Rapid Lipid Mediator Profiling by Convergence Chromatography-MS/MS.

Bioactive lipid mediators derived from arachidonic acid constitute an attractive pool of metabolites that reflect cellular function and signaling, as well as potential biomarkers that may respond quantitatively to disease progression or pharmacological treatment. Their quantitative measurement in biological samples is complicated by the number of isomers that share common structural features, which are not easily distinguished by immunoassays or reverse phase chromatography-tandem mass spectrometry. Here, we present a method that enables the rapid analysis of a panel of over 25 biologically important eicosanoids in a 96-well format for cell culture supernatants, plasma, and organ tissues using convergence chromatography-tandem mass spectrometry to resolve these analytes of interest.

High frequency of acquired virulence factors in carbapenemase-producing Klebsiella pneumoniae isolates from a large German university hospital, 2013-2021.

Carbapenemase-producing Klebsiella pneumoniae (CP-Kp) isolates are a public health concern as they can cause severe hospital-acquired infections that are difficult to treat. It has recently been shown that CP-Kp can take up virulence factors from hypervirulent K. pneumoniae lineages. In this study, 109 clinical CP-Kp isolates from the University Hospital Cologne were examined for the presence of acquired virulence factors using whole-genome sequencing and phenotypic tests, and results were linked to clinical data. The virulence factor iuc was present in 18/109 of the CP-Kp isolates. Other acquired virulence factors, such as ybt, cbt, iro, rmpA/rmpA2, peg-344, and hypervirulence-associated capsule types were detected in various combinations among these isolates. The iuc-positive isolates produced OXA-232 (n = 7), OXA-48 (n = 6), OXA-48+NDM (n = 3), NDM, and KPC (each n = 1), and 7/18 isolates were resistant to ceftazidime-avibactam, colistin, and/or cefiderocol. Four isolates carried hybrid plasmids that harbored acquired virulence factors alongside the carbapenemase genes blaNDM-1/5 or blaOXA-48. In 15/18 patients, iuc-positive CP-Kp were isolated from a clinically manifest infection site. Among these, four patients had osteomyelitis, and four patients died from pneumonia with OXA-232-producing ST231 isolates, three of them as part of an outbreak. In conclusion, acquired virulence factors are frequently detected in various combinations in carbapenemase-producing K. pneumoniae isolates in Germany, warranting continuous monitoring of infections caused by these strains.

Analysis of the spatio-temporal variability and convergence of green development efficiency of city clusters in the middle reaches of the Yangtze River in China.

The advantageous geographical location of the middle reaches of the Yangtze River (YRMR) plays an important role in promoting high-quality development in China and accelerating the development of the Yangtze River Economic Belt(YREB). In the new stage of development, green development efficiency (GDE) is an important metric for assessing the balance between economic development and ecological civilization. Therefore, taking three city clusters in China's YRMR as the study area, this research employs the Super-SBM model to assess their GDE in 2010-2020 in order to analyze the problem of GDE at the city scale. On this basis, spatio-temporal analyses, dynamic evolution, and convergence analyses have been carried out using the Thiel index, GML index model, and convergence model. The findings indicate that overall GDE has not yet reached an effective level and generally exhibits a two-stage fluctuating upward trend. Spatially, the pattern of distribution is "high in the southwest, low in the northeast". The differences within the city clusters in the YRMR in terms of green development are gradually narrowing, with differences within the same regions contributing the most to overall differences. The GML index shows a trend of fluctuating growth, indicating that the overall GDE growth is in good condition. GDE has grown significantly as a result of technological advancements, with the Wuhan metropolitan area (cluster A) experiencing the fastest growth in this regard, followed by the Chang-Zhu-Tan and the Poyang Lake rim city clusters (clusters B and C). The YRMR and its three major city clusters exhibit both σ- and ß-convergence patterns. The convergence of GDE is simultaneously affected by several factors, including economic development (RGDP), urbanization level (UR), industrial structure (IND), technological development (TEC), and the level of openness (LO). Regional heterogeneity also exists. The above study provides decision-making references and empirical evidence for promoting green development in China's city clusters in the YRMR and advancing the improvement of economic-environmental incongruence in this area.

Evolving trends, regional differences, determinants, and disease sources of provincial-level health inequalities in china 1990-2019: a temporal convergence and novel triple decomposition analysis.

BACKGROUND: Promoting health equity has been a worldwide goal, but serious challenges remain globally and within China. Multiple decomposition of the sources and determinants of health inequalities has significant implications for narrowing health inequalities and improve health equity. METHODS: Life expectancy (LE), healthy life expectancy (HALE), age-standardized mortality rate (ASMR), and age-standardized disability-adjusted life-year (DALY) rates in 31 provinces of mainland China were selected as health status indicators, obtained from the Global Burden of Disease (GBD) database. Temporal convergence analysis was used to test the evolving trends of health status. Dagum's Gini coefficient decomposition was used to decompose the overall Gini coefficient based on intraregional and interregional differences. Oaxaca-Blinder decomposition was used to calculate contributions of determinants to interregional differences. The factor-decomposed Gini coefficient was used to analyze the absolute and marginal contribution of each component to overall Gini coefficients. RESULTS: From 1990-2019, China witnessed notable improvements in health status measured by LE, HALE, ASMR and age-standardized DALY rates.Nevertheless, the three regions (East, Central and West) exhibited significant inter-regional differences in health status, with the differences between the East and West being the largest. The adjusted short-term conditional ß-convergence model indicated that the inter-provincial differences in LE, HALE, ASMR, and age-standardized DALY rates significantly converged at annual rates of 0.31%, 0.35%, 0.19%, and 0.28% over 30 years. The overall Gini coefficients of LE, HALE, and age-standardized DALY rates decreased, while the ASMR exhibited an opposite trend. Inter-regional and intra-regional differences accounted for >70% and <30% of overall Gini coefficients, respectively. Attribution analysis showed that socioeconomic determinants explained 85.77% to 91.93% of the eastern-western differences between 2010-2019, followed by health system determinants explaining 7.79% to 11.61%. The source-analysis of Gini coefficients of ASMR and age-standardized DALY rates revealed that noncommunicable diseases (NCDs) made the largest and increasing absolute contribution, while communicable, maternal, neonatal, and nutritional diseases (CMNNDs) had a diminishing and lower impact. However, NCDs exerted a negative marginal effect on the Gini coefficient, whereas CMNNDs exhibited a positive marginal effect, indicating that controlling CMNNDs may be more effective in reducing health inequities. CONCLUSIONS: Regional differences are a major source of health inequities in China. Prioritizing prevention and control of CMNNDs, rather than NCDs, may yield more pronounced impacts on reducing health inequalities from the perspective of marginal effect, although NCDs remain the largest absolute contributor to health inequalities.

A novel intelligent control of discrete-time nonlinear systems in the presence of output saturation.

In this paper, a model free control method for a class of discrete time nonlinear systems is introduced. A type-3 fuzzy system estimates the unknown parameters required by the control system. The control system only uses the input and output data of the plant and therefore does not need to know its mathematical equations. On the other hand, the phenomenon of output saturation is a challenging problem for all control systems, addressed in detail in the proposed method. The convergence of the proposed method is guaranteed, and the control system is very robust in the face of changes in the dynamics of the plant. The simulation results on discrete-time nonlinear systems show that the proposed method is very accurate despite the high speed of convergence. In addition, the proposed method is robust for modeling uncertainties and has a better root mean square error and step response time compared to the other methods. Also, a comparison has been made between type-1 to type-3 fuzzy systems and control system based on trial and error, which shows firstly the importance of the presence of fuzzy system and secondly the superiority of type-3 fuzzy system compared to the other two types.

Long-Term Photochemical and Microbial Alterations Lead to the Compositional Convergence of Algal and Terrestrial Dissolved Organic Matter.

Lakes are expected to become more active in processing dissolved organic matter (DOM), but the fate of DOM with different origins remains poorly constrained. We conducted long-term incubation experiments (∼1 year) with sole light, sole microbial, and combined light and microbial treatments using DOM from algal and terrestrial sources (DOMa and DOMt, respectively). Fourier transform ion cyclotron resonance mass spectrometry and 16s rRNA were used to analyze the DOM molecular composition and bacterial community, respectively. We observed that DOMa and DOMt converged toward a similar composition under the combined light and microbial treatment, driven by the removal of source-specific compositions along with the production of refractory, carboxylic-rich alicyclic molecules (CRAM). For CRAM enrichment, microbial processes played a greater role for DOMa, while phototransformation was more important for DOMt. The co-occurrence patterns between DOM molecules and bacteria showed that DOM molecular composition influenced the bacterial community. More complex DOM-bacteria interactions were observed for DOMt compared to DOMa, suggesting that greater bacterial cooperation was necessary for transforming DOMt. Collectively, these findings offer new insights into the mechanisms underlying the uniformity of DOM from various sources through prolonged environmental transformations in lakes.

A Wasserstein perspective of Vanilla GANs.

The empirical success of Generative Adversarial Networks (GANs) caused an increasing interest in theoretical research. The statistical literature is mainly focused on Wasserstein GANs and generalizations thereof, which especially allow for good dimension reduction properties. Statistical results for Vanilla GANs, the original optimization problem, are still rather limited and require assumptions such as smooth activation functions and equal dimensions of the latent space and the ambient space. To bridge this gap, we draw a connection from Vanilla GANs to the Wasserstein distance. By doing so, existing results for Wasserstein GANs can be extended to Vanilla GANs. In particular, we obtain an oracle inequality for Vanilla GANs in Wasserstein distance. The assumptions of this oracle inequality are designed to be satisfied by network architectures commonly used in practice, such as feedforward ReLU networks. By providing a quantitative result for the approximation of a Lipschitz function by a feedforward ReLU network with bounded Hölder norm, we conclude a rate of convergence for Vanilla GANs as well as Wasserstein GANs as estimators of the unknown probability distribution.

Preoperative Joint Line Convergence Angle as an Indicator of Clinical Outcomes and Accuracy of Alignment Correction After Double-Level Osteotomy.

Background: The relationship between postoperative alignment and clinical outcomes after double-level osteotomy (DLO) has not been clarified. Purpose: To examine the radiological and clinical outcomes after DLO and specifically evaluate the influence of the joint-line convergence angle (JLCA) on the accuracy of alignment correction and surgical outcomes. Study Design: Case-control study; Level of evidence, 3. Methods: Included were 74 knees in 51 patients (mean age, 61.0 years) who underwent DLO for varus osteoarthritic knees and who had a minimum of 2 years of follow-up. The target hip-knee-ankle angle (HKAA) for the intended limb alignment was set to 1° valgus. The lateral distal femoral angle, medial proximal tibial angle, JLCA, and HKAA were measured on preoperative and postoperative radiographs. Outliers in alignment correction were defined as a deviation of ≥3° from the originally intended HKAA. Clinical outcomes were assessed using the Knee injury and Osteoarthritis Outcome Score (KOOS). In the data analysis, the influence of the radiological parameters on the postoperative outcomes was statistically assessed. Results: Radiological and clinical evaluation at 2-year follow-up showed significant improvement from preoperative values (P < .001). The HKAA was corrected from 13.4°± 3.0° varus preoperatively to 0.5°± 2.8° varus at 2 years, indicating a slight undercorrection. Regarding clinical outcomes, significant pre- to postoperative improvement was found on the KOOS (from 185.0 ± 71.2 to 387.9 ± 70.5; P < .001). Overall, 22 of the 74 knees (29.7%) were deemed to be outliers at the 2-year follow-up (19 knees [25.7%] in undercorrection, 3 knees [4.1%] in overcorrection). Postoperative KOOS values were significantly worse in the outliers than in the nonoutliers (344.4 ± 77.7 vs 405.8 ± 59.3; P < .001), and both pre- and postoperative JLCA was significantly larger in the outlier group. The receiver operating characteristic curve analysis indicated a preoperative cutoff JLCA of 6.0° for predicting postoperative alignment outliers. Conclusion: A preoperative JLCA of ≥6° was found to be a significant prognostic factor affecting the radiological and clinical outcomes after DLO for varus osteoarthritic knees by compromising the accuracy of deformity correction, resulting in suboptimal postoperative alignment.

Computational Fuzzy Modelling Approach to Analyze Neuronal Calcium Dynamics With Intracellular Fluxes.

Mathematical neuroscience investigates how calcium distribution in nerve cells affects the neurological system. The interaction of numerous systems is necessary for the operation of several cellular processes in neuron cells, such as calcium, buffer, ER etc. The dynamics of interacting parameters give useful information on neural cell function. This work uses a mathematical model to analyze the dynamic interactions of buffer and ER inside neurons, considering their spatial properties. While buffers bind to calcium ions and lower their concentration, the endoplasmic reticulum (ER) serves as a reservoir, holding a significant number of free calcium ions. The uncertainty of initial values of calcium concentration poses challenges for researchers to develop calcium signaling models. In this article, we examined the exact solution and approximate solution of the mathematical model that was analyzed using the fuzzy undetermined coefficient approach. MATLAB is being used to perform the simulation. Endoplasmic reticulum and buffer have been found to have a substantial impact on calcium signaling. Fuzzy differential equation Provides a useful tool for evaluating complicated processes with imprecise values when ordinary differential equations perform not precisely. They allow for the examination of dynamic processes under fuzzy settings, which contributes to advances research.

Dynamic convergence of autism disorder risk genes across neurodevelopment.

Over a hundred risk genes underlie risk for autism spectrum disorder (ASD) but the extent to which they converge on shared downstream targets to increase ASD risk is unknown. To test the hypothesis that cellular context impacts the nature of convergence, here we apply a pooled CRISPR approach to target 29 ASD loss-of-function genes in human induced pluripotent stem cell (hiPSC)-derived neural progenitor cells, glutamatergic neurons, and GABAergic neurons. Two distinct approaches (gene-level and network-level analyses) demonstrate that convergence is greatest in mature glutamatergic neurons. Convergent effects are dynamic, varying in strength, composition, and biological role between cell types, increasing with functional similarity of the ASD genes examined, and driven by cell-type-specific gene co-expression patterns. Stratification of ASD genes yield targeted drug predictions capable of reversing gene-specific convergent signatures in human cells and ASD-related behaviors in zebrafish. Altogether, convergent networks downstream of ASD risk genes represent novel points of individualized therapeutic intervention.

Distinguishing mutants that resist drugs via different mechanisms by examining fitness tradeoffs.

There is growing interest in designing multidrug therapies that leverage tradeoffs to combat resistance. Tradeoffs are common in evolution and occur when, for example, resistance to one drug results in sensitivity to another. Major questions remain about the extent to which tradeoffs are reliable, specifically, whether the mutants that provide resistance to a given drug all suffer similar tradeoffs. This question is difficult because the drug-resistant mutants observed in the clinic, and even those evolved in controlled laboratory settings, are often biased towards those that provide large fitness benefits. Thus, the mutations (and mechanisms) that provide drug resistance may be more diverse than current data suggests. Here, we perform evolution experiments utilizing lineage-tracking to capture a fuller spectrum of mutations that give yeast cells a fitness advantage in fluconazole, a common antifungal drug. We then quantify fitness tradeoffs for each of 774 evolved mutants across 12 environments, finding these mutants group into classes with characteristically different tradeoffs. Their unique tradeoffs may imply that each group of mutants affects fitness through different underlying mechanisms. Some of the groupings we find are surprising. For example, we find some mutants that resist single drugs do not resist their combination, while others do. And some mutants to the same gene have different tradeoffs than others. These findings, on one hand, demonstrate the difficulty in relying on consistent or intuitive tradeoffs when designing multidrug treatments. On the other hand, by demonstrating that hundreds of adaptive mutations can be reduced to a few groups with characteristic tradeoffs, our findings may yet empower multidrug strategies that leverage tradeoffs to combat resistance. More generally speaking, by grouping mutants that likely affect fitness through similar underlying mechanisms, our work guides efforts to map the phenotypic effects of mutation.

Mutations in an organism's DNA make the individual more likely to survive and reproduce in its environment, passing on its mutations to the next generation. Mutations can alter the proteins that a gene codes for in many ways. This leads to a situation where seemingly similar mutations ­ such as two mutations in the same gene ­ can have different effects. For example, two different mutations could affect the primary function of the encoded protein in the same way but have different side effects. One mutation might also cause the protein to interact with a new molecule or protein. Organisms possessing one or the other mutation will thus have similar odds of surviving and reproducing in some environments, but differences in environments where the new interaction is important. In microorganisms, mutations can lead to drug resistance. If drug-resistant mutations have different side effects, it can be challenging to treat microbial infections, as drug-resistant pathogens are often treated with sequential drug strategies. These strategies rely on mutations that cause resistance to the first drug all having susceptibility to the second drug. But if similar seeming mutations can have diverse side effects, predictions about how they will respond to a second drug are more complicated. To address this issue, Schmidlin, Apodaca et al. collected a diverse group of nearly a thousand mutant yeast strains that were resistant to a drug called fluconazole. Next, they asked to what extent the fitness ­ the ability to survive and reproduce ­ of these mutants responded similarly to environmental change. They used this information to cluster mutations into groups that likely have similar effects at the molecular level, finding at least six such groups with unique trade-offs across environments. For example, some groups resisted only low drug concentrations, and others were unique in that they resisted treatment with two single drugs but not their combination. These diverse types of fluconazole-resistant yeast lineages highlight the challenges of designing a simple sequential drug treatment that targets all drug-resistant mutants. However, the results also suggest some predictability in how drug-resistant infections can evolve and be treated.

Skink systematics inside out: Comparative cranial osteology of the New World Mabuyinae.

The Mabuyinae subfamily exhibits remarkable diversity, encompassing 26 genera and 236 currently recognized species. Traditionally, the entire range of the group was attributed to the single genus Mabuya, which had a wide distribution along tropical regions of the Planet. In recent studies, phylogenetic hypotheses based on molecular data have identified four major groups, which have been further divided into geographically distinct clades. At least two phylogenetically distinct lineages of Mabuyinae are distributed in the Neotropical Region: Trachylepis atlantica and the remaining 16 genera within the Mabuyinae clade from the mainland and the Caribbean islands. Our understanding of Mabuyinae osteology is still quite limited, particularly concerning interspecific variation. This lack of information hinders our ability to make strong contributions to the phylogenetic relationships within this group or even to confirm the existence of certain new taxa considering their relatively conserved external morphology. This work provides a comprehensive anatomical reference for the adult skull of Neotropical Mabuyinae lizards, highlighting osteological features that might be useful for delimiting each genus. This descriptive guide includes illustrations and employs multiple techniques, such as dry preparation, clearing and staining, and high-resolution computerized microtomography. Our results provide additional diagnostic characteristics that include specific cranial bone arrangements, dental patterns, and cranial adaptations, such as dorsoventral head flattening, and their functional implications for bite force and cranial biomechanics. This study reinforces the importance of cranial morphology in understanding the phylogenetic relationships and evolutionary trajectories of New World Mabuyinae lizards, advocating for broader morphological sampling to enrich our understanding of these diverse reptiles.

Microglial process convergence onto injured axonal swellings, a human postmortem brain tissue study.

Traumatic brain injury (TBI) affects millions globally, with a majority of TBI cases being classified as mild, in which diffuse pathologies prevail. Two of the pathological hallmarks of TBI are diffuse axonal injury (DAI) and microglial activation. While progress has been made investigating the breadth of TBI-induced axonal injury and microglial changes in rodents, the neuroinflammatory progression and interaction between microglia and injured axons in humans is less well understood. Our group previously investigated microglial process convergence (MPC), in which processes of non-phagocytic microglia directly contact injured proximal axonal swellings, in rats and micropigs acutely following TBI. These studies demonstrated that MPC occurred on injured axons in the micropig, but not in the rat, following diffuse TBI. While it has been shown that microglia co-exist and interact with injured axons in humans post-TBI, the occurrence of MPC has not been quantitatively measured in the human brain. Therefore, in the current study we sought to validate our pig findings in human postmortem tissue. We investigated MPC onto injured axonal swellings and intact myelinated fibers in cases from individuals with confirmed DAI and control human brain tissue using multiplex immunofluorescent histochemistry. We found an increase in MPC onto injured axonal swellings, consistent with our previous findings in micropigs, indicating that MPC is a clinically relevant phenomenon that warrants further investigation.

Slanted and Standard Lateral Rectus Recession Procedures for Convergence Insufficiency-Type Intermittent Exotropia in Children: A Retrospective Cohort Study.

Purpose: To evaluate the efficacy and safety of slanted bilateral lateral rectus recession (BLR-rec) for treating convergence insufficiency-type intermittent exotropia (CI-IXT) in children. Methods: In this retrospective cohort study, 26 patients aged <16 years with CI-IXT who underwent BLR-rec between August 2016 and July 2021 with six months of follow-up data post-surgery were classified into slanted BLR-rec group (n = 14) and standard BLR-rec group (n = 12; equal-length recession of the upper and lower horns of the LR muscle). Surgical outcomes were compared between the groups. Results: In the slanted and standard groups, the preoperative distance exodeviation was 27.9 ± 5.5 and 30.8 ± 10.0 prism diopter (PD) (p = 0.63), near exodeviation was 41.1 ± 5.6 and 42.9 ± 9.2 PD (p = 0.75), and difference between near and distance deviation (N-D deviation difference) was 13.2 ± 3.2 and 12.1 ± 3.3 PD (p = 0.30), respectively. The ratio of postoperative and preoperative N-D deviation difference was compared between the slanted BLR and standard BLR groups at six months postoperatively. The results revealed that the ratio for slanted-BLR was 0.44 ± 0.19, and for standard-BLR was 0.84 ± 0.24. In the standard group, stereoacuity remained unchanged post-surgery compared to that pre-surgery, while the slanted group showed significant improvement (p < 0.05, Wilcoxon signed-rank test). Conclusion: Compared with the standard BLR-rec procedure, the slanted BLR-rec procedure reduced N-D deviation differences in CI-IXT, positively impacting gross stereopsis.

The Josefson-Nissenzweig theorem and filters on ω.

For a free filter F on ω , endow the space N F = ω ∪ { p F } , where p F ∉ ω , with the topology in which every element of ω is isolated whereas all open neighborhoods of p F are of the form A ∪ { p F } for A ∈ F . Spaces of the form N F constitute the class of the simplest non-discrete Tychonoff spaces. The aim of this paper is to study them in the context of the celebrated Josefson-Nissenzweig theorem from Banach space theory. We prove, e.g., that, for a filter F, the space N F carries a sequence ⟨ µ n : n ∈ ω ⟩ of normalized finitely supported signed measures such that µ n ( f ) → 0 for every bounded continuous real-valued function f on N F if and only if F ∗ ≤ K Z , that is, the dual ideal F ∗ is Katetov below the asymptotic density ideal Z . Consequently, we get that if F ∗ ≤ K Z , then: (1) if X is a Tychonoff space and N F is homeomorphic to a subspace of X, then the space C p ∗ ( X ) of bounded continuous real-valued functions on X contains a complemented copy of the space c 0 endowed with the pointwise topology, (2) if K is a compact Hausdorff space and N F is homeomorphic to a subspace of K, then the Banach space C(K) of continuous real-valued functions on K is not a Grothendieck space. The latter result generalizes the well-known fact stating that if a compact Hausdorff space K contains a non-trivial convergent sequence, then the space C(K) is not Grothendieck.

On the importance of assessing topological convergence in Bayesian phylogenetic inference.

Modern phylogenetics research is often performed within a Bayesian framework, using sampling algorithms such as Markov chain Monte Carlo (MCMC) to approximate the posterior distribution. These algorithms require careful evaluation of the quality of the generated samples. Within the field of phylogenetics, one frequently adopted diagnostic approach is to evaluate the effective sample size (ESS) and to investigate trace graphs of the sampled parameters. A major limitation of these approaches is that they are developed for continuous parameters and therefore incompatible with a crucial parameter in these inferences: the tree topology. Several recent advancements have aimed at extending these diagnostics to topological space. In this reflection paper, we present two case studies - one on Ebola virus and one on HIV - illustrating how these topological diagnostics can contain information not found in standard diagnostics, and how decisions regarding which of these diagnostics to compute can impact inferences regarding MCMC convergence and mixing. Our results show the importance of running multiple replicate analyses and of carefully assessing topological convergence using the output of these replicate analyses. To this end, we illustrate different ways of assessing and visualizing the topological convergence of these replicates. Given the major importance of detecting convergence and mixing issues in Bayesian phylogenetic analyses, the lack of a unified approach to this problem warrants further action, especially now that additional tools are becoming available to researchers.

The Janus (dual) model of immunoglobulin isotype evolution: Conservation and plasticity are the defining paradigms.

The study of antibodies in jawed vertebrates (gnathostomes) provides every immunologist with a bird's eye view of how human immunoglobulins (Igs) came into existence and subsequently evolved into their present forms. It is a fascinating Darwinian history of conservation on the one hand and flexibility on the other, exemplified by the Ig heavy chain (H) isotypes IgM and IgD/W, respectively. The cartilaginous fish (e.g., sharks) Igs provide a glimpse of "how everything got off the ground," while the amphibians (e.g., the model Xenopus) reveal how the adaptive immune system made an about face with the emergence of Ig isotype switching and IgG-like structure/function. The evolution of mucosal Igs is a captivating account of malleability, convergence, and conservation, and a call to arms for future study! In between there are spellbinding chronicles of antibody evolution in each class of vertebrates and rather incredible stories of how antibodies can adapt to occupy niches, for example, single-domain variable regions, cold-adapted Igs, convergent mechanisms to dampen antibody function, provision of mucosal defense, and many more. The purpose here is not to provide an encyclopedic examination of antibody evolution, but rather to hit the high points and entice readers to appreciate how things "came to be."

Complex-valued soft-log threshold reweighting for sparsity of complex-valued convolutional neural networks.

Complex-valued convolutional neural networks (CVCNNs) have been demonstrated effectiveness in classifying complex signals and synthetic aperture radar (SAR) images. However, due to the introduction of complex-valued parameters, CVCNNs tend to become redundant with heavy floating-point operations. Model sparsity is emerged as an efficient method of removing the redundancy without much loss of performance. Currently, there are few studies on the sparsity problem of CVCNNs. Therefore, a complex-valued soft-log threshold reweighting (CV-SLTR) algorithm is proposed for the design of sparse CVCNN to reduce the number of weight parameters and simplify the structure of CVCNN. On one hand, considering the difference between complex and real numbers, we redefine and derive the complex-valued log-sum threshold method. On the other hand, by considering the distinctive characteristics of complex-valued convolutional (CConv) layers and complex-valued fully connected (CFC) layers of CVCNNs, the complex-valued soft and log-sum threshold methods are respectively developed to prune the weights of different layers during the forward propagation, and the sparsity thresholds are optimized during the backward propagation by inducing a sparsity budget. Furthermore, different optimizers can be integrated with CV-SLTR. When stochastic gradient descent (SGD) is used, the convergence of CV-SLTR is proved if Lipschitzian continuity is satisfied. Experiments on the RadioML 2016.10A and S1SLC-CVDL datasets show that the proposed algorithm is efficient for the sparsity of CVCNNs. It is worth noting that the proposed algorithm has fast sparsity speed while maintaining high classification accuracy. These demonstrate the feasibility and potential of the CV-SLTR algorithm.

Diverging destinies: How children are faring under demographic transition.

India reached the replacement level of fertility in 2020. However, the journey of fertility transition is unconventional and heterogeneous within the country and across the different socio-economic groups. The fertility transition is considered to be faster than its socio-economic and health transition in several states. Thus, it has been presumed that the returns to fertility decline are heterogeneous across the states and population sub-groups. Our specific hypothesis is that although rich and poor, and educated and un-educated, everyone had significantly contributed to the fertility decline in response to family planning policies, only those socio-economically better-off have been investing relatively more in their children compared to the poor, and this has led to diverging destinies for children. We tested this supposition using a macro-level panel dataset (1992-2021), fixed and random effects, and IV regression models. The results confirm that child health care and outcomes have diverged while fertility declined from 1992 to 2021. These results are sustained in multiple robustness checks. While fertility is declining with highly state-sponsored family planning programmes, the persistent socio-economic inequalities are leading to unequal progress in health outcomes for children in India.

Adjusted planning based on the joint line convergence angle improves correction accuracy in the standing position after opening wedge high tibial osteotomy.

BACKGROUND: Postoperative change of the joint line convergence angle (JLCA) is known to be a factor affecting correction error in opening wedge high tibial osteotomy (OWHTO). The purpose of this study was to assess whether preoperative planning that considers change of the JLCA can achieve accurate correction in the standing position after OWHTO. METHODS: OWHTO was performed for 109 knees with osteoarthritis of the knee. The amount of angular correction was planned aiming to achieve mechanical valgus of 5° in 55 knees (conventional planning), and it was adjusted in 54 knees (adjusted planning) according to the preoperative JLCA as follows: not changed with JLCA ≤ 3°; decreased 1° with JLCA 4-6°; decreased 2° with JLCA 7-8°; and decreased 3° with JLCA ≥ 9°. The hip-knee-ankle (HKA) angle, JLCA, and medial proximal tibial angle (MPTA) were measured on standing long-leg radiographs. Correction error ≤ 2º was defined as the acceptable range, and correction error > 2º was defined as an outlier. RESULTS: The conventional planning group had a significantly greater postoperative HKA angle than the adjusted planning group (6.1º and 4.9º, respectively). The mean JLCA decreased from 4.8º to 2.6º in the conventional planning group and from 4.6º to 2.7º in the adjusted planning group. The conventional planning group had significantly greater postoperative MPTA than the adjusted planning group (96.2º and 94.7º, respectively). The rate of outliers with correction error > 2º was significantly lower in the adjusted planning group (9%) than in the conventional planning group (24%). The rate of the MPTA > 95º was significantly lower in the adjusted planning group (30%) than in the conventional planning group (69%). CONCLUSIONS: This study demonstrated that preoperative planning with adjustment of the correction angle according to the preoperative JLCA improved correction accuracy in the standing position after OWHTO.