Photocatalytic proton reduction with ruthenium and cobalt complexes immobilized on fumed reversed-phase silica.

Heterogeneous photocatalytic hydrogen production with a non-covalently immobilized molecular ruthenium based photosensitizer (PS) and a cobalt polypyridyl based water reducing catalyst (WRC) is reported. PS and WRC were derivatized with C18-alkyl chains and immobilized by adsorption on hydrophobic fumed silica. The resulting loaded support was suspended in water with anionic or cationic surfactants and subjected to heterogeneous photocatalytic H2 production with ascorbate as sacrificial electron donor (SED). No leaching was observed under catalytic conditions, thus catalysis was truly heterogeneous. The catalytic performance of immobilized PS and WRC clearly exceeded that of homogeneous catalysis at low concentrations. At high concentration, diffusion and light limitation lead to lower reaction rates, but the same stability as for homogeneous reactions was still achieved. WRC concentration variations indicated a relatively high stability (up to 1300 H2/Co) and mobility of amphiphilic catalysts on the hydrophobic silica surface. Comparison of fumed silica with porous and non-porous silica showed, that a high BET surface area along with a good accessibility from the reaction media are crucial for catalytic performance. Mechanistic investigations by transient absorption spectroscopy displayed reductive quenching of excited PS by ascorbate followed by on particle electron transfer to WRC as reaction pathway. Particles with additional cationic surfactants exhibited a significantly higher catalytic performance as compared to anionic surfactants. Non-covalent anchoring of correspondingly derivatized WRCs or PSs to reversed-phase silica offers a rapid and versatile transition from homogeneous to heterogeneous molecular proton reduction.

Mongolian Telepathology Network (MonTelNet) / Монголын Анагаах Ухаан

IntroductionMongolian rural population lack of access to adequate health services due to the fact that they live remotefrom urban hospitals. With the rapid spread of telemedicine in most countries, has been promoted as apromising tool to address deficiencies in delivering health care in developing countries.In late 2008 the Swiss Surgical Team (SST) started the telemedicine project MonTelNet in Mongolia incollaboration and with financial support of the Swiss Agency for Development and Cooperation (SDC).GoalThis study aims at evaluating the diagnostic accuracy of such a service by reviewing 212 telepathologydiagnoses delivered to the local experts in Ulaanbaatar between January 2009 and June 2013.Materials and MethodsUnder the MonTelNet project all province (Aimag) hospitals were equipped with hardware necessaryfor practicing telemedicine, in particular with computers with digitalized microscopes and cameras. Thesoftware CampusMedicus® (CM) was developed together with Klughammer GmbH. Software and alldata and comments exchanged over the MonTelNet are stored on a central server. Each of the originaldiagnoses issued through the CM telepathology (TP) server was compared to an independent reviewdiagnosis based on the original glass slides.RESULT For 188 specimens (89.9%) the TP diagnosis were completely identical with the review diagnosison the original glass slide. 12 specimens (5.7%) showed minor discrepancies (clinically identical) and 5specimens (2.4%) showed moderate discrepancies which were not clinically relevant. four cases (1.9%)exhibited a marked discrepancy (clinically relevant) between the TP diagnosis and the review diagnosis.Three specimens were classified as “other”.DISCUSSION The results of the study show a very high accuracy of the TP diagnosis provided. The TPdiagnoses differed markedly from the review diagnoses based on the original glass slide in only 1.9%of the 212 cases. 89.9% of all cases showed complete concordance between TP and review. Thesefigures are comparable to figures from other evaluations of static image telepathology.Conclusion:1. The results of the study show a very high accuracy (94.7%) of the TP diagnosis provided. TheTP diagnoses 89.9% of all cases showed complete concordance between TP and conventionalreview.2. Problem with image selection show a different picture and occur more often in cases with markeddiscrepancies between TP and review - χ2-test shows significant correlation (p<0.001).

[Oncological data elements in histopathology]. / Onkologische Datenelemente in der Histopathologie.

In order to cope with increasing demands to supply information to a variety of documentation systems outside pathology, pathologists need to set standards both for the content and the use of the information they generate. Oncological datasets based on a set vocabulary are urgently required for use both in pathology and in further processing. Data elements were defined according to German pathology report guidelines for colorectal cancers in line with ISO 11179 requirements for the relations between data element concepts and value domains, as well as for further formal conditions, which can be exported in XML together with metadata information. Tests on 100 conventionally written diagnoses showed their principal usability and an increasing degree of guideline conformity in diagnoses commensurate with training time. This set of oncological data elements is a valuable checklist tool for pathologists, enabling formatted information export for further use and saving documentation effort.

Abundant expression of AMACR in many distinct tumour types.

AIMS: Alpha-methylacyl-CoA racemase (AMACR), a mitochondrial and peroxisomal enzyme, is a valuable tool to confirm the diagnosis of prostate cancer, especially if combined with basal cell markers. To extend this diagnostic utility to other neoplasias, we comprehensively surveyed AMACR expression in human tumours. METHODS: We performed immunohistochemical analyses on tissue microarrays of AMACR expression in over 125 different human tumour types and 80 normal tissues. RESULTS: Microarray analysis revealed that tumours with prominent AMACR expression included adenocarcinomas of the prostate (72%), hepatocellular carcinomas (77%), papillary renal cell carcinomas (70%), and colorectal adenocarcinomas (71%). AMACR expression was equally frequent in colorectal adenomas and carcinomas. No significant difference in AMACR expression between untreated and hormone-refractory prostate cancers was observed. In the thyroid, AMACR expression was found in 42% of the follicular carcinomas but in only 16% of follicular adenomas. However, a more detailed analysis on a thyroid tissue microarray did not confirm a significant difference of AMACR expression in follicular adenoma and carcinomas. CONCLUSION: Taken together, the results indicate that AMACR is expressed in a wide variety of adenocarcinomas, and its diagnostic utility is restricted to specific areas.

Plasma cell quantification in bone marrow by computer-assisted image analysis.

BACKGROUND: Minor and major criteria for the diagnosis of multiple meloma according to the definition of the WHO classification include different categories of the bone marrow plasma cell count: a shift from the 10-30% group to the > 30% group equals a shift from a minor to a major criterium, while the < 10% group does not contribute to the diagnosis. Plasma cell fraction in the bone marrow is therefore critical for the classification and optimal clinical management of patients with plasma cell dyscrasias. The aim of this study was (i) to establish a digital image analysis system able to quantify bone marrow plasma cells and (ii) to evaluate two quantification techniques in bone marrow trephines i.e. computer-assisted digital image analysis and conventional light-microscopic evaluation. The results were compared regarding inter-observer variation of the obtained results. MATERIAL AND METHODS: Eighty-seven patients, 28 with multiple myeloma, 29 with monoclonal gammopathy of undetermined significance, and 30 with reactive plasmocytosis were included in the study. Plasma cells in H&E- and CD138-stained slides were quantified by two investigators using light-microscopic estimation and computer-assisted digital analysis. The sets of results were correlated with rank correlation coefficients. Patients were categorized according to WHO criteria addressing the plasma cell content of the bone marrow (group 1: 0-10%, group 2: 11-30%, group 3: > 30%), and the results compared by kappa statistics. RESULTS: The degree of agreement in CD138-stained slides was higher for results obtained using the computer-assisted image analysis system compared to light microscopic evaluation (corr.coeff. = 0.782), as was seen in the intra- (corr.coeff. = 0.960) and inter-individual results correlations (corr.coeff. = 0.899). Inter-observer agreement for categorized results (SM/PW: kappa 0.833) was in a high range. CONCLUSIONS: Computer-assisted image analysis demonstrated a higher reproducibility of bone marrow plasma cell quantification. This might be of critical importance for diagnosis, clinical management and prognostics when plasma cell numbers are low, which makes exact quantifications difficult.

[Atypical erythema induratum Bazin with tuberculous osteomyelitis]. / Atypisches erythema induratum Bazin bei tuberkulöser osteomyelitis.

Diagnosis of all types of cutaneous tuberculosis is challenging because the clinical picture of these diseases is highly variable. We describe the case of a 79-year old woman with an atypical presentation of Erythema induratum Bazin (EIB) on the chest and left arm in association with a tuberculous osteomyelitis of the left olecranon. Surprisingly, M. tuberculosis grew also from biopsies of the EIB-lesions. This contradicts the conventional view that considers EIB (a tuberculid) to be caused by a hypersensitivity reaction to mycobacteria. The presented case supports the hypothesis that EIB may also be caused by hematogenous or lymphatic spread of viable M. tuberculosis.

Presymptomatic thyroidectomy in multiple endocrine neoplasia 2a.

AIMS: To evaluate the value of prophylactic total thyroidectomy in multiple endocrine neoplasia 2a (MEN 2a), based on results of genetic testing, in a presymptomatic early stage of the disease. METHODS: Fourteen presymptomatic patients genetically diagnosed and surgically treated at our centre. We analysed age, gender, location of the RET mutation, calcitonin tests, surgery, histologic findings, TNM classification, and postoperative follow-up. RESULTS: The 14 patients belonged to two families with MTC (MEN 2a). Median age was 16 years. The RET mutation was located in codon 618 and 634. Basal calcitonin (CT) levels were normal in all patients. Twelve had pathologic peak CT measurements. Total thyroidectomy was performed in all and associated central neck dissection in 12 patients. Pathohistologic assessment showed C-cell hyperplasia in all specimens and 11 MTCs; the median size of the tumours was 0.2 cm; two patient had lymph-node metastases. According to TNM, three had stage 0, nine had stage I, one had stage II, and one had stage III disease. Postsurgery basal and peak CT values were normal in all but one patients, indicating a biochemical curative rate of 95%. Calcitonin determination did not distinguish between MTC and C-cell hyperplasia. CONCLUSION: Prophylactic thyroidectomy based on genetic testing allows identification and treatment of patients at an early stage of the disease. Pathologic peak CT values are markers for the presence of microscopic MTC and should be considered in selecting operative procedures for these patients.

iPath - a Telemedicine Platform to Support Health Providers in Low Resource Settings.

In many developing countries there is an acute shortage of medical specialists. The specialists and services that are available are usually concentrated in cities and health workers in rural health care, who serve most of the population, are isolated from specialist support [1]. Besides, the few remaining specialist are often isolated from colleagues. With the recent development in information and communication technologies, new option for telemedicine and generally for sharing knowledge at a distance are becoming increasingly accessible to health workers also in developing countries. Since 2001 the Department of Pathology in Basel, Switzerland is operating an Internet based telemedicine platform to assist health workers in developing countries. Over 1800 consultation have been performed since. This paper will give an introduction to iPath - the telemedicine platform developed for this project - and analyse two case studies: a teledermatology project from South Africa and a telepathology project from Solomon Islands.

Telepathology on the Solomon Islands--two years' experience with a hybrid Web- and email-based telepathology system.

The National Referral Hospital in Honiara, Solomon Islands, has used an Internet-based system in Switzerland for telepathology consultations since September 2001. Due to the limited bandwidth of Internet connections on the Solomon Islands, an email interface was developed that allows users in Honiara to submit cases and receive reports by email. At the other end, consultants can use a more sophisticated Web-based interface that allows discussion of cases among an expert panel. The result is a hybrid email- and Web-based telepathology system. Over two years, 333 consultations were performed, in which 94% of cases could be diagnosed by a remote pathologist. A computer-assisted 'virtual institute' of pathologists was established. This form of organization helped to reduce the median time from submission of the request to a report from 28 h to 8.5 h for a preliminary diagnosis and 13 h for a final report. A final report was possible in 77% of all submitted cases.

Ciprofloxacin-induced acute interstitial pneumonitis.

The current authors present the case of a 68-yr-old female patient who developed severe respiratory failure after medication with ciprofloxacin for acute urinary tract infection. A chronic subdural haematoma was surgical evacuated. Postoperatively, an acute urinary tract infection was treated with ciprofloxacin. Six days later, C-reactive protein was rising and the patient was suffering from intermittent high fever, dyspnoea and severe hypoxaemia. The high-resolution-computed tomography (HRCT) showed an interstitial lung disease in the anterior upper lobe on the left side as well as in the lingula. Assuming a bacterial infection amoxyl/clavulanic acid was started which did not improve the clinical symptoms. Bronchoalveolar lavage revealed a marked lymphocytosis (87%). Analysis for typical bacterial infections, Tuberculosis, Mycoplasma, Chlamydia and Legionella spp. were all negative. Another HRCT scan was made because of worsening of symptoms and this showed rapidly progressive infiltrates in most lobes. An open lingular biopsy showed an interstitial lymphoplasmocytotic infiltrate with some eosinophilic granulocytes and a few scattered giant cell granulomas, consistent with hypersensitivity pneumonitis. The patient's symptoms rapidly improved with systemic corticosteroid therapy and another HRCT scan revealed complete remission of pulmonary infiltrates. Ciprofloxacin can induce interstitial pneumonitis with acute respiratory failure. This is an important fact considering that ciprofloxacin is a widely used antibiotic agent in treatment of urinary tract infection.

Pacific Telepathlogy Service at Fiji School of Medicine.

Pacific Telepathology service has been established at Fiji school of Medicine (FSM) with technical support from University of Basel. The service is designed for remote consultation, continuing medical education (CME) health care research (HCR). To develop Telepathology services for participation with international Telepathology community for improving quality of health care in the Pacific. Telepathology server for "Pacific Pathology Group" has been set up at http://telepath.patho.unibas.ch/, which is dedicated for Telepathology consultations bring together health care professionals in the Pacific to overcome limitations of distance, lack of resources and to improve quality of healthcare services, Accessed by a computer possessing Internet and email connection, members send cases and questions, review and comment on other cases and receive consultation via web or email. Benefits are tremendous in terms of remote consultation, CME, HCR and improving quality of modern health care even at remote islands devoid of health care resources. Internet speed or reliability is not a limiting factor. Virtual institute of pathology has been established in Switzerland with over 400 Pathologists and is providing consultations to many countries including Solomon Islands where there is no pathologist. The institute is functioning efficiently with average reporting turnaround time of 48 hours. Efficiency is the result of organization and communication. Presently this Service has been established at the FSM in Fiji Islands primarily for education & remote consultation with plans to expand to other island countries.

[The future of telepathology. An Internet "distributed system" with "open standards"]. / Die Zukunft der Telepathologie. Ein im Internet "verteiltes System" mit "offenen Standards".

With the availability of Internet, the interest in the possibilities of telepathology has increased considerably. In the foreground is thereby the need of the non-expert to bring in the opinions of experts on morphological findings by means of a fast and simple procedure. The new telepathology system iPath is in compliance with these needs. The system is based on small, but when possible independently working modules. This concept allows a simple adaptation of the system to the individual environment of the user (e.g. for different cameras, frame-grabbers, microscope steering tables etc.) and for individual needs. iPath has been in use for 6 months with various working groups. In telepathology a distinction is made between "passive" and "active" consultations but for both forms a non-expert brings in the opinion of an expert. In an active consultation both are in direct connection with each other (orally or via a chat-function), this is however not the case with a passive consultation. An active consultation can include the interactive discussion of the expert with the non-expert on images in an image database or the direct interpretation of images from a microscope by the expert. Four software modules are available for a free and as fast as possible application: (1) the module "Microscope control", (2) the module "Connector" (insertion of images directly from the microscope without a motorized microscope), (3) the module "Client-application" via the web-browser and (4) the module "Server" with a database. The server is placed in the internet and not behind a firewall. The server permanently receives information from the periphery and returns the information to the periphery on request. The only thing which the expert, the non-expert and the microscope have to know is how contact can made with the server.

Telemicroscopy by the Internet revisited.

This paper reports a fundamentally new concept for internet-based telemicroscopy. By separating a telemicroscopy application into three tasks - microscope control program, external server, and client application - it is possible to establish a telemicroscopy session between two arbitrary end points on the Internet even if both of the end points are secured by firewall (microscope and client application). The advantages of such a distributed system, compared with the classical point-to-point systems, are discussed. The telemicroscopy system is combined with a telepathology database, which is capable of automatically recording telemicroscopy sessions, allowing a convenient combination of interactive remote microscopy and store and forward telepathology. In addition to remote primary diagnosis, it is easily possible to discuss difficult cases within dedicated user groups, no matter whether images originate from a telemicroscopy session, or are manually entered into the database.

[Water jet dissection in fatty tissue]. / Wasser-Jet Dissektion im Fettgewebe.

BACKGROUND: The first report about the use of water-jet dissection in surgery dates 1982. The advantage compared to conventional cutting is the preservation of vessels and nerves, thus facilitating the precise coagulation thereafter. Devices of the new generation with coherent jet are used in liver surgery in order to reduce blood loss. The use of water-jet dissectors in other fields of surgery is currently under investigation. The preparation of vessels in fatty tissue is of special interest for plastic surgeons. The technical parameters of the hydro- or water-jet device have to be optimised. METHOD: Abdominal fat tissue of fresh cadavers was cut under standardised conditions with different parameters of the dissector. The depth of the cuts and the morphology of the blood vessels were analysed. RESULTS: Between 20 and 60 Bar cutting pressure of the water-jet and one single pass the cuts are 8 mm deep. Deeper cuts can be achieved by repeated application on the same cut. When using 40 Bar and 5 passes the cutting depth is 1.7 cm. Higher pressure as 50 or 60 Bar do not lead to deeper cuts. The water-jet dissection leads to a water uptake of the cut tissue. Morphologically all the vessels, lying in the cut are undamaged if the pressure doesn't exceed 40 Bar pressure range. CONCLUSION: The optimal pressure for water-jet dissection of fatty tissue lies between 30 and 40 Bar. Higher pressure does not lead to deeper cuts, but increases the risk of vessel damage. The vessels in the remain morphologically intact if he cutting pressure lies below 50 Bar. The effect of the mechanical irritation of the vessels has to be investigated in vivo, before using the water-jet dissector for preparation of blood vessels in humans e.g. for flap dissection.

Fourth updated ESACP consensus report on diagnostic DNA image cytometry.

A task force of experts in the field of diagnostic DNA image cytometry, invited by the ESACP, and further scientists or physicians revealing experience in that diagnostic procedure (names are given in Addendum A), agreed upon the following 4th updated Consensus Report on Standardised Diagnostic DNA Image Cytometry during the 7th International Congress of that society in Caen, 2001. This report is based on the three preceding ones [6,14,17]. It deals with the following items:- Critical review and update of the definitions given in the 1997 Consensus Update;- Review and detailed description of basic terms, principles and algorithms for diagnostic interpretation;- Recommendations concerning diagnostic or prognostic applications in specific fields of tumour pathology. This update is not aimed to substitute the 1997 consensus, but to make necessary addenda and give more detailed descriptions of those items not unequivocally to interpret by potential users of the methodology.

[Amiodarone-induced thyrotoxicosis]. / Amiodaron-induzierte Hyperthyreose.

Amiodarone is the most important drug in the treatment of ventricular arrhythmias and is widely used for atrial fibrillation. Thyrotoxicosis, a classical side effect, was thought to be iodine induced, but recent evidence suggests that other mechanisms play an important role (toxic effect on thyreocytes, immunological effects). Thyrotoxicosis due to amiodarone is difficult to treat and is further complicated by the pro-arrhythmic potential of thyrotoxicosis and the fading antiarrhythmic effect after amiodarone withdrawal. The mechanism, diagnosis and therapy of amiodarone-induced thyrotoxicosis are discussed in the light of the available literature.

Intralipid-based short-term total parenteral nutrition does not impair small intestinal mucosa-related cellular immune reactivity in the healthy rat.

BACKGROUND: The lipid component of total parenteral nutrition (TPN) has reportedly been associated with trophic effects on the intestinal mucosa and suppressive effects on the immune system. METHODS: We have challenged these hypotheses using a 7-day TPN rodent model comparing the effects of isocaloric, isonitrogenous lipid-based (TPN-lipid, 50% of calories as long-chain triacylglycerol) and carbohydrate-based TPN (TPN-CH, 100% of calories as carbohydrates) on mucosal morphology and immune function. Enterally fed animals were included to establish a baseline for immunologic read-outs. The study was performed in healthy, metabolically stable animals to avoid interference by septic or trauma-related stress factors. RESULTS: Both TPN regimens resulted in a significantly smaller weight gain (TPN-lipid, 29.8 +/- 4.0 g; TPN-CH, 30.3 +/- 4.4 g) compared with enterally fed reference animals (49.2 +/- 3.2 g; p = .007), with no difference in nitrogen balance between the TPN groups. Mucosal sucrase activity was significantly lower in both TPN groups (TPN-lipid, 8.8 +/- 1.0 x 10(-7) katal per gram (kat/g) of protein; CH: 11.9 +/- 1.6 x 10(-7) kat/g of protein) compared with enteral feeding (17.4 +/- 0.9 x 10(-7) kat/g of protein; ANOVA: p = .0007). Morphometric analysis of the small intestine revealed no differences between the two TPN groups although a significantly depressed villus height in the TPN-lipid group could be observed in comparison to enterally fed reference rats (TPN-lipid, 0.47 +/- 0.02; TPN-CH, 0.50 +/- 0.01; enteral, 0.56 +/- 0.02 mm; ANOVA: p = .0298). Light and electron microscopy revealed a normal surface architecture in all three groups of rats. Cellular immune reactivity was evaluated using a novel specific immunization protocol: animals were immunized against OVA 4 weeks before TPN. OVA-induced lymphoproliferative responses and phenotypic data from draining popliteal and mesenteric lymph nodes were evaluated after the different regimens. Results did not differ among the three groups. CONCLUSIONS: In healthy rodents, short-term lipid-based and carbohydrate-based TPN regimens lead to limited mucosal atrophy with preserved surface architecture compared with enteral feeding. However, peripheral and mesenteric cellular immune responsiveness after both TPN regimens remained comparable to enterally fed reference animals. Therefore, mesenteric and systemic cellular immune reactivity does not appear to be impaired by lipid-based or carbohydrate-based TPN.

Competence on demand in DNA image cytometry.

Quantitation methods in clinical pathology have to be normalized and standardized both from the instrumental and the methodological point of view to guarantee a defined level of precision and accuracy independent of the site where they are applied. The comparability of results obtained in different laboratories is the basis for the application of standardized diagnostic classification systems and therapeutic schemes. Remote quantitation based on standardized evaluation tools could be a way to reach the goals mentioned above. Diagnostic DNA image cytometry, increasingly used as a routine method in clinical pathology, will serve as an example for demonstrating the feasibility and usefulness of a concept of remote quantitation. We report a system for a remote DNA ploidy analysis, based on client server technology, and accessible via Internet or ISDN connections (Quantitation Server EUROQUANT). This system (i) allows the cytometric measurement of the DNA content of cells for diagnostic purposes, (ii) provides the user with comprehensive quality control of such measurements, (iii) helps in trouble-shooting, and (iv) gives assistance in diagnostic interpretation. The system uses the principles of telepathology and Internet technology. To date, more than 40 laboratories from Europe, USA, and Asia have successfully performed analyses on about 3,000 ploidy data sets.

[Telemedicine: perspectives and multidisciplinary approach]. / Télémédecine: perspectives et approche pluridisciplinaire.

BACKGROUND: Telemedicine is use of the new computer-based communication technologies for medical purposes. It augments the exchange of scientific information, while its applications in the fields of patient care and medical education cover remote diagnosis and therapy as well as remote education and training. METHOD: This article reviews the development of telemedicine and its application to specialties such as anaesthesiology, dermatology, medicine, surgery and pathology at the University Hospital of Basle, Switzerland. RESULTS: Since 1980 the Department of Medicine has held multidisciplinary teleconferences for expert consultation and medical education. Since 1992 the Institute of Pathology has been linked to remote hospitals for real-time biopsy, and, since 1997, remote dermato-histopathological diagnosis has been performed in conjunction with a number of centres and practitioners. International academic teleconferences have been held in the field of surgery since 1986 and there is an interactive education programme via telemedicine in the field of anaesthesiology. The technology in use must be adapted to needs: since few practitioners are currently connected to the Internet, teleconferencing will still be the rule in the Department of Medicine. Remote diagnosis in dermatology and pathology requires high-resolution images transmitted by self-developed software via 64 Kb/s ISDN connection, while surgery works with ISDN teleconferencing at 384 Kb/s to ensure live transmission of surgical procedures with high-quality images. CONCLUSION: Our practice, based on several hundred cases, suggests that telemedicine is useful in simplifying and expanding access to remote interdisciplinary expertise, as well as improving medical education in a number of specialties. Telemedicine's multidisciplinary approach is to be recommended.

Telepathology: design of a modular system.

Although telepathology systems have been developed for more than a decade, they are still not a widespread tool for routine diagnostic applications. Lacking interoperability, software that is not satisfying user needs as well as high costs have been identified as reasons. In this paper we would like to demonstrate that with a clear separation of the tasks required for a telepathology application, telepathology systems can be built in a modular way, where many modules can be implemented using standard software components. With such a modular design, systems can be easily adapted to changing user needs and new technological developments and it is easier to integrate modular systems into existing environments.