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Targeted muscle reinnervation after upper-extremity amputation has demonstrated improved outcomes with myoelectric prosthesis function and postoperative neuropathic pain. This technique has been established in the setting of shoulder disarticulation as well as transhumeral and transradial amputations, but a detailed technique of targeted muscle reinnervation with free tissue transfer from the volar forearm after forequarter amputation has not yet been described. Here, we describe a technique using a volar forearm filet flap to achieve simultaneously satisfactory soft tissue coverage after resection of a tumor from the chest wall and targeted muscle reinnervation of the brachial plexus.

Abstract Background In order for aging to evolve in response to a declining strength of selection with age, a genetic architecture that allows for mutations with age-specific effects on organismal performance is required. Our understanding of how selective effects of individual mutations are distributed across ages is however poor. Established evolutionary theories assume that mutations causing aging have negative late-life effects, coupled to either positive or neutral effects early in life. New theory now suggests evolution of aging may also result from deleterious mutations with increasing negative effects with age, a possibility that has not yet been empirically explored. Results To directly test how the effects of deleterious mutations are distributed across ages, we separately measure age-specific effects on fecundity for each of 20 mutations in Drosophila melanogaster. We find that deleterious mutations in general have a negative effect that increases with age and that the rate of increase depends on how deleterious a mutation is early in life. Conclusions Our findings suggest that aging does not exclusively depend on genetic variants assumed by the established evolutionary theories of aging. Instead, aging can result from deleterious mutations with negative effects that amplify with age. If increasing negative effect with age is a general property of deleterious mutations, the proportion of mutations with the capacity to contribute towards aging may be considerably larger than previously believed.

Social Impact Statement Positive interactions between people and nature inspire behaviours that are in harmony with biodiversity conservation and also afford physical and mental health benefits. Since most people live in towns and cities, urban greenspaces are key points of influence for conservation, but also provide diverse ecosystem services. City trees are a foundation for biodiversity in urban ecosystems, and their belowground interactions with mycorrhizal fungi and aboveground interactions with pollinators must be central to urban ecosystem planning. Messaging about biodiversity must be clearer to avoid unintended negative outcomes from conservation actions such as low diversity tree planting and unsustainable levels of urban beekeeping Summary Trees are a foundation for biodiversity in urban ecosystems and therefore must be able to withstand global change and biological challenges over decades and even centuries to prevent urban ecosystems from deteriorating. Tree quality and diversity should be prioritized over simply numbers to optimize resilience to these challenges. Successful establishment and renewal of trees in cities must also consider belowground (e.g., mycorrhizas) and aboveground (e.g., pollinators) interactions to ensure urban ecosystem longevity, biodiversity conservation and continued provision of the full range of ecosystem services provided by trees. Positive interactions with nature inspire people to live more sustainable lifestyles that are consistent with stopping biodiversity loss and to participate in conservation actions such as tree‐planting and supporting pollinators. Interacting with nature simultaneously provides mental and physical health benefits to people. Since most people live in cities, here we argue that urban ecosystems provide important opportunities for increasing engagement with nature and educating people about biodiversity conservation. While advocacy on biodiversity must communicate in language that is relevant to a diverse audience, over‐simplified messaging, may result in unintended negative outcomes. For example, tree planting actions typically focus on numbers rather than diversity while the call to save bees has inspired unsustainable proliferation of urban beekeeping that may damage wild bee conservation through increased competition for limited forage in cities and disease spread. Ultimately multiple ecosystem services must be considered (and measured) to optimize their delivery in urban ecosystems and messaging to promote the value of nature in cities must be made widely available and more clearly defined.

Abstract Theory maintains that when future environment is predictable, parents should adjust the phenotype of their offspring to match the anticipated environment. The plausibility of positive anticipatory parental effects is hotly debated and the experimental evidence for the evolution of such effects is currently lacking. We experimentally investigated the evolution of anticipatory maternal effects in a range of environments that differ drastically in how predictable they are. Populations of the nematode Caenorhabditis remanei, adapted to 20°C, were exposed to a novel temperature (25°C) for 30 generations with either positive or zero correlation between parent and offspring environment. We found that populations evolving in novel environments that were predictable across generations evolved a positive anticipatory maternal effect, because they required maternal exposure to 25°C to achieve maximum reproduction in that temperature. In contrast, populations evolving under zero environmental correlation had lost this anticipatory maternal effect. Similar but weaker patterns were found if instead rate‐sensitive population growth was used as a fitness measure. These findings demonstrate that anticipatory parental effects evolve in response to environmental change so that ill‐fitting parental effects can be rapidly lost. Evolution of positive anticipatory parental effects can aid population viability in rapidly changing but predictable environments.

Abstract Background Quantitative traits are typically considered to be under additive genetic control. Although there are indications that non-additive factors have the potential to contribute to trait variation, experimental demonstration remains scarce. Here, we investigated the genetic basis of growth in Atlantic salmon by exploiting the high level of genetic diversity and trait expression among domesticated, hybrid and wild populations. Results After rearing fish in common-garden experiments under aquaculture conditions, we performed a variance component analysis in four mapping populations totaling ~ 7000 individuals from six wild, two domesticated and three F1 wild/domesticated hybrid strains. Across the four independent datasets, genome-wide significant quantitative trait loci (QTLs) associated with weight and length were detected on a total of 18 chromosomes, reflecting the polygenic nature of growth. Significant QTLs correlated with both length and weight were detected on chromosomes 2, 6 and 9 in multiple datasets. Significantly, epistatic QTLs were detected in all datasets. Discussion The observed interactions demonstrated that the phenotypic effect of inheriting an allele deviated between half-sib families. Gene-by-gene interactions were also suggested, where the combined effect of two loci resulted in a genetic effect upon phenotypic variance, while no genetic effect was detected when the two loci were considered separately. To our knowledge, this is the first documentation of epistasis in a quantitative trait in Atlantic salmon. These novel results are of relevance for breeding programs, and for predicting the evolutionary consequences of domestication-introgression in wild populations.

Background. Liver transplantation (LT) has been employed for hepatic adenoma (HA) on a case-oriented basis. We aimed to describe the characteristics, waitlist, and post-LT outcomes of patients requiring LT for HA. Methods. All patients listed or transplanted for HA in the United States were identified in the United Network for Organ Sharing (UNOS) database (1987–2020). A systematic literature review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement. Results. A total of 199 HA patients were listed for LT in UNOS and the crude waitlist mortality was 9.0%. A total of 142 HA patients underwent LT; 118 of these were among those listed with an indication of HA who underwent LT, and 24 were diagnosed incidentally. Most did not experience hepatocellular carcinoma transformation (89.4%). Over a median follow-up of 62.9 mo, death was reported in 18.3%. The 1-, 3-, and 5-y patient survival rates were 94.2%, 89.7%, and 86.3% in the UNOS cohort. The systematic review yielded 61 articles reporting on 99 nonoverlapping patients undergoing LT for HA and 2 articles reporting on multicenter studies. The most common LT indications were suspected malignancy (39.7%), unresectable HA (31.7%), and increasing size (27.0%), whereas 53.1% had glycogen storage disease. Over a median follow-up of 36.5 mo, death was reported in 6.0% (n=5/84). The 1-, 3-, and 5-y patient survival rates were all 95.0% in the systematic review. Conclusions. LT for HA can lead to excellent long-term outcomes in well-selected patients. Prospective granular data are needed to develop more optimal selection criteria and further improve outcomes.

Binge drinking refers to a pattern of alcohol intake that raises blood alcohol concentration to or above legal intoxication levels. It is common among young adults and is associated with health risks that scale up with alcohol intake. Acute intoxication depresses neural activity via complex signaling mechanisms by enhancing inhibition mediated by gamma-amino butyric acid (GABA), and by decreasing excitatory glutamatergic effects. Evidence primarily rooted in animal research indicates that the brain compensates for the acute depressant effects under the conditions of habitual heavy use. These neuroadaptive changes are reflected in neural hyperexcitability via downregulated inhibitory signaling, which becomes apparent as withdrawal symptoms. However, human evidence on the compensatory reduction in GABA signaling is scant. The neurochemical aspect of this mechanistic model was evaluated in the present study with proton magnetic resonance spectroscopy (1H-MRS) which is sensitive to GABA plus macromolecule signal (GABA + ). Furthermore, we examined sex differences in GABA + levels as a function of a recent history of binge drinking, given interactions between endogenous neurosteroids, GABA signaling, and alcohol.The study recruited young adult women and men (22.2 ± 2.8 years of age) who were classified as binge drinkers (BDs, N = 52) if they reported ≥ 5 binge episodes in the previous six months. Light drinkers (LDs, N = 49) reported drinking regularly, but not exceeding ≤ 2 binge episodes in the past six months. GABA-edited 1H-MR spectra were acquired from the occipital cortex at 3 T with the MEGA-PRESS sequence. GABA + signal was analyzed relative to water and total creatine (Cr) levels as a function of binge drinking history and sex. Controlling for within-voxel tissue composition, both GABA + indices showed decreased GABA + levels in BDs relative to LDs. The reduced GABA + concentration was associated with occasional high-intensity drinking in the BD group.This evidence is consistent with compensatory GABA downregulation that accompanies alcohol misuse, tipping the excitation/inhibition balance towards hyperexcitability. Analysis of the time course of GABA + neuroplasticity indicated that GABA + was lowest when measured one day after the last drinking occasion in BDs. While the BD vs LD differences were primarily driven by LD women, there was no interaction between Sex and a history of binge drinking. GABA + was higher in LD women compared to LD men.Aligned with the allostasis model, the mechanistic compensatory GABA downregulation observed in young emerging adults engaging in occasional binge drinking complements direct neural measures of hyperexcitability in BDs. Notably, these results suggest that neuroadaptation to alcohol is detectable at the levels of consumption that are within a normative range, and may contribute to adverse health outcomes.

ABSTRACT There is a critical need for improved pharmacodynamic markers for use in human tuberculosis (TB) drug trials. Pharmacodynamic monitoring in TB has conventionally used culture or molecular methods to enumerate the burden of Mycobacterium tuberculosis organisms in sputum. A recently proposed assay called the rRNA synthesis (RS) ratio measures a fundamentally novel property, how drugs impact ongoing bacterial rRNA synthesis. Here, we evaluated RS ratio as a potential pharmacodynamic monitoring tool by testing pretreatment sputa from 38 Ugandan adults with drug-susceptible pulmonary TB. We quantified the RS ratio in paired pretreatment sputa and evaluated the relationship between the RS ratio and microbiologic and molecular markers of M. tuberculosis burden. We found that the RS ratio was highly repeatable and reproducible in sputum samples. The RS ratio was independent of M. tuberculosis burden, confirming that it measures a distinct new property. In contrast, markers of M. tuberculosis burden were strongly associated with each other. These results indicate that the RS ratio is repeatable and reproducible and provides a distinct type of information from markers of M. tuberculosis burden. IMPORTANCE This study takes a major next step toward practical application of a novel pharmacodynamic marker that we believe will have transformative implications for tuberculosis. This article follows our recent report in Nature Communications that an assay called the rRNA synthesis (RS) ratio indicates the treatment-shortening of drugs and regimens. Distinct from traditional measures of bacterial burden, the RS ratio measures a fundamentally novel property, how drugs impact ongoing bacterial rRNA synthesis.

Summary: Agrochemical fungicidal leads have been prepared from photochemically derived 1-aminonorbornane building blocks. The unique 1-aminonorbornane core is generated via direct excitation of a Schiff base precursor, leveraging the N-centered radical character of the excited state species to facilitate a series of radical reactions that construct the norbornane core. This process requires no exogenous reagents, only solvent and photons; thus, it represents an exceptionally simple and efficient means of generating the key building blocks. These (hetero)arene-fused 1-aminonorbornanes are unprecedented in both the agrochemical and pharmaceutical discovery literature; therefore, photochemical advances have provided the unique opportunity to explore the functional utility of novel chemical space. Toward this end, the 1-aminonorbornanes were used to generate next-generation succinate dehydrogenase inhibitors. In vitro fungicidal activity is demonstrated against three fungal plant pathogens affecting field crops, specifically: Fusarium graminearum, Sclerotinia sclerotiorum, and Macrophomina phaseolina. The in vitro performance against F. graminearum was shown to translate into a greenhouse setting. The discovery of in planta fungicidal activity illustrates the interdisciplinary value available via photochemical innovation.

Crop production has been substantially reduced by devastating fungal and oomycete pathogens, and these pathogens continue to threaten global food security. Although chemical and cultural controls have been used for crop protection, these involve continuous costs and time and fungicide resistance among plant pathogens has been increasingly reported. The most efficient way to protect crops from plant pathogens is cultivation of disease-resistant cultivars. However, traditional breeding approaches are laborious and time intensive. Recently, the CRISPR/Cas9 system has been utilized to enhance disease resistance among different crops such as rice, cacao, wheat, tomato, and grape. This system allows for precise genome editing of various organisms via RNA-guided DNA endonuclease activity. Beyond genome editing in crops, editing the genomes of fungal and oomycete pathogens can also provide new strategies for plant disease management. This review focuses on the recent studies of plant disease resistance against fungal and oomycete pathogens using the CRISPR/Cas9 system. For long-term plant disease management, the targeting of multiple plant disease resistance mechanisms with CRISPR/Cas9 and insights gained by probing fungal and oomycete genomes with this system will be powerful approaches.

Background The generic term “exacerbation” does not reflect the heterogeneity of acute exacerbations of COPD (AECOPD). We utilised a novel algorithmic strategy to profile exacerbation phenotypes based on underlying aetiologies. Methods Patients hospitalised for AECOPD (n=146) were investigated for aetiological contributors summarised in a mnemonic acronym ABCDEFGX (A: airway virus; B: bacterial; C: co-infection; D: depression/anxiety; E: eosinophils; F: failure (cardiac); G: general environment; X: unknown). Results from clinical investigations were combined to construct AECOPD phenotypes. Relationships to clinical outcomes were examined for both composite phenotypes and their specific aetiological components. Aetiologies identified at exacerbation were reassessed at outpatient follow-up. Results Hospitalised AECOPDs were remarkably diverse, with 26 distinct phenotypes identified. Multiple aetiologies were common (70%) and unidentifiable aetiology rare (4.1%). If viruses were detected (29.5%), patients had longer hospitalisation (7.7±5.6 versus 6.0±3.9 days, p=0.03) despite fewer “frequent exacerbators” (9.3% versus 37%, p=0.001) and lower mortality at 1 year (p=0.03). If bacterial infection was found (40.4%), patients were commonly “frequent exacerbators” (44% versus 18.4%, p=0.001). Eosinophilic exacerbations (28%) were associated with lower pH (7.32±0.06 versus 7.36±0.09, p=0.04), higher venous carbon dioxide tension (PvCO2) (53.7±10.5 versus 48.8±12.8, p=0.04), greater noninvasive ventilation (NIV) usage (34.1% versus 18.1%) but shorter hospitalisation (4 (3–5) versus 6 (4–9) days, p

Abstract Background Soybean production around the globe faces significant annual yield losses due to pests and diseases. One of the most significant causes of soybean yield loss annually in the U.S. is sudden death syndrome (SDS), caused by soil-borne fungi in the Fusarium solani species complex. Two of these species, F. virguliforme and F. brasiliense, have been discovered in the U.S. The genetic mechanisms that these pathogens employ to induce root rot and SDS are largely unknown. Previous methods describing F. virguliforme protoplast generation and transformation have been used to study gene function, but these methods lack important details and controls. In addition, no reports of protoplast generation and genetic transformation have been made for F. brasiliense. Results We developed a new protocol for developing fungal protoplasts in these Fusarium species and test the protoplasts for the ability to take up foreign DNA. We show that wild-type strains of F. virguliforme and F. brasiliense are sensitive to the antibiotics hygromycin and nourseothricin, but strains transformed with resistance genes displayed resistance to these antibiotics. In addition, integration of fluorescent protein reporter genes demonstrates that the foreign DNA is expressed and results in a functional protein, providing fluorescence to both pathogens. Conclusions This protocol provides significant details for reproducibly producing protoplasts and transforming F. virguliforme and F. brasiliense. The protocol can be used to develop high quality protoplasts for further investigations into genetic mechanisms of growth and pathogenicity of F. virguliforme and F. brasiliense. Fluorescent strains developed in this study can be used to investigate temporal colonization and potential host preferences of these species.

Needle aponeurotomy (NA) and collagenase injections (CI) for treatment of Dupuytren disease are practical and clinically efficient techniques. The purpose of this report is to review the comparative literature and present postprocedure survey data on NA. We reviewed the current literature on treatment of Dupuytren disease with NA and report on direct and indirect comparisons of the 2 treatment options. We also retrospectively identified patients treated with NA for Dupuytren disease, reviewed the demographic details of treatment in the medical records, and solicited patients’ feedback on satisfaction, recurrence, and complications using a phone survey. The results of the survey are discussed in the context of current literature. A total of 250 completed the survey an average of 34 months after treatment. Of those, 178 (71%) were very satisfied or satisfied, 187 (75%) reported some recurrence, and 5% reported a complication. Patients less than 2 years from the procedure were statistically significantly more likely to be satisfied with the procedure and more likely to have it again, and reported less recurrence of disease. Current literature does not clearly suggest a best treatment option for Dupuytren disease. Recent analyses suggest that there is a cost difference, with NA presenting as a more cost-effective option. Survey results demonstrated a low complication rate although the rate of recurrence was high, which was consistent with other studies. Needle aponeurotomy is safe and effective, and results in high patient satisfaction despite a high recurrence rate. Key words: complications, Dupuytren disease, hand surgery, needle aponeurotomy, patient-reported satisfaction, recurrence

Abstract Background Information and emotions towards public health issues could spread widely through online social networks. Although aggregate metrics on the volume of information diffusion are available, we know little about how information spreads on online social networks. Health information could be transmitted from one to many (i.e. broadcasting) or from a chain of individual to individual (i.e. viral spreading). The aim of this study is to examine the spreading pattern of Ebola information on Twitter and identify influential users regarding Ebola messages. Methods Our data was purchased from GNIP. We obtained all Ebola-related tweets posted globally from March 23, 2014 to May 31, 2015. We reconstructed Ebola-related retweeting paths based on Twitter content and the follower-followee relationships. Social network analysis was performed to investigate retweeting patterns. In addition to describing the diffusion structures, we classify users in the network into four categories (i.e., influential user, hidden influential user, disseminator, common user) based on following and retweeting patterns. Results On average, 91% of the retweets were directly retweeted from the initial message. Moreover, 47.5% of the retweeting paths of the original tweets had a depth of 1 (i.e., from the seed user to its immediate followers). These observations suggested that the broadcasting was more pervasive than viral spreading. We found that influential users and hidden influential users triggered more retweets than disseminators and common users. Disseminators and common users relied more on the viral model for spreading information beyond their immediate followers via influential and hidden influential users. Conclusions Broadcasting was the dominant mechanism of information diffusion of a major health event on Twitter. It suggests that public health communicators can work beneficially with influential and hidden influential users to get the message across, because influential and hidden influential users can reach more people that are not following the public health Twitter accounts. Although both influential users and hidden influential users can trigger many retweets, recognizing and using the hidden influential users as the source of information could potentially be a cost-effective communication strategy for public health promotion. However, challenges remain due to uncertain credibility of these hidden influential users.

Abstract Classical theory maintains that ageing evolves via energy trade‐offs between reproduction and survival leading to accumulation of unrepaired cellular damage with age. In contrast, the emerging new theory postulates that ageing evolves because of deleterious late‐life hyper‐function of reproduction‐promoting genes leading to excessive biosynthesis in late‐life. The hyper‐function theory uniquely predicts that optimizing nutrient‐sensing molecular signaling in adulthood can simultaneously postpone ageing and increase Darwinian fitness. Here, we show that reducing evolutionarily conserved insulin/IGF‐1 nutrient‐sensing signaling via daf‐2 RNA interference (RNAi) fulfils this prediction in Caenorhabditis elegans nematodes. Long‐lived daf‐2 RNAi parents showed normal fecundity as self‐fertilizing hermaphrodites and improved late‐life reproduction when mated to males. Remarkably, the offspring of daf‐2 RNAi parents had higher Darwinian fitness across three different genotypes. Thus, reduced nutrient‐sensing signaling in adulthood improves both parental longevity and offspring fitness supporting the emerging view that suboptimal gene expression in late‐life lies at the heart of ageing.

Abstract Background In the event of a shigellosis outbreak in a childcare setting, exclusion policies are typically applied to afflicted children to limit shigellosis transmission. However, there is scarce evidence of their impact. Methods We evaluated five exclusion policies: Children return to childcare after: i) two consecutive laboratory tests (either PCR or culture) do not detect Shigella, ii) a single negative laboratory test (PCR or culture) does not detect Shigella, iii) seven days after beginning antimicrobial treatment, iv) after being symptom-free for 24 h, or v) 14 days after symptom onset. We also included four treatments to assess the policy options: i) immediate, effective treatment; ii) effective treatment after laboratory diagnosis; iii) no treatment; iv) ineffective treatment. Relying on published data, we calculated the likelihood that a child reentering childcare would be infectious, and the number of childcare-days lost per policy. Results Requiring two consecutive negative PCR tests yielded a probability of onward transmission of

Background: Athletes, coaches, sport psychology practitioners, and researchers suggest that mental toughness represents an important construct that is associated with athletic performance. Unfortunately, the absence of real-world performance as a dependent variable has limited our ability to substantiate this claim. The concern of a lack of ecologically valid measures of sports performance might be addressed by examining the relationship between mental toughness and sports performance using a standardized measure of personal best (PB) triathlon time and a validated unidimensional measure of mental toughness. Methods: Three hundred and sixteen triathletes completed the 8-item mental toughness index (MTI), reported their age, and provided a PB Olympic distance triathlon time and the total number of triathlons they had completed to date. Given that males are typically quicker than females, a standardized time was calculated by dividing the PB by the current Olympic record for gender; we also hypothesized that more experienced triathletes would report quicker PB times because of greater frequency and duration of training. Once we had controlled for gender and experience, we predicted that mental toughness would be negatively associated with triathlon time and the size of the relationship would be of a moderate magnitude. Results: Results revealed small- to moderate-sized negative relationships between both completed number of triathlons and mental toughness with standardized PB time. Conclusion: The hierarchical regression analysis showed that mental toughness provided a unique contribution to the variability in standardized Olympic triathlon PB after controlling for the total number of triathlons completed. Keywords: Endurance sport, Factorial validity, Mental toughness, Olympic distance triathlon, Performance, Personal best times

Mycotoxins are secondary metabolites produced by fungi that, depending on the type and exposure levels, can be a threat to human and animal health. When multiple mycotoxins occur together, their risk effects on human and animal health can be additive or synergistic. Little information is known about the specific types of mycotoxins or their co-occurrence in the state of Michigan and the Great Lakes region of the United States. To understand the types, incidences, severities, and frequency of co-occurrence of mycotoxins in maize grain (Zea mays L.), samples were collected from across Michigan over two years and analyzed for 20 different mycotoxins. Every sample was contaminated with at least four and six mycotoxins in 2017 and 2018, respectively. Incidence and severity of each mycotoxin varied by year and across locations. Correlations were found between mycotoxins, particularly mycotoxins produced by Fusarium spp. Environmental differences at each location played a role in which mycotoxins were present and at what levels. Overall, data from this study demonstrated that mycotoxin co-occurrence occurs at high levels in Michigan, especially with mycotoxins produced by Fusarium spp., such as deoxynivalenol.

BackgroundWe review original papers on ovarian-hormone status in two areas of emotional processing: facial emotion recognition and emotional memory. Ovarian-hormone status is operationalized by the levels of the steroid sex hormones 17β-estradiol (E2) and progesterone (P4), fluctuating over the natural menstrual cycle and suppressed under oral contraceptive (OCs) use. We extend previous reviews addressing single areas of emotional processing. Moreover, we systematically examine the role of stimulus features such as emotion type or stimulus valence and aim at elucidating factors that reconcile the inconsistent results.MethodsWe followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and included papers published until September 2020 indexed in PubMed and Web of Science databases. Search terms were MeSH terms (emotional OR emotion) AND (X) AND (estrogen OR progesterone OR menstrual cycle OR oral contraceptives) with (X) representing our separately searched areas, resulting in (processing OR recognition OR empathy), and (memory OR recall). To be included, articles had to (1) be written and published in English, (2) examine healthy, non-pregnant adult women in their reproductive age, and (3) measure or at least estimate levels of E2 and P4. In PubMed, the search was (4) limited to humans and (5) to the search term present in the title or abstract.ResultsFeatures of the provided stimulus material (emotion type and/or valence) constitute a relevant influence that interacts with E2- and P4-related ovarian-hormone status. For instance, recognition of basic emotions appears to be more related to P4- than E2-levels. Quite consistent, OC intake (vs. natural menstrual cycling) was accompanied by impaired recognition accuracy of basic and also complex emotions, although not in a recent large-sample study assessing complex emotions. Memory recall of negative content was mainly enhanced by P4, especially after having been stressed.Discussion and ConclusionWe document the methodological diversity in the field, presumably contributing to the heterogeneity of results. More studies explicitly contrasting the early follicular phase, mid-cycle phase, mid-luteal, and OC intake while standardizing tasks are needed. Research would take advantage of using within-subject designs and accounting for the recognition of complex emotions.

Psychophysical experiments have demonstrated large and highly systematic perceptual distortions of tactile space. Such a space can be referred to our experience of the spatial organisation of objects, at representational level, through touch, in analogy with the familiar concept of visual space. We investigated the neural basis of tactile space by analysing activity patterns induced by tactile stimulation of nine points on a 3 × 3 square grid on the hand dorsum using functional magnetic resonance imaging. We used a searchlight approach within pre-defined regions of interests to compute the pairwise Euclidean distances between the activity patterns elicited by tactile stimulation. Then, we used multidimensional scaling to reconstruct tactile space at the neural level and compare it with skin space at the perceptual level. Our reconstructions of the shape of skin space in contralateral primary somatosensory and motor cortices reveal that it is distorted in a way that matches the perceptual shape of skin space. This suggests that early sensorimotor areas critically contribute to the distorted internal representation of tactile space on the hand dorsum.

BackgroundKnowledge about the psychosocial experiences of sick-listed workers in the first months of sick leave is sparse even though early interventions are recommended. The aim of this study was to explore psychosocial experiences of being on sick leave and thoughts about returning to work after 8–12 weeks of sickness absence.MethodsSixteen individuals at 9–13 weeks of sick leave participated in semi-structured individual interviews. Data was analyzed through Giorgi’s descriptive phenomenological method.ResultsThree themes emerged: (1) energy depleted, (2) losing normal life, (3) searching for a solution. A combination of health, work, and family challenges contributed to being drained of energy, which affected both work- and non-work roles. Being on sick leave led to a loss of social arenas and their identity as a contributing member of society. Participants required assistance to find solutions toward returning to work.ConclusionEven in this early stage of long-term sick leave, sick listed workers faced complex challenges in multiple domains. Continuing sick leave was experienced as necessary but may challenge personal identity and social life. Those not finding solutions may benefit from additional early follow-up that examine work-related, social and personal factors that influence return to work.

BackgroundRabies is a viral zoonosis that imposes a substantial disease and economic burden in many developing countries. Dogs are the primary source of rabies transmission; eliminating dog rabies reduces the risk of exposure in humans significantly. Through mass annual dog rabies vaccination campaigns, the national program of rabies control in Mexico progressively reduced rabies cases in dogs and humans since 1990. In 2019, the World Health Organization validated Mexico for eliminating rabies as a public health problem. Using a governmental perspective, we retrospectively assessed the economic costs, effectiveness, and cost-effectiveness of the national program of rabies control in Mexico, 1990-2015.MethodologyCombining various data sources, including administrative records, national statistics, and scientific literature, we retrospectively compared the current scenario of annual dog vaccination campaigns and post-exposure prophylaxis (PEP) with a counterfactual scenario without an annual dog vaccination campaign but including PEP. The counterfactual scenario was estimated using a mathematical model of dog rabies transmission (RabiesEcon). We performed a thorough sensitivity analysis of the main results.Principal findingsResults suggest that in 1990 through 2015, the national dog rabies vaccination program in Mexico prevented about 13,000 human rabies deaths, at an incremental cost (MXN 2015) of $4,700 million (USD 300 million). We estimated an average cost of $360,000 (USD 23,000) per human rabies death averted, $6,500 (USD 410) per additional year-of-life, and $3,000 (USD 190) per dog rabies death averted. Results were robust to several counterfactual scenarios, including high and low rabies transmission scenarios and various assumptions about potential costs without mass dog rabies vaccination campaigns.ConclusionsAnnual dog rabies vaccination campaigns have eliminated the transmission of dog-to-dog rabies and dog-mediated human rabies deaths in Mexico. According to World Health Organization standards, our results show that the national program of rabies control in Mexico has been highly cost-effective.

Introduction Acute exacerbations of COPD (AECOPD) are accompanied by escalations in cardiac risk superimposed upon elevated baseline risk. Appropriate treatment for coronary artery disease (CAD) and heart failure with reduced ejection fraction (HFrEF) could improve outcomes. However, securing these diagnoses during AECOPD is difficult, so their true prevalence remains unknown, as does the magnitude of this treatment opportunity. We aimed to determine the prevalence of severe CAD and severe HFrEF during hospitalised AECOPD using dynamic computed tomography (CT). Methods A cross-sectional study of 148 patients with hospitalised AECOPD was conducted. Dynamic CT was used to identify severe CAD (Agatston score ≥400) and HFrEF (left ventricular ejection fraction ≤40% and/or right ventricular ejection fraction ≤35%). Results Severe CAD was detected in 51 of 148 patients (35%), left ventricular systolic dysfunction was identified in 12 cases (8%) and right ventricular systolic dysfunction was present in 18 (12%). Clinical history and examination did not identify severe CAD in approximately one-third of cases and missed HFrEF in two-thirds of cases. Elevated troponin and brain natriuretic peptide did not differentiate subjects with severe CAD from nonsevere CAD, nor distinguish HFrEF from normal ejection fraction. Undertreatment was common. Of those with severe CAD, only 39% were prescribed an antiplatelet agent, and 53% received a statin. Of individuals with HFrEF, 50% or less received angiotensin blockers, beta blockers or antimineralocorticoids. Conclusion Dynamic CT detects clinically covert CAD and HFrEF during AECOPD, identifying opportunities to improve outcomes via well-established cardiac treatments.

The gut microbiome has combined with other person-specific information, such as blood parameters, dietary habits, anthropometrics, and physical activity been found to predict personalized postprandial glucose responses (PPGRs) to various foods. Yet, the contributions of specific microbiome taxa, measures of fermentation, and abiotic factors in the colon to glycemic control remain elusive. We tested whether PPGRs 60 min after a standardized breakfast was associated with gut microbial α-diversity (primary outcome) and explored whether postprandial responses of glucose and insulin were associated with specific microbiome taxa, colonic fermentation as reflected by fecal short-chain fatty acids (SCFAs), and breath hydrogen and methane exhalation, as well as abiotic factors including fecal pH, fecal water content, fecal energy density, intestinal transit time (ITT), and stool consistency. A single-arm meal trial was conducted. A total of 31 healthy (24 female and seven male) subjects consumed a standardized evening meal and a subsequent standardized breakfast (1,499 kJ) where blood was collected for analysis of postprandial glucose and insulin responses. PPGRs to the same breakfast varied across the healthy subjects. The largest inter-individual variability in PPGRs was observed 60 min after the meal but was not associated with gut microbial α-diversity. In addition, no significant associations were observed between postprandial responses and specific taxa of the gut microbiome, measures of colonic fermentation, ITT, or other abiotic factors. However, fasting glucose concentrations were negatively associated with ITT, and fasting insulin was positively associated with fasting breath hydrogen. In conclusion, the gut microbiome, measures of colonic fermentation, and abiotic factors were not shown to be significantly associated with variability in postprandial responses, suggesting that contributions of the gut microbiome, colonic fermentation, and abiotic factors to PPGRs may be subtle in healthy adults.

The purpose of this study was to explore the evolving perspectives of young players experiences going through the junior to senior transition in professional football. A primary objective was to adopt novel methods – weekly video diaries – to allow participants to control and report their own narratives as the transition unfolded over 40 weeks. Semi structured interviews, held at four time points, allowed the lead researcher to probe further on themes that were developing. Six participants from the academy volunteered to take part, but only the three who earned professional contracts completed the study. The primary themes in the academy were the pressure experienced waiting for the contract decision, and then preparation for senior football and the first team environment once contracts were awarded. Adaptation to senior football included not only increased physical and mental demands but also those related to the different style of play, the pressure to win, and how these both impacted decision-making. The football club set up two pathways to support this adaptation, loan moves and time with the U23’s. In the following season, the move to the senior squad was characterized by a lack of opportunity to play for the first team, resulting in additional loan moves. These moves, and the associated perceived lack of support structures, led to the participants experiencing issues with their club identity, their motivation and their confidence. Internal (mindset) and external (social support) coping strategies were developed over the study’s duration. Concluding comments from participants were related to greater acceptance of the need to be patient, perhaps reflecting on the club’s reputation of giving young players a sound football education. These phases of the transition came with ups and downs for each participant illuminating key elements of the adaptation to senior competition, barriers to transition without early success, and social aspects of the transition. Enhanced detail to these key areas poses important questions for future research and applied practice.

Soybean (Glycine max) is an important leguminous crop that is grown throughout the United States and around the world. In 2016, soybean was valued at $41 billion USD in the United States alone. Increasingly, soybean farmers are adopting alternative management strategies to improve the sustainability and profitability of their crop. Various benefits have been demonstrated for alternative management systems, but their effects on soybean-associated microbial communities are not well-understood. In order to better understand the impact of crop management systems on the soybean-associated microbiome, we employed DNA amplicon sequencing of the Internal Transcribed Spacer (ITS) region and 16S rRNA genes to analyze fungal and prokaryotic communities associated with soil, roots, stems, and leaves. Soybean plants were sampled from replicated fields under long-term conventional, no-till, and organic management systems at three time points throughout the growing season. Results indicated that sample origin was the main driver of beta diversity in soybean-associated microbial communities, but management regime and plant growth stage were also significant factors. Similarly, differences in alpha diversity are driven by compartment and sample origin. Overall, the organic management system had lower fungal and bacterial Shannon diversity. In prokaryotic communities, aboveground tissues were dominated by Sphingomonas and Methylobacterium while belowground samples were dominated by Bradyrhizobium and Sphingomonas. Aboveground fungal communities were dominated by Davidiella across all management systems, while belowground samples were dominated by Fusarium and Mortierella. Specific taxa including potential plant beneficials such as Mortierella were indicator species of the conventional and organic management systems. No-till management increased the abundance of groups known to contain plant beneficial organisms such as Bradyrhizobium and Glomeromycotina. Network analyses show different highly connected hub taxa were present in each management system. Overall, this research demonstrates how specific long-term cropping management systems alter microbial communities and how those communities change throughout the growth of soybean.

Elevated postprandial plasma glucose is a risk factor for development of type 2 diabetes and cardiovascular disease. We hypothesized that the inter-individual postprandial plasma glucose response varies partly depending on the intestinal microbiome composition and function. We analyzed data from Danish adults (n = 106), who were self-reported healthy and attended the baseline visit of two previously reported randomized controlled cross-over trials within the Gut, Grain and Greens project. Plasma glucose concentrations at five time points were measured before and during three hours after a standardized breakfast. Based on these data, we devised machine learning algorithms integrating bio-clinical, as well as shotgun-sequencing-derived taxa and functional potentials of the intestinal microbiome to predict individual postprandial glucose excursions. In this post hoc study, we found microbial and clinical features, which predicted up to 48% of the inter-individual variance of postprandial plasma glucose responses (Pearson correlation coefficient of measured vs. predicted values, R = 0.69, 95% CI: 0.45 to 0.84, p

Summary: Background: Transportation of laboratory samples in low-income and middle-income countries is often constrained by poor road conditions, difficult geographical terrain, and insecurity. These constraints can lead to long turnaround times for laboratory diagnostic tests and hamper epidemic control or patient treatment efforts. Although uncrewed aircraft systems (UAS)—ie, drones—can mitigate some of these transportation constraints, their cost-effectiveness compared with land-based transportation systems is unclear. Methods: We did a comparative economic study of the costs and cost-effectiveness of UAS versus motorcycles in Liberia (west Africa) for transportation of laboratory samples under simulated routine conditions and public health emergency conditions (based on the 2013–16 west African Ebola virus disease epidemic). We modelled three UAS with operational ranges of 30 km, 65 km, and 100 km (UAS30, UAS65, and UAS100) and lifespans of 1000 to 10 000 h, and compared the costs and number of samples transported with an established motorcycle transportation programme (most commonly used by the Liberian Ministry of Health and the charity Riders for Health). Data for UAS were obtained from Skyfire (a UAS consultancy), Vayu (a UAS manufacturer), and Sandia National Laboratories (a private company with UAS research experience). Motorcycle operational data were obtained from Riders for Health. In our model, we included costs for personnel, equipment, maintenance, and training, and did univariate and probabilistic sensitivity analyses for UAS lifespans, range, and accident or failures. Findings: Under the routine scenario, the per sample transport costs were US$0·65 (95% CI 0·01–2·85) and $0·82 (0·56–5·05) for motorcycles and UAS65, respectively. Per-sample transport costs under the emergency scenario were $24·06 (95% CI 21·14–28·20) for motorcycles, $27·42 (95% CI 19·25–136·75) for an unadjusted UAS model with insufficient geographical coverage, and $34·09 (95% CI 26·70–127·40) for an adjusted UAS model with complementary motorcycles. Motorcycles were more cost-effective than short-range UAS (ie, UAS30). However, with increasing range and operational lifespans, UAS became increasingly more cost-effective. Interpretation: Given the current level of technology, purchase prices, equipment lifespans, and operational flying ranges, UAS are not a viable option for routine transport of laboratory samples in west Africa. Field studies are required to generate evidence about UAS lifespan, failure rates, and performance under different weather conditions and payloads. Funding: None.

Gluten-free diets are increasingly common in the general population. Here, the authors report the results of a randomised cross-over trial involving middle-aged, healthy Danish adults, showing evidence that a low-gluten diet leads to gut microbiome changes, possibly due to variations in dietary fibres.

Pythium root rot is one of the significant diseases of soybean (Glycine max (L.) Merr.) in the United States. The causal agent of the disease is a soil-borne oomycete pathogen Pythium irregulare, the most prevalent and aggressive species of Pythium in North Central United States. However, few studies have been conducted in soybean for the identification of quantitative trait loci (QTL) for tolerance to P. irregulare. In this study, two recombinant inbred line (RIL) populations (designated as POP1 and POP2) were challenged with P. irregulare (isolate CMISO2-5-14) in a greenhouse assay. POP1 and POP2 were derived from ‘E09014’ × ‘E05226-T’ and ‘E05226-T’ × ‘E09088’, and contained 113 and 79 lines, respectively. Parental tests indicated that ‘E05226-T’ and ‘E09014’ were more tolerant than ‘E09088’, while ‘E09088’ was highly susceptible to the pathogen. The disease indices, root weight of inoculation (RWI) and ratio of root weight (RRW) of both populations showed near normal distributions, with transgressive segregation, suggesting the involvement of multiple QTL from both parents contributed to the tolerance. All the lines were genotyped using Illumina Infinium BARCSoySNP6K iSelect BeadChip and yielded 1373 and 1384 polymorphic markers for POP1 and POP2, respectively. Notably, despite high density, polymorphic markers coverage was incomplete in some genomic regions. As such, 28 and 37 linkage groups were obtained in POP1 and POP2, respectively corresponding to the 20 soybean chromosomes. Using RRW, one QTL was identified in POP1 on Chromosome 20 that explained 12.7–13.3% of phenotypic variation. The desirable allele of this QTL was from ‘E05226-T’. Another QTL was found in POP2 on Chromosome 11. It explained 15.4% of the phenotypic variation and the desirable allele was from ‘E09088’. However, no QTL were identified using RWI in either population. These results supported that RRW was more suitable to be used to evaluate P. irregulare tolerance in soybean.

Abstract Background West African countries Liberia, Sierra Leone, and Guinea experienced the largest and longest epidemic of Ebola virus disease from 2014 to 2016; after the epidemic was declared to be over, Liberia, Guinea, and Sierra Leone still experienced Ebola cases/clusters. The United States Centers for Disease Control and Prevention (US CDC) participated in the response efforts to the latter Ebola clusters, by assisting with case investigation, contact identification, and monitoring. This study aims to estimate the cost to the US CDC of responding to three different Ebola clusters after the end of the Ebola epidemic in 2015: i) Sierra Leone, Tonkolili (Jan 2016, 2 Ebola cases, 5 affected regions); ii) Guinea, Nzerekore (Mar-May 2016, 10 Ebola cases, 2 affected regions); iii) Liberia, Somali Drive (Mar 2016, 3 Ebola cases, 1 affected region). Main text After interviewing team members that had participated in the response, we estimated total costs (expressed in 2016 US Dollars [USD]), where total costs correspond to travel costs, deployed personnel costs, costs to prepare for deployment, procurement and interagency collaboration costs, among others. We also estimated cost per cluster case (corresponding to the total costs divided by the total number of cluster cases); and cost per case-affected-region (equal to the total costs divided by the product of the number of cases times the number of regions affected). We found that the response cost varied sixteenfold between USD 113 166 in Liberia and USD 1 764 271 in Guinea, where the main cost drivers were travel and personnel costs. The cost per cluster case varied tenfold between 37 722 in Liberia (three cases) and USD 347 226 in Sierra Leone, and the cost per case-affected-region varied threefold between USD 37 722 in Liberia and USD 88 214 in Guinea. Conclusions Costs vary with the characteristics of each cluster, with those spanning more regions and cases requiring more resources for case investigation and contact identification and monitoring. These data will assist policy makers plan for similar post-epidemic responses.

BackgroundOnce a canine rabies-free status has been achieved, there is little guidance available on vaccination standards to maintain that status. In areas with risk of reintroduction, it may be practical to continue vaccinating portions of susceptible dogs to prevent re-establishment of canine rabies.MethodsWe used a modified version of RabiesEcon, a deterministic mathematical model, to evaluate the potential impacts and cost-effectiveness of preventing the reintroduction of canine rabies through proactive dog vaccination. We analyzed four scenarios to simulate varying risk levels involving the reintroduction of canine rabies into an area where it is no longer present. In a sensitivity analysis, we examined the influences of reintroduction frequency and intensity, the density of susceptible dog population, dog birth rate, dog life expectancy, vaccine efficacy, rate of loss of vaccine immunity, and the basic reproduction number (R0).ResultsTo prevent the re-establishment of canine rabies, it is necessary to vaccinate 38% to 56% of free-roaming dogs that have no immunity to rabies. These coverage levels were most sensitive to adjustments in R0 followed by the vaccine efficacy and the rate of loss of vaccine immunity. Among the various preventive vaccination strategies, it was most cost-effective to continue dog vaccination at the minimum coverage required, with the average cost per human death averted ranging from $257 to $398 USD.ConclusionsWithout strong surveillance systems, rabies-free countries are vulnerable to becoming endemic when incursions happen. To prevent this, it may be necessary to vaccinate at least 38% to 56% of the susceptible dog population depending on the risk of reintroduction and transmission dynamics.

Abstract Background The 2014–2016 Ebola crisis in West Africa had approximately eight times as many reported deaths as the sum of all previous Ebola outbreaks. The outbreak magnitude and occurrence of multiple Ebola cases in at least seven countries beyond Liberia, Sierra Leone, and Guinea, hinted at the possibility of broad-scale transmission of Ebola. Main text Using a modeling tool developed by the US Centers for Disease Control and Prevention during the Ebola outbreak, we estimated the number of Ebola cases that might have occurred had the disease spread beyond the three countries in West Africa to cities in other countries at high risk for disease transmission (based on late 2014 air travel patterns). We estimated Ebola cases in three scenarios: a delayed response, a Liberia-like response, and a fast response scenario. Based on our estimates of the number of Ebola cases that could have occurred had Ebola spread to other countries beyond the West African foci, we emphasize the need for improved levels of preparedness and response to public health threats, which is the goal of the Global Health Security Agenda. Our estimates suggest that Ebola could have potentially spread widely beyond the West Africa foci, had local and international health workers and organizations not committed to a major response effort. Our results underscore the importance of rapid detection and initiation of an effective, organized response, and the challenges faced by countries with limited public health systems. Actionable lessons for strengthening local public health systems in countries at high risk of disease transmission include increasing health personnel, bolstering primary and critical healthcare facilities, developing public health infrastructure (e.g. laboratory capacity), and improving disease surveillance. With stronger local public health systems infectious disease outbreaks would still occur, but their rapid escalation would be considerably less likely, minimizing the impact of public health threats such as Ebola. Conclusions The Ebola outbreak could have potentially spread to other countries, where limited public health surveillance and response capabilities may have resulted in additional foci. Health security requires robust local health systems that can rapidly detect and effectively respond to an infectious disease outbreak.

Background: Long noncoding RNAs (lncRNAs) have been implicated in the pathogenesis of cardiovascular diseases. We aimed to identify novel lncRNAs associated with the early response to ischemia in the heart. Methods and Results: RNA sequencing data gathered from 81 paired left ventricle samples from patients undergoing cardiopulmonary bypass was collected before and after a period of ischemia. Novel lncRNAs were validated with Oxford Nanopore Technologies long-read sequencing. Gene modules associated with an early ischemic response were identified and the subcellular location of selected lncRNAs was determined with RNAscope. A total of 2446 mRNAs, 270 annotated lncRNAs and one novel lncRNA differed in response to ischemia (adjusted p < 0.001, absolute fold change >1.2). The novel lncRNA belonged to a gene module of highly correlated genes that also included 39 annotated lncRNAs. This module associated with ischemia (Pearson correlation coefficient = −0.69, p = 1 × 10−23) and activation of cell death pathways (p < 6 × 10−9). A further nine novel cardiac lncRNAs were identified, of which, one overlapped five cis-eQTL eSNPs for the gene RWD Domain-Containing Sumoylation Enhancer (RWDD3) and was itself correlated with RWDD3 expression (Pearson correlation coefficient −0.2, p = 0.002). Conclusion: We have identified 10 novel lncRNAs, one of which was associated with myocardial ischemia and may have potential as a novel therapeutic target or early marker for myocardial dysfunction.

Defects in neural crest development have been implicated in many human disorders, but information about human neural crest formation mostly depends on extrapolation from model organisms. Human pluripotent stem cells (hPSCs) can be differentiated into in vitro counterparts of the neural crest, and some of the signals known to induce neural crest formation in vivo are required during this process. However, the protocols in current use tend to produce variable results, and there is no consensus as to the precise signals required for optimal neural crest differentiation. Using a fully defined culture system, we have now found that the efficient differentiation of hPSCs to neural crest depends on precise levels of BMP signaling, which are vulnerable to fluctuations in endogenous BMP production. We present a method that controls for this phenomenon and could be applied to other systems where endogenous signaling can also affect the outcome of differentiation protocols.

Bacterial etiolation and decline (BED), caused by Acidovorax avenae, is an emerging disease of creeping bentgrass on golf courses in the United States. We performed the first comprehensive analysis of A. avenae on a nationwide collection of turfgrass- and maize-pathogenic A. avenae. Surprisingly, our results reveal that the turfgrass-pathogenic A. avenae in North America are not only highly divergent but also belong to two distinct phylogroups. Both phylogroups specifically infect turfgrass but are more closely related to maize pathogens than to each other. This suggests that, although the disease is only recently reported, it has likely been infecting turfgrass for a long time. To identify a genetic basis for the host specificity, we searched for genes closely related among turfgrass strains but distantly related to their homologs from maize strains. We found a cluster of 11 such genes generated by three ancient recombination events within the type III secretion system (T3SS) pathogenicity island. Ever since the recombination, the cluster has been conserved by strong purifying selection, hinting at its selective importance. Together our analyses suggest that BED is an ancient disease that may owe its host specificity to a highly conserved cluster of 11 T3SS genes.

Abstract Background Tracheal obstruction resulting from expiratory tracheal deformation has been associated with respiratory symptoms and severe airway exacerbations. In chronic obstructive pulmonary disease (COPD), acute exacerbations (AECOPD) create large intrathoracic pressure swings which may increase tracheal deformation. Excessive central airway collapse (ECAC) may be diagnosed when the tracheal area on expiration is less than 50% of that on inspiration. The prevalence of ECAC in AECOPD and its temporal course have not been systematically studied. Methods We prospectively recruited healthy volunteers (n = 53), stable outpatients with COPD (n = 40) and patients with hospitalised acute exacerbations of COPD (AECOPD, n = 64). 17 of the AECOPD group returned for repeat evaluation when clinically well at 6–12 weeks. All subjects underwent dynamic 320-slice computed tomography of the larynx and trachea during tidal breathing, enabling quantitation of tracheal area and dimensions (mean ± SD). Results No healthy individuals had ECAC. The prevalence of ECAC in stable COPD and AECOPD was 35% and 39% respectively. Mean tracheal collapse did not differ between stable COPD (57.5 ± 19.8%), AECOPD (53.8 ± 19.3%) and in the subset who returned when convalescent (54.9 ± 17.2%). AECOPD patients with and without ECAC had similar clinical characteristics. Conclusions Tracheal collapse in both stable and AECOPD is considerably more prevalent than in healthy individuals. ECAC warrants assessment as part of comprehensive COPD evaluation and management. Further studies should evaluate the aetiology of ECAC and whether it predisposes to exacerbations.

Abstract Background Both ambulatory atrial fibrillation (AF) and post-operative AF (poAF) are associated with substantial morbidity and mortality. Analyzing the tissue-specific gene expression in the left atrium (LA) can identify novel genes associated with AF and further the understanding of the mechanism by which previously identified genetic variants associated with AF mediate their effects. Methods LA free wall samples were obtained intraoperatively immediately prior to mitral valve surgery in 62 Caucasian individuals. Gene expression was quantified on mRNA harvested from these samples using RNA sequencing. An expression quantitative trait loci (eQTL) analysis was performed, comparing gene expression between different genotypes of 1.0 million genetic markers, emphasizing genomic regions and genes associated with AF. Results Comparison of whole-genome expression between patients who later developed poAF and those who did not identified 23 differentially expressed genes. These included genes associated with the resting membrane potential modified by potassium currents, as well as genes within Wnt signaling and cyclic GMP metabolism. The eQTL analysis identified 16,139 cis eQTL relationships in the LA, including several involving genes and single nucleotide polymorphisms (SNPs) linked to AF. A previous relationship between rs3744029 and MYOZ1 expression was confirmed, and a novel relationship between rs6795970 and the expression of the SCN10A gene was identified. Conclusions The current study is the first analysis of the human LA expression landscape using high-throughput RNA sequencing. Several novel genes and variants likely involved in AF pathogenesis were identified, thus furthering the understanding of how variants associated with AF mediate their effects via altered gene expression. Trial registration ClinicalTrials.gov ID: NCT00833313 , registered 5. January 2009

Health officials lack field-implementable tools for forecasting the effects that a large-scale release of Bacillus anthracis spores would have on public health and hospitals. We created a modeling tool (combining inhalational anthrax caseload projections based on initial case reports, effects of variable postexposure prophylaxis campaigns, and healthcare facility surge capacity requirements) to project hospitalizations and casualties from a newly detected inhalation anthrax event, and we examined the consequences of intervention choices. With only 3 days of case counts, the model can predict final attack sizes for simulated Sverdlovsk-like events (1979 USSR) with sufficient accuracy for decision making and confirms the value of early postexposure prophylaxis initiation. According to a baseline scenario, hospital treatment volume peaks 15 days after exposure, deaths peak earlier (day 5), and recovery peaks later (day 23). This tool gives public health, hospital, and emergency planners scenario-specific information for developing quantitative response plans for this threat.

Critical theoretical approaches to information literacy are an important part of the growing LIS focus on the context of information. This concern for information’s social environment and the awareness of new models of interaction between learners and librarians open the possibility for using social epistemology to better understand information literacy. The concept of social epistemology—the study of the ways in which an individual’s knowledge is shaped by their interactions with the world around them—has long been part of epistemology. However, LIS theorists Margaret Egan and Jesse Shera, who coined the term, intended it to address librarianship specifically. This paper argues that social epistemology is well positioned to strengthen the critical practice of information literacy, based both on the social epistemological characteristics of critical theory and the information literacy aspects of the social epistemology stream in the field of philosophy. A review of the critical theoretical trend in LIS literature on information literacy reveals an already-present social epistemological foundation on which LIS research can build to expand the application of critical theory to information literacy. Placing this literature in conversation with itself illuminates the ways in which engagement with social epistemological concerns is already evolving. This paper then critiques the literature and highlights some concerns. Recognition of these weaknesses in otherwise valuable work alerts us to opportunities for improvement. This paper suggests that future progress will be tied to better understanding of the social context of knowledge.

The diversity of reproduction and associated mating patterns in Atlantic salmon (Salmo salar) has long captivated evolutionary biologists. Salmo salar exhibit strategies involving migration, bold mating behaviours and radical morphological and physiological change. One such radical change is the elongation and curvature of the lower jaw in sexually mature males into a hook-like appendage called the kype. The kype is a secondary sexual characteristic used in mating hierarchies and a prime candidate for sexual selection. As one of the core global aquaculture fish species, however, mate choice, and thus sexual selection, has been replaced by industrial artificial fertilization seeking to develop more commercially viable strains. Removal of mate choice provides a unique opportunity to examine the kype over successive generations in the absence of sexual selection. Here we use a large-scale common-garden experiment, incorporating six experimental strains (wild, farmed and wild × farmed hybrids), experiencing one to three sea winters, to assess the impact of age and genetic background. After controlling for allometry, fork length-adjusted kype height (AKH) was significantly reduced in the domesticated strain in comparison to two wild strains. Furthermore, genetic variation at a locus on linkage group SSA1 was associated with kype height, and a locus on linkage group SSA23 was associated with fork length-adjusted kype length (AKL). The reduction in fork length-AKH in domesticated salmon suggests that the kype is of importance in mate choice and that it has decreased due to relaxation of sexual selection. Fork length-AKL showed an increase in domesticated individuals, highlighting that it may not be an important cue in mate choice. These results give us insight into the evolutionary significance of the kype, as well as implications of genetic induced phenotypic change caused by domesticated individuals escaping into the natural environment.

ABSTRACT Sclerotinia sclerotiorum is a plant-pathogenic ascomycete fungus and infects over 400 host plants, including pea (Pisum sativum L.). The fungus causes white mold on pea, and substantial yield loss is attributed to the disease. To improve white mold management, further understanding of S. sclerotiorum pathogenicity is crucial. In this study, 389 transcription factors (TFs) were mined from the complete genome sequence of S. sclerotiorum and their in planta expression patterns were determined in susceptible and partially resistant pea lines and compared to in vitro expression patterns on culture medium. One of the transcription factors was significantly induced in planta at 24 and 48 h postinfection compared to the expression in vitro. This putative C6 transcription factor of S. sclerotiorum (SsC6TF1) was knocked down using a gene-silencing approach to investigate its functions in vegetative growth and sclerotial development as well as its virulence and pathogenicity in pea. While the SsC6TF1 knockdown mutants had hyphal growth rates identical to those of the wild-type strain and were capable of infection, the knockdown mutants produced no sclerotia or significantly fewer and smaller sclerotia on the culture medium and exhibited reduced virulence on both pea lines. This study profiled genome-wide expression for S. sclerotiorum transcription factors in planta and in vitro and functionally characterized a novel transcription factor, SsC6TF1, which positively regulates sclerotial development and virulence on pea. The finding provides molecular insights into S. sclerotiorum biology and interaction with pea and other economically important crops. IMPORTANCE White mold, caused by Sclerotinia sclerotiorum, is a destructive disease on important legume species such as soybean, dry bean, and pea. This study investigated expression levels of transcription factors in S. sclerotiorum in planta (pea lines) and in vitro (culture medium). One transcription factor displaying high expression in planta was found to be involved in sclerotial development and virulence on pea. This report provides a new understanding regarding transcription factors of S. sclerotiorum in development and virulence.

The secretion of peptides and proteins is essential for survival and ecological adaptation of bacteria. Dual-functional ATP-binding cassette transporters export antimicrobial or quorum signaling peptides in Gram-positive bacteria. Their substrates contain a leader sequence that is excised by an N-terminal peptidase C39 domain at a double Gly motif. We characterized the protease domain (LahT150) of a transporter from a lanthipeptide biosynthetic operon in Lachnospiraceae and demonstrate that this protease can remove the leader peptide from a diverse set of peptides. The 2.0 Å resolution crystal structure of the protease domain in complex with a covalently bound leader peptide demonstrates the basis for substrate recognition across the entire class of such transporters. The structural data also provide a model for understanding the role of leader peptide recognition in the translocation cycle, and the function of degenerate, non-functional C39-like domains (CLD) in substrate recruitment in toxin exporters in Gram-negative bacteria.