Aspects of the design and operation of production control systems in manufacturing industry

Computerised production control developments have concentrated on Manufacturing Resources Planning (MRP II) systems. The literature suggests however, that despite the massive investment in hardware, software and management education, successful implementation of such systems in manufacturing industries has proved difficult. This thesis reviews the development of production planning and control systems, in particular, investigates the causes of failures in implementing MRP/MRP II systems in industrial environments and argues that the centralised and top-down planning structure, as well as the routine operational methodology of such systems, is inherently prone to failure. The thesis reviews the control benefits of cellular manufacturing systems but concludes that in more dynamic manufacturing environments, techniques such as Kanban are inappropriate. The basic shortcomings of MRP II systems are highlighted and a new enhanced operational methodology based on distributed planning and control principles is introduced. Distributed Manufacturing Resources Planning (DMRP), was developed as a capacity sensitive production planning and control solution for cellular manufacturing environments. The system utilises cell based, independently operated MRP II systems, integrated into a plant-wide control system through a Local Area Network. The potential benefits of adopting the system in industrial environments is discussed and the results of computer simulation experiments to compare the performance of the DMRP system against the conventional MRP II systems presented. DMRP methodology is shown to offer significant potential advantages which include ease of implementation, cost effectiveness, capacity sensitivity, shorter manufacturing lead times, lower working in progress levels and improved customer service.

Amino acids in oral drug delivery:salts, ion-pairs and transcriptomics

Oral drug delivery is considered the most popular route of delivery because of the ease of administration, availability of a wide range of dosage forms and the large surface area for drug absorption via the intestinal membrane. However, besides the unfavourable biopharmaceutical properties of the therapeutic agents, efflux transporters such as Pglycoprotein (P-gp) and multiple resistance proteins (MRP) decrease the overall drug uptake by extruding the drug from the cells. Although, prodrugs have been investigated to improve drug partitioning by masking the polar groups covalently with pre-moieties promoting increased uptake, they present significant challenges including reduced solubility and increased toxicity. The current work investigates the use of amino acids as ion-pairs for three model drugs: indomethacin (weak acid), trimethoprim (weak base) and ciprofloxacin (zwitter ion) in an attempt to improve both solubility and uptake. Solubility was studied by salt formation while creating new routes for uptake across the membranes via amino acids transporter proteins or dipeptidyl transporters was the rationale to enhance absorption. New salts were prepared for the model drugs and the oppositely charged amino acids by freeze drying and they were characterised using FTIR, 1HNMR, DSC, SEM, pH solubility profile, solubility and dissolution. Permeability profiles were assessed using an in vitro cell based method; Caco-2 cells and the genetic changes occurring across the transporter genes and various pathways involved in the cellular activities were studied using DNA microarrays. Solubility data showed a significant increase in drug solubility upon preparing the new salts with the oppositely charged counter ions (ciprofloxacin glutamate salt exhibiting 2.9x103 fold enhancement when compared to the free drug). Moreover, permeability studies showed a 3 fold increase in trimethoprim and indomethacin permeabilities upon ion-pairing with amino acids and more than 10 fold when the zwitter ionic drug was paired with glutamic acid. Microarray data revealed that trimethoprim was absorbed actively via OCTN1 transporters while MRP7 is the main transporter gene that mediates its efflux. The absorption of trimethoprim from trimethoprim glutamic acid ion-paired formulations was affected by the ratio of glutamic acid in the formulation which was inversely proportional to the degree of expression of OCTN1. Interestingly, ciprofloxacin glutamic acid ion-pairs were found to decrease the up-regulation of ciprofloxacin efflux proteins (P-gp and MRP4) and over-express two solute carrier transporters; (PEPT2 and SLCO1A2) suggesting that a high aqueous binding constant (K11aq) enables the ion-paired formulations to be absorbed as one entity. In conclusion, formation of ion-pairs with amino acids can influence in a positive way solubility, transfer and gene expression effects of drugs.

Introduction : the role of quality, production and technological innovation in improving competitive performance

Quality, production and technological innovation management rank among the most important matters of concern to modern manufacturing organisations. They can provide companies with the decisive means of gaining a competitive advantage, especially within industries where there is an increasing similarity in product design and manufacturing processes. The papers in this special issue of International Journal of Technology Management have all been selected as examples of how aspects of quality, production and technological innovation can help to improve competitive performance. Most are based on presentations made at the UK Operations Management Association's Sixth International Conference held at Aston University at which the theme was 'Getting Ahead Through Technology and People'. At the conference itself over 80 papers were presented by authors from 15 countries around the world. Among the many topics addressed within the conference theme, technological innovation, quality and production management emerged as attracting the greatest concern and interest of delegates, particularly those from industry. For any new initiative to be implemented successfully, it should be led from the top of the organization. Achieving the desired level of commitment from top management can, however, be a difficulty. In the first paper of this issue, Mackness investigates this question by explaining how systems thinking can help. In the systems approach, properties such as 'emergence', 'hierarchy', 'commnication' and 'control' are used to assist top managers in preparing for change. Mackness's paper is then complemented by Iijima and Hasegawa's contribution in which they investigate the development of Quality Information Management (QIM) in Japan. They present the idea of a Design Review and demonstrate how it can be used to trace and reduce quality-related losses. The next paper on the subject of quality is by Whittle and colleagues. It relates to total quality and the process of culture change within organisations. Using the findings of investigations carried out in a number of case study companies, they describe four generic models which have been identified as characterising methods of implementing total quality within existing organisation cultures. Boaden and Dale's paper also relates to the management of quality, but looks specifically at the construction industry where it has been found there is still some confusion over the role of Quality Assurance (QA) and Total Quality Management (TQM). They describe the results of a questionnaire survey of forty companies in the industry and compare them to similar work carried out in other industries. Szakonyi's contribution then completes this group of papers which all relate specifically to the question of quality. His concern is with the two ways in which R&D or engineering managers can work on improving quality. The first is by improving it in the laboratory, while the second is by working with other functions to improve quality in the company. The next group of papers in this issue all address aspects of production management. Umeda's paper proposes a new manufacturing-oriented simulation package for production management which provides important information for both design and operation of manufacturing systems. A simulation for production strategy in a Computer Integrated Manufacturing (CIM) environment is also discussed. This paper is then followed by a contribution by Tanaka and colleagues in which they consider loading schedules for manufacturing orders in a Material Requirements Planning (MRP) environment. They compare mathematical programming with a knowledge-based approach, and comment on their relative effectiveness for different practical situations. Engstrom and Medbo's paper then looks at a particular aspect of production system design, namely the question of devising group working arrangements for assembly with new product structures. Using the case of a Swedish vehicle assembly plant where long cycle assembly work has been adopted, they advocate the use of a generally applicable product structure which can be adapted to suit individual local conditions. In the last paper of this particular group, Tay considers how automation has affected the production efficiency in Singapore. Using data from ten major industries he identifies several factors which are positively correlated with efficiency, with capital intensity being of greatest interest to policy makers. The two following papers examine the case of electronic data interchange (EDI) as a means of improving the efficiency and quality of trading relationships. Banerjee and Banerjee consider a particular approach to material provisioning for production systems using orderless inventory replenishment. Using the example of a single supplier and multiple buyers they develop an analytical model which is applicable for the exchange of information between trading partners using EDI. They conclude that EDI-based inventory control can be attractive from economic as well as other standpoints and that the approach is consistent with and can be instrumental in moving towards just-in-time (JIT) inventory management. Slacker's complementary viewpoint on EDI is from the perspective of the quality relation-ship between the customer and supplier. Based on the experience of Lucas, a supplier within the automotive industry, he concludes that both banks and trading companies must take responsibility for the development of payment mechanisms which satisfy the requirements of quality trading. The three final papers of this issue relate to technological innovation and are all country based. Berman and Khalil report on a survey of US technological effectiveness in the global economy. The importance of education is supported in their conclusions, although it remains unclear to what extent the US government can play a wider role in promoting technological innovation and new industries. The role of technology in national development is taken up by Martinsons and Valdemars who examine the case of the former Soviet Union. The failure to successfully infuse technology into Soviet enterprises is seen as a factor in that country's demise, and it is anticipated that the newly liberalised economies will be able to encourage greater technological creativity. This point is then taken up in Perminov's concluding paper which looks in detail at Russia. Here a similar analysis is made of the concluding paper which looks in detail at Russia. Here a similar analysis is made of the Soviet Union's technological decline, but a development strategy is also presented within the context of the change from a centralised to a free market economy. The papers included in this special issue of the International Journal of Technology Management each represent a unique and particular contribution to their own specific area of concern. Together, however, they also argue or demonstrate the general improvements in competitive performance that can be achieved through the application of modern principles and practice to the management of quality, production and technological innovation.

The effects of material variations in high value manufacturing industries

It has never been easy for manufacturing companies to understand their confidence level in terms of how accurate and to what degree of flexibility parts can be made. This brings uncertainty in finding the most suitable manufacturing method as well as in controlling their product and process verification systems. The aim of this research is to develop a system for capturing the company’s knowledge and expertise and then reflect it into an MRP (Manufacturing Resource Planning) system. A key activity here is measuring manufacturing and machining capabilities to a reasonable confidence level. For this purpose an in-line control measurement system is introduced to the company. Using SPC (Statistical Process Control) not only helps to predict the trend in manufacturing of parts but also minimises the human error in measurement. Gauge R&R (Repeatability and Reproducibility) study identifies problems in measurement systems. Measurement is like any other process in terms of variability. Reducing this variation via an automated machine probing system helps to avoid defects in future products.Developments in aerospace, nuclear, oil and gas industries demand materials with high performance and high temperature resistance under corrosive and oxidising environments. Superalloys were developed in the latter half of the 20th century as high strength materials for such purposes. For the same characteristics superalloys are considered as difficult-to-cut alloys when it comes to formation and machining. Furthermore due to the sensitivity of superalloy applications, in many cases they should be manufactured with tight tolerances. In addition superalloys, specifically Nickel based, have unique features such as low thermal conductivity due to having a high amount of Nickel in their material composition. This causes a high surface temperature on the work-piece at the machining stage which leads to deformation in the final product.Like every process, the material variations have a significant impact on machining quality. The main cause of variations can originate from chemical composition and mechanical hardness. The non-uniform distribution of metal elements is a major source of variation in metallurgical structures. Different heat treatment standards are designed for processing the material to the desired hardness levels based on application. In order to take corrective actions, a study on the material aspects of superalloys has been conducted. In this study samples from different batches of material have been analysed. This involved material preparation for microscopy analysis, and the effect of chemical compositions on hardness (before and after heat treatment). Some of the results are discussed and presented in this paper.

Bevezetés a lean menedzsmentbe – a lean stratégiai alapjai = Introduction to lean management – basic strategic elements of lean

A lean menedzsment az értékteremtő folyamatok stratégiai és operatív szintjének meghatározó formálójává vált az elmúlt évtizedekben. Jelen tanulmány stratégiai nézőpontból tárgyalja a lean menedzsment teljes bevezetését. Részletes áttekintést ad a Womack és Jones (2003) által lefektetett lean alapelvekről. Az operatív teljesítményjavulásból származó vevői értékteremtés mellett foglalkozik a tulajdonosi értékteremtéssel, az MRP és a lean szinergikus összekapcsolásával, valamint a lean ideális szervezeti környezetével is. A lean a kapcsolódó területek illesztését is megköveteli, a műhelytanulmány röviden kitér az emberi erőforrás, a teljesítménymérés, az ellátási lánc és a termékfejlesztés legfontosabb kérdéseire. = Lean management has become the dominant strategic and operative framework of value creating processes in the last decades. The working paper describes the strategic approach of full lean implementation. It is mainly built on Womack and Jones’s (2003) lean principles. Beside the five lean principles the study is concerned with customer and shareholder value creation, touches upon the relationship of lean and MRP, and describes ideal lean organizational environment. Lean redesigns value creating processes and requires functional fit of related departments, so the most important issues of human resource, performance, supply chain management and product design are discussed as well.

Visszutas logisztika és termeléstervezés (Reverse logistics and production planning)

A dolgozat a visszutas logisztikát, az újrahasznosítást igyekszik beilleszteni a vállalati termeléstervezés keretei közé. A szükséglettervezési rendszerek (material requirements planning, MRP) célja a készletek és beszerzendő anyagok, alkatrészek időben ütemezett gyártásának és beszerzésének megtervezése. A klasszikus MRP rendszereket az utóbbi időben próbálja a tudomány az újrahasznosítással kibővíteni. Mivel ebben az esetben az új, és újrafelhasználható anyagokat külön kell nyilvántartani, ezért az MRP-táblák és készletek növekednek. A rendelési tételnagyságok meghatározása is nehezebb, összetettebb tételnagysághoz vezet. A dolgozatban egy visszutas logisztikai készletmodellt ismertetünk, valamint annak dinamikus kiterjesztését, amely alapja lehet az SAP-ba beépíthető rendelés állomány meghatározó heurisztikának. ____ The aim of the paper is to extend production planning with reverse logistics and reuse. Material requirements planning (MRP) systems plan and control invetory levels and purchasing activities of the firm. In the last decade scientists on this field try to involve reverse logistics activities in MRP systems. Size of MRP-tables is growing in this case because of the alternative use of newly purchased products and reusable old items. Determination of order quantities will be more complex with these two modes of material supplies. An EOQ-type reverse logistics model is presented in the paper with a dynamic lot size generalization. The generalized model can be seen as a basic model to build in production planning and control system like SAP.

The use of treatment theories and procedures for postural control in adult with hemiplegia: A national survey

This study investigated the use of treatment theories and procedures for postural control training used by Occupational Therapists (OTs) when working with hemiplegic adults who have had cerebrovascular accident (CVA) or traumatic brain injury (TBI). The method of data collection was a national survey of 400 randomly selected physical disability OTs with 127 usable surveys returned. Results showed that the most common used treatment theory was neurodevelopmental treatment (NDT), followed by motor relearning program (MRP), proprioceptive neuromuscular facilitation (PNF), Brunnstrom's approach, and the approach of Rood. The most common treatment posture used was sitting, followed by standing, mat activity, equilibrium reaction training, and walking. The factors affecting the use of various treatment theories procedures were years certified, years of clinical experience, work situation and work status. Pearson correlation coefficient analyses found significant positive relationships between treatment theories and postures. There were significant high correlations between usage of all pairs of treatment procedures. ^

Specific Increase in MDR1 Mediated Drug-Efflux in Human Brain Endothelial Cells following Co-Exposure to HIV-1 and Saquinavir

Persistence of HIV-1 reservoirs within the Central Nervous System (CNS) remains a significant challenge to the efficacy of potent anti-HIV-1 drugs. The primary human Brain Microvascular Endothelial Cells (HBMVEC) constitutes the Blood Brain Barrier (BBB) which interferes with anti-HIV drug delivery into the CNS. The ATP binding cassette (ABC) transporters expressed on HBMVEC can efflux HIV-1 protease inhibitors (HPI), enabling the persistence of HIV-1 in CNS. Constitutive low level expression of several ABC-transporters, such as MDR1 (a.k.a. P-gp) and MRPs are documented in HBMVEC. Although it is recognized that inflammatory cytokines and exposure to xenobiotic drug substrates (e.g HPI) can augment the expression of these transporters, it is not known whether concomitant exposure to virus and anti-retroviral drugs can increase drug-efflux functions in HBMVEC. Our in vitro studies showed that exposure of HBMVEC to HIV-1 significantly up-regulates both MDR1 gene expression and protein levels; however, no significant increases in either MRP-1 or MRP-2 were observed. Furthermore, calcein-AM dye-efflux assays using HBMVEC showed that, compared to virus exposure alone, the MDR1 mediated drug-efflux function was significantly induced following concomitant exposure to both HIV-1 and saquinavir (SQV). This increase in MDR1 mediated drug-efflux was further substantiated via increased intracellular retention of radiolabeled [3H-] SQV. The crucial role of MDR1 in 3H-SQV efflux from HBMVEC was further confirmed by using both a MDR1 specific blocker (PSC-833) and MDR1 specific siRNAs. Therefore, MDR1 specific drug-efflux function increases in HBMVEC following co-exposure to HIV-1 and SQV which can reduce the penetration of HPIs into the infected brain reservoirs of HIV-1. A targeted suppression of MDR1 in the BBB may thus provide a novel strategy to suppress residual viral replication in the CNS, by augmenting the therapeutic efficacy of HAART drugs.

Frequência e significado clínico da expressão da glicoproteína P e da proteína relacionada a resistência a múltiplas drogas na leucemia mielóide aguda

Despite the advances in the cure rate for acute myeloid leukemia, a considerable number of patients die from their disease due to the occurrence of multidrug resistance (MDR). Overexpression of the transporter proteins P-glycoprotein (Pgp) and multidrug resistance-associated protein (MRP) confer resistance to the treatment these leukemias. OBJECTIVE: To analyze the expression of the Gpp and MRP1 in patients with AML by flow cytometry (FC) and to determine the correlation between expression and demographic and also clinical and laboratorial variables. METHODS: Bone marrow and peripheral blood samples from 346 patients with a diagnosis of AML were assessed for the expression of Pgp and MRP1 by FC. RESULTS: The expression of Pgp and MRP1 was found in 111 (32.1%) and 133 (38.4%) patients, respectively, with greater prevalence in older patients and lower in adolescents, observing also a high incidence in patients with refractory disease, recurrence and secondary in comparison with the cases of de novo AML. Regarding the laboratory findings, we observed a higher correlation statistically significant between the expression of Pgp and MRP1 in AML CD34+ and FAB AML M7, M5A and M2 and lower the M3 subtype, not observed statistically significant correlation between the phenotype MDR and other laboratory data such with hemoglobin, leukocyte count, platelet count, aberrant expression of lymphoid antigens (CD2, CD7 and CD19) and clinical signs related to the disease. CONCLUSIONS: The results showed that the detection of MDR phenotype by flow cytometry can be a molecular marker for prognosis independent patients diagnosed with AML.

Características dos programas de residência médica em cardiologia do estado do Rio Grande do Norte

The present study had as goal to evaluate Rio Grande do Norte state’s medical residency programs (MRP) in Cardiology. It’s a descriptive study, including a documental analysis of the program’s accreditation processes (PAP) of cardiology’s medical residency in Rio Grande do Norte state in 2014 and the analysis of the resident’s perception about his professional education as a specialist in Cardiology. Beside the documental analysis of the PAPs, it was applied a semi-structured questionnaire with closed questions Likert style and open questions to all the current and former residents of the MRPs analyzed. Two MRPs in Cardiology were identified in Rio Grande do Norte state, one hosted in a public institution and the other in a private institution. The documental analysis showed a greater amount of preceptors with a good level of ownership on the public institution in comparison with the private one, as well as a bigger number of publications, participation in congresses and in book’s publications. The private institution presents a better Urgency’s infrastructure, with emergency room and cardiologic ICU. It IS clear that the residents are aware of how a good residency must work, as well as the strengths and fragilities of their own residences. Most of Onofre Lopes Universitary Hospital’s residents point out as a strength the organization, participation and quality of the preceptors, practice activities and scientific debates, great amount of patients and the visits and debates with the preceptors on the sickrooms. As the greatest fragilities, they emphasize the lack of a urgency service of their own and a specialized ICU. In Coração Hospital of Natal (HCor), it is listed as weak points the theoretic scheduling and the few ambulatory practices. As positive aspects, they report the preceptors, the agility on the execution of exams, a good number of serious patients and procedures. In both residences, it is seen a certain difficulty in accepting the important and mandatory items imposed by the rules of the Medical Residences’ National Committee, such as: biostatistics, bioethics, medical ethic, epidemiology and research methodology. Besides that, the residents recognize that both hospitals have a good infrastructure and technological support, especially in imaging methods. The evaluation of PRMCs identifies the strengths of each program and the aspects to be improved in both programs. It also allowed the observation of difficulties in accepting some regulations contained in the CNRM resolution by the resident, such as participation in activities such as biostatistics, epidemiology and research methodology as well as the improvement needs of specific technical training, such as in emergency care. Thus, our results make possible to develop strategies for continued improvement of PRMC in RN state. In addition, it enabled the preparation of the resident’s manual in cardiology, containing even a breakdown of resident evaluation system, which could serve as a model for other residency programs.

Arsenic exposure and outcomes of antimonial treatment in visceral leishmaniasis patients in Bihar, India : a retrospective cohort study

Funding: This work was supported by a Clinical PhD Fellowship to MRP (090665) and a Principal Research Fellowship to AHF (079838) from the Wellcome Trust (http://www.wellcome.ac.uk). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Improving minimum rate predictors algorithm for compression of volumetric medical images

Medical imaging technologies are experiencing a growth in terms of usage and image resolution, namely in diagnostics systems that require a large set of images, like CT or MRI. Furthermore, legal restrictions impose that these scans must be archived for several years. These facts led to the increase of storage costs in medical image databases and institutions. Thus, a demand for more efficient compression tools, used for archiving and communication, is arising. Currently, the DICOM standard, that makes recommendations for medical communications and imaging compression, recommends lossless encoders such as JPEG, RLE, JPEG-LS and JPEG2000. However, none of these encoders include inter-slice prediction in their algorithms. This dissertation presents the research work on medical image compression, using the MRP encoder. MRP is one of the most efficient lossless image compression algorithm. Several processing techniques are proposed to adapt the input medical images to the encoder characteristics. Two of these techniques, namely changing the alignment of slices for compression and a pixel-wise difference predictor, increased the compression efficiency of MRP, by up to 27.9%. Inter-slice prediction support was also added to MRP, using uni and bi-directional techniques. Also, the pixel-wise difference predictor was added to the algorithm. Overall, the compression efficiency of MRP was improved by 46.1%. Thus, these techniques allow for compression ratio savings of 57.1%, compared to DICOM encoders, and 33.2%, compared to HEVC RExt Random Access. This makes MRP the most efficient of the encoders under study.

Análise da organização da rede de saúde da Paraíba a partir do modelo de regionalização

Este artigo analisa a organização da rede de saúde da Paraíba a partir do modelo de regionalização proposto pelo estado da Paraíba. Material e Métodos: Trata-se de um estudo documental que tomou por base, prioritariamente, o Plano Diretor de Regionalização da Paraíba e os documentos oficiais do Ministério da Saúde que orientam a construção dos mesmos pelos Estados. Resultados: A análise dos dados revelou alguns limites no processo de implantação do PDR/ PB, tais como a ausência de análise das características sociais, econômicas e culturais durante a escolha das sedes das regiões de saúde e a inexistente descrição da organização da assistência à saúde do território estadual. Conclusão: O processo de regionalização e a formulação do PDR da Paraíba não seguiram a Instrução Normativa do Ministério da Saúde em alguns aspectos, desconsiderando as especificidades de cada região de saúde, o que pode resultar em problemas no acesso e na articulação da rede de serviços com vistas à legitimação das regiões de saúde desse Estado

Análise da organização da rede de saúde da Paraíba a partir do modelo de regionalização

Este artigo analisa a organização da rede de saúde da Paraíba a partir do modelo de regionalização proposto pelo estado da Paraíba. Material e Métodos: Trata-se de um estudo documental que tomou por base, prioritariamente, o Plano Diretor de Regionalização da Paraíba e os documentos oficiais do Ministério da Saúde que orientam a construção dos mesmos pelos Estados. Resultados: A análise dos dados revelou alguns limites no processo de implantação do PDR/ PB, tais como a ausência de análise das características sociais, econômicas e culturais durante a escolha das sedes das regiões de saúde e a inexistente descrição da organização da assistência à saúde do território estadual. Conclusão: O processo de regionalização e a formulação do PDR da Paraíba não seguiram a Instrução Normativa do Ministério da Saúde em alguns aspectos, desconsiderando as especificidades de cada região de saúde, o que pode resultar em problemas no acesso e na articulação da rede de serviços com vistas à legitimação das regiões de saúde desse Estado

Pharmacogenetic: screening relevant polymorphisms on antiretroviral therapy in a HIV Portuguese population

Poster presented at the 15th European AIDS Conference. Barcelona, 21-24 October 2015