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The Repugnant Conclusion is an implication of some approaches to population ethics. It states, in Derek Parfit's original formulation,
For any possible population of at least ten billion people, all with a very high quality of life, there must be some much larger imaginable population whose existence, if other things are equal, would be better, even though its members have lives that are barely worth living. (Parfit 1984: 388)
In 1954, archaeologists James Allen Lancaster and Don Watson and dendrochronologist Edmund Schulman asserted that a small grove of Douglas-fir (Pseudotsuga menziesii [Mirbel] Franco var. glauca [Beissener] Franco) trees in Navajo Canyon on the west side of Chapin Mesa in Mesa Verde National Park contained evidence of stone-axe-cut tree limbs. In 1965, archaeologists Robert Nichols and David Smith published an article entitled “Evidence of Prehistoric Cultivation of Douglas-Fir Trees at Mesa Verde,” in which they supported the Lancaster/Watson/Schulman assertion with tree-ring dates from suspected stone-axe-cut limbs. If correct, Nichols and Smith (1965) document the only trees in the entire U.S. Southwest that contain ancient stone-axe-cut stubs and evidence of precolumbian forest management. Rather than accept their interpretations at face value, we attempt to replicate their dates through the (re)analysis of archived and recently collected tree-ring samples, and through a controlled analysis and comparison of archived and published records. We could not confirm their results, and we have no option but to reject their claim that Schulman Grove contains evidence of precolumbian tree manipulation by Ancestral Puebloan inhabitants of Mesa Verde.
The COVID-19 pandemic prompted the development and implementation of hundreds of clinical trials across the USA. The Trial Innovation Network (TIN), funded by the National Center for Advancing Translational Sciences, was an established clinical research network that pivoted to respond to the pandemic.
The TIN’s three Trial Innovation Centers, Recruitment Innovation Center, and 66 Clinical and Translational Science Award Hub institutions, collaborated to adapt to the pandemic’s rapidly changing landscape, playing central roles in the planning and execution of pivotal studies addressing COVID-19. Our objective was to summarize the results of these collaborations and lessons learned.
The TIN provided 29 COVID-related consults between March 2020 and December 2020, including 6 trial participation expressions of interest and 8 community engagement studios from the Recruitment Innovation Center. Key lessons learned from these experiences include the benefits of leveraging an established infrastructure, innovations surrounding remote research activities, data harmonization and central safety reviews, and early community engagement and involvement.
Our experience highlighted the benefits and challenges of a multi-institutional approach to clinical research during a pandemic.
The distribution of genetic diversity in invasive plant populations can have important management implications. Alligatorweed [Alternanthera philoxeroides (Mart.) Griseb.] was introduced into the United States around 1900 and has since spread throughout much of the southern United States and California. A successful biological control program was initiated in the late 1960s that reduced A. philoxeroides in the southern United States, although control has varied geographically. The degree to which variation among genotypes may be responsible for variation in control efficacy has not been well studied due to a lack of genetic data. We sampled 373 plants from 90 sites across the United States and genotyped all samples at three chloroplast regions to help inform future management efforts. Consistent with clonal spread, there was high differentiation between sites, yet we found six haplotypes and high haplotype diversity (mean h = 0.48) across states, suggesting this plant has been introduced multiple times. Two of the haplotypes correspond to previously described biotypes that differ in their susceptibility to herbicides and herbivory. The geographic distribution of the three common haplotypes varied by latitude and longitude, while the other haplotypes were widespread or localized to one or a few sites. All the haplotypes we screened are hexaploid (6n = 102), which may enhance biological control. Future studies can use these genetic data to determine whether genotypes differ in their invasiveness or respond differently to control measures. Some states, for instance, have mainly a single haplotype that may respond more uniformly to a single control strategy, whereas other states may require a variety of control strategies. These data will also provide the basis for identifying the source regions in South America, which may lead to the discovery of new biological control agents more closely matched to particular genotypes.
Dietary protein is a pre-requisite for the maintenance of skeletal muscle mass; stimulating increases in muscle protein synthesis (MPS), via essential amino acids (EAA), and attenuating muscle protein breakdown, via insulin. Muscles are receptive to the anabolic effects of dietary protein, and in particular the EAA leucine, for only a short period (i.e. about 2–3 h) in the rested state. Thereafter, MPS exhibits tachyphylaxis despite continued EAA availability and sustained mechanistic target of rapamycin complex 1 signalling. Other notable characteristics of this ‘muscle full’ phenomenon include: (i) it cannot be overcome by proximal intake of additional nutrient signals/substrates regulating MPS; meaning a refractory period exists before a next stimulation is possible, (ii) it is refractory to pharmacological/nutraceutical enhancement of muscle blood flow and thus is not induced by muscle hypo-perfusion, (iii) it manifests independently of whether protein intake occurs in a bolus or intermittent feeding pattern, and (iv) it does not appear to be dependent on protein dose per se. Instead, the main factor associated with altering muscle full is physical activity. For instance, when coupled to protein intake, resistance exercise delays the muscle full set-point to permit additional use of available EAA for MPS to promote muscle remodelling/growth. In contrast, ageing is associated with blunted MPS responses to protein/exercise (anabolic resistance), while physical inactivity (e.g. immobilisation) induces a premature muscle full, promoting muscle atrophy. It is crucial that in catabolic scenarios, anabolic strategies are sought to mitigate muscle decline. This review highlights regulatory protein turnover interactions by dietary protein, exercise, ageing and physical inactivity.
Metabolic resistances to atrazine (atz-R) and mesotrione (meso-R) occur in several waterhemp [Amaranthus tuberculatus (Moq.) Sauer] populations in the United States. Interestingly, although metabolic atz-R but mesotrione-sensitive A. tuberculatus populations have been reported, an Amaranthus population has not been confirmed as meso-R but atrazine-sensitive, implying an association between these traits. Experiments were designed to investigate whether the single gene conferring metabolic atz-R plays a role in meso-R. An F2 population was generated from a multiple herbicide–resistant A. tuberculatus population from McLean County, IL (MCR). A cross was made between a known meso-R male clone (MCR-6) and a herbicide-sensitive female clone from Wayne County, IL (WCS-2) to develop an F1 population. Survival of MCR-6 plants following atrazine POST treatment (14.4 kg ha−1) indicated the male parent was homozygous atz-R. F1 plants were intermated to obtain a segregating pseudo-F2 population. Dose–response and metabolic studies conducted with mesotrione using F1 plants indicated intermediate biomass reductions and metabolic rates compared with MCR-6 and WCS. F2 plants were initially treated with either mesotrione (260 g ha−1) or atrazine (2 kg ha−1) POST, and after 21 d of recovery, vegetative clones from surviving resistant plants were subsequently treated with the other herbicide. When mesotrione was applied first, the meso-R frequency was 8.2%, and when atrazine was applied first, the atz-R frequency was 75%. However, the meso-R frequency increased to 16.5% following preselection for atz-R, and 100% of surviving meso-R plants were atz-R. Our findings indicate that the gene conferring metabolic atz-R is also involved with the meso-R trait within the population tested.
Transoesophageal and epicardial echocardiography are indispensible intraoperative imaging modalities to guide paediatric heart disease surgeries and influence surgical decision-making. A less well-described role of intraoperative imaging is its utility in evaluating coronary artery patency and flow. Focused two-dimensional, colour, and spectral Doppler imaging of the coronary arteries should be performed during surgeries involving coronary manipulation or re-implantation, or in cases where there is unexpected ventricular dysfunction or electrographic signs concerning for ischaemia. Intraoperative imaging allows for any anatomical issues to be detected and addressed promptly in the operating room. Imaging of the coronary arteries should identify unobstructed coronary ostia and proximal course without kinking, angulation, narrowing, or significant calibre change to suggest stenosis or extrinsic compression from neighbouring structures. The aim of this review is to highlight the usefulness of transoesophageal and epicardial echocardiography in evaluating coronary artery patency and flow, provide a how-to guide for optimal imaging, and to introduce a practical guideline to achieve best clinical practice.
Evidence suggests that dietary intake of UK children is currently suboptimal. It is therefore imperative to identify effective and sustainable methods of improving dietary habits and knowledge in this population, whilst also promoting the value of healthiness of food products beyond price. Schools are ideally placed to influence children's knowledge and health, and Project Daire, in partnership with schools, food industry partners and stakeholders, aims to improve children's knowledge of, and interest in, food to improve health, wellbeing and educational attainment.
Daire is a randomised-controlled, factorial design trial evaluating two interventions. In total, n = 880 Key Stage (KS) 1 and 2 pupils have been recruited from 18 primary schools in the North West of Northern Ireland and will be randomised to one of four 6-month intervention arms: i) ‘Engage’, ii) ‘Nourish’, iii) ‘Engage’ and ‘Nourish’ and iv) Delayed. ‘Engage’ is an age-appropriate, cross-curricular educational intervention on food, agriculture, science and careers linked to the current curriculum. ‘Nourish’ is an intervention aiming to alter schools’ food environments and increase exposure to local foods. Study outcomes include food knowledge, attitudes, trust, diet, behaviour, health and wellbeing and will be collected at baseline and six months. Qualitative data on teacher/pupil opinions will also be collected. The intervention phase is currently ongoing. We present baseline results from our involvement and food attitudes measure from all participating schools. Results were compared by Key Stage and sex using Pearson Chi-Squared test.
Baseline results from our food involvement and attitudes measure are presented for n = 880 KS1 (n = 454) and KS2 (n = 426) pupils. KS1 pupils were more likely to always or sometimes help with food shopping (89.0%) whilst KS2 pupils were more likely to always or sometimes help with food preparation (69.0%). A higher proportion of KS1 pupils reported liking to try new foods (66.1%) and that it was important that food looked (64.5%), tasted (71.1%) and smelled good (60.6%) compared with KS2 children (P < 0.01). Girls were more likely to always or sometimes help with food shopping (96.2%) and preparation (73%) when compared with boys; whilst a higher proportion of girls reported they liked to try new foods (48.2%) and that it was important that food looked (68%) smelled (50.5%) and tasted (71.8%) good compared with boys (P < 0.01).
Results suggest that involvement in food preparation and shopping, willingness to try new foods and attitudes towards food presentation varied by KS and sex in this cohort.
The recall of conditionally discharged forensic patients in England is a formal order from the Ministry of Justice under the Mental Health Act (1983) which has the power to revoke conditional release and direct readmission to hospital. Recall has significant implications for the individual and for hospital services, but despite this, little is known about predictors of recall for forensic patients.
We examined the rate of recall for 101 patients conditionally discharged from medium secure forensic inpatient services between 2007 and 2013. Demographic, clinical, and forensic factors were examined as possible predictors of time to recall using Cox regression survival techniques.
Conditionally discharged patients were followed for an average of 811 days, during which 45 (44.5%) were recalled to hospital. Younger age (HR 1.89; 95% CI 1.02–3.49; p = 0.04), non-white ethnicity (HR 3.44; 95% CI 1.45–8.13), substance abuse history (HR 2.52; 95% CI 1.17–5.43), early violence (HR 1.90; 95% CI 1.03–3.50), early childhood maladjustment (HR 1.92; 95% CI 1.01–3.68), treatment with a depot medication (HR 2.17; 95% CI 1.14–4.11), being known to mental health services (HR 3.44; 95% CI 1.06–11.16), and a psychiatric admission prior to the index admission (HR 2.44; 95% CI 1.08–5.52) were significantly associated with a shorter time to recall. Treatment with clozapine reduced the risk of recall to hospital (HR 0.40; 95% CI 0.20–0.79).
Time to recall can be predicted by a range of factors that are readily available to clinical teams. Further research is required to determine if targeted interventions can modify the likelihood or time to recall for conditionally released forensic patients.
This paper combines the property rights approach of Barzel with models from renewable resource and evolutionary economics to examine the domestication of wild animals. Wild animals are governed by weak property rights to stocks and individuals while domesticated animals are governed by private ownership of stocks and individuals. The complex evolutionary process of domestication can be viewed as a conversion of wild populations into private property, as well as a transition from natural selection to economic selection controlled by owners of populations and individuals. In our framework domestication is not the explicit goal of any economic agent, but it emerges as a long-run outcome of an innovation in hunting strategies in a hunter–gatherer society. Our formal model also suggests that the domestication process moves slowly at first but then proceeds rapidly, and is aligned with the archeological evidence on domestication events.
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
Field experiments were conducted in 2016 and 2017 in Champaign County, IL, to study a waterhemp [Amaranthus tuberculatus (Moq.) J. D. Sauer] population (CHR) resistant to 2,4-D and 4-hydroxyphenylpyruvate dioxygenase (HPPD)-, photosystem II–, acetolactate synthase (ALS)-, and protoporphyrinogen oxidase–inhibiting herbicides. Two field experiments were designed to investigate the efficacy of very-long-chain fatty-acid (VLCFA)-inhibiting herbicides, including a comparison of active ingredients at labeled use rates and a rate titration experiment. Amaranthus tuberculatus density and control were evaluated at 28 and 42 d after treatment (DAT). Nonencapsulated acetochlor, alachlor, and pyroxasulfone provided the greatest PRE control of CHR (56% to 75%) at 28 DAT, while metolachlor, S-metolachlor, dimethenamid-P, and encapsulated acetochlor provided less than 27% control. In the rate titration study, nonencapsulated acetochlor controlled CHR more than equivalent field use rates of S-metolachlor. Subsequent dose–response experiments with acetochlor, S-metolachlor, dimethenamid-P, and pyroxasulfone in the greenhouse included three multiple herbicide–resistant (MHR) A. tuberculatus populations: CHR-M6 (progeny generated from CHR), MCR-NH40 (progeny generated from Mclean County, IL), and ACR (Adams County, IL), in comparison with a sensitive population (WUS). Both CHR-M6 and MCR-NH40 are MHR to atrazine and HPPD, and ALS inhibitors and demonstrated higher survival rates (LD50) to S-metolachlor, acetochlor, dimethenamid-P, or pyroxasulfone than ACR (atrazine resistant but HPPD-inhibitor sensitive) and WUS. Based on biomass reduction (GR50), resistant to sensitive (R:S) ratios between CHR-M6 and WUS were 7.5, 6.1, 5.5, and 2.9 for S-metolachlor, acetochlor, dimethenamid-P, and pyroxasulfone, respectively. Values were greater for MCR-NH40 than CHR-M6, and ACR was the most sensitive to all VLCFA inhibitors tested. Complete control of all populations was achieved at or below a field use rate of acetochlor. In summary, field studies demonstrated CHR is not controlled by several VLCFA-inhibiting herbicides. Greenhouse dose–response experiments corroborated field results and generated R:S ratios (LD50) ranging from 4.5 to 64 for CHR-M6 and MCR-NH40 among the four VLCFA-inhibiting herbicides evaluated.
Experiments were initiated to characterize a waterhemp population (CHR) discovered in a central Illinois corn field after it was not controlled by the 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitor topramezone. Field experiments conducted during 2014–2015 indicated that acetolactate synthase (ALS)-, protoporphyrinogen oxidase (PPO)-, photosystem II (PSII)-, and HPPD-inhibiting herbicides and the synthetic auxin 2,4-D did not control the CHR population. Laboratory experiments confirmed target site–based resistance mechanisms to ALS- and PPO-inhibiting herbicides. Herbicide doses required to reduce dry biomass 50% (GR50) were determined in greenhouse dose–response experiments, and indicated 16-fold resistance to the HPPD inhibitor mesotrione, 9.5-fold resistance to the synthetic auxin 2,4-D, and 252-fold resistance to the PSII inhibitor atrazine. Complementary results from field, laboratory, and greenhouse investigations indicate that the CHR population has evolved resistance to herbicides from five sites of action (SOAs): ALS-, PPO-, PSII-, and HPPD-inhibiting herbicides and 2,4-D. Herbicide use history for the field in which CHR was discovered indicates no previous use of 2,4-D.
Objectives: Research has shown that analyzing intrusion errors generated on verbal learning and memory measures is helpful for distinguishing between the memory disorders associated with Alzheimer’s disease (AD) and other neurological disorders, including Huntington’s disease (HD). Moreover, preliminary evidence suggests that certain clinical populations may be prone to exhibit different types of intrusion errors. Methods: We examined the prevalence of two new California Verbal Learning Test-3 (CVLT-3) intrusion subtypes – across-trial novel intrusions and across/within trial repeated intrusions – in individuals with AD or HD. We hypothesized that the encoding/storage impairment associated with medial-temporal involvement in AD would result in a greater number of novel intrusions on the delayed recall trials of the CVLT-3, whereas the executive dysfunction associated with subcortical-frontal involvement in HD would result in a greater number of repeated intrusions across trials. Results: The AD group generated significantly more across-trial novel intrusions than across/within trial repeated intrusions on the delayed cued-recall trials, whereas the HD group showed the opposite pattern on the delayed free-recall trials. Conclusions: These new intrusion subtypes, combined with traditional memory analyses (e.g., recall versus recognition performance), promise to enhance our ability to distinguish between the memory disorders associated with primarily medial-temporal versus subcortical-frontal involvement.
Respiratory viral infections are a leading cause of disease worldwide. A variety of respiratory viruses produce infections in humans with effects ranging from asymptomatic to life-treathening. Standard surveillance systems typically only target severe infections (ED outpatients, hospitalisations, deaths) and fail to track asymptomatic or mild infections. Here we performed a large-scale community study across multiple age groups to assess the pathogenicity of 18 respiratory viruses. We enrolled 214 individuals at multiple New York City locations and tested weekly for respiratory viral pathogens, irrespective of symptom status, from fall 2016 to spring 2018. We combined these test results with participant-provided daily records of cold and flu symptoms and used this information to characterise symptom severity by virus and age category. Asymptomatic infection rates exceeded 70% for most viruses, excepting influenza and human metapneumovirus, which produced significantly more severe outcomes. Symptoms were negatively associated with infection frequency, with children displaying the lowest score among age groups. Upper respiratory manifestations were most common for all viruses, whereas systemic effects were less typical. These findings indicate a high burden of asymptomatic respiratory virus infection exists in the general population.
Several grass and broadleaf weed species around the world have evolved multiple-herbicide resistance at alarmingly increasing rates. Research on the biochemical and molecular resistance mechanisms of multiple-resistant weed populations indicate a prevalence of herbicide metabolism catalyzed by enzyme systems such as cytochrome P450 monooxygenases and glutathione S-transferases and, to a lesser extent, by glucosyl transferases. A symposium was conducted to gain an understanding of the current state of research on metabolic resistance mechanisms in weed species that pose major management problems around the world. These topics, as well as future directions of investigations that were identified in the symposium, are summarized herein. In addition, the latest information on selected topics such as the role of safeners in inducing crop tolerance to herbicides, selectivity to clomazone, glyphosate metabolism in crops and weeds, and bioactivation of natural molecules is reviewed.
Given the failure of psychiatry to develop clinically useful biomarkers for psychiatric disorders, and the concomitant failure to develop significant advances in diagnosis and treatment, the National Institute of Mental Health (NIMH) in 2010 launched the Research Domain Criteria (RDoC), a framework for research based on the assumption that mental disorders are disorders of identifiable brain neural circuits, with neural circuitry at the center of units of analysis ranging from genes, molecules, and cells to behavior, self-reports, and paradigms. These were to be integrated with five validated dimensional psychological constructs such as negative and positive valence systems. Four years later, the NIMH stated that the ultimate goal of RDoC is precision medicine for psychiatry, with the assumption that precision medications will normalize dysfunctional neural circuits. How this could be accomplished is not obvious, given that neural circuits are widely distributed, have unclear boundaries, and exhibit a significant degree of neuroplasticity, with multiple circuits present in any given disorder. Moreover, the early focus on neural circuitry has been criticized for its reductionism and neglect of the more recent RDoC emphasis on the integration and equivalence of biological and psychological phenomena. Yet this seems inconsistent with the priorities of the NIMH director, an advocate of the central role of neural circuitry and projects such as the Brain Initiative and the Human Connectome Project. Will such projects, at a cost of at least $10 billion, lead to precision medications for mental disorders, or further diminish funding for clinical care and research?