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Quantum mechanical phenomena are revolutionizing classical engineering fields such as signal processing or cryptography. When randomness plays an important role, like in cryptography where random bit sequences guarantee certain levels of security, quantum mechanical phenomena allow new ways of generating random bit sequences. Such sequences have a lot of applications in the communication sector, e.g., regarding data transmission, simulation, sensors or radars, and beyond. They can be generated deterministically (e.g., by using polynomials, resulting in pseudo-random sequences) or in a non-deterministic way (e.g., by using physical noise sources like external devices or sensors, resulting in random sequences). Important characteristics of such binary sequences can be modelled by gap processes in conjunction with the probability theory. Recently, all-optical approaches have attracted a lot of research interest. In this work, an adaptation of the quantum key distribution setup is utilized for generating randomised bit sequences. The simulation results show that all-optically generated sequences very well resemble the theoretically ideal probability density characteristic. Additionally, an experimental optical setup is developed that confirms the simulation results. Furthermore, m-sequences show very promising results as well as Gold sequences. Additionally, the level of burstiness, i.e., the distribution of ones and zeros throughout the sequence, is studied for the different sequences. The results enable the finding that generator polynomials with concentrated non-zero coefficients lead to more bursty bit sequences.

The large majority of South Africans identify as Christians; however, the country is plagued by numerous indecencies such as violent crime, poverty, femicide and so on. This paradox presents a challenge for South African theologians, especially regarding Christian formation. Consequently, this article offers an analysis of Martin Luther’s catechisms within their context as a contribution to this challenge. Luther’s catechisms are examined in relation to the historical context of the early church catechumenate tradition, the theological contrast to Dietrich Kolde’s catechism and considerations of genre. The analysis combines cognitive, affective and ritual perspectives into a theory of formation, highlighting how knowledge, desire and embodied action shape and form human beings. The aim of the analysis is to uncover the formative potential that Luther’s catechisms can have for South African Lutheran Churches. It is found that this potential in Luther’s catechisms is characterised by the critique of his inherited symbolic world, the Law and Gospel dynamic, sacraments as points of encounter, prioritising coherence over the number of rituals, integrating literacy and orality, and employing a holistic approach to the Christian life. Luther’s catechisms hold potential for South African churches to address the noted paradox by offering these perspectives on the various facets of theological formation.ContributionThis article combines cognitive, affective and ritual perspectives on human formation into a pedagogical theory, which is applied in a contextual analysis of Martin Luther’s catechisms. Consequently, the formative potential of Luther’s catechisms is characterised by providing conceptual approaches to Christian formation.

Non-tuberculous mycobacteria (NTM) include more than 160 ubiquitous, environmental, acid-fast-staining bacterial species, some of which may cause disease in humans. Chronic pulmonary infection is the most common clinical manifestation. Although patients suffering from chronic lung diseases are particularly susceptible to NTM pulmonary disease, many affected patients have no apparent risk factors. Host and pathogen factors leading to NTM pulmonary disease are not well understood and preventive therapies are lacking. NTM isolation and pulmonary disease are reported to rise in frequency in Europe as well as in other parts of the world. Differentiation between contamination, infection, and disease remains challenging. Treatment of NTM pulmonary disease is arduous, lengthy, and costly. Correlations between results of in vitro antibiotic susceptibility testing and clinical treatment outcomes are only evident for the Mycobacterium avium complex, M. kansasii, and some rapidly growing mycobacteria. We describe the epidemiology of NTM pulmonary disease as well as emerging NTM pathogens and their geographical distribution in non-cystic fibrosis patients in Europe. We also review recent innovations for the diagnosis of NTM pulmonary disease, summarize treatment recommendations, and identify future research priorities to improve the management of patients affected by NTM pulmonary disease.

In the absence of active tuberculosis, a positive tuberculin skin test (TST) or interferon-γ release assay (IGRA) result defines latent infection with Mycobacterium tuberculosis, although test results may vary depending on immunodeficiency. This study compared the performance of TST and IGRAs in five different groups of immunocompromised patients, and evaluated their ability to identify those at risk for development of tuberculosis. Immunocompromised patients with HIV infection, chronic renal failure, rheumatoid arthritis, solid-organ or stem-cell transplantation, and healthy control subjects were evaluated head-to-head by the TST, QuantiFERON-TB-Gold in-tube test (ELISA), and T-SPOT.TB test (enzyme-linked immunospot) at 17 centers in 11 European countries. Development of tuberculosis was assessed during follow-up. Frequencies of positive test results varied from 8.7 to 15.9% in HIV infection (n = 768), 25.3 to 30.6% in chronic renal failure (n = 270), 25.0% to 37.2% in rheumatoid arthritis (n = 199), 9.0 to 20.0% in solid-organ transplant recipients (n = 197), 0% to 5.8% in stem-cell transplant recipients (n = 103), and 11.2 to 15.2% in immunocompetent control subjects (n = 211). Eleven patients (10 with HIV infection and one solid-organ transplant recipient) developed tuberculosis during a median follow-up of 1.8 (interquartile range, 0.2-3.0) years. Six of the 11 patients had a negative or indeterminate test result in all three tests at the time of screening. Tuberculosis incidence was generally low, but higher in HIV-infected individuals with a positive TST (3.25 cases per 100 person-years) than with a positive ELISA (1.31 cases per 100 person-years) or enzyme-linked immunospot result (1.78 cases per 100 person-years). No cases of tuberculosis occurred in patients who received preventive chemotherapy. Among immunocompromised patients evaluated in this study, progression toward tuberculosis was highest in HIV-infected individuals and was poorly predicted by TST or IGRAs. Clinical trial registered with www.clinicaltrials.gov (NCT 00707317).

Chronic kidney disease (CKD) is a common complex condition associated with high morbidity and mortality. Polygenic prediction could enhance CKD screening and prevention; however, this approach has not been optimized for ancestrally diverse populations. By combining APOL1 risk genotypes with genome-wide association studies (GWAS) of kidney function, we designed, optimized and validated a genome-wide polygenic score (GPS) for CKD. The new GPS was tested in 15 independent cohorts, including 3 cohorts of European ancestry ( n  = 97,050), 6 cohorts of African ancestry ( n  = 14,544), 4 cohorts of Asian ancestry ( n  = 8,625) and 2 admixed Latinx cohorts ( n  = 3,625). We demonstrated score transferability with reproducible performance across all tested cohorts. The top 2% of the GPS was associated with nearly threefold increased risk of CKD across ancestries. In African ancestry cohorts, the APOL1 risk genotype and polygenic component of the GPS had additive effects on the risk of CKD. A new study generated and optimized a polygenic score for chronic kidney disease with reproducible performance across 15 cohorts of different ancestries, and identified potentially clinically relevant thresholds with predicted effects comparable to having a family history of the disease.

Dressing electronic quantum states with virtual photons creates exotic effects ranging from vacuum-field modified transport to polaritonic chemistry, and squeezing or entanglement of modes. The established paradigm of cavity quantum electrodynamics maximizes the light-matter coupling strength Ω R / ω c , defined as the ratio of the vacuum Rabi frequency and the frequency of light, by resonant interactions. Yet, the finite oscillator strength of a single electronic excitation sets a natural limit to Ω R / ω c . Here, we enter a regime of record-strong light-matter interaction which exploits the cooperative dipole moments of multiple, highly non-resonant magnetoplasmon modes tailored by our metasurface. This creates an ultrabroadband spectrum of 20 polaritons spanning 6 optical octaves, calculated vacuum ground state populations exceeding 1 virtual excitation quantum, and coupling strengths equivalent to Ω R / ω c = 3.19 . The extreme interaction drives strongly subcycle energy exchange between multiple bosonic vacuum modes akin to high-order nonlinearities, and entangles previously orthogonal electronic excitations solely via vacuum fluctuations. The authors show an original approach to achieve strong light-matter interaction harnessing the coupling between plasmonic resonators and the Landau resonances of an underlying quantum well, demonstrating remarkably high coupling strengths.

Key Points Either population-based or family-based designs can be used in gene-association studies. Population-based designs use unrelated individuals; family-based designs use probands and their relatives, typically either parents or siblings. Genetic-association studies face the obstacles of population substructures and multiple testing. Family-based designs are favoured because they are robust against confounding due to population substructures and test both linkage and association. Case–control designs are preferred for the relative ease of data collection. They have modest power advantages, depending on the prevalence of the disease. Family-based designs can be extended to incorporate pedigrees and complex phenotypes. Screening tools are available for family-based designs that allow the multiple-testing problem, which is an important issue in whole-genome association studies, to be handled. Although they are sometimes overlooked, family-based designs provide important advantages for detecting genetic associations in studies of complex disease. In particular, they provide a means of overcoming the problems that arise when multiple hypotheses are tested in genome-wide association studies. Both population-based and family-based designs are commonly used in genetic association studies to locate genes that underlie complex diseases. The simplest version of the family-based design — the transmission disequilibrium test — is well known, but the numerous extensions that broaden its scope and power are less widely appreciated. Family-based designs have unique advantages over population-based designs, as they are robust against population admixture and stratification, allow both linkage and association to be tested for and offer a solution to the problem of model building. Furthermore, the fact that family-based designs contain both within- and between-family information has substantial benefits in terms of multiple-hypothesis testing, especially in the context of whole-genome association studies.

Background Following the initial description of Mycobacterium florentinum in 2005, very few clinical cases have been reported and the optimal antimicrobial treatment and clinical outcomes are uncertain. Amikacin liposome inhalation suspension (ALIS) has received approval for the treatment of Mycobacterium avium/intracellulare complex (MAC) pulmonary disease. However, there is little experience with its use for infections caused by less common nontuberculous mycobacteria (NTM). Moreover, the awareness of uncommon adverse effects is still limited. Case presentation A 69-year-old female patient suffering from nodular bronchiectatic Mycobacterium florentinum pulmonary disease was treated with azithromycin, ethambutol, and rifampicin, administered three times per week. After 13 months, owing to treatment failure, the therapy was changed to ALIS, moxifloxacin, and clofazimine. This resulted in rapid and sustained culture conversion. Concurrently, the patient exhibited increased cough and sputum, which was consistent with a clinical diagnosis of aspergillosis, as confirmed by evidence of Aspergillus fumigatus in respiratory specimens and a significant increase in serum Aspergillus IgG antibody levels. Following a six-month course of antifungal therapy, a marked improvement in the patient’s symptoms was observed. Conclusions As with MAC pulmonary disease, combination antimicrobial therapy including ALIS was successful in a patient affected by a difficult-to-treat pulmonary infection caused by Mycobacterium florentinum, a rare NTM pathogen. Combination antibiotic treatment including ALIS may also be considered for other difficult-to-treat, non-MAC NTM- pulmonary diseases. During treatment, patients should be monitored for the emergence of Aspergillus co-infection.

Pathogenic mycobacteria, such as Mycobacterium tuberculosis complex (Mtbc), and non-tuberculous mycobacteria (NTMs) can cause severe chronic pulmonary infections. However, not all infected patients develop active disease, and it remains unclear whether key lung microbiome taxa play a role in the pathogenesis of tuberculosis (TB) and NTM lung diseases (LD). Here, we aim to further define the lung microbiome composition in TB, and NTM-LD prior to the initiation of therapy. We employed 16S rRNA amplicon sequencing to characterize the baseline microbiome in bronchoalveolar lavage fluid (BALF) from patients diagnosed with TB (n = 23), NTM-LD (n = 19), or non-infectious inflammatory disease (n = 4). We applied depletion of human cells, removal of extracellular DNA, implementation of a decontamination strategy, and exploratory whole-metagenome sequencing (WMS) of selected specimens. Genera Serratia and unclassified Yersiniaceae dominated the lung microbiome of most patients with a mean relative abundance of >15% and >70%, respectively. However, at the sub-genus level, as determined by amplicon sequence variants (ASVs), TB-patients exhibited increased community diversity, and distinct signatures of ASV_7, ASV_21 abundances which resulted in a significant association with disease state. Exploratory WMS, and ASV similarity analyses suggested the presence of Serratia liquefaciens, Serratia grimesii, Serratia myotis and/or Serratia quinivorans in TB and NTM-LD patients. The lung microbiome of TB-patients harbored a distinct, and heterogenous structure, with specific occurrences of certain Serratia traits. Some of these traits may play a role in understanding the microbial interactions in the lung microbiome of patients infected with Mtbc.

Randomness plays an important role in data communication as well as in cybersecurity. In the simulation of communication systems, randomized bit sequences are often used to model a digital source information stream. Cryptographic outputs should look more random than deterministic in order to provide an attacker with as little information as possible. Therefore, the investigation of randomness, especially in cybersecurity, has attracted a lot of attention and research activities. Common tests regarding randomness are hypothesis-based and focus on analyzing the distribution and independence of zero and non-zero elements in a given random sequence. In this work, a novel approach grounded in a gap-based burst analysis is presented and analyzed. Such approaches have been successfully implemented, e.g., in data communication systems and data networks. The focus of the current work is on detecting deviations from the ideal gap-density function describing randomized bit sequences. For testing and verification purposes, the well-researched post-quantum cryptographic CRYSTALS suite, including its Kyber and Dilithium schemes, is utilized. The proposed technique allows for quickly verifying the level of randomness in given cryptographic outputs. The results for different sequence-generation techniques are presented, thus validating the approach. The results show that key-encapsulation and key-exchange algorithms, such as CRYSTALS-Kyber, achieve a lower level of randomness compared to digital signature algorithms, such as CRYSTALS-Dilithium.