119 research outputs found
Stretched Exponential Relaxation in the Biased Random Voter Model
We study the relaxation properties of the voter model with i.i.d. random
bias. We prove under mild condions that the disorder-averaged relaxation of
this biased random voter model is faster than a stretched exponential with
exponent , where depends on the transition rates
of the non-biased voter model. Under an additional assumption, we show that the
above upper bound is optimal. The main ingredient of our proof is a result of
Donsker and Varadhan (1979).Comment: 14 pages, AMS-LaTe
The roles of the general practitioner and sexual health centre in HIV testing:comparative insights and impact on HIV incidence rates in the Rotterdam area, the Netherlands - a cross-sectional population-based study
Background: Access to HIV testing is crucial for detection, linkage to treatment, and prevention. In less urbanised areas, reliance on general practitioners (GPs) for HIV testing is probable, as sexual health centres (SHC) are mostly located within urbanised areas. Limited insight into individuals undergoing HIV testing stems from sparse standard registration of demographics at GPs. This cross-sectional study aims (1) to assess and compare HIV testing at the GP and SHC, and (2) to assess population- and provider-specific HIV incidence. Methods: Individual HIV testing data of GPs and SHC were linked to population register data (aged ≥ 15 years, Rotterdam area, 2015–2019). We reported the proportion HIV tested, and compared GP and SHC testing rates with negative binomial generalised additive models. Data on new HIV diagnoses (2015–2019) from the Dutch HIV Monitoring Foundation relative to the population were used to assess HIV incidence. Results: The overall proportion HIV tested was 1.14% for all residents, ranging from 0.41% for ≥ 40-year-olds to 4.70% for Antilleans. The GP testing rate was generally higher than the SHC testing rate with an overall rate ratio (RR) of 1.61 (95% CI: 1.56–1.65), but not for 15-24-year-olds (RR: 0.81, 95% CI: 0.74–0.88). Large differences in HIV testing rate (1.36 to 39.47 per 1,000 residents) and GP-SHC ratio (RR: 0.23 to 7.24) by geographical area were observed. The GPs’ contribution in HIV testing was greater for GP in areas further away from the SHC. In general, population groups that are relatively often tested are also the groups with most diagnoses and highest incidence (e.g., men who have sex with men, non-western). The overall incidence was 10.55 per 100,000 residents, varying from 3.09 for heterosexual men/women to 24.04 for 25–29-year-olds. Conclusions: GPs have a pivotal role in HIV testing in less urbanised areas further away from the SHC, and among some population groups. A relatively high incidence often follows relatively high testing rates. Opportunities to improve HIV testing have been found for migrants, lower-educated individuals, in areas less urbanised areas and further away from GP/SHC. Strategies include additional targeted testing, via for example SHC branch locations and outreach activities.</p
In vivo synergistic interaction of liposome-coencapsulated gentamicin and ceftazidime
Antimicrobial agents may interact synergistically. But to ensure synergy
in vivo, the drugs should both be present at the site of infection at
sufficiently high concentrations for an adequate period of time.
Coencapsulation of the drugs in a drug carrier may ensure parallel tissue
distributions. Since liposomes localize preferentially at sites of
infection, this mode of drug delivery could, in addition, increase drug
concentrations at the focus of infection. The therapeutic efficacy of
gentamicin and ceftazidime coencapsulated into liposomes was examined by
monitoring survival in a rat model of an acute unilateral pneumonia caused
by antibiotic-susceptible and antibiotic-resistant Klebsiella pneumoniae
strains. It is shown that administration of gentamicin in combination with
ceftazidime in the free form either as single dose or as 5-day treatment
resulted in an additive effect on rat survival in both models. In
contrast, targeted delivery of liposome-coencapsulated gentamicin and
ceftazidime resulted in a synergistic interaction of the antibiotics in
both models. Consequently, liposome coencapsulation of gentamicin and
ceftazidime allowed both a shorter course of treatment at lower cumulative
doses compared with administration of the antibiotics in the free form to
obtain complete survival of rats. Liposomal coencapsulation of synergistic
antibiotics may open new perspectives in the treatment of severe
infections
Nontuberculous Mycobacterium Infection and Tumor Necrosis Factor-α Antagonists
Contains fulltext :
144010.pdf (publisher's version ) (Open Access)1 oktober 200
Dolutegravir/Lamivudine Is Noninferior to Continuing Dolutegravir- and Non-Dolutegravir-Based Triple-Drug Antiretroviral Therapy in Virologically Suppressed People With Human Immunodeficiency Virus:DUALING Prospective Nationwide Matched Cohort Study
Background. Confirming the efficacy of dolutegravir/lamivudine in clinical practice solidifies recommendations on its use. Methods. Prospective cohort study (DUALING) in 24 human immunodeficiency virus (HIV) treatment centers in the Netherlands. HIV RNA–suppressed cases were on triple-drug antiretroviral regimens without prior virological failure or resistance and started dolutegravir/lamivudine. Cases were 1:2 matched to controls on triple-drug antiretroviral regimens by the use of dolutegravir-based regimens, age, sex, transmission route, CD4+ T-cell nadir, and HIV RNA zenith. The primary endpoint was the treatment failure rate in cases versus controls at 1 year by intention-to-treat and on-treatment analyses with 5% noninferiority margin. Results. The 2040 participants were 680 cases and 1380 controls. Treatment failure in the 390 dolutegravir-based cases versus controls occurred in 8.72% and 12.50% (difference: −3.78% [95% confidence interval {CI}, −7.49% to .08%]) by intention-to-treat and 1.39% and 0.80% (difference: 0.59% [95% CI, –.80% to 1.98%]) by on-treatment analyses. The treatment failure risk in 290 non-dolutegravir-based cases was also noninferior to controls. Antiretroviral regimen modifications unrelated to virological failure explained the higher treatment failure rate by intention-to-treat. A shorter time on triple-drug antiretroviral therapy and being of non-Western origin was associated with treatment failure. Treatment failure, defined as 2 consecutive HIV RNA >50 copies/mL, occurred in 4 cases and 5 controls but without genotypic resistance detected. Viral blips occured comparable in cases and controls but cases gained more weight, especially when tenofovir-based regimens were discontinued. Conclusions. In routine care, dolutegravir/lamivudine was noninferior to continuing triple-drug antiretroviral regimens after 1 year, supporting the use of dolutegravir/lamivudine in clinical practice.</p
Dolutegravir/Lamivudine Is Noninferior to Continuing Dolutegravir- and Non-Dolutegravir-Based Triple-Drug Antiretroviral Therapy in Virologically Suppressed People With Human Immunodeficiency Virus:DUALING Prospective Nationwide Matched Cohort Study
Background. Confirming the efficacy of dolutegravir/lamivudine in clinical practice solidifies recommendations on its use. Methods. Prospective cohort study (DUALING) in 24 human immunodeficiency virus (HIV) treatment centers in the Netherlands. HIV RNA–suppressed cases were on triple-drug antiretroviral regimens without prior virological failure or resistance and started dolutegravir/lamivudine. Cases were 1:2 matched to controls on triple-drug antiretroviral regimens by the use of dolutegravir-based regimens, age, sex, transmission route, CD4+ T-cell nadir, and HIV RNA zenith. The primary endpoint was the treatment failure rate in cases versus controls at 1 year by intention-to-treat and on-treatment analyses with 5% noninferiority margin. Results. The 2040 participants were 680 cases and 1380 controls. Treatment failure in the 390 dolutegravir-based cases versus controls occurred in 8.72% and 12.50% (difference: −3.78% [95% confidence interval {CI}, −7.49% to .08%]) by intention-to-treat and 1.39% and 0.80% (difference: 0.59% [95% CI, –.80% to 1.98%]) by on-treatment analyses. The treatment failure risk in 290 non-dolutegravir-based cases was also noninferior to controls. Antiretroviral regimen modifications unrelated to virological failure explained the higher treatment failure rate by intention-to-treat. A shorter time on triple-drug antiretroviral therapy and being of non-Western origin was associated with treatment failure. Treatment failure, defined as 2 consecutive HIV RNA >50 copies/mL, occurred in 4 cases and 5 controls but without genotypic resistance detected. Viral blips occured comparable in cases and controls but cases gained more weight, especially when tenofovir-based regimens were discontinued. Conclusions. In routine care, dolutegravir/lamivudine was noninferior to continuing triple-drug antiretroviral regimens after 1 year, supporting the use of dolutegravir/lamivudine in clinical practice.</p
Serial FLT PET imaging to discriminate between true progression and pseudoprogression in patients with newly diagnosed glioblastoma:a long-term follow-up study
Purpose: Response evaluation in patients with glioblastoma after chemoradiotherapy is challenging due to progressive, contrast-enhancing lesions on MRI that do not reflect true tumour progression. In this study, we prospectively evaluated the ability of the PET tracer 18F-fluorothymidine (FLT), a tracer reflecting proliferative activity, to discriminate between true progression and pseudoprogression in newly diagnosed glioblastoma patients treated with chemoradiotherapy. Methods: FLT PET and MRI scans were performed before and 4 weeks after chemoradiotherapy. MRI scans were also performed after three cycles of adjuvant temozolomide. Pseudoprogression was defined as progressive disease on MRI after chemoradiotherapy with stabilisation or reduction of contrast-enhanced lesions after three cycles of temozolomide, and was compared with the disease course during long-term follow-up. Changes in maximum standardized uptake value (SUVmax) and tumour-to-normal uptake ratios were calculated for FLT and are presented as the mean SUVmax for multiple lesions. Results: Between 2009 and 2012, 30 patients were included. Of 24 evaluable patients, 7 showed pseudoprogression and 7 had true progression as defined by MRI response. FLT PET parameters did not significantly differ between patients with true progression and pseudoprogression defined by MRI. The correlation between change in SUVmax and survival (p = 0.059) almost reached the standard level of statistical significance. Lower baseline FLT PET uptake was significantly correlated with improved survival (p = 0.022). Conclusion: Baseline FLT uptake appears to be predictive of overall survival. Furthermore, changes in SUVmax over time showed a tendency to be associated with improved survival. However, further studies are necessary to investigate the ability of FLT PET imaging to discriminate between true progression and pseudoprogression in patients with glioblastoma
Within-host and population transmission of blaOXA-48 in K. pneumoniae and E. coli
During a large hospital outbreak of OXA-48 producing bacteria, most K. pneumoniaeOXA-48 isolates were phenotypically resistant to meropenem or imipenem, whereas most E. coliOXA-48 isolates were phenotypically susceptible to these antibiotics. In the absence of molecular gene-detection E. coliOXA-48 could remain undetected, facilitating cross-transmission and horizontal gene transfer of blaOXA-48. Based on 868 longitudinal molecular microbiological screening results from patients carrying K. pneumoniaeOXA-48 (n = 24), E. coliOXA-48 (n = 17), or both (n = 40) and mathematical modelling we determined mean durations of colonisation (278 and 225 days for K. pneumoniaeOXA-48 and E. coliOXA-48, respectively), and horizontal gene transfer rates (0.0091/day from K. pneumoniae to E. coli and 0.0015/day vice versa). Based on these findings the maximum effect of horizontal gene transfer of blaOXA-48 originating from E. coliOXA-48 on the basic reproduction number (R0) is 1.9%, and it is, therefore, unlikely that phenotypically susceptible E. coliOXA-48 will contribute significantly to the spread of blaOXA-48. Copyright
Improved CARMA Locality Estimation Model for Peer List Reordering and Its Experimental Validation
The improvement of CARMA network model by addition of locality flavor as well as IPv6 support are concerned. The direct experimental evidence of the improvement of the efficiency of the peer-to-peer networks in terms of the network throughput using previously proposed CARMA locality awareness methods is established. The possible influences of the dynamics of the number of seeding and peering nodes in a swarm (including those directly connected to the test rig) are analyzed and taken into account. Main results indicate average 2,5 % improvement in transfer speed in comparison with clean unbiased transfer modes.Розглянуто вдосконалену реалізацію моделі CARMA, до якої додано новий клас локальності та обґрунтовано включення підтримки новітнього протоколу IPv6; також отримано пряме експериментальне підтвердження підвищення ефективності однорангових мереж із використанням попередньої версії оцінки локальності за моделлю CARMA. Проаналізовано та враховано вплив динаміки кількості завершених і незавершених вузлів у рої (включаючи ті, що прямо зв’язані з експериментальним стендом). Результати експериментів свідчать про підвищення середньої швидкості передачі на 2,5 % порівняно з немодифікованим режимом передачі.Рассмотрена усовершенствованная реализация модели CARMA, в которую добавлен новый класс локальности и обосновано включение поддержки новейшего протокола IPv6; также получено прямое экспериментальное подтверждение повышения эффективности одноранговых сетей с использованием предварительной версии оценки локальности по модели CARMA. Проанализировано и учтено влияние динамики количества завершенных и незавершенных узлов в рое (включая те, которые прямо связаны с экспериментальным стендом). Результаты экспериментов свидетельствуют о повышении средней скорости передачи на 2,5 % в сравнении с немодифицированным режимом передачи
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