health study in Leeds, UK between 2003 and 2006. Women were interviewed in each trimester. Dietary information was collected twice using a 24-h dietary recall about 8–12 weeks and 13–27 weeks of gestation. Multiple linear regression models adjusted for alcohol and smoking in trimester 1, showed that each additional 10 g/d CHO consumption was associated with an increase of 4 g (95 % CI 1, 7; P=0·003) in birth weight. Conversely, an additional 10 g/d fat intake was associated with a lower birth weight of 8 g (95 % CI 0, 16; P=0·04) when we accounted for energy contributing macronutrients in each model, and maternal height, weight, parity, ethnicity, gestational age at delivery and sex of the baby. There was no evidence of an association between protein intake and birth weight. Maternal diet in trimester 2 suggested that higher intakes of glucose (10 g/d) and lactose (1 g/d) were both associated with higher birth weight of 52 g (95 % CI 4, 100; P=0·03) and 5 g (95 % CI 2, 7; P<0·001) respectively. These results show that dietary macronutrient composition during pregnancy is associated with birth weight outcomes. An appropriately balanced intake of dietary CHO and fat during pregnancy could support optimum birth weight.
Objectives: Human immunodeficiency virus (HIV) disproportionately affects Hispanics/Latinos in the United States, yet little is known about neurocognitive impairment (NCI) in this group. We compared the rates of NCI in large well-characterized samples of HIV-infected (HIV+) Latinos and (non-Latino) Whites, and examined HIV-associated NCI among subgroups of Latinos. Methods: Participants included English-speaking HIV+ adults assessed at six U.S. medical centers (194 Latinos, 600 Whites). For overall group, age: M=42.65 years, SD=8.93; 86% male; education: M=13.17, SD=2.73; 54% had acquired immunodeficiency syndrome. NCI was assessed with a comprehensive test battery with normative corrections for age, education and gender. Covariates examined included HIV-disease characteristics, comorbidities, and genetic ancestry. Results: Compared with Whites, Latinos had higher rates of global NCI (42% vs. 54%), and domain NCI in executive function, learning, recall, working memory, and processing speed. Latinos also fared worse than Whites on current and historical HIV-disease characteristics, and nadir CD4 partially mediated ethnic differences in NCI. Yet, Latinos continued to have more global NCI [odds ratio (OR)=1.59; 95% confidence interval (CI)=1.13–2.23; p<.01] after adjusting for significant covariates. Higher rates of global NCI were observed with Puerto Rican (n=60; 71%) versus Mexican (n=79, 44%) origin/descent; this disparity persisted in models adjusting for significant covariates (OR=2.40; CI=1.11–5.29; p=.03). Conclusions: HIV+ Latinos, especially of Puerto Rican (vs. Mexican) origin/descent had increased rates of NCI compared with Whites. Differences in rates of NCI were not completely explained by worse HIV-disease characteristics, neurocognitive comorbidities, or genetic ancestry. Future studies should explore culturally relevant psychosocial, biomedical, and genetic factors that might explain these disparities and inform the development of targeted interventions. (JINS, 2018, 24, 163–175)
Aqueous two-phase systems and related emulsion-based structures defined within micro- and nanoscale environments enable a bottom-up synthetic biological approach to mimicking the dynamic compartmentation of biomaterial that naturally occurs within cells. Model systems we have developed to aid in understanding these phenomena include on-demand generation and triggering of reversible phase transitions in ATPS confined in microscale droplets, morpho-logical changes in networks of femtoliter-volume aqueous droplet interface bilayers (DIBs) formulated in microfluidic channels, and temperature-driven phase transitions in interfacial lipid bilayer systems supported on micro and nanostructured substrates. For each of these cases, the dynamics were intimately linked to changes in the chemical potential of water, which becomes increasingly susceptible to confinement and crowding. At these length scales, where interfacial and surface areas predominate over compartment volumes, both evaporation and osmotic forces become enhanced relative to ideal dilute solutions. Consequences of confinement and crowding in cell-sized microcompartments for increasingly complex scenarios will be discussed, from single-molecule mobility measurements with fluorescence correlation spectroscopy to spatio-temporal modulation of resource sharing in cell-free gene expression bursting.
This paper evaluates the potential of very high resolution multispectral (Worldview-3) satellite imagery for mapping yield parameters in avocado and macadamia orchards. An evaluation of 18 structural and pigment based vegetation indices (VIs) derived from Worldview-3 imagery identified a positive relationship to nut/ fruit weight (kg/tree) R2>0.69 for macadamia and R2>0.68 for avocado; and nut/ fruit number (per tree) R2>0.6 for macadamia and R2>0.61 for avocado. Using the algorithms derived between the optimal VI and the measured parameter, yield and nut/ fruit number maps were derived for each block. In the absence of a commercial yield monitor, the resulting yield maps offer significant benefit to growers for improving orchard management, harvest scheduling, and forward selling decisions.
In 2011, 14 Midwest trial locations evaluated tolerance of an AAD-1 and glyphosate-resistant corn hybrid to a 2,4-D choline+glyphosate premix formulation applied single and sequential POST at V4 and/or V7 corn with and without a PRE application of 2,4-D dimethylamine (DMA). Herbicides were applied at 1X and 2X maximum use rates with 1X rates of 1120 g ae ha−1 for glyphosate and 2,4-D DMA and 1065+1120 g ae ha−1 for the 2,4-D choline+glyphosate premix, respectively. Crop response was greatest 2 d after 2X rate applications, resulting in 4 to 10% visible injury to corn across application timings. No brace root injury or effect on corn grain yield were observed.