Frontal alpha asymmetry is associated with chronic stress and depression, but not with somatoform disorders.

Cardinal characteristics of somatoform disorders (SFDs) are worry of illness, and impaired affective processing. We used relative frontal alpha asymmetry (FAA), a method to measure functional lateralization of affective processing, to investigate psychobiological correlates of SFDs. With alpha activity being inversely related to cortical network activity, relative FAA refers to alpha activity on the right frontal lobe minus alpha activity on the left frontal lobe. Less relative left frontal activity, reflected by negative FAA scores, is associated with lower positive and greater negative affectivity, such as observed in depression. Due to its negative affective component (illness anxiety), we expected to find less relative left frontal activity pattern in SFDs, and positive associations with self-reported chronic stress and depression symptoms. We recorded resting-state EEG activity with 64 electrodes, placed in a 10-10 system in 26 patients with a primary SFD, 23 patients with a major depressive disorder and 25 healthy control participants. The groups did not differ in FAA. Nevertheless, across all participants, less relative left frontal activity was associated with chronic stress and depression symptoms. We concluded that FAA may not serve as an indicator of SFDs. As the relationship of FAA and depressive symptoms was fully mediated by chronic stress, future studies have to clarify whether the association between FAA and chronic stress may represent a shared underlying factor for the manifestation of mental health complaints, such as depression.

A Prospective, Observational, Non-interventional Clinical Study of Participants With Choroideremia: The NIGHT Study.

PURPOSE: The NIGHT study aimed to assess the natural history of choroideremia (CHM), an X-linked inherited chorioretinal degenerative disease leading to blindness, and determine which outcomes would be the most sensitive for monitoring disease progression. DESIGN: A prospective, observational, multicenter cohort study. METHODS: Males aged ≥18 years with genetically confirmed CHM, visible active disease within the macular region, and best-corrected visual acuity (BCVA) ≥34 Early Treatment Diabetic Retinopathy Study (ETDRS) letters at baseline were assessed for 20 months. The primary outcome was the change in BCVA over time at Months 4, 8, 12, 16, and 20. A range of functional and anatomical secondary outcome measures were assessed up to Month 12, including retinal sensitivity, central ellipsoid zone (EZ) area, and total area of fundus autofluorescence (FAF). Additional ocular assessments for safety were performed. RESULTS: A total of 220 participants completed the study. The mean BCVA was stable over 20 months. Most participants (81.4% in the worse eye and 77.8% in the better eye) had change from baseline > -5 ETDRS letters at Month 20. Interocular symmetry was low overall. Reductions from baseline to Month 12 were observed (worse eye, better eye) for retinal sensitivity (functional outcome; -0.68 dB, -0.48 dB), central EZ area (anatomical outcome; -0.276 mm2, -0.290 mm2), and total area of FAF (anatomical outcome; -0.605 mm2, -0.533 mm2). No assessment-related serious adverse events occurred. CONCLUSIONS: Retinal sensitivity, central EZ area, and total area of FAF are more sensitive than BCVA in measuring the natural progression of CHM.

A multiscale accuracy assessment of moisture content predictions using time-lapse electrical resistivity tomography in mine tailings.

Accurate and large-scale assessment of volumetric water content (VWC) plays a critical role in mining waste monitoring to mitigate potential geotechnical and environmental risks. In recent years, time-lapse electrical resistivity tomography (TL-ERT) has emerged as a promising monitoring approach that can be used in combination with traditional invasive and point-measurements techniques to estimate VWC in mine tailings. Moreover, the bulk electrical conductivity (EC) imaged using TL-ERT can be converted into VWC in the field using petrophysical relationships calibrated in the laboratory. This study is the first to assess the scale effect on the accuracy of ERT-predicted VWC in tailings. Simultaneous and co-located monitoring of bulk EC and VWC are carried out in tailings at five different scales, in the laboratory and in the field. The hydrogeophysical datasets are used to calibrate a petrophysical model used to predict VWC from TL-ERT data. Overall, the accuracy of ERT-predicted VWC is [Formula: see text], and the petrophysical models determined at sample-scale in the laboratory remain valid at larger scales. Notably, the impact of temperature and pore water EC evolution plays a major role in VWC predictions at the field scale (tenfold reduction of accuracy) and, therefore, must be properly taken into account during the TL-ERT data processing using complementary hydrogeological sensors. Based on these results, we suggest that future studies using TL-ERT to predict VWC in mine tailings could use sample-scale laboratory apparatus similar to the electrical resistivity Tempe cell presented here to calibrate petrophysical models and carefully upscale them to field applications.

Deep learning model for automatic differentiation of EMAP from AMD in macular atrophy.

To create a deep learning (DL) classifier pre-trained on fundus autofluorescence (FAF) images that can assist the clinician in distinguishing age-related geographic atrophy from extensive macular atrophy and pseudodrusen-like appearance (EMAP). Patients with complete outer retinal and retinal pigment epithelium atrophy secondary to either EMAP (EMAP Group) or to dry age related macular degeneration (AMD group) were retrospectively selected. Fovea-centered posterior pole (30° × 30°) and 55° × 55° degree-field-of-view FAF images of sufficiently high quality were collected and used to train two different deep learning (DL) classifiers based on ResNet-101 design. Testing was performed on a set of images coming from a different center. A total of 300 patients were recruited, 135 belonging to EMAP group and 165 belonging to AMD group. The 30° × 30° FAF based DL classifier showed a sensitivity of 84.6% and a specificity of 85.3% for the diagnosis of EMAP. The 55° × 55° FAF based DL classifier showed a sensitivity of 90% and a specificity of 84.6%, a performance that was significantly higher than that of the 30° × 30° classifer (p = 0.037). Artificial intelligence can accurately distinguish between atrophy caused by AMD or by EMAP on FAF images. Its performance are improved using wide field acquisitions.

A Review on Applications of Time-Lapse Electrical Resistivity Tomography Over the Last 30 Years : Perspectives for Mining Waste Monitoring.

Mining operations generate large amounts of wastes which are usually stored into large-scale storage facilities which pose major environmental concerns and must be properly monitored to manage the risk of catastrophic failures and also to control the generation of contaminated mine drainage. In this context, non-invasive monitoring techniques such as time-lapse electrical resistivity tomography (TL-ERT) are promising since they provide large-scale subsurface information that complements surface observations (walkover, aerial photogrammetry or remote sensing) and traditional monitoring tools, which often sample a tiny proportion of the mining waste storage facilities. The purposes of this review are as follows: (i) to understand the current state of research on TL-ERT for various applications; (ii) to create a reference library for future research on TL-ERT and geoelectrical monitoring mining waste; and (iii) to identify promising areas of development and future research needs on this issue according to our experience. This review describes the theoretical basis of geoelectrical monitoring and provides an overview of TL-ERT applications and developments over the last 30 years from a database of over 650 case studies, not limited to mining operations (e.g., landslide, permafrost). In particular, the review focuses on the applications of ERT for mining waste characterization and monitoring and a database of 150 case studies is used to identify promising applications for long-term autonomous geoelectrical monitoring of the geotechnical and geochemical stability of mining wastes. Potential challenges that could emerge from a broader adoption of TL-ERT monitoring for mining wastes are discussed. The review also considers recent advances in instrumentation, data acquisition, processing and interpretation for long-term monitoring and draws future research perspectives and promising avenues which could help improve the design and accuracy of future geoelectric monitoring programs in mining wastes.

Precision Medicine for Rheumatoid Arthritis: The Right Drug for the Right Patient-Companion Diagnostics.

Despite the growing number of biologic and JAK inhibitor therapeutic agents available to treat various systemic autoimmune illnesses, the lack of a validated companion diagnostic (CDx) to accurately predict drug responsiveness for an individual results in many patients being treated for years with expensive, ineffective, or toxic drugs. This review will focus primarily on rheumatoid arthritis (RA) therapeutics where the need is greatest due to poor patient outcomes if the optimum drug is delayed. We will review current FDA-approved biologic and small molecule drugs and why RA patients switch these medications. We will discuss the sampling of various tissues for potential CDx and review early results from studies investigating drug responsiveness utilizing advanced technologies including; multiplex testing of cytokines and proteins, autoantibody profiling, genomic analysis, proteomics, miRNA analysis, and metabolomics. By using these new technologies for CDx the goal is to improve RA patient outcomes and achieve similar successes like those seen in oncology using precision medicine guided therapeutics.

Myosteatosis rather than sarcopenia associates with non-alcoholic steatohepatitis in non-alcoholic fatty liver disease preclinical models.

BACKGROUND: Non-alcoholic fatty liver (NAFL) disease (NAFLD) is the most common chronic liver disease in the world. While most subjects have 'inert' NAFL, a subset will progress to non-alcoholic steatohepatitis (NASH) and its life-threatening complications. A substantial body of literature supports that a low muscle mass, low strength, and/or muscle fatty infiltration (myosteatosis) are associated with NAFLD severity. Here, we evaluated the muscle compartment in NASH preclinical models to decipher the kinetics of muscle alterations in relation with liver disease progression. METHODS: We developed and validated a micro-computed tomography-based methodology to prospectively study skeletal muscle mass and density in muscle and liver (i.e. reflecting fatty infiltration) in a high-throughput and non-invasive manner in three preclinical NAFLD/NASH rodent models: fat aussie (FOZ) mice fed a high-fat diet (FOZ HF), wild-type (WT) mice fed a high-fat high-fructose diet (WT HFF), and WT mice fed a high-fat diet (WT HF). We compared them with WT mice fed a normal diet (WT ND) used as controls. RESULTS: -FOZ HF with fibrosing NASH had sarcopenia characterized by a reduced muscle strength when compared with WT HF and WT HFF with early NASH and WT ND controls (165.2 ± 5.2 g vs. 237.4 ± 11.7 g, 256 ± 5.7 g, and 242.9 ± 9.3 g, respectively, P 60; 0.001). Muscle mass or strength was not lower in FOZ HF, WT HF, and WT HFF with early NASH than in controls. Myosteatosis was present in FOZ HF with fibrosing NASH, but also in FOZ HF, WT HF, and WT HFF with early NASH (muscle density = 0.50 ± 0.02, 0.62 ± 0.02, 0.70 ± 0.05, and 0.75 ± 0.03, respectively, with P 60; 0.001 when compared with respective controls). Myosteatosis degree was strongly correlated with NAFLD activity score (r = -0.87, n = 67, P 60; 0.001). In multivariate analysis, the association between myosteatosis and NASH was independent from homeostatic model assessment of insulin resistance and visceral fat area (P 60; 0.05). Myosteatosis degree powerfully discriminated NASH from benign NAFL and normal liver (area under the receiver operating characteristic = 0.96, n = 67, P 60; 0.001). CONCLUSIONS: Taken together, our data support that there is no sarcopenia in obese mice with early NASH. In contrast, the severity of myosteatosis reflects on hepatocellular damage and inflammation during early NASH development. This observation prompts us to exploit myosteatosis as a novel non-invasive marker of NASH.

Early detection of emerging zoonotic diseases with animal morbidity and mortality monitoring.

Diseases transmitted between animals and people have made up more than 50% of emerging infectious diseases in humans over the last 60 years and have continued to arise in recent months. Yet, public health and animal disease surveillance programs continue to operate independently. Here, we assessed whether recent emerging zoonotic pathogens (n = 143) are known to cause morbidity or mortality in their animal host and if so, whether they were first detected with an animal morbidity/mortality event. We show that although sick or dead animals are often associated with these pathogens (52%), only 9% were first detected from an animal morbidity or mortality event prior to or concurrent with signs of illness in humans. We propose that an animal morbidity and mortality reporting program will improve detection and should be an essential component of early warning systems for zoonotic diseases. With the use of widespread low-cost technology, such a program could engage both the public and professionals and be easily tested and further incorporated as part of surveillance efforts by public health officials.

Safety of falciparum malaria diagnostic strategy based on rapid diagnostic tests in returning travellers and migrants: a retrospective study.

BACKGROUND: Rapid diagnostic tests for malaria (RDTs) allow accurate diagnosis and prompt treatment. Validation of their usefulness in travellers with fever was needed. The safety of a strategy to diagnose falciparum malaria based on RDT followed by immediate or delayed microscopy reading at first attendance was evaluated in one referral hospital in Switzerland. METHODS: A retrospective study was conducted in the outpatient clinic and emergency ward of University Hospital, covering a period of eight years (1999-2007). The study was conducted in the outpatient clinic and emergency ward of University Hospital. All adults suspected of malaria with a diagnostic test performed were included. RDT and microscopy as immediate tests were performed during working hours, and RDT as immediate test and delayed microscopy reading out of laboratory working hours. The main outcome measure was occurrence of specific complications in RDT negative and RDT positive adults. RESULTS: 2,139 patients were recruited. 1987 had both initial RDT and blood smear (BS) result negative. Among those, 2/1987 (0.1%) developed uncomplicated malaria with both RDT and BS positive on day 1 and day 6 respectively. Among the 152 patients initially malaria positive, 137 had both RDT and BS positive, four only BS positive and five only RDT positive (PCR confirmed) (six had only one test performed). None of the four initially RDT negative/BS positive and none of the five initially BS negative/RDT positive developed severe malaria while 6/137 of both RDT and BS positive did so. The use of RDT allowed a reduction of a median of 2.1 hours to get a first malaria test result. CONCLUSIONS: A malaria diagnostic strategy based on RDTs and a delayed BS is safe in non-immune populations, and shortens the time to first malaria test result.

Sex difference and the role of leptin in the association between high-sensitivity C-reactive protein and adiposity in two different populations.

Elevated high-sensitivity C-reactive protein (hs-CRP) concentration is associated with an increased risk of cardiovascular disease but this association seems to be largely mediated via conventional cardiovascular risk factors. In particular, the association between hs-CRP and obesity has been extensively demonstrated and correlations are stronger in women than men. We used fractional polynomials--a method that allows flexible modeling of non linear relations--to investigate the dose/response mathematical relationship between hs-CRP and several indicators of adiposity in Caucasians (Switzerland) and Africans (Seychelles) surveyed in two population-based studies. This relationship was non-linear exhibiting a steeper slope for low levels of hs-CRP and a higher level in women. The observed sex difference in the relationship between hs-CRP and adiposity almost disappeared upon adjustment for leptin, suggesting that these sex differences might be partially mediated, by leptin. All these relationship were similar in Caucasians and Africans. This is the first report on a non-linear relation, stratified by gender, between hs-CRP and adiposity.

Relation between high-sensitivity C-reactive protein and cardiovascular and renal markers in a middle-income country in the African region.

BACKGROUND: High-sensitivity C-reactive protein (hs-CRP) is associated with several cardiovascular risk factors (CVRF) and with renal function markers. However, these associations have not been examined in populations in the African region. We analyzed the distribution of hs-CRP and the relationship with a broad set of CVRF, renal markers and carotid intima-media thickness (IMT), in the Seychelles (African region). METHODS: We conducted a survey in the population aged 25-64 years (n=1255, participation rate: 80.2%). Analyses were restricted to persons of predominantly African descent (n=1011). RESULTS: Mean and median hs-CRP serum concentrations (mg/l) were 3.1 (SD 7.6) and 1.4 (IQR 0.7-2.9) in men and 4.5 (SD 6.7) and 2.2 (IQR 1.0-5.4) in women (p<0.001 for difference between men and women). hs-CRP was significantly associated with several conventional CVRF, and particularly strongly with markers of adiposity. With regards to renal markers, hs-CRP was strongly associated with cystatin C and with microalbuminuria but not with creatinine. hs-CRP was not associated with IMT. CONCLUSIONS: Serum concentration of hs-CRP was significantly associated with sex, several CVRF and selected renal function markers, which extends similar findings in Europe and in North America to a population in the African region. These findings can contribute to guide recommendations for the use of hs-CRP in clinical practice in the region.

Grand challenges in migration biology.

Billions of animals migrate each year. To successfully reach their destination, migrants must have evolved an appropriate genetic program and suitable developmental, morphological, physiological, biomechanical, behavioral, and life-history traits. Moreover, they must interact successfully with biotic and abiotic factors in their environment. Migration therefore provides an excellent model system in which to address several of the "grand challenges" in organismal biology. Previous research on migration, however, has often focused on a single aspect of the phenomenon, largely due to methodological, geographical, or financial constraints. Integrative migration biology asks 'big questions' such as how, when, where, and why animals migrate, which can be answered by examining the process from multiple ecological and evolutionary perspectives, incorporating multifaceted knowledge from various other scientific disciplines, and using new technologies and modeling approaches, all within the context of an annual cycle. Adopting an integrative research strategy will provide a better understanding of the interactions between biological levels of organization, of what role migrants play in disease transmission, and of how to conserve migrants and the habitats upon which they depend.

Evidence for repeated independent evolution of migration in the largest family of bats.

BACKGROUND: How migration evolved represents one of the most poignant questions in evolutionary biology. While studies on the evolution of migration in birds are well represented in the literature, migration in bats has received relatively little attention. Yet, more than 30 species of bats are known to migrate annually from breeding to non-breeding locations. Our study is the first to test hypotheses on the evolutionary history of migration in bats using a phylogenetic framework. METHODS AND PRINCIPAL FINDINGS: In addition to providing a review of bat migration in relation to existing hypotheses on the evolution of migration in birds, we use a previously published supertree to formulate and test hypotheses on the evolutionary history of migration in bats. Our results suggest that migration in bats has evolved independently in several lineages potentially as the need arises to track resources (food, roosting site) but not through a series of steps from short- to long-distance migrants, as has been suggested for birds. Moreover, our analyses do not indicate that migration is an ancestral state but has relatively recently evolved in bats. Our results also show that migration is significantly less likely to evolve in cave roosting bats than in tree roosting species. CONCLUSIONS AND SIGNIFICANCE: This is the first study to provide evidence that migration has evolved independently in bat lineages that are not closely related. If migration evolved as a need to track seasonal resources or seek adequate roosting sites, climate change may have a pivotal impact on bat migratory habits. Our study provides a strong framework for future research on the evolution of migration in chiropterans.

Inferior vena cava syndrome due to Echinococcus multilocularis.

Alveolar echinococcosis is an invasive, tumor-like zoonosis, accidentally transmitted to humans. We present a case of recurrent inferior vena cava (IVC) syndrome due to alveolar echinococcosis and strongly suspected on transthoracic echocardiographic examination.

Adrenocortical responses to offspring-directed threats in two open-nesting birds.

Dependent young are often easy targets for predators, so for many parent vertebrates, responding to offspring-directed threats is a fundamental part of reproduction. We tested the parental adrenocortical response of the endangered black-capped vireo (Vireo atricapilla) and the common white-eyed vireo (V. griseus) to acute and chronic threats to their offspring. Like many open-nesting birds, our study species experience high offspring mortality. Parents responded behaviorally to a predator decoy or human 1-2m from their nests, but, in contrast to similar studies of cavity-nesting birds, neither these acute threats nor chronic offspring-directed threats altered plasma corticosterone concentrations of parents. Although parents in this study showed no corticosterone response to offspring-directed threats, they always increased corticosterone concentrations in response to capture. To explain these results, we propose that parents perceive their risk of nest-associated death differently depending on nest type, with cavity-nesting adults perceiving greater risk to themselves than open-nesters that can readily detect and escape from offspring-directed threats. Our results agree with previous studies suggesting that the hypothalamic-pituitary-adrenal axis, a major physiological mechanism for coping with threats to survival, probably plays no role in coping with threats to offspring when risks to parents and offspring are not correlated. We extend that paradigm by demonstrating that nest style may influence how adults perceive the correlation between offspring-directed and self-directed threats.

No energetic cost of anthropogenic disturbance in a songbird.

Anthropogenic or natural disturbances can have a significant impact on wild animals. Therefore, understanding when, how and what type of human and natural events disturb animals is a central problem in wildlife conservation. However, it can be difficult to identify which particular environmental stressor affects an individual most. We use heart rate telemetry to quantify the energy expenditure associated with different types of human-mediated and natural disturbances in a breeding passerine, the white-eyed vireo (Vireo griseus). We fitted 0.5g heart rate transmitters to 14 male vireos and continuously recorded heart rate and activity for two days and three nights on a military installation. We calibrated heart rate to energy expenditure for five additional males using an open-flow, push-through respirometry system showing that heart rate predicted 74 per cent of energy expenditure. We conducted standardized disturbance trials in the field to experimentally simulate a natural stressor (predator presence) and two anthropogenic stressors. Although birds initially showed behavioural and heart rate reactions to some disturbances, we could not detect an overall increase in energy expenditure during 1- or 4-hours disturbances. Similarly, overall activity rates were unaltered between control and experimental periods, and birds continued to perform parental duties despite the experimental disturbances. We suggest that vireos quickly determined that disturbances were non-threatening and thus showed no (costly) physiological response. We hypothesize that the lack of a significant response to disturbance in vireos is adaptive and may be representative of animals with fast life histories (e.g. short lifespan, high reproductive output) so as to maximize energy allocation to reproduction. Conversely, we predict that energetic cost of human-mediated disturbances will be significant in slow-living animals.

Intercepting free falling objects: better use Occam's razor than internalize Newton's law.

Several studies have recently provided empirical data supporting the view that gravity has been embodied in a quantitative internal model of gravity thereby permitting access to exact time-to-contact (TTC) when intercepting a free falling object. In this review, we discuss theoretical and methodological concerns with the experiments that supposedly support the assumption of a predictive and accurate model of gravity. Having done so, we then propose that only a "qualitative implicit physics knowledge" of the effects of gravity is used as an approximate pre-information that influences timing of interceptive actions in the specific case of free falling objects. Clear evidence remains to be provided to define how this knowledge is combined with optical information for on-line timing of interceptive actions.

A molecular comparison of plumage and soil bacteria across biogeographic, ecological, and taxonomic scales.

We used molecular methods to determine the microbial community of soil and avian plumage across biogeographic, ecological, and taxonomic scales. A total of 17 soil and 116 feather samples were collected from five avian species across multiple habitat types within one Neotropical and one temperate locality. Hypotheses regarding patterns of microbial composition relative to acquisition and dispersal of plumage bacteria in the ecosystem were tested by comparing microbial communities within and between soil and plumage. Samples from the plumage of American Redstarts (Setophaga ruticilla) were collected across both habitat types and geographic scales for intraspecific comparisons. The microbial diversity in avian plumage was moderately diverse and was dominated by Pseudomonas species. Despite a highly significant individual bird effect on microbial composition of the plumage, we detected significant biogeographic and type of habitat effects. Pseudomonas species were more abundant on the temperate site when all avian species were included in the analysis, and Bacillus subtilis and Xanthomonas groups were more abundant on the Neotropical site for redstarts alone. However, 16S rDNA sequence libraries were not significantly different between Jamaican and Maryland redstarts. Biogeographic and habitat effects were significant and more pronounced for soil samples indicating lower dispersal of soil microbiota. We detected a significant difference between soil and plumage microbial communities suggesting that soil plays a small role in plumage bacterial acquisition. Our results suggest bacterial communities on the plumage of birds are dynamic and may change at different stages in a bird's annual cycle.