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01 juli 2023, Contains fulltext : 292520.pdf (Publisher’s version ) (Open Access), BACKGROUND: Certain patients are at greater risk of developing nontuberculous mycobacterial pulmonary disease (NTM-PD), including those with lung conditions such as bronchiectasis. Testing for nontuberculous mycobacteria (NTM) in patients at risk is necessary to identify NTM-PD and start appropriate management. The aim of this survey was to evaluate current testing practices for NTM and identify testing triggers. METHODS: Physicians (n=455) who see at least one patient with NTM-PD in a typical 12-month period and test for NTM as part of practice from Europe, USA, Canada, Australia, New Zealand and Japan participated in a 10-min anonymised survey on NTM testing practices. RESULTS: Bronchiectasis, COPD and use of immunosuppressants were the factors most likely to prompt testing among physicians in this survey (90%, 64% and 64%, respectively), with radiological findings the most common reason leading to considering NTM testing in patients with bronchiectasis and COPD (62% and 74%, respectively). Macrolide monotherapy in patients with bronchiectasis and inhaled corticosteroid use in patients with COPD were not important triggers for testing (15% and 9% of physicians, respectively). Persistent cough and weight loss triggered testing in >75% of physicians. Testing triggers were markedly different for physicians in Japan, with cystic fibrosis prompting testing in fewer physicians compared with other regions. CONCLUSIONS: Testing for NTM is influenced by underlying disease, clinical symptoms or radiological changes, but clinical practice varies considerably. Adherence to guideline recommendations for NTM testing is limited in certain patient subgroups and varies across regions. Clear recommendations on NTM testing are needed.

Item does not contain fulltext, PURPOSE: Real-world data on antibiotic management of nontuberculous mycobacterial lung disease (NTM-LD) is limited for many countries. This study aimed to evaluate real-world treatment practices of NTM-LD in the Netherlands using medication dispensing data. METHODS: A retrospective longitudinal real-world study was conducted using IQVIA's Dutch pharmaceutical dispensing database. The data are collected monthly and include approximately 70% of all outpatient prescriptions in the Netherlands. Patients initiated on specific NTM-LD treatment regimens between October 2015 and September 2020 were included. The main areas of investigation were initial treatment regimens, persistence on treatment, treatment switching, treatment compliance in terms of medication possession rate (MPR) and restarts of treatment. RESULTS: The database included 465 unique patients initiated on triple- or dual-drug regimens for the treatment of NTM-LD. Treatment switches were common and occurred approximately 1.6 per quarter throughout the treatment period. The average MPR of patients initiated on triple-drug therapy was 90%. The median time on therapy for these patients was 119 days; after six months and one year, 47% and 20% of the patients, respectively, were still on antibiotic therapy. Of 187 patients initiated on triple-drug therapy, 33 (18%) patients restarted antibiotic therapy after the initial treatment had been stopped. CONCLUSION: When on therapy, patients were compliant with the NTM-LD treatment; however, many patients stopped their therapy prematurely, treatment switches often occurred, and part of patients had to restart their therapy after a longer treatment gap. NTM-LD management should be improved through greater guideline adherence and appropriate involvement of expert centers.

Contains fulltext : 300162.pdf (Publisher’s version ) (Open Access), BACKGROUND: Nontuberculous mycobacterial pulmonary disease (NTM-PD) is widely underdiagnosed, and certain patient groups, such as those with underlying respiratory diseases, are at increased risk of developing the disease. Understanding patients at risk is essential to allow for prompt testing and diagnosis and appropriate management to prevent disease progression. RESEARCH QUESTION: What are the risk factors for NTM-PD that should prompt a physician to consider NTM testing and diagnosis? STUDY DESIGN AND METHODS: Electronic searches of PubMed and EMBASE were conducted in July 2021 for the period 2011-2021. Inclusion criteria were studies of patients with NTM-PD with associated risk factors. Data were extracted and assessed using the Newcastle-Ottawa Scale. Data analysis was conducted using the R-based "meta" package. Only studies that reported association outcomes for cases with NTM-PD compared with control participants (healthy populations or participants without NTM-PD) were considered for the meta-analysis. RESULTS: Of the 9,530 searched publications, 99 met the criteria for the study. Of these, 24 formally reported an association between possible risk factors and the presence of NTM-PD against a control population and were included in the meta-analysis. Comorbid respiratory disease was associated with a significant increase in the OR for NTM-PD (bronchiectasis [OR, 21.43; 95% CI, 5.90-77.82], history of TB [OR, 12.69; 95% CI, 2.39-67.26], interstitial lung disease [OR, 6.39; 95% CI, 2.65-15.37], COPD [OR, 6.63; 95% CI, 4.57-9.63], and asthma [OR, 4.15; 95% CI, 2.81-6.14]). Other factors noted to be associated with an increased risk of NTM-PD were the use of inhaled corticosteroids (OR 4.46; 95% CI, 2.13-9.35), solid tumors (OR, 4.66; 95% CI, 1.04-20.94) and the presence of pneumonia (OR, 5.54; 95% CI, 2.72-11.26). INTERPRETATION: The greatest risk for NTM-PD is conferred by comorbid respiratory diseases such as bronchiectasis. These findings could help with ide, 01 november 2023

Contains fulltext : 220118.pdf (publisher's version ) (Open Access), BACKGROUND: Patients with bronchiectasis are at increased risk of developing non-tuberculous mycobacteria lung disease (NTM-LD), and published guidelines recommend regular testing for NTM infection in this patient population. OBJECTIVE: This study aimed to survey physicians managing patients with bronchiectasis to understand the perceived risk of NTM to their patients, perceived disease severity and frequency of testing for NTM. METHODS: The study comprised an online survey of hospital-based physicians in the UK, Germany, Italy, France and the Netherlands. The target group were hospital-based physicians who had managed at least 10 adult patients with bronchiectasis over the preceding 12 months. RESULTS: In total, 280 physicians completed the survey. Most (87%) thought their patients to be at particular risk of NTM, although it was perceived as a moderate risk versus other respiratory pathogens. Most perceived NTM-LD to impact patient morbidity (84%), and 61% indicated that NTM-LD significantly impacted mortality. 68% of all respondents did not test for NTM prior to initiating macrolide monotherapy, despite guidelines recommending testing. The perceived risk of and screening for NTM varied among countries. CONCLUSIONS: The study demonstrates that physicians understand the risk of NTM-LD and associated morbidity in patients with bronchiectasis; however, a minority do not perceive that NTM-LD significantly affects mortality. Greater awareness of the need to test for NTM infection before initiating macrolide monotherapy for bronchiectasis is essential due to potential emergence of drug-resistant NTM.

Contains fulltext : 220118.pdf (publisher's version ) (Open Access), BACKGROUND: Patients with bronchiectasis are at increased risk of developing non-tuberculous mycobacteria lung disease (NTM-LD), and published guidelines recommend regular testing for NTM infection in this patient population. OBJECTIVE: This study aimed to survey physicians managing patients with bronchiectasis to understand the perceived risk of NTM to their patients, perceived disease severity and frequency of testing for NTM. METHODS: The study comprised an online survey of hospital-based physicians in the UK, Germany, Italy, France and the Netherlands. The target group were hospital-based physicians who had managed at least 10 adult patients with bronchiectasis over the preceding 12 months. RESULTS: In total, 280 physicians completed the survey. Most (87%) thought their patients to be at particular risk of NTM, although it was perceived as a moderate risk versus other respiratory pathogens. Most perceived NTM-LD to impact patient morbidity (84%), and 61% indicated that NTM-LD significantly impacted mortality. 68% of all respondents did not test for NTM prior to initiating macrolide monotherapy, despite guidelines recommending testing. The perceived risk of and screening for NTM varied among countries. CONCLUSIONS: The study demonstrates that physicians understand the risk of NTM-LD and associated morbidity in patients with bronchiectasis; however, a minority do not perceive that NTM-LD significantly affects mortality. Greater awareness of the need to test for NTM infection before initiating macrolide monotherapy for bronchiectasis is essential due to potential emergence of drug-resistant NTM.

Contains fulltext : 208558.pdf (publisher's version ) (Open Access), INTRODUCTION: In women with gestational diabetes mellitus (GDM) requiring pharmacotherapy, insulin was the established first-line treatment. More recently, oral glucose lowering drugs (OGLDs) have gained popularity as a patient-friendly, less expensive and safe alternative. Monotherapy with metformin or glibenclamide (glyburide) is incorporated in several international guidelines. In women who do not reach sufficient glucose control with OGLD monotherapy, usually insulin is added, either with or without continuation of OGLDs. No reliable data from clinical trials, however, are available on the effectiveness of a treatment strategy using all three agents, metformin, glibenclamide and insulin, in a stepwise approach, compared with insulin-only therapy for improving pregnancy outcomes. In this trial, we aim to assess the clinical effectiveness, cost-effectiveness and patient experience of a stepwise combined OGLD treatment protocol, compared with conventional insulin-based therapy for GDM. METHODS: The SUGAR-DIP trial is an open-label, multicentre randomised controlled non-inferiority trial. Participants are women with GDM who do not reach target glycaemic control with modification of diet, between 16 and 34 weeks of gestation. Participants will be randomised to either treatment with OGLDs, starting with metformin and supplemented as needed with glibenclamide, or randomised to treatment with insulin. In women who do not reach target glycaemic control with combined metformin and glibenclamide, glibenclamide will be substituted with insulin, while continuing metformin. The primary outcome will be the incidence of large-for-gestational-age infants (birth weight >90th percentile). Secondary outcome measures are maternal diabetes-related endpoints, obstetric complications, neonatal complications and cost-effectiveness analysis. Outcomes will be analysed according to the intention-to-treat principle. ETHICS AND DISSEMINATION: The study protocol was approved by the Ethics Com

Introduction In women with gestational diabetes mellitus (GDM) requiring pharmacotherapy, insulin was the established first-line treatment. More recently, oral glucose lowering drugs (OGLDs) have gained popularity as a patient-friendly, less expensive and safe alternative. Monotherapy with metformin or glibenclamide (glyburide) is incorporated in several international guidelines. In women who do not reach sufficient glucose control with OGLD monotherapy, usually insulin is added, either with or without continuation of OGLDs. No reliable data from clinical trials, however, are available on the effectiveness of a treatment strategy using all three agents, metformin, glibenclamide and insulin, in a stepwise approach, compared with insulin-only therapy for improving pregnancy outcomes. In this trial, we aim to assess the clinical effectiveness, cost-effectiveness and patient experience of a stepwise combined OGLD treatment protocol, compared with conventional insulin-based therapy for GDM. Methods The SUGAR-DIP trial is an open-label, multicentre randomised controlled non-inferiority trial. Participants are women with GDM who do not reach target glycaemic control with modification of diet, between 16 and 34 weeks of gestation. Participants will be randomised to either treatment with OGLDs, starting with metformin and supplemented as needed with glibenclamide, or randomised to treatment with insulin. In women who do not reach target glycaemic control with combined metformin and glibenclamide, glibenclamide will be substituted with insulin, while continuing metformin. The primary outcome will be the incidence of large-for-gestational-age infants (birth weight >90th percentile). Secondary outcome measures are maternal diabetes-related endpoints, obstetric complications, neonatal complications and cost-effectiveness analysis. Outcomes will be analysed according to the intention-to-treat principle. Ethics and dissemination The study protocol was approved by the Ethics Commit

Contains fulltext : 208558.pdf (publisher's version ) (Open Access), INTRODUCTION: In women with gestational diabetes mellitus (GDM) requiring pharmacotherapy, insulin was the established first-line treatment. More recently, oral glucose lowering drugs (OGLDs) have gained popularity as a patient-friendly, less expensive and safe alternative. Monotherapy with metformin or glibenclamide (glyburide) is incorporated in several international guidelines. In women who do not reach sufficient glucose control with OGLD monotherapy, usually insulin is added, either with or without continuation of OGLDs. No reliable data from clinical trials, however, are available on the effectiveness of a treatment strategy using all three agents, metformin, glibenclamide and insulin, in a stepwise approach, compared with insulin-only therapy for improving pregnancy outcomes. In this trial, we aim to assess the clinical effectiveness, cost-effectiveness and patient experience of a stepwise combined OGLD treatment protocol, compared with conventional insulin-based therapy for GDM. METHODS: The SUGAR-DIP trial is an open-label, multicentre randomised controlled non-inferiority trial. Participants are women with GDM who do not reach target glycaemic control with modification of diet, between 16 and 34 weeks of gestation. Participants will be randomised to either treatment with OGLDs, starting with metformin and supplemented as needed with glibenclamide, or randomised to treatment with insulin. In women who do not reach target glycaemic control with combined metformin and glibenclamide, glibenclamide will be substituted with insulin, while continuing metformin. The primary outcome will be the incidence of large-for-gestational-age infants (birth weight >90th percentile). Secondary outcome measures are maternal diabetes-related endpoints, obstetric complications, neonatal complications and cost-effectiveness analysis. Outcomes will be analysed according to the intention-to-treat principle. ETHICS AND DISSEMINATION: The study protocol was approved by the Ethics Com

One of the core functionalities of De Energiebespaarders platform, a tech-start-up in the heart of Amsterdam and the company for which this project was done, is the communication with their customers. The company provides a service that connects homeowners with local installers of energy saving products. Their problem was that a lot of time is lost in managing the communication between these two stakeholders. Currently they are still growing and the problem is manageable, but when the amount of customers increases in the near future it will become a big problem. This report documents the development process of E-Captain, the system which was developed to tackle this problem. Our system automatically categorizes messages from customers. These categories are used to prioritize certain conversations and to assign them to the person that is most suited to answer them. One of the greater difficulties of this project was the lack of data for training a classifier that uses machine learning. Therefore, the data used to train the classifier is collected by scraping the content of websites found by searching the web with manually entered queries in an administrative panel. In addition, our system learns continuously by adding messages from customers to the data set of categories they belong to. Our system differs from existing solutions in a few aspects. Our system is designed to easily modify and create new categories through automatic data collection to train the classifier. Furthermore, many similar products are optimized for English, but all communication of De Energiebespaarders is done in Dutch., Electrical Engineering, Mathematics and Computer Science, Intelligent Systems

One of the core functionalities of De Energiebespaarders platform, a tech-start-up in the heart of Amsterdam and the company for which this project was done, is the communication with their customers. The company provides a service that connects homeowners with local installers of energy saving products. Their problem was that a lot of time is lost in managing the communication between these two stakeholders. Currently they are still growing and the problem is manageable, but when the amount of customers increases in the near future it will become a big problem. This report documents the development process of E-Captain, the system which was developed to tackle this problem. Our system automatically categorizes messages from customers. These categories are used to prioritize certain conversations and to assign them to the person that is most suited to answer them. One of the greater difficulties of this project was the lack of data for training a classifier that uses machine learning. Therefore, the data used to train the classifier is collected by scraping the content of websites found by searching the web with manually entered queries in an administrative panel. In addition, our system learns continuously by adding messages from customers to the data set of categories they belong to. Our system differs from existing solutions in a few aspects. Our system is designed to easily modify and create new categories through automatic data collection to train the classifier. Furthermore, many similar products are optimized for English, but all communication of De Energiebespaarders is done in Dutch., Electrical Engineering, Mathematics and Computer Science, Intelligent Systems

Item does not contain fulltext, Providing clinical teachers with feedback about their teaching skills is a powerful tool to improve teaching. Evaluations are mostly based on questionnaires completed by residents. We investigated to what extent characteristics of residents, clinical teachers, and the clinical environment influenced these evaluations, and the relation between residents' scores and their teachers' self-scores. The evaluation and feedback for effective clinical teaching questionnaire (EFFECT) was used to (self)assess clinical teachers from 12 disciplines (15 departments, four hospitals). Items were scored on a five-point Likert scale. Main outcome measures were residents' mean overall scores (MOSs), specific scale scores (MSSs), and clinical teachers' self-evaluation scores. Multilevel regression analysis was used to identify predictors. Residents' scores and self-evaluations were compared. Residents filled in 1,013 questionnaires, evaluating 230 clinical teachers. We received 160 self-evaluations. 'Planning Teaching' and 'Personal Support' (4.52, SD .61 and 4.53, SD .59) were rated highest, 'Feedback Content' (CanMEDS related) (4.12, SD .71) was rated lowest. Teachers in affiliated hospitals showed highest MOS and MSS. Medical specialty did not influence MOS. Female clinical teachers were rated higher for most MSS, achieving statistical significance. Residents in year 1-2 were most positive about their teachers. Residents' gender did not affect the mean scores, except for role modeling. At group level, self-evaluations and residents' ratings correlated highly (Kendall's tau 0.859). Resident evaluations of clinical teachers are influenced by teacher's gender, year of residency training, type of hospital, and to a lesser extent teachers' gender. Clinical teachers and residents agree on strong and weak points of clinical teaching.

Item does not contain fulltext, Providing clinical teachers with feedback about their teaching skills is a powerful tool to improve teaching. Evaluations are mostly based on questionnaires completed by residents. We investigated to what extent characteristics of residents, clinical teachers, and the clinical environment influenced these evaluations, and the relation between residents' scores and their teachers' self-scores. The evaluation and feedback for effective clinical teaching questionnaire (EFFECT) was used to (self)assess clinical teachers from 12 disciplines (15 departments, four hospitals). Items were scored on a five-point Likert scale. Main outcome measures were residents' mean overall scores (MOSs), specific scale scores (MSSs), and clinical teachers' self-evaluation scores. Multilevel regression analysis was used to identify predictors. Residents' scores and self-evaluations were compared. Residents filled in 1,013 questionnaires, evaluating 230 clinical teachers. We received 160 self-evaluations. 'Planning Teaching' and 'Personal Support' (4.52, SD .61 and 4.53, SD .59) were rated highest, 'Feedback Content' (CanMEDS related) (4.12, SD .71) was rated lowest. Teachers in affiliated hospitals showed highest MOS and MSS. Medical specialty did not influence MOS. Female clinical teachers were rated higher for most MSS, achieving statistical significance. Residents in year 1-2 were most positive about their teachers. Residents' gender did not affect the mean scores, except for role modeling. At group level, self-evaluations and residents' ratings correlated highly (Kendall's tau 0.859). Resident evaluations of clinical teachers are influenced by teacher's gender, year of residency training, type of hospital, and to a lesser extent teachers' gender. Clinical teachers and residents agree on strong and weak points of clinical teaching.

Item does not contain fulltext, Providing clinical teachers with feedback about their teaching skills is a powerful tool to improve teaching. Evaluations are mostly based on questionnaires completed by residents. We investigated to what extent characteristics of residents, clinical teachers, and the clinical environment influenced these evaluations, and the relation between residents' scores and their teachers' self-scores. The evaluation and feedback for effective clinical teaching questionnaire (EFFECT) was used to (self)assess clinical teachers from 12 disciplines (15 departments, four hospitals). Items were scored on a five-point Likert scale. Main outcome measures were residents' mean overall scores (MOSs), specific scale scores (MSSs), and clinical teachers' self-evaluation scores. Multilevel regression analysis was used to identify predictors. Residents' scores and self-evaluations were compared. Residents filled in 1,013 questionnaires, evaluating 230 clinical teachers. We received 160 self-evaluations. 'Planning Teaching' and 'Personal Support' (4.52, SD .61 and 4.53, SD .59) were rated highest, 'Feedback Content' (CanMEDS related) (4.12, SD .71) was rated lowest. Teachers in affiliated hospitals showed highest MOS and MSS. Medical specialty did not influence MOS. Female clinical teachers were rated higher for most MSS, achieving statistical significance. Residents in year 1-2 were most positive about their teachers. Residents' gender did not affect the mean scores, except for role modeling. At group level, self-evaluations and residents' ratings correlated highly (Kendall's tau 0.859). Resident evaluations of clinical teachers are influenced by teacher's gender, year of residency training, type of hospital, and to a lesser extent teachers' gender. Clinical teachers and residents agree on strong and weak points of clinical teaching.

De Stichting Vissenbescherming heeft de hulp van de wetenschapswinkel van Wageningen UR ingeroepen. Zij vraagt haar te ondersteunen met onderzoek dat een stap voorwaarts kan betekenen op weg naar een vissenwelzijnskeurmerk voor in het wild gevangen (zee)vis. In totaal 19 studenten (3 studententeams en 2 masterstudenten) deden voor de wetenschapswinkel (literatuur)onderzoek naar a) welzijn van vissen (met name platvis) in relatie tot de visserij en b) maatschappelijke agendering op het gebied van vissenwelzijn. Op grond van een literatuurstudie wordt geconcludeerd dat steeds meer wetenschappelijke argumenten erop wijzen dat ook vissen pijn lijden en emoties kunnen ervaren. Voor diegenen die deze argumenten in twijfel trekken wordt door Elder bepleit het “voorzorgsprincipe” te hanteren, waarbij ernaar gestreefd wordt het risico op pijn en leed bij vissen zoveel mogelijk te voorkomen.

In dit onderzoek, uitgevoerd binnen de bovenschoolse managementorganisatie GPO-WN (Gereformeerd Primair Onderwijs – West-Nederland), staat de vergelijking tussen de visie van de leerkrachten en de visie van GPO-WN centraal. De dataverzameling is uitgevoerd door middel van een inhoudsanalyse van het koersplan van GPO-WN, enquêtes onder leerkrachten (n=116) en directie (n=10) en interviews met de directie (n=7) en met leerkrachten (n=8). Uit het onderzoek blijkt dat de enquêtes verkeerd ingevuld zijn voor verdere analyse en daarom worden ze verder achterwege gelaten Uit de interviews blijkt dat de uitgedragen visie van de leerkrachten en de directie over het algemeen overeenkomt met de visie zoals beschreven in het koersplan.

We analyze the impact of leniency programs on the behavior of firms participating in illegal cartel agreements in a two-stage repeated game model. Our approach takes into account asymmetric punishment effect and allows to discuss the design of leniency programs in the setting with asymmetries. The main contribution of the paper is that we consider heterogeneous firms. This heterogeneity results in additional costs in case of disclosure of the cartel, which are caused by asymmetric punishments. Next, following current antitrust rules, we analyze effects of the strictness of leniency programs, which reflects the likelihood of getting a complete exemption from fine even in case many firms self-report simultaneously. Our main conclusion is that leniency programs work better for small companies, since a lower rate of law enforcement is needed in order to induce self-reporting by smaller firms, while big firms are less likely to start a cartel in the first place given the possibility of self-reporting in future. Finally, we analyze optimal enforcement strategies of the antitrust authority and conclude that the authority with limited resources should implement more generous leniency rules the more cartelized the economy is. © 2011 The Author(s).

In dit onderzoek, uitgevoerd binnen de bovenschoolse managementorganisatie GPO-WN (Gereformeerd Primair Onderwijs – West-Nederland), staat de vergelijking tussen de visie van de leerkrachten en de visie van GPO-WN centraal. De dataverzameling is uitgevoerd door middel van een inhoudsanalyse van het koersplan van GPO-WN, enquêtes onder leerkrachten (n=116) en directie (n=10) en interviews met de directie (n=7) en met leerkrachten (n=8). Uit het onderzoek blijkt dat de enquêtes verkeerd ingevuld zijn voor verdere analyse en daarom worden ze verder achterwege gelaten Uit de interviews blijkt dat de uitgedragen visie van de leerkrachten en de directie over het algemeen overeenkomt met de visie zoals beschreven in het koersplan.

We analyze the impact of leniency programs on the behavior of firms participating in illegal cartel agreements in a two-stage repeated game model. Our approach takes into account asymmetric punishment effect and allows to discuss the design of leniency programs in the setting with asymmetries. The main contribution of the paper is that we consider heterogeneous firms. This heterogeneity results in additional costs in case of disclosure of the cartel, which are caused by asymmetric punishments. Next, following current antitrust rules, we analyze effects of the strictness of leniency programs, which reflects the likelihood of getting a complete exemption from fine even in case many firms self-report simultaneously. Our main conclusion is that leniency programs work better for small companies, since a lower rate of law enforcement is needed in order to induce self-reporting by smaller firms, while big firms are less likely to start a cartel in the first place given the possibility of self-reporting in future. Finally, we analyze optimal enforcement strategies of the antitrust authority and conclude that the authority with limited resources should implement more generous leniency rules the more cartelized the economy is. © 2011 The Author(s).

Contains fulltext : 45627.pdf (publisher's version ) (Closed access)

Contains fulltext : 45627.pdf (publisher's version ) (Closed access)

Contains fulltext : 45627.pdf (publisher's version ) (Closed access)

During meiotic prophase in male mammals, the X and Y chromosomes are incorporated in the XY body. This heterochromatic body is transcriptionally silenced and marked by increased ubiquitination of histone H2A. This led us to investigate the relationship between histone H2A ubiquitination and chromatin silencing in more detail. First, we found that ubiquitinated H2A also marks the silenced X chromosome of the Barr body in female somatic cells. Next, we studied a possible relationship between H2A ubiquitination, chromatin silencing, and unpaired chromatin in meiotic prophase. The mouse models used carry an unpaired autosomal region in male meiosis or unpaired X and Y chromosomes in female meiosis. We show that ubiquitinated histone H2A is associated with transcriptional silencing of large chromatin regions. This silencing in mammalian meiotic prophase cells concerns unpaired chromatin regions and resembles a phenomenon described for the fungus Neurospora crassa and named meiotic silencing by unpaired DNA.

This paper studies the effects of leniency programs on the behavior of firms participating in illegal cartel agreements.The main contribution of the paper is that we consider asymmetric firms.In general, firms differ in size and operate in several different markets.In our model, they form a cartel in one market only.This asymmetry results in additional costs in case of disclosure of the cartel, which are caused by an asymmetric reduction of the sales in other markets due to a negative reputation effect.This modeling framework can also be applied to the case of international cartels, where firms are subject to different punishment procedures according to the laws of their countries, or in situations where following an application for leniency firms are subject to costs other than the fine itself and where these costs depend on individual characteristics of the firm.Moreover, following the rules of existing Leniency Programs, we analyze the effects of the strictness of the Leniency Programs, which reflects the likelihood of getting complete exemption from the fine even in case many firms self-report simultaneously.Our main results are that, first, leniency programs work better for small (less diversified) companies, in the sense that a lower rate of law enforcement is needed in order to induce self-reporting by less diversified firms.At the same time, big (more diversified) firms are less likely to start a cartel in the first place given the possibility of self-reporting in the future.Second, the more cartelized the economy, the less strict the rules of leniency programs should be.

In replicative damage bypass (RDB) in yeast, the ubiquitin-conjugating enzyme RAD6 interacts with the ubiquitin ligase RAD18. In the mouse, these enzymes are represented by two homologs of RAD6, HR6a and HR6b, and one homolog of RAD18, Rad18Sc. Expression of these genes and the encoded proteins is ubiquitous, but there is relatively high expression in the testis. We have studied the subcellular localization by immunostaining Rad18Sc and other RDB proteins in mouse primary spermatocytes passing through meiotic prophase in spermatogenesis. The highest Rad18Sc protein level is found at pachytene and diplotene, and the protein localizes mainly to the XY body, a subnuclea

Combizorgsysteem is een voorbeeld van een modern zorgsysteem, dat nauw in handen die de moderne ondernemer nodig heeft. De ervaringen in het project combizorg in de bloembollensector, waaraan 8 bedrijven uit de bollensector in het seizoen '99-2000 deelnamen, bevestigen de verwachtte gunstige effecten van het systematisch beschrijven en denken over het eigen bedrijf

Combizorg is makkelijk samen te vatten: Het gaat om de vragen: wie, wat, waar, waarom, wanneer en hoe? Het opzetten van het combizorgsysteem is niet in korte tijd klaar en verloopt in verschillende fasen. Systematisch meer structuur in uw bedrijf aanbrengen verbetert continu de resultaten.

In mammals, there is a complex and intriguing relationship between DNA repair and gametogenesis. DNA repair mechanisms are involved not only in the repair of different types of DNA damage in developing germline cells, but also take part in the meiotic recombination process. Furthermore, the DNA repair mechanisms should tolerate mutations occurring during gametogenesis, to a limited extent. In the present review, several gametogenic aspects of DNA mismatch repair, homologous recombination repair and postreplication repair are discussed. In addition, the role of DNA damage-induced cell cycle checkpoint control is considered briefly. It appears that many genes encoding proteins that take part in DNA repair mechanisms show enhanced or specialized expression during mammalian gametogenesis, and several gene knockout mouse models show male or female infertility. On the basis of such knowledge and models, future experiments may provide more information about the precise relationship between DNA repair, chromatin dynamics, and genomic stability versus instability during gametogenesis.

Onderzoek 'Meerwaarde kwaliteitszorg in de groene praktijk ' dat valt binnen het LNV-programma 'Integrale kwaliteitszorg in de plantaardige productie ' D.m.v. interviews op bedrijven in de sectoren bloembollen, fruitteelt, glastuinbouw en akkerbouw en vollegrondsgroente.

De directe effecten van een (sub)optimale grondwaterstand voor de groei en opbrengst van de belangrijkste bloembolgewassen in de Bollenstreek zijn bepaald. Daarnaast zijn indirecte effecten van een (sub)optimale grondwaterstand, als structuurbederf en uitstellen van veldwerkzaamheden, bepaald. De kosten ten gevolge van een suboptimaal peil zijn berekend aan de hand van een voorbeeldbedrijf en vier ontwateringsscenario's. Daarnaast is een opschaling van deze kosten naar regioniveau gemaakt voor de Bollenstreek

Contains fulltext : 24855___.PDF (publisher's version ) (Open Access)

RIVM rapport:Onderzoek is uitgevoerd naar verbetering van de relatieve detectiegrenzen van gaschromatografie met infraroodspectrometrische detectie (GC-IR) door toepassing van zogenaamde large-volume injectie (LVI) technieken. Twee technieken zijn onderzocht, loop-type interfacing en on-column interfacing. Optimalisatie is uitgevoerd met n-alkanen in verschillende oplosmiddelen. Pesticiden, polyaromatische koolwaterstoffen en andere contaminanten zijn gebruikt voor het testen van de bruikbaarheid van het ontwikkelde systeem in de milieu-analyse. Bij 100 ul injecties blijkt de relatieve detecteerbaarheid van de niet vluchtige analieten in vergelijking met 1 ul split/splitless injecties, voor beide typen interfacing vrijwel evenredig toe te nemen met het geinjecteerde volume. Bij injectie van grotere volumes (200-400 ul) wordt de winst in relatieve gevoeligheid gedeeltelijk teniet gedaan door verontreinigingen in het oplosmiddel. De prestaties van de on-column interfacing zijn relatief beter door het geringere verlies aan vluchtige componenten en de inbouw van een detector-schakelsysteem. De praktische mogelijkheden van LVI-GC-IR worden gedemonstreerd aan de hand van de analyse van enkele monsters drink- en oppervlaktewater waaraan veel voorkomende contaminanten zijn toegevoegd op een niveau van 0.1-1 ug/l. De toegevoegde componenten zijn gedetecteerd en geidentificeerd (i) via injectie van extracten verkregen via vloeistof-vloeistof extractie en (ii) door on-line desorptie van elders bemonsterde solid phase extracted (SPE) cartridges. De mogelijkheid van (LVI-)GC-IR om door middel van functionele groepschromatogrammen te screenen op de aanwezigheid van specifieke stofklassen is een waardevolle aanvulling op gaschromatografie met massaspectrometrische en atoomemissie detectie., Research has been carried out to enlarge the analyte detectability of gaschromatography with infrared spectrometric detection (GC-IR) by techniques that allow injection of large volumes of liquid samples (100 ul typical). Two techniques have been investigated; loop-type and on-column interfacing. Alkanes dissolved in various solvents have been used for optimisation. Pesticides, polyaromatic hydrocarbons and other micro-contaminants have been used to test the usefulness of the eveloped system in environmental trace analysis. The increase in analyte detectability of high boiling compounds compared to conventional 1 ul split/splitless injection is almost proportional to the injected volume for injection of 100 ul. At larger sample volumes, the increase of the relative sensitivity is partly detracted by impurities of the solvent. The performance of the on-column interface is better due to the reduced loss of volatiles and the incorporation of a detector switching module that minimizes interfering solvent condensation in the IR detection interface. The potentials of LVI-GC-IR are demonstrated by the analysis of samples of drinking and surface water spiked at levels of 0.1-1 ug/l with components that commonly occur as micro-contaminants. Analytes have been detected and identified (i) by direct injection of solutions obtained by liquid-liquid extraction and (ii) by on-line desorption of at site sampled solid phase extracted cartridges. The possibility of (LVI-)GC-IR of selective screening on the prescence of specific compound classes by means of functional group chromatograms makes the technique a valuable tool in addition to GC with mass spectrometric and atomic emission detection.

RIVM rapport:Research has been carried out to enlarge the analyte detectability of gaschromatography with infrared spectrometric detection (GC-IR) by techniques that allow injection of large volumes of liquid samples (100 ul typical). Two techniques have been investigated; loop-type and on-column interfacing. Alkanes dissolved in various solvents have been used for optimisation. Pesticides, polyaromatic hydrocarbons and other micro-contaminants have been used to test the usefulness of the eveloped system in environmental trace analysis. The increase in analyte detectability of high boiling compounds compared to conventional 1 ul split/splitless injection is almost proportional to the injected volume for injection of 100 ul. At larger sample volumes, the increase of the relative sensitivity is partly detracted by impurities of the solvent. The performance of the on-column interface is better due to the reduced loss of volatiles and the incorporation of a detector switching module that minimizes interfering solvent condensation in the IR detection interface. The potentials of LVI-GC-IR are demonstrated by the analysis of samples of drinking and surface water spiked at levels of 0.1-1 ug/l with components that commonly occur as micro-contaminants. Analytes have been detected and identified (i) by direct injection of solutions obtained by liquid-liquid extraction and (ii) by on-line desorption of at site sampled solid phase extracted cartridges. The possibility of (LVI-)GC-IR of selective screening on the prescence of specific compound classes by means of functional group chromatograms makes the technique a valuable tool in addition to GC with mass spectrometric and atomic emission detection., Onderzoek is uitgevoerd naar verbetering van de relatieve detectiegrenzen van gaschromatografie met infraroodspectrometrische detectie (GC-IR) door toepassing van zogenaamde large-volume injectie (LVI) technieken. Twee technieken zijn onderzocht, loop-type interfacing en on-column interfacing. Optimalisatie is uitgevoerd met n-alkanen in verschillende oplosmiddelen. Pesticiden, polyaromatische koolwaterstoffen en andere contaminanten zijn gebruikt voor het testen van de bruikbaarheid van het ontwikkelde systeem in de milieu-analyse. Bij 100 ul injecties blijkt de relatieve detecteerbaarheid van de niet vluchtige analieten in vergelijking met 1 ul split/splitless injecties, voor beide typen interfacing vrijwel evenredig toe te nemen met het geinjecteerde volume. Bij injectie van grotere volumes (200-400 ul) wordt de winst in relatieve gevoeligheid gedeeltelijk teniet gedaan door verontreinigingen in het oplosmiddel. De prestaties van de on-column interfacing zijn relatief beter door het geringere verlies aan vluchtige componenten en de inbouw van een detector-schakelsysteem. De praktische mogelijkheden van LVI-GC-IR worden gedemonstreerd aan de hand van de analyse van enkele monsters drink- en oppervlaktewater waaraan veel voorkomende contaminanten zijn toegevoegd op een niveau van 0.1-1 ug/l. De toegevoegde componenten zijn gedetecteerd en geidentificeerd (i) via injectie van extracten verkregen via vloeistof-vloeistof extractie en (ii) door on-line desorptie van elders bemonsterde solid phase extracted (SPE) cartridges. De mogelijkheid van (LVI-)GC-IR om door middel van functionele groepschromatogrammen te screenen op de aanwezigheid van specifieke stofklassen is een waardevolle aanvulling op gaschromatografie met massaspectrometrische en atoomemissie detectie.

RIVM rapport:Onderzoek is uitgevoerd naar verbetering van de relatieve detectiegrenzen van gaschromatografie met infraroodspectrometrische detectie (GC-IR) door toepassing van zogenaamde large-volume injectie (LVI) technieken. Twee technieken zijn onderzocht, loop-type interfacing en on-column interfacing. Optimalisatie is uitgevoerd met n-alkanen in verschillende oplosmiddelen. Pesticiden, polyaromatische koolwaterstoffen en andere contaminanten zijn gebruikt voor het testen van de bruikbaarheid van het ontwikkelde systeem in de milieu-analyse. Bij 100 ul injecties blijkt de relatieve detecteerbaarheid van de niet vluchtige analieten in vergelijking met 1 ul split/splitless injecties, voor beide typen interfacing vrijwel evenredig toe te nemen met het geinjecteerde volume. Bij injectie van grotere volumes (200-400 ul) wordt de winst in relatieve gevoeligheid gedeeltelijk teniet gedaan door verontreinigingen in het oplosmiddel. De prestaties van de on-column interfacing zijn relatief beter door het geringere verlies aan vluchtige componenten en de inbouw van een detector-schakelsysteem. De praktische mogelijkheden van LVI-GC-IR worden gedemonstreerd aan de hand van de analyse van enkele monsters drink- en oppervlaktewater waaraan veel voorkomende contaminanten zijn toegevoegd op een niveau van 0.1-1 ug/l. De toegevoegde componenten zijn gedetecteerd en geidentificeerd (i) via injectie van extracten verkregen via vloeistof-vloeistof extractie en (ii) door on-line desorptie van elders bemonsterde solid phase extracted (SPE) cartridges. De mogelijkheid van (LVI-)GC-IR om door middel van functionele groepschromatogrammen te screenen op de aanwezigheid van specifieke stofklassen is een waardevolle aanvulling op gaschromatografie met massaspectrometrische en atoomemissie detectie., Research has been carried out to enlarge the analyte detectability of gaschromatography with infrared spectrometric detection (GC-IR) by techniques that allow injection of large volumes of liquid samples (100 ul typical). Two techniques have been investigated; loop-type and on-column interfacing. Alkanes dissolved in various solvents have been used for optimisation. Pesticides, polyaromatic hydrocarbons and other micro-contaminants have been used to test the usefulness of the eveloped system in environmental trace analysis. The increase in analyte detectability of high boiling compounds compared to conventional 1 ul split/splitless injection is almost proportional to the injected volume for injection of 100 ul. At larger sample volumes, the increase of the relative sensitivity is partly detracted by impurities of the solvent. The performance of the on-column interface is better due to the reduced loss of volatiles and the incorporation of a detector switching module that minimizes interfering solvent condensation in the IR detection interface. The potentials of LVI-GC-IR are demonstrated by the analysis of samples of drinking and surface water spiked at levels of 0.1-1 ug/l with components that commonly occur as micro-contaminants. Analytes have been detected and identified (i) by direct injection of solutions obtained by liquid-liquid extraction and (ii) by on-line desorption of at site sampled solid phase extracted cartridges. The possibility of (LVI-)GC-IR of selective screening on the prescence of specific compound classes by means of functional group chromatograms makes the technique a valuable tool in addition to GC with mass spectrometric and atomic emission detection.

RIVM rapport:Research has been carried out to enlarge the analyte detectability of gaschromatography with infrared spectrometric detection (GC-IR) by techniques that allow injection of large volumes of liquid samples (100 ul typical). Two techniques have been investigated; loop-type and on-column interfacing. Alkanes dissolved in various solvents have been used for optimisation. Pesticides, polyaromatic hydrocarbons and other micro-contaminants have been used to test the usefulness of the eveloped system in environmental trace analysis. The increase in analyte detectability of high boiling compounds compared to conventional 1 ul split/splitless injection is almost proportional to the injected volume for injection of 100 ul. At larger sample volumes, the increase of the relative sensitivity is partly detracted by impurities of the solvent. The performance of the on-column interface is better due to the reduced loss of volatiles and the incorporation of a detector switching module that minimizes interfering solvent condensation in the IR detection interface. The potentials of LVI-GC-IR are demonstrated by the analysis of samples of drinking and surface water spiked at levels of 0.1-1 ug/l with components that commonly occur as micro-contaminants. Analytes have been detected and identified (i) by direct injection of solutions obtained by liquid-liquid extraction and (ii) by on-line desorption of at site sampled solid phase extracted cartridges. The possibility of (LVI-)GC-IR of selective screening on the prescence of specific compound classes by means of functional group chromatograms makes the technique a valuable tool in addition to GC with mass spectrometric and atomic emission detection., Onderzoek is uitgevoerd naar verbetering van de relatieve detectiegrenzen van gaschromatografie met infraroodspectrometrische detectie (GC-IR) door toepassing van zogenaamde large-volume injectie (LVI) technieken. Twee technieken zijn onderzocht, loop-type interfacing en on-column interfacing. Optimalisatie is uitgevoerd met n-alkanen in verschillende oplosmiddelen. Pesticiden, polyaromatische koolwaterstoffen en andere contaminanten zijn gebruikt voor het testen van de bruikbaarheid van het ontwikkelde systeem in de milieu-analyse. Bij 100 ul injecties blijkt de relatieve detecteerbaarheid van de niet vluchtige analieten in vergelijking met 1 ul split/splitless injecties, voor beide typen interfacing vrijwel evenredig toe te nemen met het geinjecteerde volume. Bij injectie van grotere volumes (200-400 ul) wordt de winst in relatieve gevoeligheid gedeeltelijk teniet gedaan door verontreinigingen in het oplosmiddel. De prestaties van de on-column interfacing zijn relatief beter door het geringere verlies aan vluchtige componenten en de inbouw van een detector-schakelsysteem. De praktische mogelijkheden van LVI-GC-IR worden gedemonstreerd aan de hand van de analyse van enkele monsters drink- en oppervlaktewater waaraan veel voorkomende contaminanten zijn toegevoegd op een niveau van 0.1-1 ug/l. De toegevoegde componenten zijn gedetecteerd en geidentificeerd (i) via injectie van extracten verkregen via vloeistof-vloeistof extractie en (ii) door on-line desorptie van elders bemonsterde solid phase extracted (SPE) cartridges. De mogelijkheid van (LVI-)GC-IR om door middel van functionele groepschromatogrammen te screenen op de aanwezigheid van specifieke stofklassen is een waardevolle aanvulling op gaschromatografie met massaspectrometrische en atoomemissie detectie.

Contains fulltext : 24855___.PDF (publisher's version ) (Open Access)

RIVM rapport:Onderzoek is uitgevoerd naar verbetering van de relatieve detectiegrenzen van gaschromatografie met infraroodspectrometrische detectie (GC-IR) door toepassing van zogenaamde large-volume injectie (LVI) technieken. Twee technieken zijn onderzocht, loop-type interfacing en on-column interfacing. Optimalisatie is uitgevoerd met n-alkanen in verschillende oplosmiddelen. Pesticiden, polyaromatische koolwaterstoffen en andere contaminanten zijn gebruikt voor het testen van de bruikbaarheid van het ontwikkelde systeem in de milieu-analyse. Bij 100 ul injecties blijkt de relatieve detecteerbaarheid van de niet vluchtige analieten in vergelijking met 1 ul split/splitless injecties, voor beide typen interfacing vrijwel evenredig toe te nemen met het geinjecteerde volume. Bij injectie van grotere volumes (200-400 ul) wordt de winst in relatieve gevoeligheid gedeeltelijk teniet gedaan door verontreinigingen in het oplosmiddel. De prestaties van de on-column interfacing zijn relatief beter door het geringere verlies aan vluchtige componenten en de inbouw van een detector-schakelsysteem. De praktische mogelijkheden van LVI-GC-IR worden gedemonstreerd aan de hand van de analyse van enkele monsters drink- en oppervlaktewater waaraan veel voorkomende contaminanten zijn toegevoegd op een niveau van 0.1-1 ug/l. De toegevoegde componenten zijn gedetecteerd en geidentificeerd (i) via injectie van extracten verkregen via vloeistof-vloeistof extractie en (ii) door on-line desorptie van elders bemonsterde solid phase extracted (SPE) cartridges. De mogelijkheid van (LVI-)GC-IR om door middel van functionele groepschromatogrammen te screenen op de aanwezigheid van specifieke stofklassen is een waardevolle aanvulling op gaschromatografie met massaspectrometrische en atoomemissie detectie., Research has been carried out to enlarge the analyte detectability of gaschromatography with infrared spectrometric detection (GC-IR) by techniques that allow injection of large volumes of liquid samples (100 ul typical). Two techniques have been investigated; loop-type and on-column interfacing. Alkanes dissolved in various solvents have been used for optimisation. Pesticides, polyaromatic hydrocarbons and other micro-contaminants have been used to test the usefulness of the eveloped system in environmental trace analysis. The increase in analyte detectability of high boiling compounds compared to conventional 1 ul split/splitless injection is almost proportional to the injected volume for injection of 100 ul. At larger sample volumes, the increase of the relative sensitivity is partly detracted by impurities of the solvent. The performance of the on-column interface is better due to the reduced loss of volatiles and the incorporation of a detector switching module that minimizes interfering solvent condensation in the IR detection interface. The potentials of LVI-GC-IR are demonstrated by the analysis of samples of drinking and surface water spiked at levels of 0.1-1 ug/l with components that commonly occur as micro-contaminants. Analytes have been detected and identified (i) by direct injection of solutions obtained by liquid-liquid extraction and (ii) by on-line desorption of at site sampled solid phase extracted cartridges. The possibility of (LVI-)GC-IR of selective screening on the prescence of specific compound classes by means of functional group chromatograms makes the technique a valuable tool in addition to GC with mass spectrometric and atomic emission detection.

RIVM rapport:Research has been carried out to enlarge the analyte detectability of gaschromatography with infrared spectrometric detection (GC-IR) by techniques that allow injection of large volumes of liquid samples (100 ul typical). Two techniques have been investigated; loop-type and on-column interfacing. Alkanes dissolved in various solvents have been used for optimisation. Pesticides, polyaromatic hydrocarbons and other micro-contaminants have been used to test the usefulness of the eveloped system in environmental trace analysis. The increase in analyte detectability of high boiling compounds compared to conventional 1 ul split/splitless injection is almost proportional to the injected volume for injection of 100 ul. At larger sample volumes, the increase of the relative sensitivity is partly detracted by impurities of the solvent. The performance of the on-column interface is better due to the reduced loss of volatiles and the incorporation of a detector switching module that minimizes interfering solvent condensation in the IR detection interface. The potentials of LVI-GC-IR are demonstrated by the analysis of samples of drinking and surface water spiked at levels of 0.1-1 ug/l with components that commonly occur as micro-contaminants. Analytes have been detected and identified (i) by direct injection of solutions obtained by liquid-liquid extraction and (ii) by on-line desorption of at site sampled solid phase extracted cartridges. The possibility of (LVI-)GC-IR of selective screening on the prescence of specific compound classes by means of functional group chromatograms makes the technique a valuable tool in addition to GC with mass spectrometric and atomic emission detection., Onderzoek is uitgevoerd naar verbetering van de relatieve detectiegrenzen van gaschromatografie met infraroodspectrometrische detectie (GC-IR) door toepassing van zogenaamde large-volume injectie (LVI) technieken. Twee technieken zijn onderzocht, loop-type interfacing en on-column interfacing. Optimalisatie is uitgevoerd met n-alkanen in verschillende oplosmiddelen. Pesticiden, polyaromatische koolwaterstoffen en andere contaminanten zijn gebruikt voor het testen van de bruikbaarheid van het ontwikkelde systeem in de milieu-analyse. Bij 100 ul injecties blijkt de relatieve detecteerbaarheid van de niet vluchtige analieten in vergelijking met 1 ul split/splitless injecties, voor beide typen interfacing vrijwel evenredig toe te nemen met het geinjecteerde volume. Bij injectie van grotere volumes (200-400 ul) wordt de winst in relatieve gevoeligheid gedeeltelijk teniet gedaan door verontreinigingen in het oplosmiddel. De prestaties van de on-column interfacing zijn relatief beter door het geringere verlies aan vluchtige componenten en de inbouw van een detector-schakelsysteem. De praktische mogelijkheden van LVI-GC-IR worden gedemonstreerd aan de hand van de analyse van enkele monsters drink- en oppervlaktewater waaraan veel voorkomende contaminanten zijn toegevoegd op een niveau van 0.1-1 ug/l. De toegevoegde componenten zijn gedetecteerd en geidentificeerd (i) via injectie van extracten verkregen via vloeistof-vloeistof extractie en (ii) door on-line desorptie van elders bemonsterde solid phase extracted (SPE) cartridges. De mogelijkheid van (LVI-)GC-IR om door middel van functionele groepschromatogrammen te screenen op de aanwezigheid van specifieke stofklassen is een waardevolle aanvulling op gaschromatografie met massaspectrometrische en atoomemissie detectie.