Efficacy and safety of delafloxacin compared with vancomycin plus aztreonam for acute bacterial skin and skin structure infections : A Phase 3, double-blind, randomized study

Funding Information: This work was funded by Melinta Therapeutics. In addition the editorial assistance (see below) was funded by Melinta Therapeutics. Publisher Copyright: © The Author 2017.Background: Delafloxacin is an investigational anionic fluoroquinolone in development for oral or intravenous administration for the treatment of infections caused by Gram-positive (including MRSA), Gram-negative, atypical and anaerobic organisms. Objectives: To establish the non-inferiority of delafloxacin compared with vancomycin plus aztreonam for the treatment of acute bacterial skin and skin structure infections and to compare the safety of the two antimicrobials. Patients and methods: A Phase 3, multicentre, randomized, double-blind, active-controlled study with 660 patients compared delafloxacin 300mg or vancomycin 15 mg/kg plus aztreonam2 g each administered twice daily intravenously for 5-14 days. Non-inferiority was evaluated by objective response ( ≥ 20% erythema reduction) at 48-72 h after initiation of study drug, investigator subjective assessment of outcome and microbiological responses. Clinical Trials Registration: NCT01811732. EudraCT number: 2012-001767-71. Results: In the ITT analysis set, the objective response was 78.2% in the delafloxacin arm and 80.9% in the vancomycin/aztreonam arm (mean treatment difference, -2.6%; 95% CI, -8.78% to 3.57%). Investigatorassessed cure was similar between the two groups at follow-up (52.0% versus 50.5%) and late follow-up (70.4% versus 66.6%). Bacterial eradication of MRSA was 100% and 98.5% in the delafloxacin group and the vancomycin/ aztreonamgroup, respectively. Frequency of treatment-emergent adverse events in the delafloxacin and vancomycin/aztreonam groups was similar. Treatment-emergent adverse events leading to study drug discontinuation were higher in the vancomycin/aztreonam group compared with the delafloxacin group (4.3% versus 0.9%). Conclusions: Delafloxacin, an anionic fluoroquinolone, was statistically non-inferior to vancomycin/aztreonam at 48-72 h following the start of therapy and was well tolerated as monotherapy in the treatment of acute bacterial skin and skin structure infections.publishersversionPeer reviewe

assessing the biodiversity of fermenting yeasts associated with marula fruits (Sclerocarya birrea)

The research work was funded by Botswana International University of Science and Technology (BIUST). © 2023 The Author(s). Published by Oxford University Press on behalf of the Guarantors of Brain.The inebriation of wild African elephants from eating the ripened and rotting fruit of the marula tree is a persistent myth in Southern Africa. However,the yeasts responsible for alcoholic fermentation to intoxicate the elephants remain poorly documented.In this study, we considered Botswana, a country with the world’s largest population of wild elephants, and where the marula tree is indigenous, abundant and protected, to assess the occurrence and biodiversity of yeasts with a potential to ferment and subsequently inebriate the wild elephants. We collected marula fruits from over a stretch of 800 km in Botswana and isolated 106 yeast strains representing 24 yeast species. Over 93% of these isolates,typically known to ferment simple sugars and produce ethanol comprising of high ethanol producers belonging to Saccharomyces, Brettanomyces, and Pichia, and intermediate ethanol producers Wickerhamomyces, Zygotorulaspora, Candida, Hanseniaspora, and Kluyveromyces. Fermentation of marula juice revealed convincing fermentative and aromatic bouquet credentials to suggest the potential to influence foraging behaviour and inebriate elephants in nature. There is insufficient evidence to refute the aforementioned myth. This work serves as the first work towards understanding the biodiversity marula associated yeasts to debunk the myth or approve the facts.publishersversionpublishe

Development and first application of an audit system for screening programs based on the PRECEDE-PROCEED model. An experience with breast cancer screening in the region of Lombardy (Italy)

Background: High participation and performance are necessary conditions for the effectiveness of breast cancer screening programs. Here we describe the process to define and test a planning software application and an audit cycle based on the PRECEDE-PROCEED model applied to improving breast cancer screening. We developed a planning software application following the phases of the PRECEDE-PROCEED model. The application was co-designed by local cancer screening program coordinators. An audit model was also developed. The revised application and the audit model were tested by all the coordinators of 15 breast cancer screening programs in the region of Lombardy in a 3-day workshop. The project plans produced using the application were compared with those produced in the previous year for clarity and completeness. Results: The 9 phases of the PRECEDE-PROCEED model were adapted to screening as follows: 1) identification of program goals (i.e., participation, sensitivity, false positive); 2) epidemiological issues; 3) best practices analysis; 4) evidence-based actions to be implemented in the screening center and the relationships with partners and stakeholders; 5) priority setting and identification of solutions for each issue; 6) definition of indicators; 7) monitoring; 8) evaluation; 9) impact assessment. The application automatically generated reports for each phase. During the audit cycle, the regional health authority negotiated the targets to be reached with local authorities and collected the improvement plans generated by the application. The plans produced after the application was adopted were more standardized and had clearer indicators for monitoring and evaluation compared to those produced in the previous year. Conclusions: The software application helps standardize criteria for planning interventions to improve screening programs and facilitates the implementation of the audit cycle

Are disability laws in Zimbabwe compatible with the provisions of the United Nations Convention on the Rights of Persons with Disabilities (CRPD)?

AbstractThis article analyzes and reviews the legal framework for the protection, promotion and fulfilment of rights of Persons with Disabilities (PWDs) in Zimbabwe. The analysis and review shed light on the degree of compliance of disability legislation in Zimbabwe with the provisions of the United Nations Convention on the Rights of Persons with Disabilities (hereinafter the CRPD). The author has used the CRPD as a measuring stick because the whole world is approaching disability issues based on the CRPD. The laws under scrutiny include the Constitution of Zimbabwe2, the Disabled Persons Act3 (DPA) of 1992, the Mental Health Act4, the War Victims Compensation Act5, the Criminal law (Codification and Reform) Act6, the Social Welfare Assistance Act7 and the State Service (Disability Benefits) Act8. The paper argues that save for the Constitution; other laws addressing disability in Zimbabwe are in need of reform. Such an observation is made in light of the shortcomings of the laws when measured against the provisions of the CRPD. The article concludes by underscoring the need of overhauling or aligning Zimbabwe’s disability legislation with the CRPD

The law and practice on Environmental Impact Assessments (EAIS) in Zambia: strengths and weaknesses

AbstractThis article reviews the Zambian EIA laws against a set of criteria to determine their strengths and weaknesses. The criteria employed include, the legal origins and the procedural aspects of the EIA process as well as the legal and institutional arrangements for EIA administration in the country. The paper also laments absence of a constitutional guarantee of the right to environmental protection as a factor that may negatively impinge upon EIA implementation. Furthermore, the paper agitates the entrenchment of a specific provision for environmental protection in the Zambian Constitution as a condition sine qua non for the promotion of sound environmental management in the country. The purpose of a constitutional protection of the right to environmental protection will be to give it higher latitude. What is more, the article sought to unravel the pluses and shortfalls inherent in the Zambian EIA legislation. The article concludes by proffering recommendations on how to improve on the existing legal framework for EIA administration in Zambia

Theorem 1 Min-cost labeling of an ADG is NP-complete, even considering only straight-line programs involving two-dimensional arrays with transpose and addition operations.

ring of the transformed graph that violates only "same" edges. 1 Lemma 1 In step 3 of the algorithm in Figure 4, the graph G#e; E# with e included and E removed is satisfiable. Proof: A satisfiable CG remains so when edges are removed. Removing the set E breaks the CG into separate, satisfiable subgraphs G 1 and G 2 , which are then connected by the edge e; wlog, e =#x; y# is directed from subgraph G 1 to subgraph G 2 . We rely on the fact that the nonzero pattern of any D-matrix can be changed to the that of any other D-matrix of the same shape by a row permutation. Furthermore, the satisfying labelings of a CG are closed under left multiplication of all label matrices L by any row permutation of a nonsingular diagonal matrix. Construct a labeling of subgraph G 1 that satisfies its edge constraints. We show that there is a satisfying labeling of the vertices of G 2 and a modified satisfying labeling of the vertices of G 1 that satisfy the constraint over e. We proceed as follows