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A general reaction norm model of any order can be formulated as a linear mixed model. From this follows that estimates of mean phenotypic traits in a population (fixed effects), and predictions of individual additive genetic deviations from mean reaction norm parameter values (random effects), can be found from the best linear unbiased predictions (BLUP) equation in matrix form. The resulting BLUP model is dynamical in the sense that the incidence matrix varies with time. This leads to a straightforward and multivariate alternative to infinite-dimensional and random regression modeling of reaction norms. Based on such a BLUP model, the within-generation changes in predicted mean reaction norm parameter values can be found by use of the Robertson-Price identity, applied on the predicted random effects. From this follows that the between-generation change in the mean values are found from Robertson’s secondary theorem of natural selection, applied on the predicted random effects. This explains why and to which extent the variances of BLUP random effects are underestimated, which is a well-known observation. The dynamical BLUP model will thus produce the mean reaction norms over time, which makes it possible to disentangle the microevolutionary and plasticity components in for example climate change responses. The BLUP responses will depend on the additive genetic relationship matrix A_t. When A_t is an identity matrix, the results will be identical to the results from a variant of the multivariate breeder’s equation, based on the selection gradient with respect to the individual phenotypic trait values. Parameters are assumed to be known and constant, but it is discussed how they can be estimated by means of a prediction error method. Generations are assumed to be non-overlapping, but adjustments for overlapping generations can easily be done.

Congenital Lobar Emphysema: A diagnostic dilemma with co-existent Congenital Heart Defects

# There is no abstract for a Brevia article Endemism is a measure of geographic range restriction which is used to highlight regions with unique biota, found nowhere else on earth. Here, we develop a trait-based metric for a functional approach to endemism studies - functional endemism - and explore global patterns in birds. We find that the world’s islands and mountain ranges are hotspots of functional endemism in birds, highlighting the importance of these ecosystems for conservation.

Prediction categories in the Critical Assessment of Structure Prediction (CASP) experiments change with the need to address specific problems in structure modeling. In CASP15, four new prediction categories were introduced: RNA structure, ligand-protein complexes, accuracy of oligomeric structures and their interfaces, and ensembles of alternative conformations. This paper lists technical specifications for these categories and describes their integration in the CASP data management system.

Local adaptation is often facilitated by loci clustered in relatively few regions of the genome, termed genomic islands of divergence. However, the mechanisms that create, mold, and maintain these islands are poorly understood. Here, we use sockeye salmon as a model species to investigate the mechanisms responsible for creating islands of divergence linked to adaptive variation. Previous research suggests that multiple islands are involved in adaptive radiation of sockeye salmon. However, these studies were based on low-density genomic methods that genotyped tens to thousands of loci, making it difficult to elucidate the mechanisms responsible for islands. We used whole genome resequencing to genotype millions of loci to investigate these mechanisms. We discovered 64 islands, 16 of which were shared between two isolated populations; these 16 islands were clustered in four genomic regions. Characterization of the shared regions suggested that three of four were likely created by chromosomal inversions, while the other was created by processes not involving structural variation. Additionally, all four regions were relatively small (< 600 kb), suggesting inversions and other low recombination regions do not have to span megabases to be important for adaptive divergence. In sum, our study demonstrates that heterogeneous selection can lead to a mosaic of islands created by different mechanisms within the same genome. Future studies should continue to investigate how gene flow, selection, and the architecture of genetic traits interact to influence the genomic landscape of adaptive divergence.

This article researches the trajectory tracking problem for unmanned marine vehicles (UMVs) with disturbances and under denial-of-services (DoS) attacks in the wireless channel. By applying the partial form dynamic linearization algorithm, an equivalent data-driven model of the UMVs with ocean disturbances is firstly established. And the disturbances are estimated by using extended state observer, which improves the immunity of the UMVs to disturbances in the environment, and the robustness of the UMVs systems is better. It is the first time that the DoS attacks are considered under the data model for UMVs, and a novel data-driven adaptive trajectory tracking control framework is constructed. When the proposed equivalent data model suffers from DoS attacks which follows the Bernoulli distribution, an attack predictive compensation mechanism is devised to relieve the influence of DoS attacks. Based on it, the data-driven adaptive trajectory tracking controller is designed such that the error of trajectory tracking is convergent under DoS attacks and external disturbances. Finally, the effectiveness of the proposed data-driven control scheme and the predictive compensation mechanism is validated through the simulations.

Transient receptor potential vanilloid type-1 (TRPV1) channels play key roles in chronic pain conditions and are modulated by different inflammatory mediators to elicit heat sensitisation. Bradykinin is a 9-amino acid peptide chain that promotes inflammation. The aim of present study is to investigate how bradykinin and prostaglandin receptors (EP3 and EP4) modulate the sensitisation of TRPV1-mediated responses. Calcium imaging studies of rat dorsal root ganglion (DRG) neurons were employed to investigate the desensitizing responses of TRPV1 ion channels by capsaicin, and the re-sensitization of TRPV1 by bradykinin, then to explore the role EP3 and EP4 receptors in mediating these bradykinin-dependent effects. Immunocytochemistry was used to study the co-expression and distribution of EP4, TRPV1, COX-1 and B2 in rat DRG neurons. Desensitization was seen upon repeated capsaicin application, we show that bradykinin-mediated sensitization of capsaicin-evoked calcium responses in rat DRG neurons occurs is dependent on COX-1 activity, and utilises a pathway that invovles EP4 but not EP3 receptors. The present study provides evidence for a novel signalling pathway through which bradykinin can regulate the TRPV1 ion channel function via the EP4 but not EP3 receptors and provides the anatomical basis for this regulation

Background: The seroepidemiological characteristics of SARS-CoV-2 infection in Mali are not yet well understood. This study assessed SARS-CoV-2 antibody seroprevalence and factors associated with infection in the general population of Bamako, the capital city and epicenter of COVID-19, to determine the magnitude of the pandemic and contribute to control strategies improvement in Mali. Methods: A cross-sectional survey was conducted in September 2022 to collect data on sociodemographic information, clinical characteristics, comorbid factors, and blood samples. ELISA was performed to determine anti-Spike (S) and anti-RBD antibody levels, and RT-PCR to confirm SARS-CoV-2 infection in oropharyngeal swabs. A total of 3601 participants were enrolled in RedCap. Result: the mean age of participants was 33.5±15.9 years old; the sex ratio female: male was 3.6:1. The most representative were the 20–29 (28.9%, n=1043) and the 30–39 (26.9%, n=967) years-old. The COVID-19 vaccine coverage among the participants was 35.8%, with vaccines from Covidshield AstraZeneca (AZ, 13.4%), Johnson and Johnson (J&J, 16.7%), Sinovac (3.9%), and BioNTech Pfizer (1.8%). Overall, S protein and RBD antibodies seroprevalence was remarkably high in the general population (98% and 97%, respectively). Factors such as youth (1–9 years old) and male sex were associated with lower antibody responses against S and RBD, whereas previous exposure to patients with COVID-19 and receiving the COVID-19 vaccine were associated with increased odds of antibody responses. Conclusion: This serosurvey demonstrated the high seroprevalence of SARS-CoV-2 antibodies and highlighted the factors that may influence antibody responses, clearly underlining an underestimation of the pandemic in Mali.

Title: Recurrent Staphylococcal Scalded Skin Syndrome in a 20 month old – A case reportAuthors: Camille Basurto, M.S.1, Nada Baah-Owusu, M.D. 2, Kyla Berreth, D.O.2Institutional Affiliations: 1Liberty College of Osteopathic Medicine, 306 Liberty View Lane, Lynchburg, VA, 24502;2Sovah Pediatrics - Danville, 201 S. Main Street, Suite 2100, Danville, VA 24541Corresponding Author Present Address: 40 Glen Hill Road, Wilton, CT 06897Keywords: Staph scalded skin syndrome, exotoxins, Staphylococcus, toxic epidermal necrolysis, atopic dermatitisWord, Figure, reference count: 1406, 2, 13Conflict of Interest Statement: The authors have no disclosures to report.Consent statement: Patient’s guardians provided written consent for the use of patient photographs and related materials for publication.Abstract: We present a case of a 20 month old child with a history of atopic dermatitis that exhibited recurrent erythematous-bullous lesions consistent with Staphylococcal Scalded Skin syndrome (SSSS). SSSS is an exfoliative toxin mediated skin disorder most commonly found in children. In this paper, we discuss the importance of recognizing the clinical symptomatology and progressive nature of SSSS, particularly in patients with a history of atopic dermatitis, to assure prompt treatment and resolution of the syndrome.

Recurrent Pyogenic CholangitisA 59-year-old South Asian female presented with the complain of pain upper abdomen and recurrent fever for one year. There was no history of vomiting, jaundice, anorexia or weight loss. Family history was unsupportive of diagnosis. On laboratory examination, alkaline phosphatase was elevated by two times. Serum bilirubin was normal and her leukocytes count was 11200/mm3. Rest of the systemic examination was normal. Contrast enhanced computed tomography(CECT) revealed multiple hypodense/hyperdense lesion in segment 3 of liver. Magnetic resonance imaging(MRI) showed hypo-hyperdense focal lesions with conglomerate appearance on segment 3 of liver suggestive of hepatolithiasis (Figure 1). Left lateral segmental resection (Figure 2) and intrahepatic choledochoscopy from dilated left hepatic duct and stone clearances was done. On histopathological examination, definitive diagnosis of recurrent pyogenic cholangitis was established with no evidence of malignancy. At a 3-year follow-up, the patient is free of recurrence.The incidence of hepatolithiasis is variable. It is highly prevalent in parts of Asia, such as China, Japan, and South Korea, with a reported incidence between 3.1% and 21.2%.1 However, with an incidence of about 1%, hepatolithiasis is rare in Western countries.The mechanism of development of hepatolithiasis is yet to be fully elucidated. Cholestasis, cholangitis, an anatomical abnormality of the bile ducts, abnormal bile metabolism, malnutrition, and low socio-economic status are significant risk factors for hepatolithiasis. According to several studies, indications of hepatectomy for hepatolithiasis include the following instances: (i ) unilobar hepatolithiasis, and particularly that on the left; (ii ) atrophy or severe fibrosis of the affected liver segments or lobe; (iii ) presence of a liver abscess; (iv ) cholangiocarcinoma; and (v ) multiple intrahepatic stones causing marked biliary stricture or dilation.2 Globalization, apart from changing the socioeconomic status of regions, has additionally altered disease dynamics globally. Hepatolithiasis, as a result of recurrent pyogenic cholangitis, although still rare, is becoming progressively evident in the West because of immigration from the Asia-Pacific region, where the disease is endemic. Such rare but emerging disease has imposed significant challenges to the physicians and surgeons. Uenishi et al.3 presented outcomes for 86 patients who underwent a hepatectomy from 1998 to 2012. Seventy-six patients (88%) had immediate stone clearance whereas 82 patients (95%) had final stone clearance.3 A multi-disciplinary team approach involving radiologists, internists, pathologists, oncologists, and surgeons is deemed necessary for the timely diagnosis and safe, affordable treatment, thus ensuring good prognosis to the patients.Low socio-economic status of our patient could have been the attributing factor. Also, unilobar hepatolithiasis, and particularly that on the left was the main indication for left lateral segmental hepatectomy in our case. With this image, we would like to recommend that the differential diagnosis of hepatolithiasis should be thought in the back of mind if an elderly person from endemic region presents with the complain of pain upper abdomen and recurrent fever. Surgical intervention is deemed necessary with the aforementioned indications and it can provide good prognosis to the patient with an excellent stone clearances.Conflict of interests: NoneConsent: Written informed consent was obtained from the patient for the accompanying images.

Background: Multiple studies have now shown that a significant proportion of hemophilia carriers meet criteria for having hemophilia and/or report abnormal bleeding. However, to date, investigations of hemophilia carriers have almost exclusively involved women over 18 years of age. Little is known about factor activity levels and bleeding scores in carriers during childhood. We queried a large deidentified database of subjects with bleeding disorders residing in the United States to determine factor activity levels and bleeding scores. Procedures: The ATHNdataset was queried for hemophilia carriers under 18 years of age. Collected information included demographics, factor activity levels, bleeding scores. Results: Over 700 carriers in the pediatric age group were identified of which 626 submitted factor activity levels. Nearly half had factor activity levels less than 40 IU/dL, thereby meeting criteria for having hemophilia. Of those reporting bleeding scores, only 13.5% reported an abnormal bleeding score for age. The proportion reporting abnormal bleeding scores was higher in those with factor levels less than 40 IU/dL (23%) than those greater than 40 IU/dL (9.7%). Conclusions: The proportion of pediatric carriers with hemophilia was double of that previously reported for adults. Of those with hemophilia reporting a bleeding score, the majority (77%) did not report an abnormal bleeding score for age. However, nearly 10% of pediatric carriers not meeting criteria for having hemophilia reported abnormal bleeding scores for age. Similar results are reported in adults suggesting that factor activity levels may not be predictive of bleeding symptoms in carriers.

Purpose/Objectives: To evaluate dosimetric differences between auto-planned Volumetric Modulated Arc Therapy (VMAT) Total Body Irradiation (TBI) technique and 2D AP/PA TBI technique. Methods: Ten pediatric patients treated with VMAT-TBI on Varian c-arm linac were included in this study. VMAT-TBI plans were generated using our in-house developed and publicly shared auto-planning scripts. For each VMAT-TBI plan, a 2D AP/PA plan was created replicating the institution’s clinical setup with the patient positioned at extended SSD with a compensator to account for differences in patient thickness, 50%-transmission daily lung blocks and electron chest-wall boosts prescribed to 50% of the photon prescription. Clinically relevant metrics were analyzed and compared between the VMAT and 2D plans. Results: All VMAT-TBI plans achieved PTV D90%≥100% of prescription. VMAT-TBI PTV D90% significantly increased (6.2%±2.4%, p<0.001) compared to the 2D technique, whereas no differences were observed in global Dmax (p<0.2) and PTV V110% (p<0.4). Compared to the 2D plans, significant decreases in the Dmean to the lungs (-25.6%±11.5%, p<0.001) and lungs-1cm (-34.1%±10.1%, p<0.001) were observed with the VMAT plans. The VMAT technique also provided additional sparing to other organs: for 12Gy prescription, kidneys Dmean of 64.7%±3.3%; for 2Gy prescription, testes/ovaries (Dmean of 31.6%±10.7%), brain (Dmean of 74.8%±1.6%) and thyroid (Dmean of 72.5±3.5%). Conclusions: Superior lung sparing with improved target coverage and similar global Dmax were observed with the VMAT plans as compared to 2D plans. In addition, VMAT-TBI plans provided greater dose reductions in gonads, kidneys, brain, and thyroid.

To alleviate the greenhouse gas emissions by the chemical industry, electrification has been proposed as a solution where electricity from renewable sources is used to power processes. The adoption of renewable energy is complicated by its spatial and temporal variations. To address this challenge, we investigate the potential of distributed manufacturing for electrified chemical processes installed in a microgrid. We propose a multi-scale mixed-integer linear programming model for locating modular electrified plants, renewable-based generating units, and power lines in a microgrid that includes monthly transportation and hourly scheduling decisions. We propose a K-means clustering-based aggregation disaggregation matheuristic to solve the model efficiently. The model and algorithm are tested using a case study with 20 candidate locations in Western Texas. Additionally, we define a new concept, “the Value of the Multi-scale Model”, to demonstrate the additional economic benefits of our model compared with a single-scale model.

This paper considers the problem of state observation for nonlinear dynamics. While model-based observer synthesis is difficult due to the need of solving partial differential equations, this work proposes an efficient model-free, data-driven approach based on online learning. Specifically, by considering the observer dynamics as a Chen-Fliess series, the estimation of its coefficients has a least squares formulation. Since the series converges only locally, the coefficients are recursively updated, resulting in an online optimization scheme driven by instantaneous gradients. When the state trajectories are available, the online least squares guarantees an ultimate upper bound of average observation error proportional to the average variation of states. In the realistic situations where the states cannot be measured, the immersed linear dynamics based on the Kazantzis-Kravaris/Luenberger structure is assigned, followed by online kernel principal component analysis for dimensionality reduction. The proposed approach is demonstrated by a limit cycle dynamics and a chaotic system.

Drug-metabolizing enzymes play an important role in the metabolism of drugs in vivo. Their activity is an important factor affecting the rate of drug metabolism, which directly determines the intensity and persistence of drug action. Patients taking medication can be divided into different metabolic types through detection of CYP2C19 drug-metabolizing enzyme gene polymorphisms, which can then be used for medication guidance for clopidogrel. Here, we describe a detection method based on real-time polymerase chain reaction. This method uses multicolor melting curve analysis to accurately identify different mutation sites and genotypes of CYP2C19 * 2, CYP2C19 * 3, and CYP2C19 * 17. The detection limit of plasmid samples was 1 copies/µl; that of genomic samples was 0.1 ng/µl. The system can detect nine types of CYP2C19 * 2/3/17 at three sites in one tube, quickly achieving detection within 1 h. Combined with the sample release agent, sample extraction was completed in 5 s, achieving rapid diagnosis without extraction for timely diagnosis and treatment. Furthermore, the system is not limited to blood samples and can also be applied to oropharyngeal and saliva samples, increasing sampling diversity and convenience. When using clinical blood samples (n=93), the detection system we established was able to quickly and accurately identify different genotypes, and the accuracy and effectiveness of the detection were confirmed by Sanger sequencing.

Performing afib ablation combined with the placement of the Watchman device for LAA occlusion has been evaluated before, with results showing evidence of safety and ability to perform (6). This can save time and materials allowing patients to have two procedures simultaneously, preventing repeating exposure to possible risks that come with