PCR detection of Burkholderia multivorans in water and soil samples

Background: Although semi-selective growth media have been developed for the isolation of Burkholderia cepacia complex bacteria from the environment, thus far Burkholderia multivorans has rarely been isolated from such samples. Because environmental B. multivorans isolates mainly originate from water samples, we hypothesized that water rather than soil is its most likely environmental niche. The aim of the present study was to assess the occurrence of B. multivorans in water samples from Flanders (Belgium) using a fast, culture-independent PCR assay. Results: A nested PCR approach was used to achieve high sensitivity, and specificity was confirmed by sequencing the resulting amplicons. B. multivorans was detected in 11 % of the water samples (n = 112) and 92 % of the soil samples (n = 25) tested. The percentage of false positives was higher for water samples compared to soil samples, showing that the presently available B. multivorans recA primers lack specificity when applied to the analysis of water samples. Conclusions: The results of the present study demonstrate that B. multivorans DNA is commonly present in soil samples and to a lesser extent in water samples in Flanders (Belgium)

Retention of Physician Assistants within a Specialty after Completion of a Postgraduate Training Program

Background: The advantages of a specialized training program have led to over 84 postgraduate training programs for Physician Assistants (PAs) covering over 25 specialties. Employee lateral mobility is more prevalent within the PA profession, which allows PA providers to switch between medical specialties. The versatility of PAs promotes higher turnover rates compared to physician counterparts. These high turnover rates can result in increased institutional burden. Postgraduate PA programs provide pre-employment exposure to more in-depth medical training, enabling a well-rounded knowledge base of the PA’s roles and responsibilities, minimizing turnover rates. Purpose: The goal of this survey study is to identify PA graduates’ perceptions of their retention rate, job satisfaction within a given specialty, factors influencing a PA’s decision to change their specialty, and specialty preparation provided by postgraduate training programs and specific educational training. Methods: A mixed method design was utilized to survey both program directors and graduates of PA postgraduate training programs. Results: Of the 398 postgraduate program graduates, 196 (49%) accepted a job within the institution where they trained. Across all postgraduate training programs, 87% of graduates have not changed their specialty since program completion. Ninety-six percent of respondents felt their postgraduate training gave them an accurate preview of employment in their specialty of interest, and all postgraduates would recommend a postgraduate training program to a new PA graduate

On the spectral problem of N=4 SYM with orthogonal or symplectic gauge group

We study the spectral problem of N=4 SYM with gauge group SO(N) and Sp(N). At the planar level, the difference to the case of gauge group SU(N) is only due to certain states being projected out, however at the non-planar level novel effects appear: While 1/N-corrections in the SU(N) case are always associated with splitting and joining of spin chains, this is not so for SO(N) and Sp(N). Here the leading 1/N-corrections, which are due to non-orientable Feynman diagrams in the field theory, originate from a term in the dilatation operator which acts inside a single spin chain. This makes it possible to test for integrability of the leading 1/N-corrections by standard (Bethe ansatz) means and we carry out various such tests. For orthogonal and symplectic gauge group the dual string theory lives on the orientifold AdS5xRP5. We discuss various issues related to semi-classical strings on this background.Comment: 25 pages, 3 figures. v2: Minor clarifications, section 5 expande

Plasma proteome profiling identifies changes associated to AD but not to FTD

Background Frontotemporal dementia (FTD) is caused by frontotemporal lobar degeneration (FTLD), characterized mainly by inclusions of Tau (FTLD-Tau) or TAR DNA binding43 (FTLD-TDP) proteins. Plasma biomarkers are strongly needed for specific diagnosis and potential treatment monitoring of FTD. We aimed to identify specific FTD plasma biomarker profiles discriminating FTD from AD and controls, and between FTD pathological subtypes. In addition, we compared plasma results with results in post-mortem frontal cortex of FTD cases to understand the underlying process. Methods Plasma proteins (n = 1303) from pathologically and/or genetically confirmed FTD patients (n = 56; FTLD-Tau n = 16; age = 58.2 +/- 6.2; 44% female, FTLD-TDP n = 40; age = 59.8 +/- 7.9; 45% female), AD patients (n = 57; age = 65.5 +/- 8.0; 39% female), and non-demented controls (n = 148; 61.3 +/- 7.9; 41% female) were measured using an aptamer-based proteomic technology (SomaScan). In addition, exploratory analysis in post-mortem frontal brain cortex of FTD (n = 10; FTLD-Tau n = 5; age = 56.2 +/- 6.9, 60% female, and FTLD-TDP n = 5; age = 64.0 +/- 7.7, 60% female) and non-demented controls (n = 4; age = 61.3 +/- 8.1; 75% female) were also performed. Differentially regulated plasma and tissue proteins were identified by global testing adjusting for demographic variables and multiple testing. Logistic lasso regression was used to identify plasma protein panels discriminating FTD from non-demented controls and AD, or FTLD-Tau from FTLD-TDP. Performance of the discriminatory plasma protein panels was based on predictions obtained from bootstrapping with 1000 resampled analysis. Results Overall plasma protein expression profiles differed between FTD, AD and controls (6 proteins; p = 0.005), but none of the plasma proteins was specifically associated to FTD. The overall tissue protein expression profile differed between FTD and controls (7-proteins; p = 0.003). There was no difference in overall plasma or tissue expression profile between FTD subtypes. Regression analysis revealed a panel of 12-plasma proteins discriminating FTD from AD with high accuracy (AUC: 0.99). No plasma protein panels discriminating FTD from controls or FTD pathological subtypes were identified. Conclusions We identified a promising plasma protein panel as a minimally-invasive tool to aid in the differential diagnosis of FTD from AD, which was primarily associated to AD pathophysiology. The lack of plasma profiles specifically associated to FTD or its pathological subtypes might be explained by FTD heterogeneity, calling for FTD studies using large and well-characterize cohorts

Re-imagining malaria: heterogeneity of human and mosquito behaviour in relation to residual malaria transmission in Cambodia

BackgroundIn certain regions in Southeast Asia, where malaria is reduced to forested regions populated by ethnic minorities dependent on slash-and-burn agriculture, malaria vector populations have developed a propensity to feed early and outdoors, limiting the effectiveness of long-lasting insecticide-treated nets (LLIN) and indoor residual spraying (IRS). The interplay between heterogeneous human, as well as mosquito behaviour, radically challenges malaria control in such residual transmission contexts. This study examines human behavioural patterns in relation to the vector behaviour.MethodsThe anthropological research used a sequential mixed-methods study design in which quantitative survey research methods were used to complement findings from qualitative ethnographic research. The qualitative research existed of in-depth interviews and participant observation. For the entomological research, indoor and outdoor human landing collections were performed. All research was conducted in selected villages in Ratanakiri province, Cambodia.ResultsVariability in human behaviour resulted in variable exposure to outdoor and early biting vectors: (i) indigenous people were found to commute between farms in the forest, where malaria exposure is higher, and village homes; (ii) the indoor/outdoor biting distinction was less clear in forest housing often completely or partly open to the outside; (iii) reported sleeping times varied according to the context of economic activities, impacting on the proportion of infections that could be accounted for by early or nighttime biting; (iv) protection by LLINs may not be as high as self-reported survey data indicate, as observations showed around 40% (non-treated) market net use while (v) unprotected evening resting and deep forest activities impacted further on the suboptimal use of LLINs.ConclusionsThe heterogeneity of human behaviour and the variation of vector densities and biting behaviours may lead to a considerable proportion of exposure occurring during times that people are assumed to be protected by the distributed LLINs. Additional efforts in improving LLIN use during times when people are resting in the evening and during the night might still have an impact on further reducing malaria transmission in Cambodia

‘Some anti-malarials are too strong for your body, they will harm you.’ Socio-cultural factors influencing pregnant women’s adherence to anti-malarial treatment in rural Gambia

Background Despite declining prevalence of malaria in The Gambia, non-adherence to anti-malarial treatment still remains a challenge to control efforts. There is limited evidence on the socio-cultural factors that influence adherence to anti-malarial treatment in pregnancy. This study explored perceptions of malaria in pregnancy and their influence on adherence to anti-malarial treatment in a rural area of The Gambia. Methods An exploratory ethnographic study was conducted ancillary to a cluster-randomized trial on scheduled screening and treatment of malaria in pregnancy at village level in the Upper River Region of The Gambia from June to August 2014. Qualitative data were collected through interviewing and participant observation. Analysis was concurrent to data collection and carried out using NVivo 10. Results Although women had good bio-medical knowledge of malaria in pregnancy, adherence to anti-malarial treatment was generally perceived to be low. Pregnant women were perceived to discontinue the provided anti-malarial treatment after one or 2 days mainly due to non-recognition of symptoms, perceived ineffectiveness of the anti-malarial treatment, the perceived risks of medication and advice received from mothers-in-law. Conclusion Improving women’s knowledge of malaria in pregnancy is not sufficient to assure adherence to anti-malarial treatment. Addressing structural barriers such as unclear health workers’ messages about medication dosage, illness recognition, side effects of the medication and the integration of relatives, especially the mothers-in-law, in community-based programmes are additionally required

Incidence and outcome of acquired demyelinating syndromes in Dutch children: update of a nationwide and prospective study

Introduction: Acquired demyelinating syndromes (ADS) are immune-mediated demyelinating disorders of the central nervous system in children. A nationwide, multicentre and prospective cohort study was initiated in the Netherlands in 2006, with a reported ADS incidence of 0.66/100,000 per year and MS incidence of 0.15/100,000 per year in the period between 2007 and 2010. In this study, we provide an update on the incidence and the long-term follow-up of ADS in the Netherlands. Methods: Children < 18 years with a first attack of demyelination were included consecutively from January 2006 to December 2016. Diagnoses were based on the International Paediatric MS study group consensus criteria. Outcome data were collected by neurological and neuropsychological assessments, and telephone call assessments. Results: Between 2011 and 2016, 55/165 of the ADS patients were diagnosed with MS (33%). This resulted in an increased ADS and MS incidence of 0.80/100,000 per year and 0.26/100,000 per year, respectively. Since 2006 a total of 243 ADS patients have been included. During follow-up (median 55 months, IQR 28–84), 137 patients were diagnosed with monophasic disease (56%), 89 with MS (37%) and 17 with multiphasic disease other than MS (7%). At least one form of residual deficit including cognitive impairment was observed in 69% of all ADS patients, even in monophasic ADS. An Expanded Disability Status Scale score of ≥ 5.5 was reached in 3/89 MS patients (3%). Conclusion: The reported incidence of ADS in Dutch children has increased since 2010. Residual deficits are common in this group, even in monophasic patients. Therefore, long-term follow-up in ADS patients is warranted

Nucleoside Reverse Transcriptase Inhibitor Resistance Mutations Associated with First-Line Stavudine-Containing Antiretroviral Therapy: Programmatic Implications for Countries Phasing Out Stavudine

Background The World Health Organization Antiretroviral Treatment Guidelines recommend phasing-out stavudine because of its risk of long-term toxicity. There are two mutational pathways of stavudine resistance with different implications for zidovudine and tenofovir cross-resistance, the primary candidates for replacing stavudine. However, because resistance testing is rarely available in resource-limited settings, it is critical to identify the cross-resistance patterns associated with first-line stavudine failure. Methods We analyzed HIV-1 resistance mutations following first-line stavudine failure from 35 publications comprising 1,825 individuals. We also assessed the influence of concomitant nevirapine vs. efavirenz, therapy duration, and HIV-1 subtype on the proportions of mutations associated with zidovudine vs. tenofovir cross-resistance. Results Mutations with preferential zidovudine activity, K65R or K70E, occurred in 5.3% of individuals. Mutations with preferential tenofovir activity, ≥two thymidine analog mutations (TAMs) or Q151M, occurred in 22% of individuals. Nevirapine increased the risk of TAMs, K65R, and Q151M. Longer therapy increased the risk of TAMs and Q151M but not K65R. Subtype C and CRF01_AE increased the risk of K65R, but only CRF01_AE increased the risk of K65R without Q151M. Conclusions Regardless of concomitant nevirapine vs. efavirenz, therapy duration, or subtype, tenofovir was more likely than zidovudine to retain antiviral activity following first-line d4T therap