Effective Altruism as an Ethical Lens on Research Priorities.

Effective altruism is an ethical framework for identifying the greatest potential benefits from investments. Here, we apply effective altruism concepts to maximize research benefits through identification of priority stakeholders, pathosystems, and research questions and technologies. Priority stakeholders for research benefits may include smallholder farmers who have not yet attained the minimal standards set out by the United Nations Sustainable Development Goals; these farmers would often have the most to gain from better crop disease management, if their management problems are tractable. In wildlands, prioritization has been based on the risk of extirpating keystone species, protecting ecosystem services, and preserving wild resources of importance to vulnerable people. Pathosystems may be prioritized based on yield and quality loss, and also factors such as whether other researchers would be unlikely to replace the research efforts if efforts were withdrawn, such as in the case of orphan crops and orphan pathosystems. Research products that help build sustainable and resilient systems can be particularly beneficial. The "value of information" from research can be evaluated in epidemic networks and landscapes, to identify priority locations for both benefits to individuals and to constrain regional epidemics. As decision-making becomes more consolidated and more networked in digital agricultural systems, the range of ethical considerations expands. Low-likelihood but high-damage scenarios such as generalist doomsday pathogens may be research priorities because of the extreme potential cost. Regional microbiomes constitute a commons, and avoiding the "tragedy of the microbiome commons" may depend on shifting research products from "common pool goods" to "public goods" or other categories. We provide suggestions for how individual researchers and funders may make altruism-driven research more effective.[Formula: see text] Copyright © 2020 The Author(s). This is an open access article distributed under the CC BY 4.0 International license.

Differential Susceptibility of 39 Tomato Varieties to Phytophthora infestans Clonal Lineage US-23.

During the summers of 2012 and 2013, 39 tomato (Solanum lycopersicum) lines or varieties were evaluated for resistance to late blight in three separate field trials. In each trial, late blight was caused by field isolates of Phytophthora infestans clonal lineage US-23. Varieties with the late blight resistance genes Ph-1, Ph-2, Ph-3, and Ph-2 + Ph-3 were included, along with several heirloom varieties with grower-reported resistance and varieties with no known resistance. All six varieties with Ph-2 + Ph-3, along with NC25P, which is homozygous for Ph-3 only, showed a high level of resistance. Plum Regal F1, which is heterozygous for Ph-3 only, showed moderate resistance. Legend, the only variety with Ph-2 alone, also showed moderate resistance. Three heirloom varieties, Matt's Wild Cherry, Lemon Drop, and Mr. Stripey, showed a high level of resistance comparable with that of varieties with Ph-2 + Ph-3. New Yorker, possessing Ph-1 only, showed no resistance. Indeterminate varieties had significantly less disease than determinate varieties in two of the three trials. Overall, this study suggests that tomato varieties with both Ph-2 and Ph-3 can be used to effectively manage late blight caused by P. infestans clonal lineage US-23. Varieties possessing only Ph-2, or heterozygous for Ph-3, were better protected than those without any late blight resistance but might still require supplemental fungicide applications, while the variety that was homozygous for Ph-3 was highly resistant. Several heirloom varieties were also highly resistant, and the unknown mechanism of their resistance warrants further research. Finally, the plasticity observed in United States P. infestans populations over the past several decades necessitates continued monitoring for genetic changes within P. infestans that could lead to the breakdown of resistance reported here.

The prevalence of PFS and prevalence and characteristics of reported food allergy; a survey of UK adults aged 18-75 incorporating a validated PFS diagnostic questionnaire.

BACKGROUND: Pollen-food syndrome (PFS), a food allergy affecting pollen-sensitized individuals, is likely to be the most prevalent food allergy in adults, estimated to affect 50-90% of people allergic to birch tree pollen. OBJECTIVE: A validated PFS diagnostic questionnaire (PFSDQ2) was used to determine the prevalence of PFS and also to characterize those who report reactions to foods. METHODS: Five UK General practices each sent the PFSDQ2 by post to 2000 patients aged 18-75 years randomly selected from their practice database. The validated questionnaire was accompanied by an additional set of questions to ascertain the demographic of the population, the foods involved and the age of onset. RESULTS: There were 3590 subjects who returned completed questionnaires, with an average return rate from each practice of 36% (range 22-47%). Of these, 73 were diagnosed with PFS according to the questionnaire (PFS+ve) giving a population prevalence of 2%. A further 482 subjects reported reactions to foods but did not fulfil the diagnostic criteria for PFS. The greatest prevalence of PFS was in the Croydon (SE England) urban practice (4.1%) and the lowest in the Aberdeen (Scotland) urban practice (0.8%) (P < 0.001).The most frequently reported trigger foods were apples, hazelnuts and kiwifruit and the majority of those with PFS first experienced symptoms below the age of 20 years. PFS+ve subjects were also more likely to be female and have a higher socio-economic status than those who did not report reactions to foods. CONCLUSIONS: The UK prevalence of PFS was 2%, although this varied according to the location of the practice population. The majority of PFS+ve subjects first reported symptoms in their teens. The reported age of onset has important implications for the diagnosis of primary and cross-reactive peanut and tree nut allergies in teenagers and young adults. The continuing rise in aeroallergen sensitization is likely to result in an increased frequency of PFS presenting in both primary and secondary care.

Phenotypic Characterization of Recent Clonal Lineages of Phytophthora infestans in the United States.

Phytophthora infestans, the causal agent of late blight disease, has been reported in the United States and Canada since the mid-nineteenth century. Due to the lack of or very limited sexual reproduction, the populations of P. infestans in the United States are primarily reproducing asexually and, thus, show a simple genetic structure. The emergence of new clonal lineages of P. infestans (US-22, US-23, and US-24) responsible for the late blight epidemics in the northeastern region of the United States in the summers of 2009 and 2010 stimulated an investigation into phenotypic traits associated with these genotypes. Mating type, differences in sensitivity to mefenoxam, differences in pathogenicity on potato and tomato, and differences in rate of germination were studied for clonal lineages US-8, US-22, US-23, and US-24. Both A1 and A2 mating types were detected. Lineages US-22, US-23, and US-24 were generally sensitive to mefenoxam while US-8 was resistant. US-8 and US-24 were primarily pathogenic on potato while US-22 and US-23 were pathogenic on both potato and tomato. Indirect germination was favored at lower temperatures (5 and 10°C) whereas direct germination, though uncommon, was favored at higher temperatures (20 and 25°C). Sporangia of US-24 released zoospores more rapidly than did sporangia of US-22 and US-23. The association of characteristic phenotypic traits with genotype enables the prediction of phenotypic traits from rapid genotypic analyses for improved disease management.

The 2009 Late Blight Pandemic in the Eastern United States - Causes and Results.

The tomato late blight pandemic of 2009 made late blight into a household term in much of the eastern United States. Many home gardeners and many organic producers lost most if not all of their tomato crop, and their experiences were reported in the mainstream press. Some CSAs (Community Supported Agriculture) could not provide tomatoes to their members. In response, many questions emerged: How did it happen? What was unusual about this event compared to previous late blight epidemics? What is the current situation in 2012 and what can be done? It's easiest to answer these questions, and to understand the recent epidemics of late blight, if one knows a bit of the history of the disease and the biology of the causal agent, Phytophthora infestans.

Resistance in Maize Inbred Lines to Fusarium verticillioides and Fumonisin Accumulation in South Africa.

Fusarium ear rot of maize, caused by Fusarium verticillioides, is an important disease affecting maize production worldwide. Apart from reducing yield and grain quality, F. verticillioides produces fumonisins which have been associated with mycotoxicoses of animals and humans. Currently, no maize breeding lines are known with resistance to F. verticillioides in South Africa. The objective of this study, therefore, was to evaluate 24 genetically diverse maize inbred lines as potential sources of resistance to Fusarium ear rot and fumonisin accumulation in field trials at Potchefstroom and Vaalharts in South Africa. After artificial silk channel inoculation with F. verticillioides, Fusarium ear rot development was determined at harvest and fumonisins B1, B2, and B3 quantified. A significant inbred line by location effect was observed for Fusarium ear rot severity (P ≤ 0.001), although certain lines proved to be consistently resistant across both locations. The individual inbred lines also differed considerably in fumonisin accumulation between Potchefstroom and Vaalharts, with differentiation between susceptible and potentially resistant inbred lines only being possible at Vaalharts. A greenhouse inoculation trial was then also performed on a subset of potentially resistant and highly susceptible lines. The inbred lines CML 390, CML 444, CML 182, VO 617Y-2, and RO 549 W consistently showed a low Fusarium ear rot (<5%) incidence at both Potchefstroom and Vaalharts and in the greenhouse. Two of these inbred lines, CML 390 and CML 444, accumulated fumonisin levels <5 mg kg-1. These lines could potentially act as sources of resistance for use within a maize breeding program.

Distal Chevron Osteotomy vs The Simple, Effective, Rapid, Inexpensive Technique (SERI) for Mild to Moderate Isolated Hallux Valgus: A Randomized Controlled Study.

BACKGROUND: Hallux valgus is a common foot deformity that leads to functional disability with serious sequelae. Minimally invasive surgery is often used to treat hallux valgus in order to reduce wound complications and improve recovery time. The objective of this study was to compare a Simple, Effective, Rapid, Inexpensive (SERI) technique with a simple Chevron technique in patients with minimum of 1-year follow-up. METHODS AND MATERIALS: Between the years 2014-2015, we performed a prospective study comparing the SERI minimally invasive technique to treat symptomatic hallux valgus with a standard chevron osteotomy technique. All procedures were performed by a single fellowship trained foot and ankle surgeon. Twenty-one patients were randomized to the SERI cohort and 15 to the standard Chevron technique. RESULTS: The mean preoperative intermetatarsal angle (IMA) of the SERI group was 14.8 ± 1.9 (11.9-22.9). The mean preoperative IMA of the Chevron control group was 13.3 ± 2.3 (10.4-18.2) (p = 0.038). The mean IMA two weeks after the surgery was 6.0 ± 2.3 (2.4-12) in the SERI group, and 6.1 ± 3 (2.6-13.1) in the control group. At the two-week and 1-year follow-up, there was no significant difference found in the IMA between the two groups (p = 0.871). The mean hallux valgus angle reduction was 11.85 ± 4.88 (3-20.8) and 11.09 ± 6.51 (- 1.1 to 22.5) in the SERI and Chevron groups, respectively (p = 0.69). Neither groups reported symptomatic transfer metatarsalgia throughout the follow-up period. The SERI group had increased metatarsophalangeal joint (MTPJ) motion (p < 0.001); however, all other parameters with similar. CONCLUSION: The SERI technique provided comparable outcomes at up to 1-year follow-up when compared with a standard Chevron osteotomy for moderate hallux valgus. This study demonstrated good reproducible results using the SERI technique for moderate hallux valgus. LEVEL OF EVIDENCE: Level II Prospective Study. TRIAL REGISTRATION: Approved by local IRB at MMC.

Management of COPD in primary care in north-east Scotland.

INTRODUCTION: We wished to obtain a snapshot of current service provision and how this could best be developed approximately one year on from the introduction of the National Institute for Clinical Excellence (NICE) guidelines for the management of chronic obstructive pulmonary disease (COPD) and the inclusion of COPD care in the New GMS Contract Quality and Outcomes Framework (QOF). METHODOLOGY: A questionnaire-based survey sent to every general practice (n = 84) in Grampian. RESULTS: Responses were received from 75 of 84 practices (89%). Questionnaires were returned by both general practitioners (GPs) and practice nurses in 45 practices (54%). All responding practices reported that they had COPD registers. 60/75 (80%) of practices reported having a dedicated COPD clinic; 70/75 (93%) had a spirometer. Areas identified for service development were: quality assuring training in COPD care and spirometry; expanding pulmonary rehabilitation provision (86%), delivering this service locally (54%) and in primary care (75%); standardising referral, assessment and communication about provision of home oxygen; training in pulse oximetry (71%). CONCLUSION: This data has important implications for the validity of the quality indicators (QOF) under the new GMS contract. Our respondents identified areas where the new GMS contract QOF could be improved, as well as providing useful suggestions for service development. Respondents recognised that not all clinical services can be effectively delivered by general practice with data supporting the development of intermediate care services for people with COPD.

Dual targeting to mitochondria and chloroplasts.

Plant cells contain two organelles originally derived from endosymbiotic bacteria: mitochondria and plastids. Their endosymbiotic origin explains why these organelles contain their own DNA, nonetheless only a few dozens of genes are actually encoded by these genomes. Many of the other genes originally present have been transferred to the nuclear genome of the host, the product of their expression being targeted back to the corresponding organelle. Although targeting of proteins to mitochondria and chloroplasts is generally highly specific, an increasing number of examples have been discovered where the same protein is imported into both organelles. The object of this review is to compare and discuss these examples in order to try and identify common features of dual-targeted proteins. The study helps throw some light on the factors determining organelle targeting specificity, and suggests that dual-targeted proteins may well be far more common than once thought.

Familial associations with EEG variants in manic-depressive disease.

Electroencephalographic (EEG) studies of 60 patients with bipolar manic-depressive disease disclosed an incidence of small sharp spikes plus a few other variations in 47% of the sample. In women these EEG features were significantly associated with a history of mental illness in the patient's mother or the maternal side of the family and an absence of mental disorder in the fathers. The reverse was true of women probands without these EEG characteristics. In the men small sharp spikes did not relate to parental psychopathology but half of the sisters of men with these EEG characteristics were found to be mentally ill. On the basis of these observations and previous work, we hypothesize that the small sharp spike EEG pattern might be an inherited characteristic related in some way to the familal transmission of manic-depressive disease.

Electroconvulsive treatment compared with lithium in the management of manic states.

Thirty-four hospitalized manic patients were randomized to treatment with either lithium carbonate or an average series of nine bilateral electroconvulsive treatments (ECTs), followed by maintenance with lithium carbonate. Weekly ratings of manic, depressive, and psychotic symptoms were obtained for eight weeks, and patients were followed up monthly for up to two years. Ratings by nonblind and blind observers indicated that the patients who underwent ECT improved more during the first eight weeks than did patients who were treated with lithium carbonate. This was especially true of patients with mixed symptoms of mania and depression and/or extreme manic behavior. Clinical ratings after eight weeks showed no significant differences between the lithium carbonate- and ECT-treated patients. Likewise, the two groups had comparable rates of relapse, recurrence, and rehospitalization during the follow-up period.

Carbamazepine compared with lithium in the treatment of mania.

Fifty-two hospitalized manic patients were randomized to treatment with either carbamazepine or lithium carbonate after a 2-week drug withdrawal period. All of the probands were tertiary referrals with a high proportion of failures of previous lithium and other treatment. Weekly ratings of manic, depressive, and psychotic symptoms were obtained for 8 weeks, and responders were followed up for up to 2 years. One third of patients responded favorably. Double-blind assessments revealed no statistically reliable differences between the two treatment groups. Patients receiving carbamazepine were somewhat more manageable than patients treated with lithium early in the study, whereas lithium-treated patients remained longer in the follow-up phase. However, numbers of long-term survivors were too small to be conclusive. This study adds to the growing body of evidence that acutely manic patients respond as well to carbamazepine as to lithium. However, monotherapy with either drug is not sufficient for the majority of manic patients who are referred for tertiary care.

Electroencephalographic findings in relation to diagnostic constructs in psychiatry.

A group of 759 patients with final DSM-I and -II diagnoses of schizophrenia was identified among a cohort of 1494 adults who were hospitalized between 1965 and 1972. Admission EEG recordings were done in each patient during waking, activation procedures, drowsiness, and sleep. All cases were reclassified according to the Feighner et al. criteria, and relationships between the EEG, reassigned diagnosis, and outcome were examined. One-third of the schizophrenics were rediagnosed as having affective, organic, or other disorders. EEG abnormalities predicted diagnostic change and relatively favorable prognosis. Mean alpha frequencies were slower in schizophrenics than in patients with other DSM I-II disorders, and less in patients with Feighner et al. diagnoses of schizophrenia than in some rediagnosed categories. In 1980-82, matched samples from the original cohort with affective, schizophrenic, and mixed Feighner et al. diagnoses were followed and evaluated blindly with the SADS-L. RDC follow-up diagnoses were significantly correlated with the index EEG findings in terms of higher alpha average frequencies proportional to the amount of affective psychopathology. A subgroup of high functioning individuals within the RDC schizophrenic category was identified with affective symptomatology early in the course of illness, normal EEGs, and high alpha average frequencies. Patients with a consistent diagnosis of schizophrenia according to the three nosologic systems were shown to function better in some areas if the index EEG was abnormal. Discriminant function analysis established that DSM-I and -II categories possessed the greatest long-term predictive accuracy which was enhanced by the EEG diagnosis and alpha average to a level of more than 50%. The Feighner et al. and RDC diagnostic systems were not as relevant for prediction of long-term follow-up status.

Mechanisms of action of ECT: schizophrenia and schizoaffective disorder.

A variety of neurophysiological mechanisms have been suggested to explain the therapeutic action of electroconvulsive therapy (ECT). Processes of kindling, resolution of hemispheric dysfunctions, anticonvulsant effects, and diencephalic stimulation all have been proposed to account for the beneficial effects of ECT. To investigate these, we analyzed clinical, neuropsychological, and electroencephalographic (EEG) data from 110 ECT-treated patients with schizophrenia and schizoaffective disorders, comparing responders with nonresponders. Fifty-four percent of all the patients were rated as very much or much improved. Mechanisms of kindling or anticonvulsant effects were not supported by the data. Dominant hemispheric dysfunctions in schizophrenics were suggested by the neuropsychological test data. There was tenuous support for the sensitization theory and both the neuropsychological and EEG data contradicted the dominant accentuation theory. Taken together with our previous report on ECT-treated patients with affective disorders, we propose that ECT might act by restoration of equilibrium between the hemispheres.

Manic symptoms: an indication for bilateral ECT.

As a follow-up to pilot observations that six manic patients who failed to respond to unilateral electroconvulsive therapy (ECT) recovered rapidly when switched to bilateral treatment, a retrospective study was conducted. Twenty-five patients who responded after switchover from unilateral to bilateral ECT, 25 age- and sex-matched controls, and 25 concurrent controls who responded to right unilateral ECT alone were evaluated. Demographic variables and DSM-III diagnosis did not discriminate between the groups, nor were they different in terms of electroencephalographic (EEG) findings, neuropsychological test results, numbers of ECT, and duration of seizure discharges. Standard assessments of psychopathology performed by independent psychiatrists showed no differences in ratings of psychosis or depressive phenomena. However, scales assessing manic symptoms showed highly significant differences with many more features of unrestrained behavior, elevated mood, hurried speech, and other typical features of mania in the patients who were switched from unilateral to bilateral ECT. Although there were no differences in prescribed drugs, the use of prn medications for sleep was greater in the experimental-switched patients than in controls. Patients who responded to unilateral ECT alone exhibited virtually no manic features, whereas those who demonstrated these characteristics failed to respond to unilateral ECT but benefited when switched to bilateral treatment.

Changes in neuropsychological test performance after electroconvulsive therapy.

A group of 231 psychiatric patients were evaluated (with the Wechsler Adult Intelligence Scale and the Halstead-Reitan Neuropsychological Test Battery) before and after electroconvulsive therapy. Improvement during the course of therapy was shown in 96% of the measures and significant improvement (p less than 0.05) occurred in 37.5% of the measures, indicating generally improved functioning. The performance of these patients on the pre-ECT testing was generally in the range characteristic of patients with documented brain damage, but the score improved during the course of treatment to the borderline normal level.

Follow-up of stereotaxic amygdalotomy for seizure and behavior disorders.

Stereotaxic amygdalotomy for the control of unmanageable behavior and/or intractable seizures is a controversial treatment approach with unknown risk-to-benefit ratios. Information about this subject was obtained from a retrospective follow-up study of 58 patients who received this form of treatment 1 to 11 years earlier (average 6 years). Assessments of the patients were made by invesgators external to the surgical treatment system, using structured psychiatric interviews, neuropsychological tests, and EEGs. In addition, global assessments were made, comparing pre- versus postoperative status. The objective data revealed no indication of worsening or damage with similar pre- and postoperative test scores and EEG features. Computer-scored interviews revealed considerable psychopathology in the ambulatory patients. Overall judgments of behavior, seizures, and functional levels indicated that more than a third of the group was probably improved, although the relationship of outcome to the surgery was indeterminate.

Role of editing in plant mitochondrial transfer RNAs.

Editing in plant mitochondria consists in C to U changes and mainly affects messenger RNAs, thus providing the correct genetic information for the biosynthesis of mitochondrial (mt) proteins. But editing can also affect some of the plant mt tRNAs encoded by the mt genome. In dicots, a C to U editing event corrects a C:A mismatch into a U:A base pair in the acceptor stem of mt tRNA(Phe) (GAA). In larch mitochondria, three C to U editing events restore U:A base pairs in the acceptor stem, D stem and anticodon stem, respectively, of mt tRNA(His) (GUG). For both these mt RNA(Phe) and tRNA(His), editing of the precursors is a prerequisite for their processing into mature tRNAs. In potato mt tRNA(Cys) (GCA), editing converts a C28:U42 mismatch in the anticodon stem into a U28:U42 non-canonical base pair, and reverse transcriptase minisequencing has shown that the mature mt tRNA(Cys) is fully edited. In the bryophyte Marchantia polymorpha this U residue is encoded in the mt genome and evolutionary studies suggest that restoration of a U28 residue is necessary when it is not encoded in the gene. However, in vitro studies have shown that neither processing of the precursor, nor aminoacylation of tRNA(Cys), requires C to U editing at this position. But sequencing of the purified mt tRNA(Cys) has shown that Psi is present at position 28, indicating that C to U editing is a prerequisite for the subsequent isomerization of U into Psi at position 28.

Potential dual targeting of an Arabidopsis archaebacterial-like histidyl-tRNA synthetase to mitochondria and chloroplasts.

A cDNA clone encoding a histidyl-tRNA synthetase (HisRS) was characterized from Arabidopsis thaliana. The deduced amino acid sequence (AtHRS1) is surprisingly more similar to HisRSs from archaebacteria than those from eukaryotes and prokaryotes. AtHRS1 has an N-terminal extension with features characteristic of mitochondrial and chloroplast transit peptides. Transient expression assays in tobacco protoplasts clearly demonstrated efficient targeting of a fusion peptide consisting of the first 71 amino acids of AtHRS1 joined to jellyfish green fluorescent protein (GFP) to both mitochondria and chloroplasts. These observations suggest that the AtHisRS1 cDNA encodes both mitochondrial and chloroplast histidyl-tRNA synthetases.

Editing and import: strategies for providing plant mitochondria with a complete set of functional transfer RNAs.

The recombinations and mutations that plant mitochondrial DNA has undergone during evolution have led to the inactivation or complete loss of a number of the 'native' transfer RNA genes deriving from the genome of the ancestral endosymbiont. Following sequence divergence in their genes, some native mitochondrial tRNAs are 'rescued' by editing, a post-transcriptional process which changes the RNA primary sequence. According to in vitro studies with the native mitochondrial tRNA(Phe) from potato and tRNA(His) from larch, editing is required for efficient processing. Some of the native tRNA genes which have been inactivated or lost have been replaced by tRNA genes present in plastid DNA sequences acquired by the mitochondrial genome during evolution, which raises the problem of the transcriptional regulation of tRNA genes in plant mitochondria. Finally, tRNAs for which no gene is present in the mitochondrial genome are imported from the cytosol. This process is highly specific for certain tRNAs, and it has been suggested that the cognate aminoacyl-tRNA synthetases may be responsible for this specificity. Indeed, a mutation which blocks recognition of the cytosolic Arabidopsis thaliana tRNA(Ala) by the corresponding alanyl-tRNA synthetase also prevents mitochondrial import of this tRNA in transgenic plants. Conversely, no significant mitochondrial co-import of the normally cytosol-specific tRNA(Asp) was detected in transgenic plants expressing the yeast cytosolic aspartyl-tRNA synthetase fused to a mitochondrial targeting sequence, suggesting that, although necessary, recognition by a cognate aminoacyl-tRNA synthetase might not be sufficient to allow tRNA import into plant mitochondria.