A refinement-based development of a distributed signalling system

The decentralised railway signalling systems have a potential to increase capacity, availability and reduce maintenance costs of railway networks. However, given the safety-critical nature of railway signalling and the complexity of novel distributed signalling solutions, their safety should be guaranteed by using thorough system validation methods. To achieve such a high-level of safety assurance of these complex signalling systems, scenario-based testing methods are far from being sufficient despite that they are still widely used in the industry. Formal verification is an alternative approach which provides a rigorous approach to verifying complex systems and has been successfully used in the railway domain. Despite the successes, little work has been done in applying formal methods for distributed railway systems. In our research we are working towards a multifaceted formal development methodology of complex railway signalling systems. The methodology is based on the Event-B modelling language which provides an expressive modelling language, a stepwise development and a proof-based model verification. In this paper, we present the application of the methodology for the development and verification of a distributed protocol for reservation of railway sections. The main challenge of this work is developing a distributed protocol which ensures safety and liveness of the distributed railway system when message delays are allowed in the model.

Stepwise Development and Yearlong Assessment of a Pharmacist-Driven Molecular Rapid Diagnostic Test Result Service for Bloodstream Infections

Purpose: Provide a stepwise approach to the design and implementation of a service that integrates all staff pharmacists into the communication and interpretation of molecular rapid diagnostic tests (mRDT) for bloodstream infections and summarize outcomes from a 12-month post-implementation assessment. Physician and pharmacist impressions of the service are also described. Summary: mRDT have proven clinical benefit in the treatment of bacteremia. Pharmacy leadership can collaborate with other health system leaders to develop policies and a workflow that route result calls to pharmacists to maximize the impact of this technology. Pharmacist education, development of clinical resources and documentation templates allow all pharmacists to perform this antimicrobial stewardship service consistently and confidently. Physicians overwhelmingly recognize the value of this service and often accept the pharmacist’s recommendations. Antibiotic de-escalation was the most frequent outcome when changes to the antibiotic regimen were made. Conclusion: Pharmacists are well positioned to utilize results from mRDT to improve antibiotic selection. Through the use of competencies and internally-derived resources, all pharmacists, rather than just infectious diseases pharmacy specialists, can perform this important antibiotic stewardship activity and positively influence patient outcomes.

Drosophila Fezf functions as a transcriptional repressor to direct layer-specific synaptic connectivity in the fly visual system

The layered compartmentalization of synaptic connections, a common feature of nervous systems, underlies proper connectivity between neurons and enables parallel processing of neural information. However, the stepwise development of layered neuronal connections is not well understood. The medulla neuropil of the Drosophila visual system, which comprises 10 discrete layers (M1 to M10), where neural computations underlying distinct visual features are processed, serves as a model system for understanding layered synaptic connectivity. The first step in establishing layer-specific connectivity in the outer medulla (M1 to M6) is the innervation by lamina (L) neurons of one of two broad, primordial domains that will subsequently expand and transform into discrete layers. We previously found that the transcription factor dFezf cell-autonomously directs L3 lamina neurons to their proper primordial broad domain before they form synapses within the developing M3 layer. Here, we show that dFezf controls L3 broad domain selection through temporally precise transcriptional repression of the transcription factor slp1 (sloppy paired 1). In wild-type L3 neurons, slp1 is transiently expressed at a low level during broad domain selection. When dFezf is deleted, slp1 expression is up-regulated, and ablation of slp1 fully rescues the defect of broad domain selection in dFezf-null L3 neurons. Although the early, transient expression of slp1 is expendable for broad domain selection, it is surprisingly necessary for the subsequent L3 innervation of the M3 layer. DFezf thus functions as a transcriptional repressor to coordinate the temporal dynamics of a transcriptional cascade that orchestrates sequential steps of layer-specific synapse formation.

Criminological prognostication of the emergence of new types of narcotic drugs

The article presents the results of studying the algorithms for the emergence of new types of narcotic drugs, identifies the patterns of changes in the chemical structures of new psychoactive substances, and proposes a mechanism for criminological prognostication of the emergence of new types of substances with narcogenic potential. Analytical studies of the emergence of new psychostimulants have confirmed the correctness of the chosen model of state control of new psychoactive substances – the introduction of “derivative narcotic substances and psychotropic substances” into Russian legislation. An objective and comprehensive study of the chemical structures of molecules of new psychoactive substances also confirmed the legitimacy of establishing state control over the illegal traffic of analogues of narcotic drugs and psychotropic substances. In general, the conducted analytical study suggests considering from the scientific and analytical point of view the possible introduction into law enforcement practice of a new direction "Criminological prognostication of the emergence of new types of narcotic drugs". The general algorithms and patterns found in the process of analytical research in the new structures of molecules of psychoactive substances have confirmed both the forensic search and the logical and stepwise development of science in the field of psychoactive substances.

A Qualitative Study on the Establishment of an Interpersonal Violence Registry System in Iran

Establishment of an interpersonal-violence registry system (IPVRS) is a promising initiative to tackle violence. This qualitative study aimed to fill the gap in knowledge regarding the feasibility of establishing the IPVRS in the East-Azerbaijan province of Iran. This qualitative study using content analysis was conducted to explore the importance, challenges, and facilitating factors of establishing the IPVRS from the viewpoints of stakeholders. Forty-six individuals from the Forensic Medical Organization, the University, the Welfare Organization, the Training and Education Organization, hospitals, and primary health centers participated in the study. Six themes and 13 sub-themes were identified. The importance of the establishment of the IPVRS was sub-categorized into two main themes, including violence as a public health priority and severe consequences of violence including intensive health and social outcomes and high use of medical services. The most critical challenges of establishing the IPVRS were categorized into two main themes including victims’ under-reporting due to financial difficulties as well as psychosocial barriers and structural barriers such as organizational barriers and methodological challenges. Inter-sectoral partnership was identified as the main facilitating factor in the successful establishment of the IPVRS. The participants recommended improving the development of the IPVRS by stepwise development of the program, resource absorption from other beneficiary organizations, and making more coverage in the registry system. In conclusion, the establishment of the IPVRS is identified as an effective strategy to tackle violence-related issues. Close collaboration with different governmental and non-governmental sectors and the gradual development of the registry system can pave the way for establishing the IPVRS. This study has several implications for identifying potential challenges and facilitators of the IPVRS applicable to other developing countries with similar contexts.

Economic comparison of options for piggyback terminal arrangement at a marshalling yard

Objective: To carry out an economic comparison of alternative options for a piggyback terminal layout solution in a marshalling yard. Methods: Modern logistics, customer focus approach, synchromodality, system analysis, comparison of options, forecasting, project and situational management methods were used. Results: Scenario forecasting allowed us to assess the possible dynamic patterns of traffic volumes for three options. The position of the yard in the hub is characterized. The technical and technology design of a piggyback terminal are briefly discussed. The terminal location options based on the yard infrastructure are indicated. Schematic solutions with different terminal-yard junctions through turnout track N 22 (option 1) and N 16 of the Transfer Park (option 2) are proposed. We have analyzed benefits and drawbacks, calculated the cost of the marshalling yard development for each developed option at 2014 values. In particular, the itemized capital investments and operating costs of the marshalling yard stepwise development are calculated and presented in a tabular form. Practical importance: The comparative analysis results for a set of technical and economic indicators are presented. Using the method of comparing options for different indicators, option 1 was selected as the most rational in terms of the minimum cumulative costs

Stepwise Development of Biomimetic Chimeric Peptides for Gene Delivery

Gene-based therapy largely relies on the vector type that allows a selective and efficient transfection into the target cells with maximum efficacy and minimal toxicity. Although, genes delivered utilizing modified viruses transfect efficiently and precisely, these vectors can cause severe immunological responses and are potentially carcinogenic. A promising method of overcoming this limitation is the use of non-viral vectors, including cationic lipids, polymers, dendrimers, and peptides, which offer potential routes for compacting DNA for targeted delivery. Although non-viral vectors exhibit reduced transfection efficiency compared to their viral counterpart, their superior biocompatibility, non-immunogenicity and potential for large-scale production make them increasingly attractive for modern therapy. There has been a great deal of interest in the development of biomimetic chimeric peptides. Biomimetic chimeric peptides contain different motifs for gene translocation into the nucleus of the desired cells. They have motifs for gene targeting into the desired cell, condense DNA into nanosize particles, translocate the gene into the nucleus and enhance the release of the particle into the cytoplasm. These carriers were developed in recent years. This review highlights the stepwise development of the biomimetic chimeric peptides currently being used in gene delivery.