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PLoS ONE ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. e0262316
Xi Guo ◽  
Abhineet Gupta ◽  
Anand Sampat ◽  
Chengwei Zhai

The COVID-19 pandemic has drastically shifted the way people work. While many businesses can operate remotely, a large number of jobs can only be performed on-site. Moreover as businesses create plans for bringing workers back on-site, they are in need of tools to assess the risk of COVID-19 for their employees in the workplaces. This study aims to fill the gap in risk modeling of COVID-19 outbreaks in facilities like offices and warehouses. We propose a simulation-based stochastic contact network model to assess the cumulative incidence in workplaces. First-generation cases are introduced as a Bernoulli random variable using the local daily new case rate as the success rate. Contact networks are established through randomly sampled daily contacts for each of the first-generation cases and successful transmissions are established based on a randomized secondary attack rate (SAR). Modification factors are provided for SAR based on changes in airflow, speaking volume, and speaking activity within a facility. Control measures such as mask wearing are incorporated through modifications in SAR. We validated the model by comparing the distribution of cumulative incidence in model simulations against real-world outbreaks in workplaces and nursing homes. The comparisons support the model’s validity for estimating cumulative incidences for short forecasting periods of up to 15 days. We believe that the current study presents an effective tool for providing short-term forecasts of COVID-19 cases for workplaces and for quantifying the effectiveness of various control measures. The open source model code is made available at

Yvonne H. W. Derks ◽  
Sanne A. M. van Lith ◽  
Helene I. V. Amatdjais-Groenen ◽  
Lieke W. M. Wouters ◽  
Annemarie Kip ◽  

Abstract  Introduction The first generation ligands for prostate-specific membrane antigen (PSMA)–targeted radio- and fluorescence-guided surgery followed by adjuvant photodynamic therapy (PDT) have already shown the potential of this approach. Here, we developed three new photosensitizer-based dual-labeled PSMA ligands by crucial modification of existing PSMA ligand backbone structures (PSMA-1007/PSMA-617) for multimodal imaging and targeted PDT of PCa. Methods Various new PSMA ligands were synthesized using solid-phase chemistry and provided with a DOTA chelator for 111In labeling and the fluorophore/photosensitizer IRDye700DX. The performance of three new dual-labeled ligands was compared with a previously published first-generation ligand (PSMA-N064) and a control ligand with an incomplete PSMA-binding motif. PSMA specificity, affinity, and PDT efficacy of these ligands were determined in LS174T-PSMA cells and control LS174T wildtype cells. Tumor targeting properties were evaluated in BALB/c nude mice with subcutaneous LS174T-PSMA and LS174T wildtype tumors using µSPECT/CT imaging, fluorescence imaging, and biodistribution studies after dissection. Results In order to synthesize the new dual-labeled ligands, we modified the PSMA peptide linker by substitution of a glutamic acid into a lysine residue, providing a handle for conjugation of multiple functional moieties. Ligand optimization showed that the new backbone structure leads to high-affinity PSMA ligands (all IC50 < 50 nM). Moreover, ligand-mediated PDT led to a PSMA-specific decrease in cell viability in vitro (P < 0.001). Linker modification significantly improved tumor targeting compared to the previously developed PSMA-N064 ligand (≥ 20 ± 3%ID/g vs 14 ± 2%ID/g, P < 0.01) and enabled specific visualization of PMSA-positive tumors using both radionuclide and fluorescence imaging in mice. Conclusion The new high-affinity dual-labeled PSMA-targeting ligands with optimized backbone compositions showed increased tumor targeting and enabled multimodal image-guided PCa surgery combined with targeted photodynamic therapy.

С.П. Брюн

Статья посвящена одной из главных тем и концептов в историографии крестовых походов – конфликту между западными крестоносцами «первого поколения» и франками Заморской земли (Outremer), т.е. теми, кто был рожден на Ближнем Востоке и не знал иного дома, кроме городов и долин Леванта. Автор критически анализирует концептуальные воззрения на суть данного конфликта в историографии XIX-XXI вв. и рассматривает полувековой опыт экспансии римской знати в княжестве Антиохийском и графстве Триполийском (инициированной браком князя Боэмунда V со знатной римлянкой, Люсьен де Сеньи). В отличие от широко-известного конфликта между братьями Лузиньянами и палестинскими баронами в 1180-х гг., экспансия римлян в Триполи и Антиохии действительно может служить редким и полноценным примером острого конфликта между притязаниями западных нобилей и интересами местных, левантийских элит на Латинском Востоке. The article deals with one of the main themes and concepts in the historiography of the Crusades – the conflict between the western, «first generation» Crusaders and pilgrims with the Franks of Outremer, those who were born and knew no home outside of the Middle East. The author critically examines the perception of the conflict in the 19th—21st century historiography, and proceeds with a study of the 50-year period of Roman aristocratic expansion in the Principality of Antioch and County of Tripoli (made possible through the marriage of Prince Bohemond V with the Roman noblewoman Lucien de Segni). This expansion – unlike the infamous clash between the Lusignan brothers and the Palestinian nobility in the 1180’s – was perhaps the purest manifestation of the conflict between consolidated western expansion and the local Levantine elites in the Crusader States.

2022 ◽  
Vol 1 ◽  
pp. 11-16
Kiran Godse ◽  
Abhishek De ◽  
Bela Shah ◽  
Mukesh Girdhar ◽  
Krupa Shankar ◽  

Objectives: There are multiple guidelines for chronic spontaneous urticaria (CSU) by various dermatological associations, but in real-world practice in India, different approaches have been noted. In this paper, we courted to determine these different approaches in CSU management, adherence to various CSU guidelines, and the reasons for deviation from guidelines amidst dermatologists in India. Materials and Methods: A net-based questionnaire was created and validated by five panelists experienced in CSU management and then was circulated to all dermatologists in India in August 2020 for real-world management scenario. Results: We received 880 completed response out of 2235 response. Most of the dermatologists (97%) were aware of some urticaria guidelines. Although many of them follow guidelines about three forth of them reported to deviate from it sometimes. The most common reason for deviation was rely on clinical experience as opted by 53% of respondents. Dermatologists who follow guidelines also investigate routinely in terms of complete blood count, the erythrocyte sedimentation rate, and thyroid-stimulating hormone as compared to those who do not. About 70.5% of the dermatologist prescribe second-generation antihistamine (SGAH) at approved dose as the first line of treatment whereas 63.6% up dose it as second line of treatment. Surprisingly, 68% prescribe first-generation antihistamine in the evening and SGAH in the morning as combination therapy in CSU. Conclusion: From the findings of the present study, it can be strongly implied that guidelines play a vital role in delivering superior attributes of patient care although 75% of dermatologists deviated from it. Main reasons for deviance are reliability on self-clinical proficiency and consideration of economic impediments. Both these factors need to be worked upon by continuous medical education of dermatologists and more pharmaco-economic research.

2022 ◽  
Vol 20 (6) ◽  
pp. 120-133
A. A. Kechin ◽  
A. I. Andriyanova ◽  
M. L. Filipenko

Background. The first-generation trk inhibitors, larotrectinib and entrectinib, were approved by the u.s. Food and drug administration (Fda) for the treatment of advanced solid tumors harboring NTRK gene fusions in November 2018 and in august 2019, respectively. The purpose of the study was to present upto-date data on the structure and functions of ntrk genes, the frequency of occurrence of rearrangements with their participation, the consequences of their occurrence at the cellular level, methods of detecting such rearrangements, as well as targeted drugs used in the presence of chimeric NTRK genes. Material and methods. A systemic literature search was conducted in pubmed ncbi, Web of science, scopus databases. Results. The products of NTRK genes are receptors for neurotrophins, and their high expression is normally observed only in a narrow range of tissue types. Intrachromosomal or interchromosomal rearrangements lead to a significant increase in the level of expression of the chimeric gene regulated by the strong promoter of the partner gene. The high transcriptional activity of such a gene, along with the constant activation of the kinase activity of the protein product, leads to the activation of metabolic pathways responsible for cell escape from apoptosis and disruption of the regulation of the cell cycle. The occurrence of chimeric NTRK genes varies between different types of tumors, with the highest (up to 90 %) in rare cancers (secretory carcinoma of the breast, secretory carcinoma of the salivary glands, congenital mesoblastic nephroma, children’s fibrosarcoma). Larotrectinib and entrectinib are highly effective targeted drugs in suppressing the growth of a tumor carrying NTRK rearrangements, regardless of the type of tumor. In this regard, the introduction of new high-precision methods for the detection of chimeric NTRK genes, as well as the study of the mechanisms of the development of resistance with the assumption of ways to overcome it, seems relevant. Conclusion. Rearrangements of NTRK genes are quite common in various types of oncology and are an effective target for modern targeted drugs.

2022 ◽  
Vol 12 (1) ◽  
Lovepreet Singh ◽  
Diana Fontinha ◽  
Denise Francisco ◽  
Miguel Prudêncio ◽  
Kamaljit Singh

AbstractWith its strong effect on vector-borne diseases, and insecticidal effect on mosquito vectors of malaria, inhibition of sporogonic and blood-stage development of Plasmodium falciparum, as well as in vitro and in vivo impairment of the P. berghei development inside hepatocytes, ivermectin (IVM) continues to represent an antimalarial therapeutic worthy of investigation. The in vitro activity of the first-generation IVM hybrids synthesized by appending the IVM macrolide with heterocyclic and organometallic antimalarial pharmacophores, against the blood-stage and liver-stage infections by Plasmodium parasites prompted us to design second-generation molecular hybrids of IVM. Here, a structural modification of IVM to produce novel molecular hybrids by using sub-structures of 4- and 8-aminoquinolines, the time-tested antiplasmodial agents used for treating the blood and hepatic stage of Plasmodium infections, respectively, is presented. Successful isolation of regioisomers and epimers has been demonstrated, and the evaluation of their in vitro antiplasmodial activity against both the blood stages of P. falciparum and the hepatic stages of P. berghei have been undertaken. These compounds displayed structure-dependent antiplasmodial activity, in the nM range, which was more potent than that of IVM, its aglycon or primaquine, highlighting the superiority of this hybridization strategy in designing new antiplasmodial agents.

Foods ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 208
Amruta Kulkarni ◽  
Ai Zhao ◽  
Baoru Yang ◽  
Yumei Zhang ◽  
Kaisa M. Linderborg

The dietary intake of fatty acids (FAs) affects the composition and distribution of FAs in the body. Here, a first-generation (n-3)-deficiency study was conducted by keeping young (age 21 ± 2 days) Sprague–Dawley male rats on a peanut-oil-based diet for 33 days after weaning in order to compare the effect of mild (n-3)-deficiency on the lipid composition of different organs and feces. Soybean-oil-based diet was used as a control. The plasma FA levels corresponded to FAs levels in the organs. Lower docosahexaenoic acid (DHA) content was detected in the plasma, brain, testis, visceral fat, heart, and lungs of the (n-3)-deficient group, whereas the DHA content of the eye and feces did not differ between the experimental groups. The DHA content of the brains of the (n-3)-deficient group was 86% of the DHA content of the brains of the (n-3)-adequate group. The DHA level of the organs was affected in the order of visceral fat > liver triacylglycerols > lung > heart > liver phospholipids > testis > eye > brain, with brain being least affected. The low levels of (n-3) FAs in the liver, brain, eye, heart, and lung were offset by an increase in the (n-6) FAs, mainly arachidonic acid. These results indicate that, in rats, adequate maternal nutrition during pregnancy and weaning does not provide enough (n-3) FAs for 33 days of an (n-3)-deficient diet. Results of this study can be used also to evaluate the conditions needed to reach mild (n-3) deficiency in the first generation of rats and to evaluate the feasibility to collect data from a variety of organs or only selected ones.

Youth ◽  
2022 ◽  
Vol 2 (1) ◽  
pp. 12-22
Terese JeanLund ◽  
Belle Liang ◽  
Brenna Lincoln ◽  
Allison E. White ◽  
Angela M. DeSilva Mousseau ◽  

Purpose in life is linked with numerous positive outcomes among adolescents and emerging adults. Peer relationships may play an important role in the cultivation of purpose, especially among first-generation college (FGC) students. The present study examined the association between the quality of peer relationships and commitment to purpose among students from three universities (N = 195). Analyses also examined whether FGC student status moderated this association. The results indicated that the quality of peer relationships significantly predicted commitment to purpose. FGC status moderated this association; high-quality relationships with peers helped close the gap in purpose commitment between FGC students and their counterparts.

2022 ◽  
Vol 97 (4) ◽  
Leif Svensson

There are plenty of misconceptions about how the Luther Renais­sance in Sweden relates to Albrecht Ritschl and nineteenth-century German Luther research. This article sheds new light on the importance of Ritschl's groundbreaking Luther interpretation to the first generation of the Swedish Luther Renaissance, as represented by its leading voices – Einar Billing and Nathan Söderblom. I demonstrate that there are substantial similarities between how Ritschl, Billing, and Söderblom approach and make use of Luther's thought. They all combine a careful analysis of Luther's theology with an interest in understanding his role in history. And despite their high regard of Luther as the great Protestant reformer, Ritschl, Billing, and Söderblom at times show a considerable distance to his thinking. It is also evident that they found solutions to contemporary questions and challenges in Luther's writings. Their constructive use of Luther is, I further argue, closely related to a positive reception of histor­ical criticism and an ambition to make Lutheranism relevant to modern society. This to a large extent explains why Ritschl, Billing, and Söderblom have a freer attitude towards Luther than many of their Lutheran col­leagues, and also why they emphasize those aspects of his theology that they consider especially fruitful for modern society.

2022 ◽  
Vol 12 (1) ◽  
Junyu Chen ◽  
Haiwei Li ◽  
Liyao Song ◽  
Geng Zhang ◽  
Bingliang Hu ◽  

AbstractDeveloping an efficient and quality remote sensing (RS) technology using volume and efficient modelling in different aircraft RS images is challenging. Generative models serve as a natural and convenient simulation method. Because aircraft types belong to the fine class under the rough class, the issue of feature entanglement may occur while modelling multiple aircraft classes. Our solution to this issue was a novel first-generation realistic aircraft type simulation system (ATSS-1) based on the RS images. It realised fine modelling of the seven aircraft types based on a real scene by establishing an adaptive weighted conditional attention generative adversarial network and joint geospatial embedding (GE) network. An adaptive weighted conditional batch normalisation attention block solved the subclass entanglement by reassigning the intra-class-wise characteristic responses. Subsequently, an asymmetric residual self-attention module was developed by establishing a remote region asymmetric relationship for mining the finer potential spatial representation. The mapping relationship between the input RS scene and the potential space of the generated samples was explored through the GE network construction that used the selected prior distribution z, as an intermediate representation. A public RS dataset (OPT-Aircraft_V1.0) and two public datasets (MNIST and Fashion-MNIST) were used for simulation model testing. The results demonstrated the effectiveness of ATSS-1, promoting further development of realistic automatic RS simulation.

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