JUGGLING THE PARADOXES – GOVERNANCE MECHANISMS IN BIMODAL IT ORGANIZATIONS

The fundamental changes associated with digitalization demand businesses and public enterprises to balance exploitative and explorative capabilities in their internal IT function. One approach to balance these paradoxical demands is the adoption of twofold organizational structures often referred to as bimodal IT. While the IS literature has made recent advances in the description and analysis of bimodal organization structures, we still lack a deeper understanding of the inner workings within bimodal IT organizations and the potential tensions between traditional and agile IT. To address this research gap, we adopt IT governance mechanisms as an analytical framework to study two bimodal IT organization cases, one at a law enforcement agency and the other at an automotive company. We analyze data collected through fourteen semi-structured interviews using grounded theory techniques. We first identify challenges associated with the implementation of and the coordination within organization’s bimodal IT organizations. We then identify the structural, procedural, and relational governance mechanisms used within these organizations and elucidate how they relate to the categories of challenges. Finally, we identify and describe five novel governance paradoxes of bimodal IT organizations that emerged as core concepts from this research. Theoretical contributions and practical implications are discussed

Dual predation by bacteriophage and bdellovibrio bacteriovorus can eradicate escherichia coli prey in situations where single predation cannot

Copyright © 2020 Hobley et al. Bacteria are preyed upon by diverse microbial predators, including bacteriophage and predatory bacteria, such as Bdellovibrio bacteriovorus. While bacteriophage are used as antimicrobial therapies in Eastern Europe and are being applied for compassionate use in the United States, predatory bacteria are only just beginning to reveal their potential therapeutic uses. However, predation by either predator type can falter due to different adaptations arising in the prey bacteria. When testing poultry farm wastewater for novel Bdellovibrio isolates on Escherichia coli prey lawns, individual composite plaques were isolated containing both an RTP (rosette-tailed-phage)-like-phage and a B. bacteriovorus strain and showing central prey lysis and halos of extra lysis. Combining the purified phage with a lab strain of B. bacteriovorus HD100 recapitulated haloed plaques and increased killing of the E. coli prey in liquid culture, showing an effective side-by-side action of these predators compared to their actions alone. Using approximate Bayesian computation to select the best fitting from a variety of different mathematical models demonstrated that the experimental data could be explained only by assuming the existence of three prey phenotypes: (i) sensitive to both predators, (ii) genetically resistant to phage only, and (iii) plastic resistant to B. bacteriovorus only. Although each predator reduces prey availability for the other, high phage numbers did not abolish B. bacteriovorus predation, so both predators are competent to coexist and are causing different selective pressures on the bacterial surface while, in tandem, controlling prey bacterial numbers efficiently. This suggests that combinatorial predator therapy could overcome problems of phage resistance. Importance: With increasing levels of antibiotic resistance, the development of alternative antibacterial therapies is urgently needed. Two potential alternatives are bacteriophage and predatory bacteria. Bacteriophage therapy has been used, but prey/host specificity and the rapid acquisition of bacterial resistance to bacteriophage are practical considerations. Predatory bacteria are of interest due to their broad Gram-negative bacterial prey range and the lack of simple resistance mechanisms. Here, a bacteriophage and a strain of Bdellovibrio bacteriovorus, preyed side by side on a population of E. coli, causing a significantly greater decrease in prey numbers than either alone. Such combinatorial predator therapy may have greater potential than individual predators since prey surface changes selected for by each predator do not protect prey against the other predator

High-Throughput Detection of Induced Mutations and Natural Variation Using KeyPoint™ Technology

Reverse genetics approaches rely on the detection of sequence alterations in target genes to identify allelic variants among mutant or natural populations. Current (pre-) screening methods such as TILLING and EcoTILLING are based on the detection of single base mismatches in heteroduplexes using endonucleases such as CEL 1. However, there are drawbacks in the use of endonucleases due to their relatively poor cleavage efficiency and exonuclease activity. Moreover, pre-screening methods do not reveal information about the nature of sequence changes and their possible impact on gene function. We present KeyPoint™ technology, a high-throughput mutation/polymorphism discovery technique based on massive parallel sequencing of target genes amplified from mutant or natural populations. KeyPoint combines multi-dimensional pooling of large numbers of individual DNA samples and the use of sample identification tags (“sample barcoding”) with next-generation sequencing technology. We show the power of KeyPoint by identifying two mutants in the tomato eIF4E gene based on screening more than 3000 M2 families in a single GS FLX sequencing run, and discovery of six haplotypes of tomato eIF4E gene by re-sequencing three amplicons in a subset of 92 tomato lines from the EU-SOL core collection. We propose KeyPoint technology as a broadly applicable amplicon sequencing approach to screen mutant populations or germplasm collections for identification of (novel) allelic variation in a high-throughput fashion

Expansion of HIV testing in Eswatini: stakeholder perspectives on reaching the first 90

Achieving the United Nations' 90-90-90 goals has proven challenging in most settings and the ambitious 95-95-95 goals seem even more elusive. However, in Eswatini - a lower-middle-income country in sub-Saharan Africa with the highest HIV prevalence in the world - an estimated 92% of people living with HIV know their status. We conducted 26 in-depth interviews with stakeholders from policy, implementation, donor, local advocacy and academic sectors to elicit the facilitators and inhibitors to HIV testing uptake in Eswatini. Background data and related reports and policy documents (n = 57) were also reviewed. Essential facilitators included good governance via institutional and national budgetary commitments, which often led to swift adoption of globally recommended programs and standards. The integration of HIV testing into all points of care fostered a sense that testing was part of routine care, which reduced stigma. Challenges, however, centred on social norms that disadvantage certain groups with high ongoing HIV risk (such as key populations, adolescent girls and young women), a heavy reliance on external donor funding, and stigma that had subsided but nevertheless persisted. Amid concerns about whether the 90-90-90 targets could be achieved by 2020, the experience of Eswatini provides tangible insights into factors that have successfully influenced HIV testing uptake and may thus prove informative for other countries

Low anti-staphylococcal IgG responses in granulomatosis with polyangiitis patients despite long-term Staphylococcus aureus exposure

Chronic nasal carriage of the bacterium Staphylococcus aureus in patients with the autoimmune disease granulomatosis with polyangiitis (GPA) is a risk factor for disease relapse. To date, it was neither known whether GPA patients show similar humoral immune responses to S. aureus as healthy carriers, nor whether specific S. aureus types are associated with GPA. Therefore, this study was aimed at assessing humoral immune responses of GPA patients against S. aureus antigens in relation to the genetic diversity of their nasal S. aureus isolates. A retrospective cohort study was conducted, including 85 GPA patients and 18 healthy controls (HC). Humoral immune responses against S. aureus were investigated by determining serum IgG levels against 59 S. aureus antigens. Unexpectedly, patient sera contained lower anti-staphylococcal IgG levels than sera from HC, regardless of the patients' treatment, while total IgG levels were similar or higher. Furthermore, 210 S. aureus isolates obtained from GPA patients were characterized by different typing approaches. This showed that the S. aureus population of GPA patients is highly diverse and mirrors the general S. aureus population. Our combined findings imply that GPA patients are less capable of mounting a potentially protective antibody response to S. aureus than healthy individuals

HIV Treatment as Prevention: Systematic Comparison of Mathematical Models of the Potential Impact of Antiretroviral Therapy on HIV Incidence in South Africa

Background: Many mathematical models have investigated the impact of expanding access to antiretroviral therapy (ART) on new HIV infections. Comparing results and conclusions across models is challenging because models have addressed slightly different questions and have reported different outcome metrics. This study compares the predictions of several mathematical models simulating the same ART intervention programmes to determine the extent to which models agree about the epidemiological impact of expanded ART. Methods and Findings: Twelve independent mathematical models evaluated a set of standardised ART intervention scenarios in South Africa and reported a common set of outputs. Intervention scenarios systematically varied the CD4 count threshold for treatment eligibility, access to treatment, and programme retention. For a scenario in which 80% of HIV-infected individuals start treatment on average 1 y after their CD4 count drops below 350 cells/µl and 85% remain on treatment after 3 y, the models projected that HIV incidence would be 35% to 54% lower 8 y after the introduction of ART, compared to a counterfactual scenario in which there is no ART. More variation existed in the estimated long-term (38 y) reductions in incidence. The impact of optimistic interventions including immediate ART initiation varied widely across models, maintaining substantial uncertainty about the theoretical prospect for elimination of HIV from the population using ART alone over the next four decades. The number of person-years of ART per infection averted over 8 y ranged between 5.8 and 18.7. Considering the actual scale-up of ART in South Africa, seven models estimated that current HIV incidence is 17% to 32% lower than it would have been in the absence of ART. Differences between model assumptions about CD4 decline and HIV transmissibility over the course of infection explained only a modest amount of the variation in model results. Conclusions: Mathematical models evaluating the impact of ART vary substantially in structure, complexity, and parameter choices, but all suggest that ART, at high levels of access and with high adherence, has the potential to substantially reduce new HIV infections. There was broad agreement regarding the short-term epidemiologic impact of ambitious treatment scale-up, but more variation in longer term projections and in the efficiency with which treatment can reduce new infections. Differences between model predictions could not be explained by differences in model structure or parameterization that were hypothesized to affect intervention impact

A high affinity RIM-binding protein/Aplip1 interaction prevents the formation of ectopic axonal active zones

Synaptic vesicles (SVs) fuse at active zones (AZs) covered by a protein scaffold, at Drosophila synapses comprised of ELKS family member Bruchpilot (BRP) and RIM-binding protein (RBP). We here demonstrate axonal co-transport of BRP and RBP using intravital live imaging, with both proteins co- accumulating in axonal aggregates of several transport mutants. RBP, via its C-terminal Src-homology 3 (SH3) domains, binds Aplip1/JIP1, a transport adaptor involved in kinesin-dependent SV transport. We show in atomic detail that RBP C-terminal SH3 domains bind a proline-rich (PxxP) motif of Aplip1/JIP1 with submicromolar affinity. Pointmutating this PxxP motif provoked formation of ectopic AZ-like structures at axonal membranes. Direct interactions between AZ proteins and transport adaptors seem to provide complex avidity and shield synaptic interaction surfaces of pre-assembled scaffold protein transport complexes, thus, favouring physiological synaptic AZ assembly over premature assembly at axonal membranes. - See more at: http://elifesciences.org/content/4/e06935#sthash.oVGZ8cdi.dpu

Health benefi ts, costs, and cost-eff ectiveness of earlier eligibility for adult antiretroviral therapy and expanded treatment coverage: a combined analysis of 12 mathematical models

Background New WHO guidelines recommend initiation of antiretroviral therapy for HIV-positive adults with CD4 counts of 500 cells per μL or less, a higher threshold than was previously recommended. Country decision makers have to decide whether to further expand eligibility for antiretroviral therapy accordingly. We aimed to assess the potential health benefi ts, costs, and cost-eff ectiveness of various eligibility criteria for adult antiretroviral therapy and expanded treatment coverage. Methods We used several independent mathematical models in four settings—South Africa (generalised epidemic, moderate antiretroviral therapy coverage), Zambia (generalised epidemic, high antiretroviral therapy coverage), India (concentrated epidemic, moderate antiretroviral therapy coverage), and Vietnam (concentrated epidemic, low antiretroviral therapy coverage)—to assess the potential health benefi ts, costs, and cost-eff ectiveness of various eligibility criteria for adult antiretroviral therapy under scenarios of existing and expanded treatment coverage, with results projected over 20 years. Analyses assessed the extension of eligibility to include individuals with CD4 counts of 500 cells per μL or less, or all HIV-positive adults, compared with the previous (2010) recommendation of initiation with CD4 counts of 350 cells per μL or less. We assessed costs from a health-system perspective, and calculated the incremental cost (in US$) per disability-adjusted life-year (DALY) averted to compare competing strategies. Strategies were regarded very cost eff ective if the cost per DALY averted was less than the country’s 2012 per-head gross domestic product (GDP; South Africa:$8040; Zambia: $1425; India:$1489; Vietnam: $1407) and cost eff ective if the cost per DALY averted was less than three times the per-head GDP. Findings In South Africa, the cost per DALY averted of extending eligibility for antiretroviral therapy to adult patients with CD4 counts of 500 cells per μL or less ranged from$237 to $1691 per DALY averted compared with 2010 guidelines. In Zambia, expansion of eligibility to adults with a CD4 count threshold of 500 cells per μL ranged from improving health outcomes while reducing costs (ie, dominating the previous guidelines) to$749 per DALY averted. In both countries results were similar for expansion of eligibility to all HIV-positive adults, and when substantially expanded treatment coverage was assumed. Expansion of treatment coverage in the general population was also cost eff ective. In India, the cost for extending eligibility to all HIV-positive adults ranged from $131 to$241 per DALY averted, and in Vietnam extending eligibility to patients with CD4 counts of 500 cells per μL or less cost $290 per DALY averted. In concentrated epidemics, expanded access for key populations was also cost eff ective. Interpretation Our estimates suggest that earlier eligibility for antiretroviral therapy is very cost eff ective in lowincome and middle-income settings, although these estimates should be revisited when more data become available. Scaling up antiretroviral therapy through earlier eligibility and expanded coverage should be considered alongside other high-priority health interventions competing for health budgets