Dynamic longitudinal discriminant analysis using multiple longitudinal markers of different types

There is an emerging need in clinical research to accurately predict patients disease status and disease progression by optimally integrating multivariate clinical information. Clinical data is often collected over time for multiple biomarkers of different types (e.g. continuous, binary, counts). In this paper, we present a flexible and dynamic (time-dependent) discriminant analysis approach in which multiple biomarkers of various types are jointly modelled for classification purposes by the multivariate generalized linear mixed model. We propose a mixture of normal distributions for the random effects to allow additional flexibility when modelling the complex correlation between longitudinal biomarkers and to robustify the model and the classification procedure against misspecification of the random effects distribution. These longitudinal models are subsequently used in a multivariate time-dependent discriminant scheme to predict, at any time point, the probability of belonging to a particular risk group. The methodology is illustrated using clinical data from patients with epilepsy, where the aim is to identify patients who will not achieve remission of seizures within a 5-year follow up period

Recent Advances in Sulfidated Zerovalent Iron for Contaminant Transformation

2021 marks 10 years since controlled abiotic synthesis of sulfidated nanoscale zerovalent iron (S-nZVI) for use in site remediation and water treatment emerged as an area of active research. It was then expanded to sulfidated microscale ZVI (S-mZVI) and together with S-nZVI, they are collectively referred to as S-(n)ZVI. Heightened interest in S-(n)ZVI stemmed from its significantly higher reactivity to chlorinated solvents and heavy metals. The extremely promising research outcomes during the initial period (2011-2017) led to renewed interest in (n)ZVI-based technologies for water treatment, with an explosion in new research in the last four years (2018-2021) that is building an understanding of the novel and complex role of iron sulfides in enhancing reactivity of (n)ZVI. Numerous studies have focused on exploring different S-(n)ZVI synthesis approaches, and its colloidal, surface, and reactivity (electrochemistry, contaminant selectivity, and corrosion) properties. This review provides a critical overview of the recent milestones in S-(n)ZVI technology development: (i) clear insights into the role of iron sulfides in contaminant transformation and long-term aging, (ii) impact of sulfidation methods and particle characteristics on reactivity, (iii) broader range of treatable contaminants, (iv) synthesis for complete decontamination, (v) ecotoxicity, and (vi) field implementation. In addition, this review discusses major knowledge gaps and future avenues for research opportunities

Neuregulin repellent signaling via ErbB4 restricts GABAergic interneurons to migratory paths from ganglionic eminence to cortical destinations

<p>Abstract</p> <p>Background</p> <p>Cortical GABAergic interneurons (INs) are generated in the medial ganglionic eminence (MGE) and migrate tangentially into cortex. Because most, if not all, migrating MGE-derived INs express the neuregulin (NRG) receptor, ErbB4, we investigated influences of Nrg1 isoforms and Nrg3 on IN migration through ventral telencephalon (vTel) and within cortex.</p> <p>Results</p> <p>During IN migration, NRG expression domains and distributions of ErbB4-expressing, MGE-derived INs are complementary with minimal overlap, both in vTel and cortex. In wild-type mice, within fields of NRG expression, these INs are focused at positions of low or absent NRG expression. However, in ErbB4-/- HER4^heartmutant mice in which INs lack ErbB4, these complementary patterns are degraded with considerable overlap evident between IN distribution and NRG expression domains. These findings suggest that NRGs are repellents for migrating ErbB4-expressing INs, a function supported by <it>in vitro </it>and <it>in vivo </it>experiments. First, in collagen co-cultures, MGE-derived cells preferentially migrate away from a source of secreted NRGs. Second, cells migrating from wild-type MGE explants on living forebrain slices from wild-type embryonic mice tend to avoid endogenous NRG expression domains, whereas this avoidance behavior is not exhibited by ErbB4-deficient cells migrating from MGE explants and instead they have a radial pattern with a more uniform distribution. Third, ectopic NRG expression in the IN migration pathway produced by <it>in utero </it>electroporation blocks IN migration and results in cortex distal to the blockade being largely devoid of INs. Finally, fewer INs reach cortex in ErbB4 mutants, indicating that NRG-ErbB4 signaling is required for directing IN migration from the MGE to cortex.</p> <p>Conclusions</p> <p>Our results show that NRGs act as repellents for migrating ErbB4-expressing, MGE-derived GABAergic INs and that the patterned expression of NRGs funnels INs as they migrate from the MGE to their cortical destinations.</p

Parallel and divergent morphological adaptations underlying the evolution of jumping ability in ants

Jumping is a rapid locomotory mode widespread in terrestrial organisms. However, it is a rare specialization in ants. Forward jumping has been reported within four distantly related ant genera: Gigantiops, Harpegnathos, Myrmecia, and Odontomachus. The temporal engagement of legs/body parts during jump, however, varies across these genera. It is unknown what morphological adaptations underlie such behaviors and whether jumping in ants is solely driven directly by muscle contraction or additionally relies on elastic recoil mechanism. We investigated the morphological adaptations for jumping behavior by comparing differences in the locomotory musculature between jumping and non-jumping relatives using X-ray micro-CT and 3D morphometrics. We found that the size-specific volumes of the trochanter depressor muscle (scm6) of the middle and hind legs are 3-5 times larger in jumping ants, and that one coxal remotor muscle (scm2) is reduced in volume in the middle and/or hind legs. Notably, the enlargement in the volume of other muscle groups is directly linked to the legs or body parts engaged during the jump. Furthermore, a direct comparison of the muscle architecture revealed two significant differences between jumping vs. non-jumping ants: First, the relative Physiological Cross-Sectional Area (PCSA) of the trochanter depressor muscles of all three legs were larger in jumping ants, except in the front legs of Odontomachus rixosus and Myrmecia nigrocincta; second, the relative muscle fiber length was shorter in jumping ants compared to non-jumping counterparts, except in the front legs of O. rixosus and M. nigrocincta. These results suggest that the difference in relative muscle volume in jumping ants is largely invested in the area (PCSA), and not in fiber length. There was no clear difference in the pennation angle between jumping and non-jumping ants. Additionally, we report that the hind leg length relative to body length was longer in jumping ants. Based on direct comparison of the observed vs. possible work and power output during jumps, we surmise that direct muscle contractions suffice to explain jumping performance in three species, except for O. rixosus, where the lack of data on jumping performance prevents us from drawing definitive conclusions for this particular species. We suggest that increased investment in jumping-relevant musculature is a primary morphological adaptation that separates jumping from non-jumping ants. These results elucidate the common and idiosyncratic morphological changes underlying this rare adaptation in ants. まとぅみ (Okinawan language-Uchinaaguchi) (Japanese) РЕЗЮМЕ (Kazakh) ZUSAMMENFASSUNG (German)

Carbonization of a radicular cyst using fiber-optic diode laser: a case report

A female patient, 51 years old, complaint of painful swelling on the anatomical area of the upper left lateral incisor. The diagnosis of radicular cyst was confirmed histo-pathologically. Nowadays, radicular cysts may be treated using conventional root canal methods or surgical apicectomy. The possible soft-laser reaction to radicular cysts after contact application has not been investigated. We present an in vitro case of a diagnosed radicular cyst which carbonized after contact application of diode laser. The need for future clinical trials will be essential to prove the sensitivity of this procedure in humans

Ecological succession of a Jurassic shallow-water ichthyosaur fall.

After the discovery of whale fall communities in modern oceans, it has been hypothesized that during the Mesozoic the carcasses of marine reptiles created similar habitats supporting long-lived and specialized animal communities. Here, we report a fully documented ichthyosaur fall community, from a Late Jurassic shelf setting, and reconstruct the ecological succession of its micro- and macrofauna. The early 'mobile-scavenger' and 'enrichment-opportunist' stages were not succeeded by a 'sulphophilic stage' characterized by chemosynthetic molluscs, but instead the bones were colonized by microbial mats that attracted echinoids and other mat-grazing invertebrates. Abundant cemented suspension feeders indicate a well-developed 'reef stage' with prolonged exposure and colonization of the bones prior to final burial, unlike in modern whale falls where organisms such as the ubiquitous bone-eating worm Osedax rapidly destroy the skeleton. Shallow-water ichthyosaur falls thus fulfilled similar ecological roles to shallow whale falls, and did not support specialized chemosynthetic communities

Dynamic regulation of serum aryl hydrocarbon receptor agonists in MS

Objective: Several factors influence the clinical course of autoimmune inflammatory diseases such as MS and inflammatory bowel disease. Only recently, the complex interaction between the gut microbiome, dietary factors, and metabolism has started to be appreciated with regard to its potential to modulate acute and chronic inflammation. One of the molecular sensors that mediates the effects of these environmental signals on the immune response is the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor with key functions in immune cells. Methods: In this study, we analyzed the levels of AHR agonists in serum samples from patients with MS and healthy controls in a case-control study. Results: We detected a global decrease of circulating AHR agonists in relapsing-remitting MS patients as compared to controls. However, during acute CNS inflammation in clinically isolated syndrome or active MS, we measured increased AHR agonistic activity. Moreover, AHR ligand levels in patients with benign MS with relatively mild clinical impairment despite longstanding disease were unaltered as compared to healthy controls. Conclusions: Collectively, these data suggest that AHR agonists in serum are dynamically modulated during the course of MS. These findings may guide the development of biomarkers to monitor disease activity as well as the design of novel therapeutic interventions for MSInstituto de Salud Carlos III, Unión Europea PT13/0010/004

Surface topography of hydroxyapatite affects ROS17/2.8 cells response

Hydroxyapatite (HA) has been used in orthopedic, dental, and maxillofacial surgery as a bone substitute. The aim of this investigation was to study the effect of surface topography produced by the presence of microporosity on cell response, evaluating: cell attachment, cell morphology, cell proliferation, total protein content, and alkaline phosphatase (ALP) activity. HA discs with different percentages of microporosity (< 5%, 15%, and 30%) were confected by means of the combination of uniaxial powder pressing and different sintering conditions. ROS17/2.8 cells were cultured on HA discs. For the evaluation of attachment, cells were cultured for two hours. Cell morphology was evaluated after seven days. After seven and fourteen days, cell proliferation, total protein content, and ALP activity were measured. Data were compared by means of ANOVA and Duncan’s multiple range test, when appropriate. Cell attachment (p = 0.11) and total protein content (p = 0.31) were not affected by surface topography. Proliferation after 7 and 14 days (p = 0.0007 and p = 0.003, respectively), and ALP activity (p = 0.0007) were both significantly decreased by the most irregular surface (HA30). These results suggest that initial cell events were not affected by surface topography, while surfaces with more regular topography, as those present in HA with 15% or less of microporosity, favored intermediary and final events such as cell proliferation and ALP activity

Bilateral ischemic optic neuropathy after transurethral prostatic resection: a case report

BACKGROUND: Nonarteritic ischemic optic neuropathy affects the anterior portion of the optic nerve and is characterized by sudden, painless visual loss. The affected eye has a relative afferent pupillary defect. The typical funduscopic appearance includes optic disc edema, with associated nerve fiber layer hemorrhage. Risk factors include advanced age, systemic hypertension, nocturnal hypotension, diabetes mellitus, and a small cup-to-disc ratio. Bilateral presentation is rare. Postoperative optic neuropathy has been associated with nonocular surgery; risk factors include a combination of prolonged surgical times, acute systemic hypotension, anemia due to blood loss, or prone positioning. We report for the first time a patient with bilateral, simultaneous anterior ischemic optic neuropathy after elective transurethral prostatic resection. CASE PRESENTATION: A 66-year old man underwent surgery for benign prostatic hyperplasia. The preoperative blood pressure was 140/85 mmHg, hemoglobin 15.9 g/dL, and hematocrit 48.6%. Two hours postoperatively, the blood pressure, hemoglobin, and hematocrit dropped dramatically. One day later, transient horizontal diplopia developed. Funduscopy showed a congenitally small cup-to-disc ratio without papillary edema. Other ocular findings were unremarkable. By 4 days postoperatively, sudden and painless amaurosis bilaterally developed when the patient awoke with nausea and vomiting. Visual acuity was no light perception bilaterally. The optic discs were swollen with small hemorrhages. Scans of the head and orbits and electrolyte levels were normal. There were no responses on visual evoked potentials bilaterally. The blood pressure was 90/50 mm Hg, the hemoglobin 7.0 g/dL, and the hematocrit 22.9%, necessitating infusion of three units of packed red blood cells. The blood pressure, hematocrit, and hemoglobin increased to normal levels. Three months later the visual acuity remained no light perception. The pupils were unreactive and there was marked optic disc atrophy bilaterally. CONCLUSION: Bilateral and simultaneous acute ischemic optic neuropathy may be a rare but devastating surgical complication. The combination of anemia and hypotension may increase the risk of anterior ischemic optic neuropathy postoperatively after transurethral prostatic resection