The effects of working agile on team performance and engagement

Purpose This study aims to examine the relationship between the agile way of working and team performance and engagement. Furthermore, psychological safety climate was investigated as a mediator of this relationship. As organizations are increasingly adopting the agile way of working method beyond the information technology (IT) setting, the authors researched its effects in teams across a variety of functional domains. Design/methodology/approach Survey data was collected from 97 agile teams working in various functional domains in a multinational bank. The data was analyzed using structural equation modeling. Findings Results indicated that the agile way of working is directly and positively related to team engagement and performance. Moreover, psychological safety climate acted as a partial mediator of each of the respective outcomes. Originality/value This study illustrated that the agile way of working is beneficial for teams beyond the IT setting, as it is positively associated with psychological safety climate, engagement and performance across functional domains.

Conserved Motifs and Domains in Members of Pospiviroidae

In 1985, Keese and Symons proposed a hypothesis on the sequence and secondary structure of viroids from the family : their secondary structure can be subdivided into five structural and functional domains and “viroids have evolved by rearrangement of domains between different viroids infecting the same cell and subsequent mutations within each domain”; this article is one of the most cited in the field of viroids. Employing the pairwise alignment method used by Keese and Symons and in addition to more recent methods, we tried to reproduce the original results and extent them to further members of which were unknown in 1985. Indeed, individual members of consist of a patchwork of sequence fragments from the family but the lengths of fragments do not point to consistent points of rearrangement, which is in conflict with the original hypothesis of fixed domain borders.

Functional outcomes in children related to self-care, mobility, and social function after stroke in early childhood: a cohort study

ABSTRACT Background: Stroke has been increasingly recognized as an important morbidity and mortality factor in neonates and children. Children have different and more diverse risk factors than adults, commonly related to an underlying disease. Stroke may compromise functional capacity in children. Few studies have focused on functional outcomes related to activities and participation. Objectives: To investigate post-stroke functionality of children related to self-care, mobility, and social function. Methods: We assessed the functional outcome of 14 children younger than 7.5 years who suffered a stroke in early childhood through the use of the Pediatric Evaluation of Disability Inventory (PEDI). Results: The average age of the sample at assessment was 3.6 ± 1.4 years (2 - 6 years). The average scores in the PEDI functional domains of self-care, mobility, and social function were, respectively, 37.6 ± 15.4, 36.2 ± 15.4, and 48.7 ± 11.1. Children showed age-appropriate functional outcomes in the PEDI functional domains: 71.4% of them in self-care and mobility and 92.9% in social function. Children with bilateral injuries (p = 0.05) and longer hospital stays (r = -0.79, p = 0.001) showed the worst scores in PEDI's social function domains. Conclusions: Overall, our sample of preschool children showed age-appropriate functional outcomes on self-care, mobility, and social function domains after stroke. However, children with bilateral injuries and longer hospital stays showed the worst scores in social function domains. We recommend focusing on functional rehabilitation to promote activities and participation and to monitor the development of children's social skills after stroke.

Composite endpoint for ALS clinical trials based on patient preference: Patient-Ranked Order of Function (PROOF)

BackgroundPatients with amyotrophic lateral sclerosis (ALS) show considerable variation in symptoms. Treatments targeting an overall improvement in symptomatology may not address what the majority of patients consider to be most important. Here, we propose a composite endpoint for ALS clinical trials that weighs the improvement in symptoms compared with what the patient population actually wants.MethodsAn online questionnaire was sent out to a population-based registry in The Netherlands. Patients with ALS were asked to score functional domains with a validated self-reported questionnaire, and rank the order of importance of each domain. This information was used to estimate variability in patient preferences and to develop the Patient-Ranked Order of Function (PROOF) endpoint.ResultsThere was extensive variability in patient preferences among the 433 responders. The majority of the patients (62.1%) preferred to prioritise certain symptoms over others when evaluating treatments. The PROOF endpoint was established by comparing each patient in the treatment arm to each patient in the placebo arm, based on their preferred order of functional domains. PROOF averages all pairwise comparisons, and reflects the probability that a patient receiving treatment has a better outcome on domains that are most important to them, compared with a patient receiving placebo. By means of simulation we illustrate how incorporating patient preference may upgrade or downgrade trial results.ConclusionsThe PROOF endpoint provides a balanced patient-focused analysis of the improvement in function and may help to refine the risk–benefit assessment of new treatments for ALS.

Progress on Poxvirus E3 Ubiquitin Ligases and Adaptor Proteins

Poxviruses have evolved a variety of innate immunity evasion mechanisms, some of which involve poxvirus-encoded E3 ubiquitin ligases and adaptor proteins. Based on their functional domains and ubiquitin transfer mechanisms, these poxvirus-encoded E3 ubiquitin ligases and adaptor proteins can be divided into five categories: PRANC, ANK/BC, BBK, P28/RING, and MARCH proteins. Although the substrates of many poxvirus E3 ubiquitin ligases remain to be discovered, most of the identified substrates are components of the innate immune system. In this review, we discuss the current research progress on poxvirus-encoded E3 ubiquitin ligases and adaptor proteins to provide mechanistic insights into the interplay between these viruses and their hosts.

Small and Equipped: the Rich Repertoire of Antibiotic Resistance Genes in Candidate Phyla Radiation Genomes

To our knowledge, this study is one of the few studies that characterize the defense systems in the CPR group and describes the first repertoire of antibiotic resistance (AR) genes. The use of a BLAST approach with lenient criteria followed by a careful examination of the functional domains has yielded a variety of enzymes that mainly give three different mechanisms of action of resistance.

Systems aging clock: A novel epigenetic aging clock modeled from organ & bodily function based mortality indices

A diverse array of aging clocks, derived from a variety of omics data and clinical biomarkers, have been developed to describe aging and predict age-related disease. As such, these biomarkers are particularly applicable for use in observational studies, basic science and clinical trials focused on tackling biological aging. However, ongoing research suggests significant heterogeneity in aging, with deterioration and disease occurring in different organ systems or functional domains at various rates across individuals. Existing aging clocks only measure heterogeneity in the degree of aging, not in the manner of aging (e.g. different organ systems or functional domains). We hypothesize these unique trajectories exist and that they can be captured using a systems based approach. In our work, using clinical chemistry biomarkers from participants in the Health and Retirement Study (HRS), Framingham Heart study (FHS) and Women’s Health Initiative (WHI) , we modeled unique epigenetic aging trajectories from distinct groups of biological processes (such as Immune function, metabolic function, hepatic function, cardiac function, renal function and more). Interestingly, these biological system specific scores when combined gave an aging clock with superior mortality prediction than any published aging clock. We further validate the system aging scores and aging clock in different clinical studies to show the added advantage of such a measure, such as the fact that people with similar epigenetic age may have very different system scores. Overall, this method introduces the potential for quantitative and multi-dimensional, personalized aging scores that are indicative of an individual’s disease and disorder risk.

Advancing RNA Virus Discovery and Biology with Whole Genome Sequencing

Two RNA virus families that pose a threat to human and animal health are Hantaviridae and Coronaviridae. These RNA viruses which originate in wildlife continue and will continue to cause disease, and hence, it is critical that scientific research define the mechanisms as to how these viruses spillover and adapt to new hosts to become endemic. One gap in our ability to define these mechanisms is the lack of whole genome sequences for many of these viruses. To address this specific gap, I developed a versatile amplicon-based whole-genome sequencing (WGS) approach to identify viral genomes of hantaviruses and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within reservoir and spillover hosts. In my research studies, I used the amplicon-based WGS approach to define the genetic plasticity of viral RNA within pathogenic and nonpathogenic hantavirus species. The standing genetic variation of Andes orthohantavirus and Prospect Hill orthohantavirus was mapped out and amino acid changes occurring outside of functional domains were identified within the nucleocapsid and glycoprotein. I observed several amino acid changes in functional domains of the RNA-dependent RNA polymerase, as well as single nucleotide polymorphisms (SNPs) within the 3’ non-coding region (NCR) of the S-segment. To identify whether virus adaptation would occur within the S- and L-segments we attempted to adapt hantaviruses in vitro in a spillover host model through passaging experiments. In early passages we identified few mutations in the M-segment with the majority being identified in the S-segment 3’ NCR and the L-segment. This work suggests that hantavirus adaptation occurs in the S- and L-segments although the effect of these mutants on pathology is yet to be determined. While sequencing laboratory isolates is easily accomplished, sequencing low concentrations of virus within the reservoir is a formidable task. I further translated our amplicon-based WGS approach into a pan-oligonucleotide amplicon-based WGS approach to sequence hantavirus vRNA and mRNA from reservoir and spillover hosts in Ukraine. This approach successfully identified a novel Puumala orthohantavirus (PUUV) strain in Ukraine and using Bayesian phylogenetics we found this strain to be associated with the PUUV Latvian lineage. Early during the SARS-CoV-2 pandemic, I applied the knowledge gained in the hantavirus WGS efforts to sequencing of SARS-CoV-2 from nasopharyngeal swabs collected in April 2020. The genetic diversity of 45 SARS-CoV-2 isolates was evaluated with the methods I developed. We identified D614G, a notable mutation known for increasing transmission, in over 90% of our isolates. Two major lineages distinguish SARS-CoV-2 variants worldwide, lineages A and B. While most of our isolates were found within B lineage, we also identified one isolate within lineage A. We performed in vitro work which confirmed A lineage isolates as having poor replication in the trachea as compared to the nasal cavity. Five of these isolates presented a unique array of mutations which were assessed in the keratin 18 human angiotensin-converting enzyme 2 (K18-hACE2) mouse model for its response immunologically and pathogenically. We identified a distinction of pathogenesis between the A and B lineages with emphysema being common amongst A lineage isolates. Additionally, we discovered a small cohort of likely SNPs that defined the late induction of eosinophils during infection. In summary, this work will further define the dynamics of genetic variation and plasticity within virus populations that cause disease outbreaks and will allow a deeper understanding of the virus-host relationship.

Genetic Variability of the Functional Domains of Chromodomains Helicase DNA-Binding (CHD) Proteins

In the past few years, there has been an increasing neuroscientific interest in understanding the function of mammalian chromodomains helicase DNA-binding (CHD) proteins due to their association with severe developmental syndromes. Mammalian CHDs include nine members (CHD1 to CHD9), grouped into subfamilies according to the presence of specific functional domains, generally highly conserved in evolutionary terms. Mutations affecting these domains hold great potential to disrupt protein function, leading to meaningful pathogenic scenarios, such as embryonic defects incompatible with life. Here, we analysed the evolution of CHD proteins by performing a comparative study of the functional domains of CHD proteins between orthologous and paralogous protein sequences. Our findings show that the highest degree of inter-species conservation was observed at Group II (CHD3, CHD4, and CHD5) and that most of the pathological variations documented in humans involve amino acid residues that are conserved not only between species but also between paralogs. The parallel analysis of both orthologous and paralogous proteins, in cases where gene duplications have occurred, provided extra information showing patterns of flexibility as well as interchangeability between amino acid positions. This added complexity needs to be considered when the impact of novel mutations is assessed in terms of evolutionary conservation.