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We sequenced and comprehensively analysed the genomic architecture of 98 fluorescent pseudomonads isolated from different symptomatic and asymptomatic tissues of almond and a few other Prunus spp. Phylogenomic analyses, genome mining, field pathogenicity tests, and in vitro ice nucleation and antibiotic sensitivity tests were integrated to improve knowledge of the biology and management of bacterial blast and bacterial canker of almond. We identified Pseudomonas syringae pv. syringae, P. cerasi, and P. viridiflava as almond canker pathogens. P. syringae pv. syringae caused both canker and foliar (blast) symptoms. In contrast, P. cerasi and P. viridiflava only caused cankers, and P. viridiflava appeared to be a weak pathogen of almond. Isolates belonging to P. syringae pv. syringae were the most frequently isolated among the pathogenic species/pathovars, composing 75% of all pathogenic isolates. P. cerasi and P. viridiflava isolates composed 8.3 and 16.7% of the pathogenic isolates, respectively. Laboratory leaf infiltration bioassays produced results distinct from experiments in the field with both P. cerasi and P. syringae pv. syringae, causing significant necrosis and browning of detached leaves, whereas P. viridiflava conferred moderate effects. Genome mining revealed the absence of key epiphytic fitness-related genes in P. cerasi and P. viridiflava genomic sequences, which could explain the contrasting field and laboratory bioassay results. P. syringae pv. syringae and P. cerasi isolates harboured the ice nucleation protein, which correlated with the ice nucleation phenotype. Results of sensitivity tests to copper and kasugamycin showed a strong linkage to putative resistance genes. Isolates harbouring the ctpV gene showed resistance to copper up to 600 μg/ml. In contrast, isolates without the ctpV gene could not grow on nutrient agar amended with 200 μg/ml copper, suggesting ctpV can be used to phenotype copper resistance. All isolates were sensitive to kasugamycin at the label-recommended rate of 100μg/ml.

BackgroundWhile early autism intervention can significantly improve outcomes, gaps in implementation exist globally. These gaps are clearest in Africa, where forty percent of the world's children will live by 2050. Task-sharing early intervention to non-specialists is a key implementation strategy, given the lack of specialists in Africa. Naturalistic Developmental Behavioral Interventions (NDBI) are a class of early autism intervention that can be delivered by caregivers. As a foundational step to address the early autism intervention gap, we adapted a non-specialist delivered caregiver coaching NDBI for the South African context, and pre-piloted this cascaded task-sharing approach in an existing system of care.ObjectivesFirst, we will test the effectiveness of the caregiver coaching NDBI compared to usual care. Second, we will describe coaching implementation factors within the Western Cape Department of Education in South Africa.MethodsThis is a type 1 effectiveness-implementation hybrid design; assessor-blinded, group randomized controlled trial. Participants include 150 autistic children (18-72 months) and their caregivers who live in Cape Town, South Africa, and those involved in intervention implementation. Early Childhood Development practitioners, employed by the Department of Education, will deliver 12, one hour, coaching sessions to the intervention group. The control group will receive usual care. Distal co-primary outcomes include the Communication Domain Standard Score (Vineland Adaptive Behavior Scales, Third Edition) and the Language and Communication Developmental Quotient (Griffiths Scales of Child Development, Third Edition). Proximal secondary outcome include caregiver strategies measured by the sum of five items from the Joint Engagement Rating Inventory. We will describe key implementation determinants.ResultsParticipant enrolment started in April 2023. Estimated primary completion date is March 2027.ConclusionThe ACACIA trial will determine whether a cascaded task-sharing intervention delivered in an educational setting leads to meaningful improvements in communication abilities of autistic children, and identify implementation barriers and facilitators.Trial registrationNCT05551728 in Clinical Trial Registry (https://clinicaltrials.gov).

Response activation and inhibition are functions fundamental to executive control that are disrupted in Parkinson disease (PD). We used magnetoencephalography to examine event related changes in oscillatory power amplitude, peak latency and frequency in cortical networks subserving these functions and identified abnormalities associated with PD. Participants (N = 18 PD, 18 control) performed a cue/target task that required initiation of an un-cued movement (activation) or inhibition of a cued movement. Reaction times were variable but similar across groups. Task related responses in gamma, alpha, and beta power were found across cortical networks including motor cortex, supplementary and pre- supplementary motor cortex, posterior parietal cortex, prefrontal cortex and anterior cingulate. PD-related changes in power and latency were noted most frequently in the beta band, however, abnormal power and delayed peak latency in the alpha band in the pre-supplementary motor area was suggestive of a compensatory mechanism. PD peak power was delayed in pre-supplementary motor area, motor cortex, and medial frontal gyrus only for activation, which is consistent with deficits in un-cued (as opposed to cued) movement initiation characteristic of PD.

Bacterial contamination of angiographic materials and fluids has been shown to occur during human angiographic procedures. Angiographic examinations and experiments must be performed under sterile conditions to avoid complications due to contamination and possible subsequent infections. However, data regarding the frequency and the clinical consequences are limited. Our aim was to investigate the incidence of bacterial contamination during experimental angiographies. We tested angiographic fluids, syringes and endovascular materials from the angiographic supply tables for bacterial contamination, collecting 252 samples during 18 experimental angiographies in pigs. After sterile filtration, samples were cultured on media, and individual colony-forming units were identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry. Contamination was detected in the majority of samples (60%). There was no angiography in which all samples remained sterile. The highest contamination rates (94%) were found in fluids from the working bowls and on the outer surface of syringes (85%) at the end of angiography. At this time, working bowls were significantly more frequently and extensively contaminated than the control bowls. Among the samples, the frequency and extent of contamination increased with the duration of the experimental angiographic procedures. Our findings show that bacterial contamination during angiography is common and the manipulation of endovascular working materials as well as the duration of angiographic procedures both increase bacterial contamination. While the clinical impact on the laboratory animal remains unclear, the quality of biomedical research mandates that efforts to minimize bacterial contamination should be taken as far as possible.

Whether the presence of Candida spp. in lower respiratory tract (LRT) secretions is a marker of underlying disease, intensive care unit (ICU) treatment and antibiotic therapy or contributes to poor clinical outcome is unclear. We investigated healthy controls, patients with proposed risk factors for Candida growth in LRT (antibiotic therapy, ICU treatment with and without antibiotic therapy), ICU patients with pneumonia and antibiotic therapy and candidemic patients (for comparison of truly invasive and colonizing Candida spp.). Fungal patterns were determined by conventional culture based microbiology combined with molecular approaches (next generation sequencing, multilocus sequence typing) for description of fungal and concommitant bacterial microbiota in LRT, and host and fungal biomarkes were investigated. Admission to and treatment on ICUs shifted LRT fungal microbiota to Candida spp. dominated fungal profiles but antibiotic therapy did not. Compared to controls, Candida was part of fungal microbiota in LRT of ICU patients without pneumonia with and without antibiotic therapy (63% and 50% of total fungal genera) and of ICU patients with pneumonia with antibiotic therapy (73%) (p

Response activation and inhibition are functions fundamental to executive control that are disrupted in Parkinson disease (PD). We used magnetoencephalography to examine event related changes in oscillatory power amplitude, peak latency and frequency in cortical networks subserving these functions and identified abnormalities associated with PD. Participants (N = 18 PD, 18 control) performed a cue/target task that required initiation of an un-cued movement (activation) or inhibition of a cued movement. Reaction times were variable but similar across groups. Task related responses in gamma, alpha, and beta power were found across cortical networks including motor cortex, supplementary and pre- supplementary motor cortex, posterior parietal cortex, prefrontal cortex and anterior cingulate. PD-related changes in power and latency were noted most frequently in the beta band, however, abnormal power and delayed peak latency in the alpha band in the pre-supplementary motor area was suggestive of a compensatory mechanism. PD peak power was delayed in pre-supplementary motor area, motor cortex, and medial frontal gyrus only for activation, which is consistent with deficits in un-cued (as opposed to cued) movement initiation characteristic of PD.

Data used to train supervised machine learning models are commonly split into independent training, validation, and test sets. This paper illustrates that complex data leakage cases have occurred in the no-reference image and video quality assessment literature. Recently, papers in several journals reported performance results well above the best in the field. However, our analysis shows that information from the test set was inappropriately used in the training process in different ways and that the claimed performance results cannot be achieved. When correcting for the data leakage, the performances of the approaches drop even below the state-of-the-art by a large margin. Additionally, we investigate end-to-end variations to the discussed approaches, which do not improve upon the original.

In preterm and term infants who require intermediate or intensive care Methicillin-resistant Staphylococcus aureus (MRSA) infection can lead to significant morbidity. In this study MRSA colonization and infection were assessed in a mixed tertiary neonatal intensive and intermediate care unit in Germany over an 8-year period (2013-2020). We investigated patient-related factors, associated with nosocomial MRSA acquisition, and we discuss our infection control concept for MRSA. Of 3488 patients treated during the study period, 24 were MRSA positive patients, corresponding to 26 patient hospital stays. The incidence was 0.7 MRSA patients per 100 patients. The incidence density was 0.4 MRSA patient hospital stays per 1000 patient days. Twelve patients (50%) acquired MRSA in the hospital. One patient developed a hospital acquired MRSA bloodstream infection 9 days after birth (i.e., 0.03% of all patients on the ward during the study period). A total of 122 patients had to be screened to detect one MRSA positive patient. In a logistic regression model, the use of 3rd generation intravenous cephalosporin (cefotaxim) was associated with nosocomial MRSA acquisition compared with matched control patients who did not acquire MRSA. In sum, the burden of MRSA colonization and infection in the ward was low during the study period. A comprehensive infection control concept that included microbiologic colonization screening, prospective infection surveillance together with isolation and emphasis on basic hygiene measures is essential to handle MRSA in this specialized setting.

Recently there have been tremendous efforts to develop statistical procedures which allow to determine subgroups of patients for which certain treatments are effective. This article focuses on the selection of prognostic and predictive genetic biomarkers based on a relatively large number of candidate Single Nucleotide Polymorphisms (SNPs). We consider models which include prognostic markers as main effects and predictive markers as interaction effects with treatment. We compare different high-dimensional selection approaches including adaptive lasso, a Bayesian adaptive version of the Sorted L-One Penalized Estimator (SLOBE) and a modified version of the Bayesian Information Criterion (mBIC2). These are compared with classical multiple testing procedures for individual markers. Having identified predictive markers we consider several different approaches how to specify subgroups susceptible to treatment. Our main conclusion is that selection based on mBIC2 and SLOBE has similar predictive performance as the adaptive lasso while including substantially fewer biomarkers.

After spinal cord injury, transected axons fail to regenerate, yet significant, spontaneous functional improvement can be observed over time. Distinct central nervous system regions retain the capacity to generate new neurons and glia from an endogenous pool of progenitor cells and to compensate neural cell loss following certain lesions. The aim of the present study was to investigate whether endogenous cell replacement (neurogenesis or gliogenesis) in the brain (subventricular zone, SVZ; corpus callosum, CC; hippocampus, HC; and motor cortex, MC) or cervical spinal cord might represent a structural correlate for spontaneous locomotor recovery after a thoracic spinal cord injury. Adult Fischer 344 rats received severe contusion injuries (200 kDyn) of the mid-thoracic spinal cord using an Infinite Horizon Impactor. Uninjured rats served as controls. From 4 to 14 days post-injury, both groups received injections of bromodeoxyuridine (BrdU) to label dividing cells. Over the course of six weeks post-injury, spontaneous recovery of locomotor function occurred. Survival of newly generated cells was unaltered in the SVZ, HC, CC, and the MC. Neurogenesis, as determined by identification and quantification of doublecortin immunoreactive neuroblasts or BrdU/neuronal nuclear antigen double positive newly generated neurons, was not present in non-neurogenic regions (MC, CC, and cervical spinal cord) and unaltered in neurogenic regions (dentate gyrus and SVZ) of the brain. The lack of neuronal replacement in the brain and spinal cord after spinal cord injury precludes any relevance for spontaneous recovery of locomotor function. Gliogenesis was increased in the cervical spinal cord remote from the injury site, however, is unlikely to contribute to functional improvement.

As marine ecosystems are influenced by global and regional processes, standardized information on community structure has become crucial for assessing broad-scale responses to natural and anthropogenic disturbances. Extensive biogeographic provinces, such as the Brazilian Province in the southwest Atlantic, present numerous theoretical and methodological challenges for understanding community patterns on a macroecological scale. In particular, the Brazilian Province is composed of a complex system of heterogeneous reefs and a few offshore islands, with contrasting histories and geophysical-chemical environments. Despite the large extent of the Brazilian Province (almost 8,000 kilometers), most studies of shallow benthic communities are qualitative surveys and/or have been geographically restricted. We quantified community structure of shallow reef habitats from 0° to 27°S latitude using a standard photographic quadrat technique. Percent cover data indicated that benthic communities of Brazilian reefs were dominated by algal turfs and frondose macroalgae, with low percent cover of reef-building corals. Community composition differed significantly among localities, mostly because of their macroalgal abundance, despite reef type or geographic region, with no evident latitudinal pattern. Benthic diversity was lower in the tropics, contrary to the general latitudinal diversity gradient pattern. Richness peaked at mid-latitudes, between 20°S to 23°S, where it was ~3.5-fold higher than localities with the lowest richness. This study provides the first large-scale description of benthic communities along the southwestern Atlantic, providing a baseline for macroecological comparisons and evaluation of future impacts. Moreover, the new understanding of richness distribution along Brazilian reefs will contribute to conservation planning efforts, such as management strategies and the spatial prioritization for the creation of new marine protected areas.

Climate change and excess deposition of airborne nitrogen (N) are among the main stressors to floristic biodiversity. One particular concern is the deterioration of valuable habitats such as those protected under the European Habitat Directive. In future, climate-driven shifts (and losses) in the species potential distribution, but also N driven nutrient enrichment may threaten these habitats. We applied a dynamic geochemical soil model (VSD+) together with a novel niche-based plant response model (PROPS) to 5 forest habitat types (18 forest sites) protected under the EU Directive in Austria. We assessed how future climate change and N deposition might affect habitat suitability, defined as the capacity of a site to host its typical plant species. Our evaluation indicates that climate change will be the main driver of a decrease in habitat suitability in the future in Austria. The expected climate change will increase the occurrence of thermophilic plant species while decreasing cold-tolerant species. In addition to these direct impacts, climate change scenarios caused an increase of the occurrence probability of oligotrophic species due to a higher N immobilisation in woody biomass leading to soil N depletion. As a consequence, climate change did offset eutrophication from N deposition, even when no further reduction in N emissions was assumed. Our results show that climate change may have positive side-effects in forest habitats when multiple drivers of change are considered.

ABCF1 is an ABC transporter family protein that has been shown to regulate innate immune response and is a risk gene for autoimmune pancreatitis and arthritis. Unlike other members of ABC transporter family, ABCF1 lacks trans-membrane domains and is thought to function in translation initiation through an interaction with eukaryotic translation initiation factor 2 (eIF2). To study ABCF1 expression and function in development and disease, we used a single gene trap insertion in the Abcf1 gene in murine embryonic stem cells (ES cells) that allowed lineage tracing of the endogenous Abcf1 promoter by following the expression of a β-galactosidase reporter gene. From the ES cells, heterozygous mice (Abcf1+/-) were produced. No live born Abcf1-/- progeny were ever generated, and the lethality was not mouse strain-specific. Thus, we have determined that Abcf1 is an essential gene in development. Abcf1-/- mice were found to be embryonic lethal at 3.5 days post coitum (dpc), while Abcf1+/- mice appeared developmentally normal. Abcf1+/- mice were fertile and showed no significant differences in their anatomy when compared with their wild type littermates. The Abcf1 promoter was found to be active in all organs in adult mice, but varies in levels of expression in specific cell types within tissues. Furthermore, we observed high promoter activity in the blastocysts and embryos. Overall, Abcf1 expression in embryos is required for development and its expression in adults was highly correlated with actively proliferating and differentiating cell types.

Due to limited X-ray contrast, the use of micro-CT in histology is so far not as widespread as predicted. While specific staining procedures-mostly using iodine-address this shortcoming, long diffusion times restrict its use in the often time-constrained daily routine. Recently, a novel staining protocol has been proposed using a biochemical preconditioning step, which increases the permeability of the cells for the staining agent. This could enable the imaging of entire organs of small mammals at a yet unmatched image quality with reasonable preparation and scan times. We here propose an adaptation of this technique for virtual ophthalmology and histology by volumetrically assessing both human and porcine eyes. Hereby, we demonstrate that (contrast-enhanced) micro-CT can outperform conventional histology in the assessment of tumor entities, as well as functioning as a supplementary tool for surgeons in the positioning of intraocular implants in-vitro and as a general assessment tool for ophthalmologic specimens.

BACKGROUND:The aim of our current investigation was to analyze the autoantibody-reactivities of primary open angle glaucoma patients with optic disc hemorrhage as possibly correlated to disease progression by means of a protein microarray approach. METHODS:Sera of patients with primary open angle glaucoma and optic disc hemorrhage (n = 16) were collected directly after study inclusion (0 weeks) and after 2 weeks, 4 weeks and 12 weeks. As a control group patients with primary open angle glaucoma (n = 18) were used (0 weeks and 12 weeks). Microarrays were incubated and occurring antibody-antigen-reactions were visualized with fluorescence labeled anti-human-IgG secondary antibodies. To detect changes in autoantibodies spot intensities were digitized and compared. RESULTS:With respect to the immunoreactivity at 0 weeks level increment of anti-adaptor protein 1 complex subunit mu-1 antibodies and anti-SPRY domain-containing SOCS box protein 3 antibodies in sera of primary open angle patients with optic disc hemorrhage was detected. Linear trend analysis revealed a positive correlation with r ≥ 0.8 between antibody-level and time course. Control group show no relevant changes in the same period. Significant changes were found in time point 4 comparison between patient groups in anti-adaptor protein 1 complex subunit mu-1-level (p = 0.01). No significant changes in visual acuity were found. CONCLUSION:With this approach we were able to detect autoimmune reactivities in sera of patients with primary open angle glaucoma and optic disc hemorrhage compared to patients without optic disc hemorrhage. These antibodies could give further insights into the pathogenesis and the autoimmune component of glaucomatous optic neuropathy.

The search for traits that make alien species invasive has mostly concentrated on comparing successful invaders and different comparison groups with respect to average trait values. By contrast, little attention has been paid to trait variability among invaders. Here, we combine an analysis of trait differences between invasive and non-invasive species with a comparison of multidimensional trait variability within these two species groups. We collected data on biological and distributional traits for 1402 species of the native, non-woody vascular plant flora of Austria. We then compared the subsets of species recorded and not recorded as invasive aliens anywhere in the world, respectively, first, with respect to the sampled traits using univariate and multiple regression models; and, second, with respect to their multidimensional trait diversity by calculating functional richness and dispersion metrics. Attributes related to competitiveness (strategy type, nitrogen indicator value), habitat use (agricultural and ruderal habitats, occurrence under the montane belt), and propagule pressure (frequency) were most closely associated with invasiveness. However, even the best multiple model, including interactions, only explained a moderate fraction of the differences in invasive success. In addition, multidimensional variability in trait space was even larger among invasive than among non-invasive species. This pronounced variability suggests that invasive success has a considerable idiosyncratic component and is probably highly context specific. We conclude that basing risk assessment protocols on species trait profiles will probably face hardly reducible uncertainties.

Everolimus, a mammalian target of rapamycin (mTOR) inhibitor, has demonstrated efficacy in treating subependymal giant cell astrocytomas (SEGAs) and other manifestations of tuberous sclerosis complex (TSC). However, long-term use of mTOR inhibitors might be necessary. This analysis explored long-term efficacy and safety of everolimus from the conclusion of the EXIST-1 study (NCT00789828).EXIST-1 was an international, prospective, double-blind, placebo-controlled phase 3 trial examining everolimus in patients with new or growing TSC-related SEGA. After a double-blind core phase, all remaining patients could receive everolimus in a long-term, open-label extension. Everolimus was initiated at a dose (4.5 mg/m2/day) titrated to a target blood trough of 5-15 ng/mL. SEGA response rate (primary end point) was defined as the proportion of patients achieving confirmed ≥50% reduction in the sum volume of target SEGA lesions from baseline in the absence of worsening nontarget SEGA lesions, new target SEGA lesions, and new or worsening hydrocephalus. Of 111 patients (median age, 9.5 years) who received ≥1 dose of everolimus (median duration, 47.1 months), 57.7% (95% confidence interval [CI], 47.9-67.0) achieved SEGA response. Of 41 patients with target renal angiomyolipomas at baseline, 30 (73.2%) achieved renal angiomyolipoma response. In 105 patients with ≥1 skin lesion at baseline, skin lesion response rate was 58.1%. Incidence of adverse events (AEs) was comparable with that of previous reports, and occurrence of emergent AEs generally decreased over time. The most common AEs (≥30% incidence) suspected to be treatment-related were stomatitis (43.2%) and mouth ulceration (32.4%).Everolimus use led to sustained reduction in tumor volume, and new responses were observed for SEGA and renal angiomyolipoma from the blinded core phase of the study. These findings support the hypothesis that everolimus can safely reverse multisystem manifestations of TSC in a significant proportion of patients.ClinicalTrials.gov NCT00789828.

OBJECTIVE:To evaluate the influence of the soluble fms-like tyrosine kinase 1/placental growth factor ratio in physicians' decision making in pregnant women with signs and symptoms of preeclampsia in routine clinical practice. METHODS:A multicenter, prospective, open, non-interventional study enrolled pregnant women presenting with preeclampsia signs and symptoms in several European perinatal care centers. Before the soluble fms-like tyrosine kinase 1/placental growth factor ratio result was known, physicians documented intended clinical procedures using an iPad® application (data locked/time stamped). After the result was available, clinical decisions were confirmed or revised and documented. An independent adjudication committee evaluated the appropriateness of decisions based on maternal/fetal outcomes. Clinician decision making with regard to hospitalization was the primary outcome. RESULTS:In 16.9% of mothers (20/118) the hospitalization decision was changed after knowledge of the ratio. In 13 women (11.0%), the initial decision to hospitalize was changed to no hospitalization. In seven women (5.9%) the revised decision was hospitalization. All revised decisions were considered appropriate by the panel of adjudicators (McNemar test; p < 0.0001). CONCLUSIONS:The use of the soluble fms-like tyrosine kinase 1/placental growth factor test influenced clinical decision making towards appropriate hospitalization in a considerable proportion of women with suspected preeclampsia. This is the first study to demonstrate the impact of angiogenic biomarkers on decision making in a routine clinical practice.

OBJECTIVES:From previous data in animal models of cerebral ischemia, lipocalin-2 (LCN2), a protein related to neutrophil function and cellular iron homeostasis, is supposed to have a value as a biomarker in ischemic stroke patients. Therefore, we examined LCN2 expression in the ischemic brain in an animal model and measured plasma levels of LCN2 in ischemic stroke patients. METHODS:In the mouse model of transient middle cerebral artery occlusion (tMCAO), LCN2 expression in the brain was analyzed by immunohistochemistry and correlated to cellular nonheme iron deposition up to 42 days after tMCAO. In human stroke patients, plasma levels of LCN2 were determined one week after ischemic stroke. In addition to established predictive parameters such as age, National Institutes of Health Stroke Scale and thrombolytic therapy, LCN2 was included into linear logistic regression modeling to predict clinical outcome at 90 days after stroke. RESULTS:Immunohistochemistry revealed expression of LCN2 in the mouse brain already at one day following tMCAO, and the amount of LCN2 subsequently increased with a maximum at 2 weeks after tMCAO. Accumulation of cellular nonheme iron was detectable one week post tMCAO and continued to increase. In ischemic stroke patients, higher plasma levels of LCN2 were associated with a worse clinical outcome at 90 days and with the occurrence of post-stroke infections. CONCLUSIONS:LCN2 is expressed in the ischemic brain after temporary experimental ischemia and paralleled by the accumulation of cellular nonheme iron. Plasma levels of LCN2 measured in patients one week after ischemic stroke contribute to the prediction of clinical outcome at 90 days and reflect the systemic response to post-stroke infections.

PURPOSE:We investigated the effects of a visual picking system on ocular comfort, the ocular surface and tear function compared to those of a voice guided picking solution. DESIGN:Prospective, observational, cohort study. METHOD: SETTING:Institutional. STUDY POPULATION:A total of 25 young asymptomatic volunteers performed commissioning over 10 hours on two consecutive days. MAIN OUTCOME MEASURES:The operators were guided in the picking process by two different picking solutions, either visually or by voice while their subjective symptoms and ocular surface and tear function parameters were recorded. RESULTS:The visual analogue scale (VAS) values, according to subjective dry eye symptoms, in the visual condition were significantly higher at the end of the commissioning than the baseline measurements. In the voice condition, the VAS values remained stable during the commissioning. The tear break-up time (BUT) values declined significantly in the visual condition (pre-task: 16.6 sec and post-task: 9.6 sec) in the right eyes, that were exposed to the displays, the left eyes in the visual condition showed only a minor decline, whereas the BUT values in the voice condition remained constant (right eyes) or even increased (left eyes) over the time. No significant differences in the tear meniscus height values before and after the commissioning were observed in either condition. CONCLUSION:In our study, the use of visually guided picking solutions was correlated with post-task subjective symptoms and tear film instability.

Low vitamin D levels have been associated with depressive symptoms in population-based studies and non-clinical samples as well as with clinical depression. This study aimed to examine the association of vitamin D levels with the severity and dimensions of depressive symptoms in hospitalized patients with a current episode of depression taking into account confounding variables.We investigated 380 patients (mean age 47 ± 12 years, 70% women) who were consecutively hospitalized with a main diagnosis of an ICD-10 depressive episode. All patients self-rated depressive symptom severity with the Hospital Anxiety and Depression Scale (HADS-D), the Beck Depression Inventory-II (BDI-II), and the Brief Symptom Inventory. A principal component analysis was performed with all 34 items of these questionnaires and serum levels of 25-hydroxyvitamin D3 (25-OH D) were measured.Vitamin D deficiency (< 50 nmol/l), insufficiency (50-75 nmol/l), and sufficiency (> 75 nmol/l) were present in 55.5%, 31.8% and 12.6%, respectively, of patients. Patients with vitamin D deficiency scored higher on the HADS-D scale and on an anhedonia symptom factor than those with insufficient (p-values ≤ 0.023) or sufficient (p-values ≤ 0.008) vitamin D. Vitamin D deficient patients also scored higher on the BDI-II scale than those with sufficient vitamin D (p = 0.007); BDI-II cognitive/affective symptoms, but not somatic/affective symptoms, were higher in patients with vitamin D deficiency (p = 0.005) and insufficiency (p = 0.041) relative to those with sufficient vitamin D. Effect sizes suggested clinically relevant findings.Low vitamin D levels are frequent in hospitalized patients with a current episode of depression. Especially 25-OH D levels < 50 nmol/l were associated with cognitive/affective depressive symptoms, and anhedonia symptoms in particular.

During morphological differentiation of Streptomyces coelicolor A3(2), the sporogenic aerial hyphae are transformed into a chain of more than fifty spores in a highly coordinated manner. Synthesis of the thickened spore envelope is directed by the Streptomyces spore wall synthesizing complex SSSC which resembles the elongasome of rod-shaped bacteria. The SSSC includes the eukaryotic type serine/threonine protein kinase (eSTPK) PkaI, encoded within a cluster of five independently transcribed eSTPK genes (SCO4775-4779). To understand the role of PkaI in spore wall synthesis, we screened a S. coelicolor genomic library for PkaI interaction partners by bacterial two-hybrid analyses and identified several proteins with a documented role in sporulation. We inactivated pkaI and deleted the complete SCO4775-4779 cluster. Deletion of pkaI alone delayed sporulation and produced some aberrant spores. The five-fold mutant NLΔ4775-4779 had a more severe defect and produced 18% aberrant spores affected in the integrity of the spore envelope. Moreover, overbalancing phosphorylation activity by expressing a second copy of any of these kinases caused a similar defect. Following co-expression of pkaI with either mreC or pbp2 in E. coli, phosphorylation of MreC and PBP2 was demonstrated and multiple phosphosites were identified by LC-MS/MS. Our data suggest that elaborate protein phosphorylation controls activity of the SSSC to ensure proper sporulation by suppressing premature cross-wall synthesis.

To evaluate the association between obesity indices and blood pressure (BP) at 4 years of age, in each sex, and to quantify to which extent this association is mediated by inflammation and insulin resistance (IR).We studied 1250 4-year-old children selected from the population-based birth cohort Generation XXI. Associations between body mass index (BMI) z-score and waist-to-height ratio (WHtR), office BP, inflammation (high sensitivity C-reactive protein) and IR (HOMA-IR index) were assessed. Path Analysis, a modified multivariate regression approach, was applied to test causal models and quantify direct and indirect effects of predictors of systolic (SBP) and diastolic BP (DBP).SBP and DBP increased significantly with BMI and WHtR in both sexes. There was a strong direct association (explaining 74.1-93.2% of the total association) of both measures of adiposity with SBP, in both sexes. This association was additionally indirectly mediated by IR, particularly regarding WHtR (20.5% in girls and 9.4% in boys). Mediation by inflammation did not reach statistical significance in either sex. Regarding DBP, the direct effect of adiposity was strong (>95% for BMI and WHtR in boys) and the mediation by IR was much smaller in boys than in girls.The direct association between adiposity and BP in healthy 4-year-old children is strong and IR plays an important mediating role. The strength of effects of IR and inflammation suggests sex differences in the complex interplay between BP, adiposity and inflammation.

Often we cannot resist emotional distraction, because emotions capture our attention. For example, in TV-commercials, tempting emotional voices add an emotional expression to a formerly neutral product. Here, we used a Stroop-like conflict paradigm as a tool to investigate whether emotional capture results in contextual integration of loose mental associations. Specifically, we tested whether the associatively connected meaning of an ignored auditory emotion with a non-emotional neutral visual target would yield a modulation of activation sensitive to emotional conflict in the brain. In an fMRI-study, nineteen participants detected the presence or absence of a little worm hidden in the picture of an apple, while ignoring a voice with an emotional sound of taste (delicious/disgusting). Our results indicate a modulation due to emotional conflict, pronounced most strongly when processing conflict in the context of disgust (conflict: disgust/no-worm vs. no conflict: disgust/worm). For conflict in the context of disgust, insula activity was increased, with activity correlating positively with reaction time in the conflict case. Conflict in the context of deliciousness resulted in increased amygdala activation, possibly due to the resulting "negative" emotion in incongruent versus congruent combinations. These results indicate that our associative stimulus-combinations showed a conflict-dependent modulation of activity in emotional brain areas. This shows that the emotional sounds were successfully contextually integrated with the loosely associated neutral pictures.

Low-birth-weight (LBW) children are born with several risk factors for disease, morbidity and neonatal mortality, even if carried to term. Placental insufficiency leading to hypoxemia and reduced nutritional supply is the main cause for LBW. Brain damage and poor neurological outcome can be the consequence. LBW after being carried to term gives better chances for survival, but these children are still at risk for poor health and the development of cognitive impairments. Preventive therapies are not yet available. We studied the risk/efficacy of chronic prenatal treatment with the anti-oxidative drug allopurinol, as putative preventive treatment in piglets. LBW piglets served as a natural model for LBW. A cognitive holeboard test was applied to study the learning and memory abilities of these allopurinol treated piglets after weaning. Preliminary analysis of the plasma concentrations in sows and their piglets suggested that a daily dose of 15 mg.kg(-1) resulted in effective plasma concentration of allopurinol in piglets. No adverse effects of chronic allopurinol treatment were found on farrowing, birth weight, open field behavior, learning abilities, relative brain, hippocampus and spleen weights. LBW piglets showed increased anxiety levels in an open field test, but cognitive performance was not affected by allopurinol treatment. LBW animals treated with allopurinol showed the largest postnatal compensatory body weight gain. In contrast to a previous study, no differences in learning abilities were found between LBW and normal-birth-weight piglets. This discrepancy might be attributable to experimental differences. Our results indicate that chronic prenatal allopurinol treatment during the third trimester of pregnancy is safe, as no adverse side effects were observed. Compensatory weight gain of treated piglets is a positive indication for the chronic prenatal use of allopurinol in these animals. Further studies are needed to assess the possible preventive effects of allopurinol on brain functions in LBW piglets.

The nature of telencephalic control over premotor and motor circuits is debated. Hypotheses range from complete usurping of downstream circuitry to highly interactive mechanisms of control. We show theoretically and experimentally, that telencephalic song motor control in canaries is consistent with a highly interactive strategy. As predicted from a theoretical model of respiratory control, mild cooling of a forebrain nucleus (HVC) led to song stretching, but further cooling caused progressive restructuring of song, consistent with the hypothesis that respiratory gestures are subharmonic responses to a timescale present in the output of HVC. This interaction between a life-sustaining motor function (respiration) and telencephalic song motor control suggests a more general mechanism of how nonlinear integration of evolutionarily new brain structures into existing circuitry gives rise to diverse, new behavior.

OBJECTIVES: Phase-contrast imaging is a novel X-ray based technique that provides enhanced soft tissue contrast. The aim of this study was to evaluate the feasibility of visualizing human carotid arteries by grating-based phase-contrast tomography (PC-CT) at two different experimental set-ups: (i) applying synchrotron radiation and (ii) using a conventional X-ray tube. MATERIALS AND METHODS: Five ex-vivo carotid artery specimens were examined with PC-CT either at the European Synchrotron Radiation Facility using a monochromatic X-ray beam (2 specimens; 23 keV; pixel size 5.4 µm), or at a laboratory set-up on a conventional X-ray tube (3 specimens; 35-40 kVp; 70 mA; pixel size 100 µm). Tomographic images were reconstructed and compared to histopathology. Two independent readers determined vessel dimensions and one reader determined signal-to-noise ratios (SNR) between PC-CT and absorption images. RESULTS: In total, 51 sections were included in the analysis. Images from both set-ups provided sufficient contrast to differentiate individual vessel layers. All PCI-based measurements strongly predicted but significantly overestimated lumen, intima and vessel wall area for both the synchrotron and the laboratory-based measurements as compared with histology (all p0.53 per mm(2), 95%-CI: 0.35 to 0.70). Although synchrotron-based images were characterized by higher SNRs than laboratory-based images; both PC-CT set-ups had superior SNRs compared to corresponding conventional absorption-based images (p0.98 and >0.84 for synchrotron and for laboratory-based measurements; respectively). CONCLUSION: Experimental PC-CT of carotid specimens is feasible with both synchrotron and conventional X-ray sources, producing high-resolution images suitable for vessel characterization and atherosclerosis research.

In order to test whether rooks (Corvus frugilegus) represent good indicators for the potential circulation of antibiotics in their native habitat, two populations with different migratory behavior were tested for the presence of beta-lactamase producing Enterobacteriaceae and methicillin-resistant Staphylococcus aureus (MRSA). In all, 54 and 102 samples of fresh feces of a migratory and a resident population were investigated. A total of 24 and 3 cefotaxime-resistant enterobacterial isolates were obtained from the migratory and resident population, respectively. In these isolates CTX-M-1 (n = 15), CTX-M-3 (n = 3), and CTX-M-15 (n = 3) genes were detected. TEM-1 and OXA-1 were associated with CTX-M in 3 and 2 isolates, respectively. In two E. coli isolates CMY-2 could be detected, where from one isolate displayed an overexpression of chromosomal AmpC as well. Among E. coli isolates the most common phylogenetic group was A (n = 11) and ST1683 (n = 5). In one E. coli of B2-ST131 the rfbO25b locus was detected. Three Enterobacter isolates were stably derepressed AmpC-producers. In five samples of the migratory population, PVL positive MRSA could be isolated. Two isolates were typed SCCmec IVa, spa type t127, and ST1. Three isolates carried a SCCmec type IVc, with spa type t852 and ST22. The highly significant difference of the occurrence of antibiotic resistance between the migratory population from eastern Europe compared to resident population in our study indicates that rooks may be good indicator species for the evaluation of environmental contamination with antibiotic resistant bacteria, especially due to their ecology, foraging behavior and differing migratory behavior.

Mammary tumors are the most frequent cancers in female dogs exhibiting a variety of histopathological differences. There is lack of knowledge about the genomes of these common dog tumors. Five tumors of three different histological subtypes were evaluated. Massive parallel sequencing (MPS) was performed in comparison to the respective somatic genome of each animal. Copy number and structural aberrations were validated using droplet digital PCR (ddPCR). Using mate-pair sequencing chromosomal aneuploidies were found in two tumors, frequent smaller deletions were found in one, inter-chromosomal fusions in one other, whereas one tumor was almost normal. These aberrations affect several known cancer associated genes such as cMYC, and KIT. One common deletion of the proximal end of CFA27, harboring the tumor suppressor gene PFDN5 was detected in four tumors. Using ddPCR, this deletion was validated and detected in 50% of tumors (N = 20). Breakpoint specific dPCRs were established for four tumors and tumor specific cell-free DNA (cfDNA) was detected in the plasma. In one animal tumor-specific cfDNA was found >1 year after surgery, attributable to a lung metastasis. Paired-end sequencing proved that copy-number imbalances of the tumor are reflected by the cfDNA. This report on chromosomal instability of canine mammary cancers reveals similarities to human breast cancers as well as special canine alterations. This animal model provides a framework for using MPS for screening for individual cancer biomarkers with cost effective confirmation and monitoring using ddPCR. The possibility exists that ddPCR can be expanded to screening for common cancer related variants.

1,25-dihydroxyvitamin D3 (1,25D3) was reported to induce premature organismal aging in fibroblast growth factor-23 (Fgf23) and klotho deficient mice, which is of main interest as 1,25D3 supplementation of its precursor cholecalciferol is used in basic osteoporosis treatment. We wanted to know if 1,25D3 is able to modulate aging processes on a cellular level in human mesenchymal stem cells (hMSC). Effects of 100 nM 1,25D3 on hMSC were analyzed by cell proliferation and apoptosis assay, β-galactosidase staining, VDR and surface marker immunocytochemistry, RT-PCR of 1,25D3-responsive, quiescence- and replicative senescence-associated genes. 1,25D3 treatment significantly inhibited hMSC proliferation and apoptosis after 72 h and delayed the development of replicative senescence in long-term cultures according to β-galactosidase staining and P16 expression. Cell morphology changed from a fibroblast like appearance to broad and rounded shapes. Long term treatment did not induce lineage commitment in terms of osteogenic pathways but maintained their clonogenic capacity, their surface marker characteristics (expression of CD73, CD90, CD105) and their multipotency to develop towards the chondrogenic, adipogenic and osteogenic pathways. In conclusion, 1,25D3 delays replicative senescence in primary hMSC while the pro-aging effects seen in mouse models might mainly be due to elevated systemic phosphate levels, which propagate organismal aging.

Temporal or delay discounting refers to the phenomenon that the value of a reward is discounted as a function of time to delivery. A range of models have been proposed that approximate the shape of the discount curve describing the relationship between subjective value and time. Recent evidence suggests that more than one free parameter may be required to accurately model human temporal discounting data. Nonetheless, many temporal discounting studies in psychiatry, psychology and neuroeconomics still apply single-parameter models, despite their oftentimes poor fit to single-subject data. Previous comparisons of temporal discounting models have either not taken model complexity into account, or have overlooked particular models. Here we apply model comparison techniques in a large sample of temporal discounting datasets using several discounting models employed in the past. Among the models examined, an exponential-power model from behavioural economics (CS model, Ebert & Prelec 2007) provided the best fit to human laboratory discounting data. Inter-parameter correlations for the winning model were moderate, whereas they were substantial for other dual-parameter models examined. Analyses of previous group and context effects on temporal discounting with the winning model provided additional theoretical insights. The CS model may be a useful tool in future psychiatry, psychology and neuroscience work on inter-temporal choice.

BACKGROUND: Dopamine plays an important role in orienting and the regulation of selective attention to relevant stimulus characteristics. Thus, we examined the influences of functional variants related to dopamine inactivation in the dopamine transporter (DAT1) and catechol-O-methyltransferase genes (COMT) on the time-course of visual processing in a contingent negative variation (CNV) task. METHODS: 64-channel EEG recordings were obtained from 195 healthy adolescents of a community-based sample during a continuous performance task (A-X version). Early and late CNV as well as preceding visual evoked potential components were assessed. RESULTS: Significant additive main effects of DAT1 and COMT on the occipito-temporal early CNV were observed. In addition, there was a trend towards an interaction between the two polymorphisms. Source analysis showed early CNV generators in the ventral visual stream and in frontal regions. There was a strong negative correlation between occipito-temporal visual post-processing and the frontal early CNV component. The early CNV time interval 500-1000 ms after the visual cue was specifically affected while the preceding visual perception stages were not influenced. CONCLUSIONS: Late visual potentials allow the genomic imaging of dopamine inactivation effects on visual post-processing. The same specific time-interval has been found to be affected by DAT1 and COMT during motor post-processing but not motor preparation. We propose the hypothesis that similar dopaminergic mechanisms modulate working memory encoding in both the visual and motor and perhaps other systems.

In migrating animals protandry is the phenomenon whereby males of a species arrive at the breeding grounds earlier than females. In the present study we investigated the proximate causes of protandry in a migratory songbird, the northern wheatear Oenanthe oenanthe. Previous experiments with caged birds revealed that males and females show differentiated photoperiod-induced migratory habits. However, it remained open whether protandry would still occur without photoperiodic cues. In this study we kept captive first-year birds under constant photoperiod and environmental conditions in a "common garden" experiment. Male northern wheatears started their spring migratory activity earlier than females, even in the absence of environmental cues. This indicates that protandry in the northern wheatear has an endogenous basis with an innate earlier spring departure of males than females.

BACKGROUND: Due to the use of organophosphates (OP) as pesticides and the availability of OP-type nerve agents, an effective medical treatment for OP poisonings is still a challenging problem. The acute toxicity of an OP poisoning is mainly due to the inhibition of acetylcholinesterase (AChE) in the peripheral and central nervous systems (CNS). This results in an increase in the synaptic concentration of the neurotransmitter acetylcholine, overstimulation of cholinergic receptors and disorder of numerous body functions up to death. The standard treatment of OP poisoning includes a combination of a muscarinic antagonist and an AChE reactivator (oxime). However, these oximes can not cross the blood-brain barrier (BBB) sufficiently. Therefore, new strategies are needed to transport oximes over the BBB. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we combined different oximes (obidoxime dichloride and two different HI 6 salts, HI 6 dichloride monohydrate and HI 6 dimethanesulfonate) with human serum albumin nanoparticles and could show an oxime transport over an in vitro BBB model. In general, the nanoparticulate transported oximes achieved a better reactivation of OP-inhibited AChE than free oximes. CONCLUSIONS/SIGNIFICANCE: With these nanoparticles, for the first time, a tool exists that could enable a transport of oximes over the BBB. This is very important for survival after severe OP intoxication. Therefore, these nanoparticulate formulations are promising formulations for the treatment of the peripheral and the CNS after OP poisoning.

The present study assessed the impact of using irrigation water contaminated with Azithromycin (AZM) residues on the biomass and antioxidant compounds of purple corn; for this purpose, the plants were cultivated under ambient conditions, and the substrate used consisted of soil free from AZM residues, mixed with compost in a ratio of 1:1 (v/v). The experiment was completely randomized with four replications, with treatments of 0, 1, 10, and 100 μg/L of AZM. The results indicate that the presence of AZM in irrigation water at doses of 1 and 10 μg/L increases the weight of dry aboveground biomass, while at an amount of 100 μg/L, it decreases. Likewise, this study reveals that by increasing the concentration of AZM from 1 to 10 μg/L, total polyphenols and monomeric anthocyanins double, in contrast, with an increase to 100 μg/L, these decrease by 44 and 53%, respectively. It has been demonstrated that purple corn exposed to the antibiotic AZM at low doses has a notable antioxidant function in terms of DPPH and ORAC. The content of flavonols, phenolic acids, and flavanols increases by 57, 28, and 83%, respectively, when the AZM concentration is from 1 to 10 μg/L. However, with an increase to 100 μg/L, these compounds decrease by 17, 40, and 42%, respectively. On the other hand, stem length, root length, and dry weight of root biomass are not significantly affected by the presence of AZM in irrigation water.

IntroductionPeople with disabilities are underrepresented in higher education, facing systematic obstacles such as inaccessible communication and physical environments and difficulties obtaining accommodations. This study aims to shed light on barriers to accessibility and disability inclusion in research institutions through confidential qualitative interviews with researchers with disabilities.MethodsWe recruited participants via virtual flyers. Eligibility criteria included working in the United States (U.S.) as researchers that had applied for grant funding (last five years), and self-identifying as having a disability. We offered participants (total n = 35) the option of either semi-structured one-on-one live or written interviews based on their preference. Two study team members analyzed written and live responses using thematic analysis to identify themes.ResultsThemes included identity/visibility, career trajectories, accessibility, accommodations, bias, representation, and inclusion. Some participants reported not disclosing their disabilities at work or during hiring processes due to fear of negative perceptions from peers or potential employers. Experiences around stigma and bias were noted both in professional relationships and when interacting with disability service offices, underscoring difficulties and delays in processes to secure accommodations. Respondents highlighted the lack of disability inclusion and low representation of people with disabilities in academia and elevated the importance of self-advocacy and of role models and mentors in shaping career pathways for future researchers with disabilities.ConclusionResearchers with disabilities encounter systematic barriers at academic institutions, and lack of acknowledgement and research on these experiences has held back institutional and policy changes. To reduce disparities for researchers with disabilities, academic leadership must allocate resources to address ableism, create more inclusive environments, and raise standards beyond compliance with the Americans with Disabilities Act.

We sequenced and comprehensively analysed the genomic architecture of 98 fluorescent pseudomonads isolated from different symptomatic and asymptomatic tissues of almond and a few other Prunus spp. Phylogenomic analyses, genome mining, field pathogenicity tests, and in vitro ice nucleation and antibiotic sensitivity tests were integrated to improve knowledge of the biology and management of bacterial blast and bacterial canker of almond. We identified Pseudomonas syringae pv. syringae, P. cerasi, and P. viridiflava as almond canker pathogens. P. syringae pv. syringae caused both canker and foliar (blast) symptoms. In contrast, P. cerasi and P. viridiflava only caused cankers, and P. viridiflava appeared to be a weak pathogen of almond. Isolates belonging to P. syringae pv. syringae were the most frequently isolated among the pathogenic species/pathovars, composing 75% of all pathogenic isolates. P. cerasi and P. viridiflava isolates composed 8.3 and 16.7% of the pathogenic isolates, respectively. Laboratory leaf infiltration bioassays produced results distinct from experiments in the field with both P. cerasi and P. syringae pv. syringae, causing significant necrosis and browning of detached leaves, whereas P. viridiflava conferred moderate effects. Genome mining revealed the absence of key epiphytic fitness-related genes in P. cerasi and P. viridiflava genomic sequences, which could explain the contrasting field and laboratory bioassay results. P. syringae pv. syringae and P. cerasi isolates harboured the ice nucleation protein, which correlated with the ice nucleation phenotype. Results of sensitivity tests to copper and kasugamycin showed a strong linkage to putative resistance genes. Isolates harbouring the ctpV gene showed resistance to copper up to 600 μg/ml. In contrast, isolates without the ctpV gene could not grow on nutrient agar amended with 200 μg/ml copper, suggesting ctpV can be used to phenotype copper resistance. All isolates were sensitive to kasugamycin at the label-recommended rate of 100μg/ml.

Vancomycin-resistant enterococci (VRE) occur in hospitalized patients, causing both infection and colonization. In recent years, there has been an increase in VRE in German and other hospitals, raising the question of how to control this epidemic best. To better understand the specific epidemiology and to guide infection control, we conducted a retrospective cohort study analyzing all patients with VRE at Hannover Medical School, a tertiary university clinic in Germany that specializes in solid organ transplantation. Epidemiologic and clinical characteristics of patients with VRE from 2015-2017 were collected. Basic epidemiologic parameters, including VRE incidence and incidence density, were calculated. Independent risk factors for nosocomial VRE infection compared to colonization were assessed using a logistic regression model. There were 1,492 VRE cases corresponding to 822 individual patients. The incidence was 0.8 VRE cases per 100 cases. A total of 536 (35.9%) of the 1,492 VRE cases were acquired nosocomially. Of the 1,492 cases, 912 cases had VRE-positive samples (894 Enterococcus (E.) faecium and 18 E. faecalis) in our hospital laboratory and the remaining cases were known VRE carriers. The vanB-phenotype was observed in 369 of the 894 (41.3%) E. faecium isolates and in 6 of the 18 (33.3%) E. faecalis isolates. There was an increase over time in the vanB-phenotype proportion in E. faecium (2015: 63 of 171, 36.8%, 2016: 115 of 322, 35.7% and 2017: 191 of 401, 47.6%). A total of 107 cases had a VRE infection (7.2% of all VRE cases) according to the criteria of the German National Reference Center for Surveillance of Nosocomial Infections. The remaining cases were only colonized. Among other factors, leukocytopenia (

Male contraceptive options and infertility treatments are limited, and almost all innovation has been limited to updates to medically assisted reproduction protocols and methods. To accelerate the development of drugs that can either improve or inhibit fertility, we established a small molecule library as a toolbox for assay development and screening campaigns using human spermatozoa. We have profiled all compounds in the Sperm Toolbox in several automated high-throughput assays that measure stimulation or inhibition of sperm motility or the acrosome reaction. We have assayed motility under non-capacitating and capacitating conditions to distinguish between pathways operating under these different physiological states. We also assayed cell viability to ensure any effects on sperm function are specific. A key advantage of our studies is that all compounds are assayed together in the same experimental conditions, which allows quantitative comparisons of their effects in complementary functional assays. We have combined the resulting datasets to generate fingerprints of the Sperm Toolbox compounds on sperm function. The data are included in an on-line R-based app for convenient querying.

Cesarean births are becoming more common in India, with health implications for both mothers and infants. Between 2005 and 2015, the proportion of cesarean births to total births in India roughly doubled, from 9% to 17%. We analyze Annual Health Survey data from the state of Odisha in eastern India. These population-level, longitudinal data on births between 2007 and 2011 allows us to estimate the association between cesarean birth and breastfeeding outcomes using mother fixed effects. Mother fixed effects allow comparisons of siblings born to the same mother who experienced different types of births (vaginal and cesarean). This empirical strategy controls for many potential observable and unobservable confounders in the relationship. Ordinary Least Squares linear probability models without mother fixed effects find that babies born by cesarean in Odisha are about 14 percentage points (p

BackgroundWhile early autism intervention can significantly improve outcomes, gaps in implementation exist globally. These gaps are clearest in Africa, where forty percent of the world's children will live by 2050. Task-sharing early intervention to non-specialists is a key implementation strategy, given the lack of specialists in Africa. Naturalistic Developmental Behavioral Interventions (NDBI) are a class of early autism intervention that can be delivered by caregivers. As a foundational step to address the early autism intervention gap, we adapted a non-specialist delivered caregiver coaching NDBI for the South African context, and pre-piloted this cascaded task-sharing approach in an existing system of care.ObjectivesFirst, we will test the effectiveness of the caregiver coaching NDBI compared to usual care. Second, we will describe coaching implementation factors within the Western Cape Department of Education in South Africa.MethodsThis is a type 1 effectiveness-implementation hybrid design; assessor-blinded, group randomized controlled trial. Participants include 150 autistic children (18-72 months) and their caregivers who live in Cape Town, South Africa, and those involved in intervention implementation. Early Childhood Development practitioners, employed by the Department of Education, will deliver 12, one hour, coaching sessions to the intervention group. The control group will receive usual care. Distal co-primary outcomes include the Communication Domain Standard Score (Vineland Adaptive Behavior Scales, Third Edition) and the Language and Communication Developmental Quotient (Griffiths Scales of Child Development, Third Edition). Proximal secondary outcome include caregiver strategies measured by the sum of five items from the Joint Engagement Rating Inventory. We will describe key implementation determinants.ResultsParticipant enrolment started in April 2023. Estimated primary completion date is March 2027.ConclusionThe ACACIA trial will determine whether a cascaded task-sharing intervention delivered in an educational setting leads to meaningful improvements in communication abilities of autistic children, and identify implementation barriers and facilitators.Trial registrationNCT05551728 in Clinical Trial Registry (https://clinicaltrials.gov).

Aging elicits numerous effects that impact both musculoskeletal structure and walking function. Tendon stiffness (kT) and push-off propulsive force (FP) both impact the metabolic cost of walking and are diminished by age, yet their interaction has not been studied. We combined experimental and computational approaches to investigate whether age-related changes in function (adopting smaller FP) may be adopted to mitigate the metabolic consequences arising from changes in structure (reduced kT). We recruited 12 young adults and asked them to walk on a force-sensing treadmill while prompting them to change FP (±20% & ±40% of typical) using targeted biofeedback. In models driven by experimental data from each of those conditions, we altered the kT of personalized musculoskeletal models across a physiological range (2-8% strain) and simulated individual-muscle metabolic costs for each kT and FP combination. We found that kT and FP independently affect walking metabolic cost, increasing with higher kT or as participants deviated from their typical FP. Our results show no evidence for an interaction between kT and FP in younger adults walking at fixed speeds. We also reveal complex individual muscle responses to the kT and FP landscape. For example, although total metabolic cost increased by 5% on average with combined reductions in kT and FP, the triceps surae muscles experienced a 7% local cost reduction on average. Our simulations suggest that reducing FP during walking would not mitigate the metabolic consequences of lower kT. Wearable devices and rehabilitative strategies can focus on either kT or FP to reduce age-related increases in walking metabolic cost.

Complex systems such as the global climate, biological organisms, civilisation, technical or social networks exhibit diverse behaviours at various temporal and spatial scales, often characterized by nonlinearity, feedback loops, and emergence. These systems can be characterized by physical quantities such as entropy, information, chaoticity or fractality rather than classical quantities such as time, velocity, energy or temperature. The drawback of these complexity quantities is that their definitions are not always mathematically exact and computational algorithms provide estimates rather than exact values. Typically, evaluations can be cumbersome, necessitating specialized tools. We are therefore introducing ComsystanJ, a novel and user-friendly software suite, providing a comprehensive set of plugins for complex systems analysis, without the need for prior programming knowledge. It is platform independent, end-user friendly and extensible. ComsystanJ combines already known algorithms and newer methods for generalizable analysis of 1D signals, 2D images and 3D volume data including the generation of data sets such as signals and images for testing purposes. It is based on the framework of the open-source image processing software Fiji and ImageJ2. ComsystanJ plugins are macro recordable and are maintained as open-source software. ComsystanJ includes effective surrogate analysis in all dimensions to validate the features calculated by the different algorithms. Future enhancements of the project will include the implementation of parallel computing for image stacks and volumes and the integration of artificial intelligence methods to improve feature recognition and parameter calculation.