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With the birth of triplets, King Babar and Queen Celeste experience the pleasures and pains of parenthood.

New discoveries in the lower Popo Agie Formation (lower carbonate unit) of central Wyoming necessitated a reevaluation of USNM 494329 from the same unit, the only known hyperodapedontine rhynchosaur in western North America. Well known from Gondwanan deposits, hyperodapedontines appear to be restricted to the Carnian age (Late Triassic), with the exception of Teyumbaita in the earliest Norian age (Late Triassic) of Brazil. Initially assigned to c.f. ‘Hyperodapedon’ sanjuanensis, our phylogenetic analyses reject this hypothesis, in support of a sister relationship between USNM 494329 (Beesiiwo cooowuse, gen. et. sp. nov.) and Oryctorhynchus bairdi forming an early-diverging clade that is only distantly related to ‘H.’ sanjuanensis. Five additional specimens recovered from the lower Popo Agie are described. Three are referred to B. cooowuse, and another two are placed closer to Hyperodapedon and the remainder of Hyperodapedontinae. Our analysis demonstrates potential temporal distinction between a grade of earliest-diverging hyperodapedontines (including all Wyoming taxa) and a exclusively Late Carnian, Southern Pangaean hyperodapedontine clade (including ‘H.’ sanjuanensis). We consider the lower Popo Agie Formation to represent the first nonmarine Late Triassic unit of Western North America that can be confidently restricted to the Carnian age.

Babar and Celeste have many adventures as they travel around the world.

I have been a nurses' aide since May, 1940, and have served about 1,500 hours. Last week I went to Red Cross headquarters in New York to arrange my winter schedule. On the streets were hundreds of well-dressed women shopping, going to fittings, or on their way to cocktail bars or luncheon engagements.

After making peace with the rhinoceros, King Babar and Queen Celeste plan a model city and live happily with their friends and subjects in the country of elephants.

In December, 2019, the newly identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China, causing COVID-19, a respiratory disease presenting with fever, cough, and often pneumonia. WHO has set the strategic objective to interrupt spread of SARS-CoV-2 worldwide. An outbreak in Bavaria, Germany, starting at the end of January, 2020, provided the opportunity to study transmission events, incubation period, and secondary attack rates. A case was defined as a person with SARS-CoV-2 infection confirmed by RT-PCR. Case interviews were done to describe timing of onset and nature of symptoms and to identify and classify contacts as high risk (had cumulative face-to-face contact with a confirmed case for ≥15 min, direct contact with secretions or body fluids of a patient with confirmed COVID-19, or, in the case of health-care workers, had worked within 2 m of a patient with confirmed COVID-19 without personal protective equipment) or low risk (all other contacts). High-risk contacts were ordered to stay at home in quarantine for 14 days and were actively followed up and monitored for symptoms, and low-risk contacts were tested upon self-reporting of symptoms. We defined fever and cough as specific symptoms, and defined a prodromal phase as the presence of non-specific symptoms for at least 1 day before the onset of specific symptoms. Whole genome sequencing was used to confirm epidemiological links and clarify transmission events where contact histories were ambiguous; integration with epidemiological data enabled precise reconstruction of exposure events and incubation periods. Secondary attack rates were calculated as the number of cases divided by the number of contacts, using Fisher's exact test for the 95% CIs. Patient 0 was a Chinese resident who visited Germany for professional reasons. 16 subsequent cases, often with mild and non-specific symptoms, emerged in four transmission generations. Signature mutations in the viral genome occurred upon foundation of generation 2, as well as in one case pertaining to generation 4. The median incubation period was 4·0 days (IQR 2·3–4·3) and the median serial interval was 4·0 days (3·0–5·0). Transmission events were likely to have occurred presymptomatically for one case (possibly five more), at the day of symptom onset for four cases (possibly five more), and the remainder after the day of symptom onset or unknown. One or two cases resulted from contact with a case during the prodromal phase. Secondary attack rates were 75·0% (95% CI 19·0–99·0; three of four people) among members of a household cluster in common isolation, 10·0% (1·2–32·0; two of 20) among household contacts only together until isolation of the patient, and 5·1% (2·6–8·9; 11 of 217) among non-household, high-risk contacts. Although patients in our study presented with predominately mild, non-specific symptoms, infectiousness before or on the day of symptom onset was substantial. Additionally, the incubation period was often very short and false-negative tests occurred. These results suggest that although the outbreak was controlled, successful long-term and global containment of COVID-19 could be difficult to achieve. All authors are employed and all expenses covered by governmental, federal state, or other publicly funded institutions.

An orphaned baby elephant goes to live in the city with an old lady who gives him everything he wants, but he eventually returns to the forest where he is crowned king of the elephants.

AbstractObjectivesTo describe symptoms and symptom clusters of post-covid syndrome six to 12 months after acute infection, describe risk factors, and examine the association of symptom clusters with general health and working capacity.DesignPopulation based, cross sectional studySettingAdults aged 18-65 years with confirmed SARS-CoV-2 infection between October 2020 and March 2021 notified to health authorities in four geographically defined regions in southern Germany.Participants50 457 patients were invited to participate in the study, of whom 12 053 (24%) responded and 11 710 (58.8% (n=6881) female; mean age 44.1 years; 3.6% (412/11 602) previously admitted with covid-19; mean follow-up time 8.5 months) could be included in the analyses.Main outcome measuresSymptom frequencies (six to 12 months after versus before acute infection), symptom severity and clustering, risk factors, and associations with general health recovery and working capacity.ResultsThe symptom clusters fatigue (37.2% (4213/11 312), 95% confidence interval 36.4% to 38.1%) and neurocognitive impairment (31.3% (3561/11 361), 30.5% to 32.2%) contributed most to reduced health recovery and working capacity, but chest symptoms, anxiety/depression, headache/dizziness, and pain syndromes were also prevalent and relevant for working capacity, with some differences according to sex and age. Considering new symptoms with at least moderate impairment of daily life and ≤80% recovered general health or working capacity, the overall estimate for post-covid syndrome was 28.5% (3289/11 536, 27.7% to 29.3%) among participants or at least 6.5% (3289/50 457) in the infected adult population (assuming that all non-responders had completely recovered). The true value is likely to be between these estimates.ConclusionsDespite the limitation of a low response rate and possible selection and recall biases, this study suggests a considerable burden of self-reported post-acute symptom clusters and possible sequelae, notably fatigue and neurocognitive impairment, six to 12 months after acute SARS-CoV-2 infection, even among young and middle aged adults after mild infection, with a substantial impact on general health and working capacity.Trial registrationGerman registry of clinical studies DRKS 00027012.

Nephronophthisis (NPH) is the leading genetic cause of end-stage renal disease in children and young adults, but no effective disease-modifying therapies are currently available. Here, we identify glucagon-like peptide-1 (GLP-1) signaling as a novel therapeutic target for NPH through a systematic drug repurposing screen in zebrafish. By simultaneously depleting nphp1 and nphp4, we developed a robust zebrafish model that reproduces key features of human NPH, including glomerular cyst formation. Our screen revealed that dipeptidyl peptidase-4 (DPP4) inhibitors (Omarigliptin and Linagliptin) and GLP-1 receptor agonists (Semaglutide) significantly reduce cystogenesis in a dose-dependent manner. Genetic analysis demonstrated that GLP-1 receptor signaling is important for maintaining pronephros integrity, with gcgra and gcgrb (GLP-1 receptor genes) playing a particularly important role. Transcriptomic profiling identified adenosine receptor A2ab (adora2ab) as a key downstream effector of GLP-1 signaling, which regulates ciliary morphology and prevents cyst formation. Notably, nphp1/nphp4 double mutant zebrafish exhibited the upregulation of gcgra as a compensatory mechanism, which might explain their resistance to cystogenesis. This compensation was disrupted by the targeted depletion of GLP-1 receptors or the inhibition of adenylate cyclase, resulting in enhanced cyst formation, specifically in the mutant background. Our findings establish a signaling cascade from GLP-1 receptors to adora2ab in terms of regulating ciliary organization and preventing cystogenesis, offering new therapeutic opportunities for NPH through the repurposing of FDA-approved medications with established safety profiles.

•Phase 3 trial of an investigational 2 dose hepatitis B vaccine in diabetes mellitus.•2 doses of HBsAg-1018 induced significantly higher seroprotection rates than HBsAg-Eng.•HBsAg-1018 demonstrated better consistency of SPRs in subpopulations than HBsAg-Eng. Hepatitis B virus infection remains an important public health problem in the United States. Currently approved alum-adjuvanted vaccines require three doses and have reduced immunogenicity in adults, particularly in those who have diabetes mellitus, or are older, male, obese, or who smoke. Phase 3 observer–blinded, randomized (2:1 HBsAg-1018 [HEPLISAV-B™]:HBsAg-Eng [Engerix-B®]), active–controlled trial in adults 18–70 years of age. HBsAg-1018 was administered intramuscularly at weeks 0 and 4 and placebo at week 24 and HBsAg-Eng at weeks 0, 4, and 24. The primary immunogenicity endpoint assessed the noninferiority of the seroprotection rate at week 28 in participants with type 2 diabetes mellitus. Secondary endpoints included seroprotection rates in the total trial population and by age, sex, body mass index, and smoking status. Among 8374 participants randomized, 961 participants in the per-protocol population had type 2 diabetes mellitus. In diabetes participants, the seroprotection rate in the HBsAg-1018 group at week 28 was 90.0%, compared with 65.1% in the HBsAg-Eng group, with a difference of 24.9% (95% CI: 19.3%, 30.7%), which met the prospectively-defined criteria for noninferiority and statistical significance. In the total study per-protocol population (N = 6826) and each pre-specified subpopulation, the seroprotection rate in the HBsAg-1018 group was statistically significantly higher than in the HBsAg-Eng group. Two doses of HBsAg-1018, administered over 4 weeks, induced significantly higher seroprotection rates than three doses of HBsAg-Eng, given over 24 weeks, in adults with factors known to reduce the immune response to hepatitis B vaccines as well as in those without those factors. With fewer doses in a shorter time, and greater immunogenicity, HBsAg-1018 has the potential to significantly improve protection against hepatitis B in adults at risk for hepatitis B infection. Trial Registration clinicaltrials.gov Identifier: NCT02117934.