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Pierce’s disease is a deadly disease of grapevines caused by the bacterial pathogen Xylella fastidiosa (Xf). A Pierce’s disease resistance locus from Vitis arizonica/candicans b43-17 segregated as a single dominant gene and mapped as PdR1a and PdR1b in two F1 sibling selections. The physical mapping of the PdR1b allele allowed the identification of five ORFs of the Leucine-Rich Repeat Receptor Kinase gene family. Two ORFs: V.ari-RGA14 and V.ari-RGA18 were used to transform embryogenic callus of V. vinifera Chardonnay (CH) and Thompson Seedless (TS) and V. rupestris St George (SG) via Agrobacterium tumefaciens. Regenerated plants were inoculated with Xf under greenhouse conditions. Genetic transformation with RGA14 and 18 did not generate resistance in CH and TS, although some lines of CH showed significantly lower stem bacterial concentration and/or exhibited reduced symptoms. In transgenic SG14, improved regrowth was accompanied with lower bacterial titers and decreased pectin lyase and ß-1,3-glucanase 3 gene expression. The limited effects of the transgenes on PD resistance could be explained by the lack of suitable partners or the presence of susceptibility factors that could not be overcome under these experimental conditions. The involvement of RGA17 in b43-17 resistance to Xf should not be discarded.

Although bariatric surgery is the most effective treatment for obesity and weight-related comorbid diseases, utilization rates are disproportionately low among non-white patients. We sought to understand if variation in baseline characteristics or access to care exists between white and non-white patients.Using a statewide bariatric-specific data registry, we evaluated all patients who underwent bariatric surgery between 2006 and 2020 and completed a preoperative baseline questionnaire, which included a question about self-identification of race. Patient characteristics, co-morbidities, and time from initial preoperative clinic evaluation to date of surgery were compared among racial groups.A total of 73,141 patients met inclusion criteria with 18,741 (25.5%) self-identified as non-white. These included Black/African American (n = 11,904), Hispanic (n = 3448), Asian (n = 121), Native Hawaiian/Pacific Islander (n = 41), Middle Eastern (n = 164), Multiple (n = 2047) and other (n = 608). Non-white males were the least represented group, accounting for only 4% of all bariatric cases performed. Non-white patients were more likely to be younger (43.0 years vs. 46.6 years, p 0.0001), disabled (16% vs. 11.4%, p 0.0001) and have Medicaid (8.4% vs. 3.8%, p 0.0001) when compared to white patients, despite having higher rates of college education (78.0% vs. 76.6, p 0.0001). In addition, median time from initial evaluation to surgery was also longer among non-white patients (157 days vs. 127 days, p 0.0001), despite having higher rates of patients with a body mass index above 50 kg/mNon-white patients undergoing bariatric surgery represent an extremely diverse group of patients with more socioeconomic disadvantages and longer wait times when compared to white patients despite presenting with higher rates of severe obesity. Current guidelines and referral patterns for bariatric surgery may not be equitable and need further examination when considering the management of obesity within diverse populations to reduce disparities in care-of which non-white males are particularly at risk.

This is the first report evaluating the genetic diversity of Mexican grape species utilizing DNA-based markers to understand the distribution of grape species, and patterns of hybridization. The study utilized accessions maintained in three collections in Mexico, one in the USA and recently collected germplasm. Fifteen SSR markers were used to develop a fingerprint database to identify unique germplasm. Two different clustering analyses without prior population assignment, were used to identify groups that were verified by a Discriminant Analysis of Principal Components and a Principal Coordinate Analysis. Genetic diversity estimates were made across and within groups to validate the results obtained from the clustering analyses. Multiple clustering analyses and diversity parameters supported six genetic groups representing different geographic regions. The Northeastern group was the most diverse with a geographic range extending to Eastern and Central Mexico, while the Coahuila group was the least diverse. Vitis arizonica Engelm. and Vitis cinerea Engelm. ex Millardet were the most abundant species with many hybrid forms. We provide evidence that wild grape species in Mexico follow the physical barriers of mountain ranges like the Sierra Madre Oriental with an east–west divide and the Trans-Mexican Volcanic Belt as a corridor for gene flow among different grape species. Additional collections are required to fully understand the extent of hybridization and to clarify hybrid zones.

Microvascular haemodynamic alterations are associated with coronary artery disease (CAD). The conjunctival microcirculation can easily be assessed non-invasively. However, the microcirculation of the conjunctiva has not been previously explored in clinical algorithms aimed at identifying patients with CAD. This case–control study involved 66 patients with post-myocardial infarction and 66 gender-matched healthy controls. Haemodynamic properties of the conjunctival microcirculation were assessed with a validated iPhone and slit lamp-based imaging tool. Haemodynamic properties were extracted with semi-automated software and compared between groups. Biomarkers implicated in the development of CAD were assessed in combination with conjunctival microcirculatory parameters. The conjunctival blood vessel parameters and biomarkers were used to derive an algorithm to aid in the screening of patients for CAD. Conjunctival blood velocity measured in combination with the blood biomarkers (N-terminal pro-brain natriuretic peptide and adiponectin) had an area under receiver operator characteristic curve (AUROC) of 0.967, sensitivity 93.0%, specificity 91.5% for CAD. This study demonstrated that the novel algorithm which included a combination of conjunctival blood vessel haemodynamic properties, and blood-based biomarkers could be used as a potential screening tool for CAD and should be validated for potential utility in asymptomatic individuals.

The urgent need to scale up testing capacity during the COVID-19 pandemic has prompted the rapid development of point-of-care diagnostic tools such as lateral flow immunoassays (LFIA) for large-scale community-based rapid testing. However, studies of how the general public perform when using LFIA tests in different environmental settings are scarce. This user experience (UX) study of 264 participants in Northern Ireland aimed to gather a better understanding of how self-administered LFIA tests were performed by the general public at home. The UX performance was assessed via analysis of a post-test questionnaire including 30 polar questions and 11 7-point Likert scale questions, which covers the multidimensional aspects of UX in terms of ease of use, effectiveness, efficiency, accuracy and satisfaction. Results show that 96.6% of participants completed the test with an overall average UX score of 95.27% [95% confidence interval (CI) 92.71–97.83%], which suggests a good degree of user experience and effectiveness. Efficiency was assessed based on the use of physical resources and human support received, together with the mental effort of self-administering the test measured via NASA Task Load Index (TLX). The results for six TLX subscales show that the participants scored the test highest for mental demand and lowest for physical demand, but the average TLX score suggests that the general public have a relatively low level of mental workload when using LFIA self-testing at home. Five printed LFIA testing results (i.e. the ‘simulated’ results) were used as the ground truth to assess the participant’s performance in interpreting the test results. The overall agreement (accuracy) was 80.63% [95% CI 75.21–86.05%] with a Kappa score 0.67 [95% CI 0.58–0.75] indicating substantial agreement. The users scored lower in confidence when interpreting test results that were weak positive cases (due to the relatively low signal intensity in the test-line) compared to strong positive cases. The end-users also found that the kit was easier to use than they expected (p < 0.001) and 231 of 264 (87.5%) reported that the test kit would meet their requirements if they needed an antibody testing kit. The overall findings provide an insight into the opportunities for improving the design of self-administered SARS-CoV-2 antibody testing kits for the general public and to inform protocols for future UX studies of LFIA rapid test kits.

To date, 70 different TGFBI mutations that cause epithelial-stromal corneal dystrophies have been described. At present one commercially available test examines for the five most common of these mutations: R124H, R124C, R124L, R555W, and R555Q. To expand the capability of identifying the causative mutation in the remaining cases, 57 mutations would need to be added. The aim of this study was to obtain a better understanding of the worldwide distribution and population differences of TGFBI mutations and to assess which mutations could be included or excluded from any potential assay. A total of 184 published papers in Human Gene Mutation Database (HGMD) and PubMed from 34 countries worldwide reporting over 1600 corneal dystrophy cases were reviewed. Global data from 600,000 samples using the commercially available test were analyzed. Case studies by University College of London (UCL), Moorfield's Corneal Dystrophy Study data and 19 samples from patients with clinical abnormality or uncertainty for which the current test detected no mutation were used to predict an achievable detection rate. Data from the literature search showed no difference in the spectrum and frequency of each mutation in different populations or geographical locations. According to our analysis, an increase to the worldwide detection rate in all populations from 75 to 90% could be achieved by the addition of six mutations-H626R, A546D, H572R, G623D, R124S, and M502V-to the currently available test and that may be beneficial for LASIK pre-screening worldwide.

Lateral flow immunoassays are low cost, rapid and highly efficacious point-of-care devices, which have been used for SARS-CoV-2 antibody testing by professionals. However, there is a lack of understanding about how self-administered tests are used by the general public for mass testing in different environmental settings. The purpose of this study was to assess the user experience (UX) (including usability) of a self-testing kit to identify COVID-19 antibodies used by a representative sample of the public in their cars, which included 1544 participants in Northern Ireland. The results based on 5-point Likert ratings from a post-test questionnaire achieved an average UX score of 96.03% [95% confidence interval (CI) 95.05–97.01%], suggesting a good degree of user experience. The results of the Wilcoxon rank sum tests suggest that UX scores were independent of the user’s age and education level although the confidence in this conclusion could be strengthened by including more participants aged younger than 18 and those with only primary or secondary education. The agreement between the test result as interpreted by the participant and the researcher was 95.85% [95% CI 94.85–96.85%], Kappa score 0.75 [95% CI 0.69–0.81] (indicating substantial agreement). Text analysis via the latent Dirichlet allocation model for the free text responses in the survey suggest that the user experience could be improved for blood-sample collection, by modifying the method of sample transfer to the test device and giving clearer instructions on how to interpret the test results. The overall findings provide an insight into the opportunities for improving the design of SARS-CoV-2 antibody testing kits to be used by the general public and therefore inform protocols for future user experience studies of point-of-care tests.

Emissions of CO2 from the EU can be estimated using different system boundaries, depending on the policy question. We analyze and compare the trends in territorial emissions (1990–2016) and consumption-based emissions and emissions embodied in trade (1990–2014). We find the Global Financial Crisis (GFC) in 2008 was an important turning point. Territorial emissions were roughly stable in the years before the GFC but have since declined. Consumption-based emissions rose from 2000 to the GFC but then declined in concert with territorial emissions. A Kaya identity decomposition suggests that the main factor pushing the EU’s territorial emissions up before the GFC was a growth in GDP, balanced by constant improvements in energy and carbon intensity. The large increase in consumption-based emissions up to the GFC was mainly due to emissions from the production of imported manufactured goods, particularly from China. After the GFC, the Kaya identity decomposition suggests that lower GDP growth facilitated a sustained decrease in territorial emissions. The decline in consumption-based emissions since the GFC was partly due to decreasing territorial emissions but accelerated due to a decrease in the emissions from the production of imported products from China. Preliminary data indicates that EU CO2 emissions have increased from 2014 to 2017, with the Kaya identity decomposition suggesting the increase is due to a return to stronger GDP growth.

Background Vegetatively propagated clones accumulate somatic mutations. The purpose of this study was to better appreciate clone diversity and involved defining the nature of somatic mutations throughout the genome. Fifteen Zinfandel winegrape clone genomes were sequenced and compared to one another using a highly contiguous genome reference produced from one of the clones, Zinfandel 03. Results Though most heterozygous variants were shared, somatic mutations accumulated in individual and subsets of clones. Overall, heterozygous mutations were most frequent in intergenic space and more frequent in introns than exons. A significantly larger percentage of CpG, CHG, and CHH sites in repetitive intergenic space experienced transition mutations than in genic and non-repetitive intergenic spaces, likely because of higher levels of methylation in the region and because methylated cytosines often spontaneously deaminate. Of the minority of mutations that occurred in exons, larger proportions of these were putatively deleterious when they occurred in relatively few clones. Conclusions These data support three major conclusions. First, repetitive intergenic space is a major driver of clone genome diversification. Second, clones accumulate putatively deleterious mutations. Third, the data suggest selection against deleterious variants in coding regions or some mechanism by which mutations are less frequent in coding than noncoding regions of the genome.

This paper presents interrelated indicators for tracking progress towards the Paris Agreement. Findings show broad consistency with keeping warming below 2 °C, but technological advances are needed to achieve net-zero emissions. Current emission pledges to the Paris Agreement appear insufficient to hold the global average temperature increase to well below 2 °C above pre-industrial levels1. Yet, details are missing on how to track progress towards the ‘Paris goal’, inform the five-yearly ‘global stocktake’, and increase the ambition of Nationally Determined Contributions (NDCs). We develop a nested structure of key indicators to track progress through time. Global emissions2,3 track aggregated progress1, country-level decompositions track emerging trends4,5,6 that link directly to NDCs7, and technology diffusion8,9,10 indicates future reductions. We find the recent slowdown in global emissions growth11 is due to reduced growth in coal use since 2011, primarily in China and secondarily in the United States12. The slowdown is projected to continue in 2016, with global CO2 emissions from fossil fuels and industry similar to the 2015 level of 36 GtCO2. Explosive and policy-driven growth in wind and solar has contributed to the global emissions slowdown, but has been less important than economic factors and energy efficiency. We show that many key indicators are currently broadly consistent with emission scenarios that keep temperatures below 2 °C, but the continued lack of large-scale carbon capture and storage13 threatens 2030 targets and the longer-term Paris ambition of net-zero emissions.

Downy mildew is a highly destructive disease in grapevine production. A gene encoding pathogenesis-related (PR) thaumatin-like protein was isolated from the downy mildew-resistant grapevine "Zuoshan-1," a clonal selection from wild Vitis amurensis Rupr. The predicted thaumatin-like protein (VaTLP) has 225 amino acids and it is acidic, with a calculated isoelectric point of 4.8. The full length of the VaTLP gene was transformed into somatic embryogenic calli of V. vinifera 'Thompson Seedless' via Agrobacterium tumefaciens. Real-time RT-PCR confirmed that the VaTLP gene was expressed at a high level in the transgenic grapevines. Improved resistance of the transgenic lines against downy mildew was evaluated using leaf disks and whole plants inoculated with Plasmopara viticola, the pathogen causing grapevine downy mildew disease. Bioassay of the pathogen showed that both hyphae growth and asexual reproduction were inhibited significantly among the transgenic plants. Histological analysis also confirmed this disease resistance by demonstrating the inhibition and malformation of hyphae development in leaf tissue of the transgenic plants. These results indicated that the accumulation of VaTLP could enhance resistance to P. viticola in transgenic 'Thompson Seedless' grapevines.

A protocol was standardized to regenerate six grape cultivars through meristematic bulk (MB) induction, which was used for genetic transformation. Meristematic bulk induction worked best with Vitis vinifera ‘Thompson Seedless’ (98.4 %), followed by ‘Chardonnay’ (97.6 %), ‘Redglobe’ (90.2 %) and ‘Cabernet Sauvignon’ (86.2 %), and was less successful with Vitis rupestris ‘St. George’ (85.4 %) and ‘101-14 Millardet et de Grasset (Vitis riparia × V. rupestris)’ (79.6 %). Benzylaminopurine and naphthaleneacetic acid was the most effective combination of cytokinin and auxin for MB formation. 100 µg/ml kanamycin was a better antibiotic selection agent than 2.0 µg/ml hygromycin during transformation. The expression of green fluorescent protein was evaluated with in vitro leaves and roots. Transformation efficiency using meristematic slices was a function of the genotype. Transformation efficiency was greatest in Chardonnay (51.7 %), followed by Thompson Seedless (42.3 %), St. George (41.6 %), Redglobe (40 %), Cabernet Sauvignon (35.6 %) and 101-14 Mgt (29.9 %). This study found that MB induction was a fast and simple alternative for genetic transformation of grape cultivars.

Chinese coal consumption dropped 2.9% in 2014 according to preliminary official statistics1 released in 2015. This was hailed as historic after China’s meteoric growth in the 2000s2. The International Energy Agency used it to estimate ~1.5% reduction in Chinese fossil CO2 emissions for 20143, and an unprecedented 0.2% reduction in global emissions4. Similar preliminary coal consumption statistics are announced every year, and will be watched closely after China’s recent slowdown in emissions growth and pledge to peak emissions in 2030 or earlier. However, Chinese energy statistics are frequently revised and often contain large anomalies5, 6, implying high uncertainty. For example, BP used different Chinese data to estimate a 0.9% increase in 2014 CO2 emissions7, 8. Here, we analyse these preliminary announcements, with an approach that can be used to assess the robustness of similar future announcements. We show that the preliminary 2.9% reduction in coal consumption is inappropriate for estimating CO2 emissions, that coal-derived energy consumption stayed flat but is likely to have decreased in 2015, and that Chinese fossil CO2 emissions probably increased ~0.8% in 2014. We also analyse recent revisions of official energy statistics, and find that they imply 925 MtCO2 (11.2%) higher emissions for 2013, and 7.6 GtCO2 (9.2%) higher total emissions for 2000–2013.

Background The mountainous region between the Caucasus and China is considered to be the center of domestication for grapevine. Despite the importance of Central Asia in the history of grape growing, information about the extent and distribution of grape genetic variation in this region is limited in comparison to wild and cultivated grapevines from around the Mediterranean basin. The principal goal of this work was to survey the genetic diversity and relationships among wild and cultivated grape germplasm from the Caucasus, Central Asia, and the Mediterranean basin collectively to understand gene flow, possible domestication events and adaptive introgression. Results A total of 1378 wild and cultivated grapevines collected around the Mediterranean basin and from Central Asia were tested with a set of 20 nuclear SSR markers. Genetic data were analyzed (Cluster analysis, Principal Coordinate Analysis and STRUCTURE) to identify groups, and the results were validated by Nei’s genetic distance, pairwise FST analysis and assignment tests. All of these analyses identified three genetic groups: G1, wild accessions from Croatia, France, Italy and Spain; G2, wild accessions from Armenia, Azerbaijan and Georgia; and G3, cultivars from Spain, France, Italy, Georgia, Iran, Pakistan and Turkmenistan, which included a small group of wild accessions from Georgia and Croatia. Wild accessions from Georgia clustered with cultivated grape from the same area (proles pontica), but also with Western Europe (proles occidentalis), supporting Georgia as the ancient center of grapevine domestication. In addition, cluster analysis indicated that Western European wild grapes grouped with cultivated grapes from the same area, suggesting that the cultivated proles occidentalis contributed more to the early development of wine grapes than the wild vines from Eastern Europe. Conclusions The analysis of genetic relationships among the tested genotypes provided evidence of genetic relationships between wild and cultivated accessions in the Mediterranean basin and Central Asia. The genetic structure indicated a considerable amount of gene flow, which limited the differentiation between the two subspecies. The results also indicated that grapes with mixed ancestry occur in the regions where wild grapevines were domesticated. Electronic supplementary material The online version of this article (10.1186/s12870-018-1351-0) contains supplementary material, which is available to authorized users.

A protocol for in vitro induction of tetraploids of the grape rootstock 101-14 Millardet et de Grasset (Vitis riparia × V. rupestris) (101-14 Mgt) (2n = 2x = 38) × Muscadinia rotundifolia cv. Trayshed (2n = 2x = 40) hybrids was established. Different explant materials were exposed to the antimitotic chemical agents colchicine and oryzalin, at three concentrations, for 24, 48 and 72 h. Treated in vitro shoot tips, anthers and pre-embryogenic cultures were regenerated, and their ploidy levels were confirmed by chromosome counts and flow cytometry. It is generally considered that anatomical characteristics of leaves, including leaf stomatal size and number of chloroplasts in guard cells, correlate with ploidy levels of grape plants. Chromosome counts and flow cytometry are labor intensive and difficult, while the number of chloroplasts in stomatal guard cells and stomatal size are easily measured and can be stable and reliable markers. Analysis of stomata revealed clear differences between regenerated diploid and tetraploid plants, and these measurements were used as a preliminary screen, followed by chromosome counts and flow cytometry for confirmation. This study presents the results obtained by various combinations of explants, antimitotic agents, exposure time, concentration and ploidy analysis to evaluate in vitro chromosome doubling. These results provide an easy and effective method for production of tetraploid, potentially fertile Vitis × Muscadinia hybrids for utilization in rootstock breeding programs.

Climate policy is generally concerned with the mitigation of well-mixed greenhouse gases, allocated to the country where the emissions occur, and with different emissions weighted together with the Global Warming Potential (GWP) using a 100 year time horizon. This perspective is not unique. Recent research has considered the inclusion of Short-Lived Climate Forcers (SCLFs), allocated emissions to the consumption of goods and services, and used alternative emissions metrics. Here, for the first time, we combine these alternative perspectives to explore the potential policy implications of three alternative framings: 1) using the Global Temperature change Potential (GTP) to directly link current emissions to temperature change, 2) including SLCFs that have both warming and cooling effects on climate, and 3) allocating emissions to consuming sectors and regions. Collectively, we use these three aspects to allocate the future temperature response to the consumption of goods and services in a given year. We show, in order of importance, that the method of allocating emissions to economic sectors is the most important, followed by the emission metric (including time-horizon), and then the mix of short-lived and well-mixed climate forcers. The consumption perspective reallocates emissions from electricity and manufacturing to service sectors, which suggests different policy options for demand and supply. The net effect of multiple pollutants and GTP significantly change the importance of the sectors compared to when only considering CO2 or when using the GWP. We argue that a focus on only one accounting system and framing in climate policy can potentially limit consideration of mitigation options to a reduced set of activities, and thereby missing significant opportunities for mitigation in other aspects.

Cities are becoming increasingly important in combatting climate change, but their overall role in global solution pathways remains unclear. Here we suggest structuring urban climate solutions along the use of existing and newly built infrastructures, providing estimates of the mitigation potential.

CRISPR/Cas9 holds immense potential to treat a range of genetic disorders. Allele-specific gene disruption induced by non-homologous end-joining (NHEJ) DNA repair offers a potential treatment option for autosomal dominant disease. Here, we successfully delivered a plasmid encoding S. pyogenes Cas9 and sgRNA to the corneal epithelium by intrastromal injection and acheived long-term knockdown of a corneal epithelial reporter gene, demonstrating gene disruption via NHEJ in vivo. In addition, we used TGFBI corneal dystrophies as a model of autosomal dominant disease to assess the use of CRISPR/Cas9 in two allele-specific systems, comparing cleavage using a SNP-derived PAM to a guide specific approach. In vitro, cleavage via a SNP-derived PAM was found to confer stringent allele-specific cleavage, while a guide-specific approach lacked the ability to distinguish between the wild-type and mutant alleles. The failings of the guide-specific approach highlights the necessity for meticulous guide design and assessment, as various degrees of allele-specificity are achieved depending on the guide sequence employed. A major concern for the use of CRISPR/Cas9 is its tendency to cleave DNA non-specifically at “off-target” sites. Confirmation that S. pyogenes Cas9 lacks the specificity to discriminate between alleles differing by a single base-pair regardless of the position in the guide is demonstrated.

Human disturbance, natural environmental conditions and seed dispersal are often inferred as important drivers of plant community richness and diversity in wetland ecosystems. However, plant functional groups within a plant community have different environmental requirements and may respond differently to human disturbance. Therefore, the understanding of the relative importance of these variables in determining community and functional groups richness and diversity is important for improved management and wise use of wetland resources. We collected data on vegetation and environmental conditions, human disturbance and seed dispersal from 60 plots of 20 × 50 m, to identify variables that potentially affect total species richness and Shannon-Wiener diversity of the grassland plant community at the Kilombero Valley wetland, Tanzania. We further tested whether important predictor variables for species richness and Shannon-Wiener diversity differ among graminoid, forb and shrub functional groups. Overall, our results suggest that environmental conditions, human disturbance and seed dispersal determine spatial variation in species richness and Shannon-Wiener diversity of the grassland vegetation. The total richness and Shannon-Wiener diversity and the richness of shrubs decreased with distance from the Kilombero River, whereas the total Shannon-Wiener diversity and the Shannon-Wiener diversity of graminoids decreased with the increase in grazing intensity. Shrub species richness was related to the spatial position of plots and decreased with total organic carbon of soil. Current increase in human disturbances through cattle husbandry and changes in natural environmental conditions (e.g. through water diversion and drainage) should be discouraged in order to restore and sustain biodiversity of the Kilombero wetland.

Psychoanalysis, in Freud’s day and our own, has met with and continues to meet with staunch opposition from critics. The most ruinous criticism comes from philosophers, with a special interest in science, who claim psychoanalysis does not measure up to the above-board canons of acceptable scientific practices and, thus, is not scientific. It is common today to direct such criticisms to all metempirical forms of psychotherapy—i.e., psychotherapies that in no way concern themselves with grounding their claims with empirical research. The most common defense is to cold-shoulder the criticism and counter that psychoanalysis, whether or not Freud recognized it, is a hermeneutical, not an etiological, method of therapy. In that regard, its measure of success is not symptom-removal or redirection of drive-energy in socially condoned or acceptable ways, but broadened understanding through a commonly created myth, effected by therapist and patient, for the patient’s wellbeing. In this undertaking, I argue that the hermeneutical apologia of psychoanalysis is a dodge, not a defense—an impenetrable asylum in which therapists can find refuge by buffering themselves from the possibility of criticism of the scientificity of their discipline. Because hermeneuticism disavows the possibility of knowledge in any meaningful sense—and, with that, scientific knowledge gained through observation or experimentation—it levels the epistemological playing field. With knowledge impossible and science annulled, no “investigative” inquiry or discipline can claim a status superior to any other and, hence, psychotherapy is an investigative discipline as legitimate as any other. The literature on the hermeneutic defence of psychotherapy is vast—too vast for anything but a representative sample of it in this critique. I focus merely on some of the most recent literature.

The main objective of this paper (the second of two parts) is to show that quasioperators can be dealt with smoothly in the topological duality established in Part I. A quasioperator is an operation on a lattice that either is join preserving and meet reversing in each argument or is meet preserving and join reversing in each argument. The paper discusses several common examples, including orthocomplementation on the closed subspaces of a fixed Hilbert space (sending meets to joins), modal operators ◊ and □ on a bounded modal lattice (preserving joins, resp. meets), residuation on a bounded residuated lattice (sending joins to meets in the first argument and meets to meets in the second). This paper introduces a refinement of the topological duality of Part I that makes explicit the topological distinction between the duals of meet homomorphisms and of join homomorphisms. As a result, quasioperators can be represented by certain continuous maps on the topological duals.

The two main objectives of this paper are (a) to prove purely topological duality theorems for semilattices and bounded lattices, and (b) to show that the topological duality from (a) provides a construction of canonical extensions of bounded lattices. In previously known dualities for semilattices and bounded lattices, the dual spaces are compact 0-dimensional spaces with additional algebraic structure. For example, semilattices are dual to 0-dimensional compact semilattices. Here we establish dual categories in which the spaces are characterized purely in topological terms, with no additional algebraic structure. Thus the results can be seen as generalizing Stone’s duality for distributive lattices rather than Priestley’s. The paper is the first of two parts. The main objective of the sequel is to establish a characterization of lattice expansions, i.e., lattices with additional operations, in the topological setting built in this paper.

Plants have an intriguing tripartite genetic system: Nuclear genome × Mitochondria × Plastids and their interactions may impact germplasm breeding. In grapevine, the study of cytoplasmic genomes has been limited, and their role with respect to grapevine germplasm diversity has yet to be elucidated. In the present study, the results of an analysis of the cytoplasmic diversity among 6073 individuals (comprising cultivars, interspecific hybrids and segregating progenies) are presented. Genotyping by sequencing (GBS) was used to elucidate plastid and mitochondrial DNA sequences, and results were analyzed using multivariate techniques. Single nucleotide polymorphism (SNP) effects were annotated in reference to plastid and mitochondrial genome sequences. The cytoplasmic diversity identified was structured according to synthetic domestication groups (wine and raisin/table grape types) and interspecific-hybridization-driven groups with introgression from North American Vitis species, identifying five cytoplasmic groups and four major clusters. Fifty-two SNP markers were used to describe the diversity of the germplasm. Ten organelle genes showed distinct SNP annotations and effect predictions, of which six were chloroplast-derived and three were mitochondrial genes, in addition to one mitochondrial SNP affecting a nonannotated open reading frame. The results suggest that the application of GBS will aid in the study of cytoplasmic genomes in grapevine, which will enable further studies on the role of cytoplasmic genomes in grapevine germplasm, and then allow the exploitation of these sources of diversity in breeding.

Plato noticed a sizeable problem apropos of establishing his republic—that there was always a ready pool of zealous potential rulers, lying in wait for a suitable opportunity to rule on their own tyrannical terms. He also recognized that those persons best suited to rule, those persons with foursquare and unimpeachable virtue, would be least motivated to govern. Ruling a polis meant that those persons, fully educated and in complete realization that the most complete happiness comprises solitary study of things unchanging, would have to compromise their happiness for the wellbeing of their polis and of the people in it. Plato’s solution, in effect that the aristoi would merely recognize their duty to sacrifice personal happiness for the happiness of the polis, has perplexed and continues today to perplex scholars. Like Plato, Jefferson recognized that there was always a pool of eager sharks, ready to govern. His republicanism, comprising a ward system and general education, was founded on the fullest participation of its citizenry, suitably educated and a governing aristoi. The true aristoi, the “natural aristoi”, are the intelligent and virtuous and that government is best which allows for a “pure selection” of the natural aristoi into the governing offices. Nonetheless, as Jefferson’s own life shows, non-parochial governing meant being rent from domestic tranquility, being forced to leave behind one’s personal affairs to decay, and being tossed willy-nilly into the coliseum of nonstop political wrangling. Why would anyone, particularly one wanting to be happy, wish to govern? Thus, Jefferson faced the same problem that Plato faced. How could a state be structured so that the wisest and most virtuous would be motivated to rule? In this paper, I argue that Jefferson, in full recognition of the problem of encouraging the most intelligent and virtuous to govern, the problem of public service, offers a solution that is remarkably Platonic.

Understanding driving factors of spatial heterogeneity in plant species composition and functional structure is a key step towards wetland ecosystems restoration and biodiversity conservation. We surveyed 60 randomly selected plots of 20 × 50 m each and collected 12 explanatory variables to understand potential impacts of natural environmental conditions, human disturbance and spatial position of plots variables on plant functional groups (PFGs) and species composition within grasslands of the Kilombero Valley Floodplain wetland, Tanzania. Ordination analyses were used to identify important vegetation gradients and establish significant natural environmental conditions, human disturbance and spatial position of plots correlates. Partial redundancy analysis (RDA) and partial canonical correspondence analysis (CCA) were used to determine the individual and shared effects of these three sets of explanatory variables on the PFGs and species composition, respectively. In total, 115 plant species, including 22 weed and 3 invasive species, and five PFGs were registered. Annual graminoid was the most abundant, whereas perennial forb the least abundant PFG with 50 and 1 % relative covers, respectively. Overall, spatial position, altitude, total organic carbon, cow dung, distance to the river and distance to kraal (cattle enclosure near human settlement commonly made of wood materials for animal protection) were important descriptors of both PFGs and overall species composition. Separate CCA of only weed and invasive plant species showed that some species, particularly the invasive Polygala paniculata were strongly associated with cow dung, indicating that present increase in cattle numbers may result in future problems associated with this species. Intensification of human activities and alteration of natural environmental conditions associated with these factors should be discouraged to maintain plant species composition and functional structure for wetland restoration and sustainable biodiversity conservation.

Introduction: The acute onset of flashes and floaters is a common presentation to the emergency department (ED). The most emergent etiology is retinal detachment (RD), which requires prompt ophthalmologic assessment. Previous studies of point of care ultrasound (POCUS) have reported high sensitivity and specificity for RD, but are limited by small sample size, use of highly trained and experienced sonographers, and referral bias. Our primary objective was to assess the test characteristics of POCUS performed by a large heterogeneous group of emergency physicians (EPs) for the diagnosis of RD. Methods: This was a prospective diagnostic test assessment of POCUS performed by EPs with varying ultrasound experience on a convenience sample of ED patients presenting with the complaint of flashes or floaters in one or both eyes. Participating EPs completed a one hour didactic lecture and were expected to demonstrate appropriate performance of one practice scan before enrolling patients. After standard ED assessment, patients underwent an ocular POCUS scan targeted to detect RD. EPs recorded the presence or absence of RD on the data collection instrument based on their POCUS scan. After completing their ED visit, all patients were assessed by a retina specialist who was blinded to the results of the POCUS scan. We calculated sensitivity and specificity with associated exact binomial confidence intervals (CI) using the retina specialist’s determination of the final diagnosis as the criterion standard. Results: A total of 30 EPs, consisting of 21 staff physicians and 9 residents, participated in this study. These EPs performed a total of 128 POCUS scans. Of these scans, 13 were excluded. Of the remaining 115 enrolled patients, median age was 60 years, and 64% were female. The retina specialist diagnosed RD in 16 (14%) cases. The sensitivity and specificity of POCUS for detecting RD was 75% (95% CI 48% to 93%) and 94% (95% CI 87% to 98%), respectively. The positive likelihood ratio was 12.4 (95% CI 5.4 to 28.3), and negative likelihood ratio was 0.27 (95% CI 0.11 to 0.62). Conclusion: In a heterogeneous group of EPs with varying ultrasound experience, POCUS demonstrates high specificity but only intermediate sensitivity for the detection of RD. A negative POCUS scan is not sufficiently sensitive to rule out RD in a patient with new onset flashes or floaters.

Managerial derailment, which includes failure in the form organizational exit, poses costly consequences for organizations. We investigated the relationship between dysfunctional interpersonal tendencies, derailment potential behaviors, and actual managerial derailment in the form of voluntary and involuntary turnover. Data were from an archival database of high-level managers working for a global retail organization, including self-report interpersonal tendencies, 360-degree feedback data, and personnel history (N = 1,796). Managers who exhibit the dysfunctional interpersonal tendencies associated with “moving against people” were more likely to enact derailment potential behaviors. As a result, these managers were more likely to be fired or quit. This study advances our understanding of the managerial derailment process by providing evidence of the positive relationship between derailment potential behaviors and both voluntary and involuntary turnover as well as the potential for “moving against” people to result in derailment. Our results may help to inform the selection, promotion, and training strategies employed by practitioners and potentially reduce the costs associated with losing high-potential executives. This is one of the first studies to provide evidence of the relationship between derailment potential behaviors and turnover, and in a rarely obtained sample of high-level managers. Additionally, derailment potential ratings were collected before managers’ exit from the organization, thus helping to overcome retrospective bias evident in prior studies; managers who ultimately derail were perceived as having exhibited behaviors consistent with the potential to derail before organizational exit.

Scholars today are divided on the motivation behind what is often called Jefferson’s “moral agrarianism”. On the one hand, some scholars take Jefferson at his word when he mentions that agrarianism is a moral vision. For these individuals, Jefferson’s agrarianism is a moral vision and an indispensible part of the good life. On the other hand, other scholars maintain that Jefferson’s moral agrarianism is merely a bit of propaganda that insidiously sheaths a political or economic ideal. For them, Jefferson is through and throughout a politician, and expressions of agrarianism as a moral ideal amount to mere cant. In this paper, I examine arguments for and against Jefferson’s moral agrarianism. I defend the position that Jefferson was an aboveboard moral agrarianist and that the ideal of agrarianism was not just one that was suited for Americans, given their surfeit of land and want of laborers, but an ideal that also applied universally. I end with thoughts on Jefferson’s recognition of the rise of manufacturing in American cities throughout his life.

This paper is a comprehensive investigation of Freud’s views on technology and human well-being, with a focus on ‘Civilization and Its Discontents’. In spite of his thesis in ‘Civilization and Its Discontents’, I shall argue that Freud, always in some measure under the influence of Comtean progressivism, was consistently a meliorist: He was always at least guardedly optimistic about the realizable prospect of utopia, under the ‘soft dictatorship’ of reason and guided by advances in science and technology, in spite of due recognition in his later years of the possibility of annihilation through technological advances in warfare. The possibility of human annihilation, then, muffled Freud’s meliorism. Freud’s ‘muffled meliorism’, however, was not a quiet commitment to viewing technology as something good. Ultimately, Freud steered a middle course between techno-advocacy and techno-antagonism. The technologies of science, like the discoveries of psychoanalysis, were tools for humans that could be used for human betterment or, as war showed, for human degeneration.

Familial benign hypocalciuric hypercalcaemia (FBHH) is a genetically heterogeneous disorder that consists of three designated types, FBHH1, FBHH2 and FBHH3, whose chromosomal locations are 3q21.1, 19p and 19q13, respectively. FBHH1 is caused by mutations of a calcium-sensing receptor (CaSR), but the abnormalities underlying FBHH2 and FBHH3 are unknown. FBHH3, also referred to as the Oklahoma variant (FBHH(Ok)), has been mapped to a 12cM interval, flanked by D19S908 and D19S866. To refine the location of FBHH3, we pursued linkage studies using 24 polymorphic loci. Our results establish a linkage between FBHH3 and 17 of these loci, and indicate that FBHH3 is located in a 4.1 Mb region flanked centromerically by D19S112 and telomerically by rs245111, which in the syntenic region on mouse chromosome 7 contains four Casr-related sequences (Gprc2a-rss). However, human homologues of these Gprc2a-rss were not found and a comparative analysis of the 22.0 Mb human and 39.3 Mb mouse syntenic regions showed evolutionary conservation of two segments that were inverted with loss from the human genome of 11.6 Mb that contained the four Gprc2a-rss. Thus, FBHH3 cannot be attributed to Gprc2a-rss abnormalities. DNA sequence analysis of 12 other genes from the interval that were expressed in the parathyroids and/or kidneys did not detect any abnormalities, thereby indicating that these genes are unlikely to be the cause of FBHH3. The results of this study have refined the map location of FBHH3, which will facilitate the identification of another CaSR or a mediator of calcium homeostasis.

Pierce’s disease (PD) of grapevines is caused by the xylem-limited bacterium Xylella fastidiosa (Xf). All Vitis vinifera-based cultivars are susceptible to Xf infection; however, many grape species from the southern United States (such as V. arizonica, V. shuttleworthii, V. simpsonii, V. smalliana, and Muscadinia rotundifolia) are resistant. In this study, the effects of xylem sap from PD-resistant and PD-susceptible grapes, as well as several free cell wall constituents, on in vitro bacterial growth, biofilm formation, and cellular aggregation were investigated. Media containing xylem sap from PD-susceptible plants provided better support for bacterial growth and biofilm formation than media supplemented with xylem sap from PD-resistant plants. Culturing Xf on media containing various purified cell wall constituents demonstrated that CM-cellulose, xylan, β-D-glucan, k-carrageenan, cello-oligosaccharide and laminarin promoted bacterial growth whereas lichenan suppressed growth. However, only laminarin, xylan, and k-carrageenan promoted biofilm formation in vitro. Lichenan, oligosaccharide, k-carrageenan, laminarin, xylan and β-D-glucan all significantly decreased Xf cellular aggregation in vitro. This study suggests that differences in xylem sap composition and cell wall properties among PD-resistant and PD-susceptible grapes may affect characteristics of Xf growth, biofilm formation and cellular aggregation involved in pathogenesis.

Recombination rate data are presented for three populations of grape based on framework genetic linkage maps developed with simple-sequence repeat markers. These linkage maps were constructed from different Vitis species and represent three genetic backgrounds. The first population is pure Vitis vinifera, derived from a cross of the European cultivars Riesling and Cabernet Sauvignon. The second is an interspecific cross between two commercially used rootstock cultivars of different North American Vitis species parentage, Ramsey (Vitis champinii) and Riparia Gloire (Vitis riparia). The third population, D8909-15 (Vitis rupestris × (Vitis arizonica/Vitis girdiana form)) × F8909-17 (V. rupestris × (V. arizonica/Vitis candicans form)), is an F1 from two half-sibs. Genome-wide and chromosome-wide recombination rates varied across the three populations and among the six Vitis parents. Global recombination rates in the parents of the third F1 population, with a complex Vitis background, were significantly reduced. In the first and third populations, the recombination rate was significantly greater in the male parent. Specific genome locations with frequent heterogeneity in recombination were identified, suggesting that recombination rates are not equal across the Vitis genome. The identification of regions with suppressed or high recombination will aid grape breeders and geneticists who rely on recombination events to introgress disease resistance genes from the genomes of wild Vitis species, develop fine-scale genetic maps, and clone disease resistance genes.

Primary hyperparathyroidism is hereditary in 10% of patients. This article describes a patient with familial isolated hyperparathyroidism (FIHP) caused by a novel MEN1 missense mutation. The genetics, differential diagnosis and management of hereditary hyperparathyroidism are illustrated. Background Familial isolated primary hyperparathyroidism (FIHP) is an autosomal dominant disorder that can represent an early stage of either the multiple endocrine neoplasia type 1 (MEN1) or hyperparathyroidism-jaw tumor (HPT-JT) syndromes; alternatively, the condition can be caused by an allelic variant of MEN1 or HRPT2 (hyperparathyroidism 2 gene), or caused by a distinct entity involving another locus. We have explored these possibilities in a patient with primary hyperparathyroidism, whose mother had a history of renal calculi and primary hyperparathyroidism. Investigations Serum biochemistry and radiological investigations for primary hyperparathyroidism, MEN1 and HPT-JT, and genetic testing for MEN1 and HRPT2 mutations were undertaken. Diagnosis FIHP with primary hyperparathyroidism as the sole endocrinopathy due to a previously unreported heterozygous missense germline MEN1 mutation, Tyr351Asn. In addition, another unreported heterozygous missense germline MEN1 mutation, Trp220Leu, was identified in an unrelated male patient with FIHP, whose mother and sister also had primary hyperparathyroidism. DNA from a parathyroid tumor from the sister revealed a loss of heterozygosity in which the mutant allele was retained. This is consistent with Knudson's 'two-hit' model of hereditary cancer and a tumor suppressor role for MEN1 in FIHP. Management The patient underwent parathyroidectomy and has remained normocalcemic over a follow-up period of 6 years. The other four patients have remained normocalcemic for a follow-up period of 4–15 years following parathyroidectomy. None has developed abnormalities of the MEN1 syndrome, providing further support that FIHP is a distinct genetic variant of the MEN1 syndrome.

Relationships were examined between variability in tropical Atlantic sea level and major climate indices with the use of TOPEX/POSEIDON altimeter and island tide gauge data with the aim of learning more about the external influences on the variability of the tropical Atlantic ocean. Possible important connections were found between indices related to the El Nino–Southern Oscillation (ENSO) and the sea levels in all three tropical regions (north, equatorial, and south), although the existence of only one major ENSO event within the decade of available altimetry means that a more complete investigation of the ENSO-dependence of Atlantic sea level changes has to await for the compilation of longer data sets. An additional link was found with the Indian Ocean Dipole (IOD) in the equatorial region, this perhaps surprising observation is probably an artifact of the similarity between IOD and ENSO time series in the 1990s. No evidence was obtained for significant correlations between tropical Atlantic sea level and North Atlantic Oscillation or Antarctic Oscillation Index. The most intriguing relationship observed was between the Quasi-Biennial Oscillation and sea level in a band centered approximately on 10°S. A plausible explanation for the relationship is lacking, but possibilities for further research are suggested.

Soil N2O emissions were measured during four seasons from two highly productive grass-clover dairy pastures to assess the influences of soil moisture, temperature, availability of N (NH 4 + and NO 3 – ) and soluble C on N2O emissions, and to use the emission data to validate and refine a simulation model (DNDC). The soils at these pasture sites (Karapoti fine sandy loam, and Tokomaru silt loam) differed in texture and drainage characteristics. Emission peaks for N2O coincided with rainfall events and high soil moisture content. Large inherent variations in N2O fluxes were observed throughout the year in both the ungrazed (control) and grazed pastures. Fluxes averaged 4.3 and 5.0 g N2O/ha/day for the two ungrazed sites. The N2O fluxes from the grazed sites were much higher than for the ungrazed sites, averaging 26.4 g N2O/ha/day for the fine sandy loam soil, and 32.0 g N2O/ha/day for the silt loam soil. Our results showed that excretal and fertiliser-N input, and water-filled pore space (WFPS) were the variables that most strongly regulated N2O fluxes. The DNDC model was modified to include the effects of day length on pasture growth, and of excretal-N inputs from grazing animals; the value of the WFPS threshold was also modified. The modified model ‘NZ-DNDC’ simulated effectively most of the WFPS and N2O emission pulses and trends from both the ungrazed and grazed pastures. The modified model fairly reproduced the real variability in underlying processes regulating N2O emissions and could be suitable for simulating N2O emissions from a range of New Zealand grazed pastures. The NZ-DNDC estimates of total yearly emissions of N2O from the grazed and ungrazed sites of both farms were within the uncertainty range of the measured emissions. The measured emissions changed with changes in soil moisture resulting from rainfall and were about 20% higher in the poorly drained silt loam soil than in the well-drained sandy loam soil. The model accounts for these climatic variations in rainfall, and was also able to pick up differences in emissions resulting from differences in soil texture.

The process of translating the Short-Form Headache Impact Test (HIT-6) in 27 countries and the comparability of the content of the translations is discussed. HIT-6 translations were developed using a standard forward–backward translation process, including a cognitive debriefing step and international harmonization of the translations. Prior to translating the HIT-6, modifications were made to the English-language source form, to improve translation equivalence. In general, the HIT-6 was not difficult to translate. The most difficult items included colloquial expressions such as 'fed up' and words whose intended meaning changed in translation such as 'school' or 'lie down.' Subjects generally found the HIT-6 translations to be clear and relevant. The translation process resulted in questionnaires that are both culturally appropriate and comparable in content.