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The shift towards RES introduces challenges related to power system stability due to the characteristics of inverter-based resources (IBRs) and the intermittent nature of renewable resources. This paper addresses these challenges by conducting comprehensive time and frequency simulations on the IEEE two-area benchmark power system with detailed type 4 wind turbine generators (WTGs), including turbines, generators, converters, filters, and controllers. The simulations analyse small-signal and transient stability, considering variations in active and reactive power, short-circuit events, and wind variations. Metrics such as rate of change of frequency (RoCoF), frequency nadir, percentage of frequency variation, and probability density function (PDF) are used to evaluate the system performance. The findings emphasise the importance of including detailed models of RES in stability analyses and demonstrate the impact of RES penetration on power system dynamics. This study contributes to a deeper understanding of RES integration challenges and provides insights for ensuring the reliable and secure operation of power systems in the presence of high levels of RES penetration.
Objectives: To assess the relation between the number of clinical trials conducted and respective new drug approvals in India and South Africa.
Design: Construction and analysis of a comprehensive database of completed randomised controlled clinical trials based on clinicaltrials.gov from 1 January 2005 to 31 December 2010 and drug approval data from 2006 until 2013 for India and South Africa.
Setting: USA, the EU, India and South Africa.
Main outcome measures: Percentage of completed randomised clinical trials for an Investigational Medicinal Product (IMP) leading to new drug approval in India and South Africa.
Results: A total of 622 eligible randomised controlled trials were identified as per search criteria for India and South Africa. Clustering them for the same sponsor and the same Investigational New Drug (IND) resulted in 453 eligible trials, that is, 224 for India and 229 for South Africa. The distribution of the market application approvals between the EU/USA as well as India and South Africa revealed that out of clinical trials with the participation of test centres in India and/or South Africa, 39.6% (India) clinical trials and 60.1% (South Africa) clinical trials led to market authorisation in the EU/USA without a New Drug Application (NDA) approval in India or South Africa.
Conclusions: Despite an increase in clinical trial activities, there is a clear gap between the number of trials conducted and market availability of these new drugs in India and South Africa. Drug regulatory authorities, investigators, institutional review boards and patient groups should direct their efforts to ensuring availability of new drugs in the market that have been tested and researched on their population.
BACKGROUND: Even though physician rating websites (PRWs) have been gaining in importance in both practice and research, little evidence is available on the association of patients' online ratings with the quality of care of physicians. It thus remains unclear whether patients should rely on these ratings when selecting a physician. The objective of this study was to measure the association between online ratings and structural and quality of care measures for 65 physician practices from the German Integrated Health Care Network "Quality and Efficiency" (QuE). METHODS: Online reviews from two German PRWs were included which covered a three-year period (2011 to 2013) and included 1179 and 991 ratings, respectively. Information for 65 QuE practices was obtained for the year 2012 and included 21 measures related to structural information (N = 6), process quality (N = 10), intermediate outcomes (N = 2), patient satisfaction (N = 1), and costs (N = 2). The Spearman rank coefficient of correlation was applied to measure the association between ratings and practice-related information. RESULTS: Patient satisfaction results from offline surveys and the patients per doctor ratio in a practice were shown to be significantly associated with online ratings on both PRWs. For one PRW, additional significant associations could be shown between online ratings and cost-related measures for medication, preventative examinations, and one diabetes type 2-related intermediate outcome measure. There again, results from the second PRW showed significant associations with the age of the physicians and the number of patients per practice, four process-related quality measures for diabetes type 2 and asthma, and one cost-related measure for medication. CONCLUSIONS: Several significant associations were found which varied between the PRWs. Patients interested in the satisfaction of other patients with a physician might select a physician on the basis of online ratings. Even though our results indicate associations with some diabetes and asthma measures, but not with coronary heart disease measures, there is still insufficient evidence to draw strong conclusions. The limited number of practices in our study may have weakened our findings.
A descriptive cross-sectional study of cholera at Kakuma and Kalobeyei refugee camps, Kenya in 2018
(2020)
Introduction: cholera is a significant public health concern among displaced populations. Oral cholera vaccines are safe and can effectively be used as an adjunct to prevent cholera in settings with limited access to water and sanitation. Results from this study can inform future consideration for cholera vaccination at Kakuma and Kalobeyei.
Methods: a descriptive cross-sectional study of cholera cases at Kakuma refugee camp and Kalobeyei integrated settlement was carried out between May 2017 to May 2018 (one year). Data were extracted from the medical records and line lists at the cholera treatment centres.
Results: the results found 125 clinically suspected and confirmed cholera cases and one related death (CFR 0.8%). The cumulative incidence of all cases was 0.67 (95% CI=0.56-0.80) cases/1000 persons. Incidence of cholera was higher in children under the age of five 0.94(95% CI=0.63-1.36) cases/1000 persons. Children aged <5 years showed 51% increased risk of cholera compared to those aged ≥5 years (RR=1.51; 95% CI=1.00-2.31, p=0.051). Individuals from the Democratic Republic of Congo had nearly 9-fold risk of reporting cholera (RR=8.62; 95% CI=2.55-37.11, p<0.001) while individuals from South Sudan reported 7 times risk of cholera case compared to those from Somalia (RR=7.39; 95% CI=2.78-27.73, p<0.001).
Conclusion: in addition to the improvement of water, sanitation and hygiene (WaSH), vaccination could be implemented as a short-medium term measure of preventing cholera outbreaks. Age, country of origin and settlement independently predicted the risk of cholera.
In this paper, we consider the route coordination problem in emergency evacuation of large smart buildings. The building evacuation time is crucial in saving lives in emergency situations caused by imminent natural or man-made threats and disasters. Conventional approaches to evacuation route coordination are static and predefined. They rely on evacuation plans present only at a limited number of building locations and possibly a trained evacuation personnel to resolve unexpected contingencies. Smart buildings today are equipped with sensory infrastructure that can be used for an autonomous situation-aware evacuation guidance optimized in real time. A system providing such a guidance can help in avoiding additional evacuation casualties due to the flaws of the conventional evacuation approaches. Such a system should be robust and scalable to dynamically adapt to the number of evacuees and the size and safety conditions of a building. In this respect, we propose a distributed route recommender architecture for situation-aware evacuation guidance in smart buildings and describe its key modules in detail. We give an example of its functioning dynamics on a use case.
The transfer of historically grown monolithic software architectures into modern service-oriented architectures creates a lot of loose coupling points. This can lead to an unforeseen system behavior and can significantly impede those continuous modernization processes, since it is not clear where bottlenecks in a system arise. It is therefore necessary to monitor such modernization processes with an adaptive monitoring concept to be able to correctly record and interpret unpredictable system dynamics. This contribution presents a generic QoS measurement framework for service-based systems. The framework consists of an XML-based specification for the measurement to be performed – the Information Model (IM) – and the QoS System, which provides an execution platform for the IM. The framework will be applied to a standard business process of the German insurance industry, and the concepts of the IM and their mapping to artifacts of the QoS System will be presented. Furtherm ore, design and implementation of the QoS System’s parser and generator module and the generated artifacts are explained in detail, e.g., event model, agents, measurement module and analyzer module.
Background:
Hereditary angioedema (HAE) is a rare genetic disease and characterized by clinical features such as paroxysmal, recurrent angioedema of the skin, the gastrointestinal tract, and the upper airways. Swelling of the skin occurs primarily in the face, extremities and genitals. Gastrointestinal attacks are accompanied by painful abdominal cramps, vomiting and diarrhea. Due to the low prevalence and the fact that HAE patients often present with rather unspecific symptoms such as abdominal cramps, the final diagnosis is often made after a long delay. The aim of this German-wide survey was to characterize the period between occurrence of first symptoms and final diagnosis regarding self-perceived health, symptom burden and false diagnoses for patients with HAE.
Results:
Overall, 81 patients with HAE were included and participated in the telephone-based survey. Of those, the majority reported their current health status as “good” (47.5%) or “very good” (13.8%), which was observed to be a clear improvement compared to the year before final diagnosis (“good” (16.3%), “very good” (11.3%)). Edema in the extremities (85.2%) and in the gastrointestinal tract (81.5%) were the most currently reported symptoms and occurred earlier than other reported symptoms (mean age at onset 18.1 and 17.8 years, respectively). Misdiagnoses were observed in 50.6% of participating HAE patients with appendicitis and allergy being the most frequently reported misdiagnoses (40.0 and 30.0% of those with misdiagnosis, respectively). Patients with misdiagnosis often received mistreatment (80.0%) with pharmaceuticals and surgical interventions as the most frequently carried out mistreatments (65.6 and 56.3% of those with mistreatment, respectively). The mean observed diagnostic delay was 18.1 years (median 15.0 years). The diagnostic delay was higher in older patients and index patients.
Conclusions:
This study showed that self-perceived status of health for patients is much better once the final correct diagnosis has been made and specific treatment was available. Further challenge in the future will still be to increase awareness for HAE especially in settings which are normally approached by patients at occurrence of first symptoms to assure early referral to specialists and therefore increase the likelihood of receiving an early diagnosis.
Library of Congress Subject Headings (LCSH) are popular for indexing library records. We studied the possibility of assigning LCSH automatically by training classifiers for terms used frequently in a large collection of abstracts of the literature on hand and by extracting headings from those abstracts. The resulting classifiers reach an acceptable level of precision, but fail in terms of recall partly because we could only train classifiers for a small number of LCSH. Extraction, i.e., the matching of headings in the text, produces better recall but extremely low precision. We found that combining both methods leads to a significant improvement of recall and a slight improvement of F1 score with only a small decrease in precision.
This paper proposes an extended Petri net formalism as a suitable language for composing optimal scheduling problems of industrial production processes with real and binary decision variables. The proposed approach is modular and scalable, as the overall process dynamics and constraints can be collected by parsing of all atomic elements of the net graph. To conclude, we demonstrate the use of this framework for modeling the moulding sand preparation process of a real foundry plant.
Background: After kidney transplantation, immunosuppressive therapy causes impaired cellular immune defense leading to an increased risk of viral complications. Trough level monitoring of immunosuppressants is insufficient to estimate the individual intensity of immunosuppression. We have already shown that virus-specific T cells (Tvis) correlate with control of virus replication as well as with the intensity of immunosuppression. The multicentre IVIST01-trial should prove that additional steering of immunosuppressive and antiviral therapy by Tvis levels leads to better graft function by avoidance of over-immunosuppression (for example, viral infections) and drug toxicity (for example, nephrotoxicity).
Methods/design: The IVIST-trial starts 4 weeks after transplantation. Sixty-four pediatric kidney recipients are randomized either to a non-intervention group that is only treated conservatively or to an intervention group with additional monitoring by Tvis. The randomization is stratified by centre and cytomegalovirus (CMV) prophylaxis. In both groups the immunosuppressive medication (cyclosporine A and everolimus) is adopted in the same target range of trough levels. In the non-intervention group the immunosuppressive therapy (cyclosporine A and everolimus) is only steered by classical trough level monitoring and the antiviral therapy of a CMV infection is performed according to a standard protocol. In contrast, in the intervention group the dose of immunosuppressants is individually adopted according to Tvis levels as a direct measure of the intensity of immunosuppression in addition to classical trough level monitoring. In case of CMV infection or reactivation the antiviral management is based on the individual CMV-specific immune defense assessed by the CMV-Tvis level. Primary endpoint of the study is the glomerular filtration rate 2 years after transplantation; secondary endpoints are the number and severity of viral infections and the incidence of side effects of immunosuppressive and antiviral drugs.
Discussion: This IVIST01-trial will answer the question whether the new concept of steering immunosuppressive and antiviral therapy by Tvis levels leads to better future graft function. In terms of an effect-related drug monitoring, the study design aims to realize a personalization of immunosuppressive and antiviral management after transplantation. Based on the IVIST01-trial, immunomonitoring by Tvis might be incorporated into routine care after kidney transplantation.
HOXA9 and MEIS1 are frequently upregulated in acute myeloid leukemia (AML), including those with MLL‐rearrangement. Because of their pivotal role in hemostasis, HOXA9 and MEIS1 appear non‐druggable. We, thus, interrogated gene expression data of pre‐leukemic (overexpressing Hoxa9) and leukemogenic (overexpressing Hoxa9 and Meis1; H9M) murine cell lines to identify cancer vulnerabilities. Through gene expression analysis and gene set enrichment analyses, we compiled a list of 15 candidates for functional validation. Using a novel lentiviral multiplexing approach, we selected and tested highly active sgRNAs to knockout candidate genes by CRISPR/Cas9, and subsequently identified a H9M cell growth dependency on the cytosolic phospholipase A2 (PLA2G4A). Similar results were obtained by shRNA‐mediated suppression of Pla2g4a. Remarkably, pharmacologic inhibition of PLA2G4A with arachidonyl trifluoromethyl ketone (AACOCF3) accelerated the loss of H9M cells in bulk cultures. Additionally, AACOCF3 treatment of H9M cells reduced colony numbers and colony sizes in methylcellulose. Moreover, AACOCF3 was highly active in human AML with MLL rearrangement, in which PLA2G4A was significantly higher expressed than in AML patients without MLL rearrangement, and is sufficient as an independent prognostic marker. Our work, thus, identifies PLA2G4A as a prognostic marker and potential therapeutic target for H9M‐dependent AML with MLL‐rearrangement.
A novel method has been implemented to prepare metal oxide nanopowders covered with known quantities of adsorbed water; we subsequently studied the γ-radiolysis of ZrO2 nanopowders covered with H2O layers. H2 yields from the adsorbed water radiolysis are of importance in multiple industrial contexts – the nuclear industry being a prime example. Measured H2 yields at water coverages of just below and above one monolayer are around 350 times greater than for neat water, but these yields decrease rapidly with increasing water loading of the ZrO2 nanoparticles, approaching the yield of bulk water at coverages of tens of water layers. The observed plateau of the yields at 0.5 to 2.0 monolayers coverage can be explained by the ease with which electronic excitations in the ZrO2 can be transferred across the interface to the first one or two adsorbed water layers. However, with increasing water loading, energy transfer to water layers further away from the interface becomes less efficient, and above ~30 water layers, most of the water is not affected by any exciton formation in the ZrO2.
A semiparametric approach for meta-analysis of diagnostic accuracy studies with multiple cut-offs
(2022)
The accuracy of a diagnostic test is often expressed using a pair of measures: sensitivity (proportion of test positives among all individuals with target condition) and specificity (proportion of test negatives among all individuals without targetcondition). If the outcome of a diagnostic test is binary, results from different studies can easily be summarized in a meta-analysis. However, if the diagnostic test is based on a discrete or continuous measure (e.g., a biomarker), several cut-offs within one study as well as among different studies are published. Instead of taking all information of the cut-offs into account in the meta-analysis, a single cut-off per study is often selected arbitrarily for the analysis, even though there are statistical methods for the incorporation of several cut-offs. For these methods, distributional assumptions have to be met and/or the models may not converge when specific data structures occur. We propose a semiparametric approach to overcome both problems. Our simulation study shows that the diagnostic accuracy is underestimated, although this underestimation in sensitivity and specificity is relatively small. The comparative approach of Steinhauser et al. is better in terms of coverage probability, but may lead to convergence problems. In addition to the simulation results, we illustrate the application of the semiparametric approach using a published meta-analysis for a diagnostic test differentiating between bacterial and viral meningitis in children.
Dramatic increases in the number of cyber security attacks and breaches toward businesses and organizations have been experienced in recent years. The negative impacts of these breaches not only cause the stealing and compromising of sensitive information, malfunctioning of network devices, disruption of everyday operations, financial damage to the attacked business or organization itself, but also may navigate to peer businesses/organizations in the same industry. Therefore, prevention and early detection of these attacks play a significant role in the continuity of operations in IT-dependent organizations. At the same time detection of various types of attacks has become extremely difficult as attacks get more sophisticated, distributed and enabled by Artificial Intelligence (AI). Detection and handling of these attacks require sophisticated intrusion detection systems which run on powerful hardware and are administered by highly experienced security staff. Yet, these resources are costly to employ, especially for small and medium-sized enterprises (SMEs). To address these issues, we developed an architecture -within the GLACIER project- that can be realized as an in-house operated Security Information Event Management (SIEM) system for SMEs. It is affordable for SMEs as it is solely based on free and open-source components and thus does not require any licensing fees. Moreover, it is a Self-Contained System (SCS) and does not require too much management effort. It requires short configuration and learning phases after which it can be self-contained as long as the monitored infrastructure is stable (apart from a reaction to the generated alerts which may be outsourced to a service provider in SMEs, if necessary). Another main benefit of this system is to supply data to advanced detection algorithms, such as multidimensional analysis algorithms, in addition to traditional SIEMspecific tasks like data collection, normalization, enrichment, and storage. It supports the application of novel methods to detect security-related anomalies. The most distinct feature of this system that differentiates it from similar solutions in the market is its user feedback capability. Detected anomalies are displayed in a Graphical User Interface (GUI) to the security staff who are allowed to give feedback for anomalies. Subsequently, this feedback is utilized to fine-tune the anomaly detection algorithm. In addition, this GUI also provides access to network actors for quick incident responses. The system in general is suitable for both Information Technology (IT) and Operational Technology (OT) environments, while the detection algorithm must be specifically trained for each of these environments individually.
The objective of this student project was for the students to develop, conduct, and supervise a training course for basic work place applications (word processing and business graphics). Students were responsible for the planning, organizing and the teaching of the course. As participants, underprivileged adolescents took part in order to learn the handling of IT applications and therefore, improve their job skills and have a better chance to get into employment. Therefore the adolescents do the role of trainees at the course. Our students worked with a population that is continually overlooked by the field.
As a result, the students trained to design and implement training courses, exercised to manage projects and increased their social responsibility and awareness concerning the way of life and living conditions of other young people. The underprivileged adolescents learned to use important business applications and increased their job skills and job chances. The overall design of our concept required extensive resources to supervise and to steer the students and the adolescents. The lecturers had to teach and to counsel the students and had to be on “stand-by” just in case they were needed to solve critical situations between the two groups of young people.
Background: India has the third largest HIV epidemic in the world. The Indian epidemic is characterized by low levels in the general population and elevated concentrations among high-risk groups. The present study was planned to determine the awareness of HIV among students from Mumbai University.
Methods: A cross-sectional study was carried out among students from Mumbai University, India during May–June 2017. Two hundred and fifty students were approached to participate in the study of which 199 agreed to participate (males: 132; females: 67). Pretested questionnaire was distributed and collected data was analyzed using IBM SPSS version 23.
Results: Study participants had high knowledge (86%) and attitude score (87%). There was no significant difference between males and female participants for attitude and knowledge, except for one question regarding knowledge about HIV transmission via breastfeeding to child.
Conclusions: Present study showed that there are no misconceptions or negative attitudes regarding HIV among students. A longitudinal study with a larger sample size across India is recommended for further investigation.
A study to assess the knowledge and attitude towards HIV of pharmacy students from Mumbai university
(2020)
Background: India is the biggest HIV epidemic in the world. The role of a pharmacist is pivotal in educating the general masses. The aim of the study was to determine the knowledge and attitude of pharmacy students from University of Mumbai.
Methods: A cross-sectional study was conducted in University of Mumbai during February-March 2020. Therein, 307 students (214: females and 94: males) participated in the study. The questionnaire was distributed in the classroom and data was collected by means of Google-forms. Furthermore, the data was analysed using IBM SPSS version 23.
Results: The participants demonstrated good knowledge (84%) and attitude (76%) score. With respect to knowledge score, no significant difference was observed except for responses of two questions, aim of the antiretroviral therapy (ART) and Avoidance of sexual intercourse can decrease the risk of HIV. With respect to attitude score, Volunteering to work at an institute for the welfare of HIV patients showed a significant difference.
Conclusion: The current study showed that there were no misconceptions or negative attitude regarding HIV among the students. However, a study with greater sample size must be conducted across India for further investigation.
Background: Immunization is the most cost-effective intervention for infectious diseases which are the major cause of morbidity and mortality worldwide. There is a scarcity of information on the vaccination status of young adults and the role of socioeconomic conditions in India. Objectives: Present study explored the adult vaccination status and influence of income and education of parents on adult vaccination status in university students from Mumbai, India.
Methods: On the basis of the eligibility criterion 149 students were selected for the present study. A total of 8 vaccines namely Tdap/DTP, Varicella, MMR, Influenza, Pneumococcal, Hepatitis A, Hepatitis B and Meningococcal were included in this study for all the respondents. In addition to these vaccines, Human Papilloma Virus vaccine was also included for female respondents.
Results: There were total of 149 (75 male and 74 females) respondents with the mean age of 21.5 years. The top 3 immunizations were Td/Tdap (97.3%), MMR (66.4%) and Hepatitis B (55%) among the respondents. Only 4 (5.5%) female respondents have been immunized against the HPV. Conclusions: Td/Tdap (97.3%) and MMR (66.4%) coverage was in line with the recommendations. For all the other vaccines the coverage was low varying from 5.5% to 35.4%. The vaccination coverage was better in respondents with higher educated and higher income parents. We suggest that patient education, planning by government for the implementation of policy for adult vaccination and involvement of physicians are must for better adult vaccination coverage.
Immunization is the most cost-effective intervention for infectious diseases, which are the major cause of morbidity and mortality worldwide. Vaccines not only protect the individual who is vaccinated but also reduce the burden of infectious vaccine-preventable diseases for the entire community.
1 Adult vaccination is very important given that >25% of mortality is due to infectious diseases.
2 There is a scarcity of information on the vaccination status of young adults and the role of socioeconomic conditions in India.
The drugs we use to treat any condition – from an innocuous cough to a life-threatening cancer – are the outcome of painstaking human clinical trials. These trials are the only way to credibly determine the safety and efficacy of drugs. In recent years there has been a clear shift in clinical trial sites from core developed countries like USA, European countries to developing countries like India, China, South American countries. This shift is related to challenges and opportunities like costs of trials, recruitment issues, and regulatory challenges in developed vs. developing countries. Developing countries and developed countries have their unique disease burden patterns based on various parameters like but not limited to age, health care facilities, health insurance, sanitary conditions, environmental issues, education, nutrition
and GDP. Previous studies have reported that many of the important global diseases are not much explored in clinical trials and many published clinical trials have very less international health relevance. This study was aimed at finding the correlation between disease burdens, number of clinical trials done and trial success rates. We compared 2005 - 2010 Global Burden of Disease data for Germany, India and number of clinical trials from clinicaltrials.gov database done in the same period. Our findings indicated that there was a good correlation between the disease burden and clinical trials for Germany in 2005 and 2010. For India in 2005 there was a moderate positive correlation, 2010 data showed the improvement in India in terms of match between disease burden and clinical trials. But careful observation of the data shows still a need for more trials on Communicable, maternal, neonatal and nutritional disorders.