Abstract
Objective
Sulphadoxine–pyrimethamine (
SP
) is widely used as intermittent preventive treatment (
IPT
) for malaria in pregnant women in Sub‐
S
aharan
A
frica. There are reports of ...wide‐spread
SP
resistance in countries where
SP
had once been used as a first‐line treatment. It is unclear whether the development of
SP
resistance also affects countries where
SP
is mainly used in the context of
IPT
, as is the case in
B
urkina
F
aso. To assess the efficacy of
SP
‐based
IPT
, we monitored the prevalence of
SP
conferring genetic mutations in the genes
dhfr
and
dhps
in
P
lasmodium falciparum
populations in a rural area of
B
urkina
F
aso over a period of 13 years.
Methods
Molecular epidemiological study consisted of six consecutive cross‐sectional surveys of rainy and dry seasons (2009–2012). Data from the rainy season in 2000 served as a baseline. Mutations in
dhfr
and
dhps
associated with
SP
resistance were analysed by pyrosequencing in 861 parasite‐positive samples.
Results
The prevalence of the
SP
resistance conferring triple
dhfr
mutation 51I, 59R, 108N increased from 1.3% in the rainy season of 2000 to 35.3% in 2009, and 54.3% in 2011 (
P
≤ 0.001). Comparing rainy and dry seasons, we observed an increasing step‐like pattern with higher prevalence of the
dhfr
triple mutant in the respective dry season compared with the preceding rainy season. The proportion of the
dhps
437Gly mutation in the rainy season of 2000 was 53.2% and subsequently increased to 77.6% in 2009 (
P
≤ 0.001).
Conclusion
The increase in molecular markers linked with
SP
resistance jeopardises the efficacy of
IPT
p and the planned
IPT
i interventions in
B
urkina
F
aso, calling for careful monitoring of genotypic resistance markers and
in vivo
validation of
IPT
efficacy.
Objectif
Le sulfadoxine‐pyriméthamine (
SP
) est largement utilisé comme traitement préventif intermittent (
TPI
) du paludisme chez les femmes enceintes en Afrique subsaharienne. Il y a des rapports sur la résistance répandue au
SP
dans les pays où il avait autrefois été utilisé comme traitement de première ligne. Il est difficile de savoir si le développement de la résistance au
SP
affecte aussi les pays où il est principalement utilisé dans le contexte du
TPI
, comme par exemple au Burkina‐Faso. Pour évaluer l'efficacité du
TPI
basé sur le
SP
, nous avons surveillé la prévalence des mutations génétiques associées au
SP
dans les gènes
dhfr
et
dhps
dans des populations de
Plasmodium falciparum
dans une zone rurale du Burkina‐Faso sur plus de 13 ans.
Méthodes
Etude d’épidémiologie moléculaire composée de six enquêtes transversales consécutives en saisons sèches et pluvieuses (de 2009 à 2012). Les données de la saison des pluies de 2000 ont servi de base. Les mutations dans
dhfr
et
dhps
associées à la résistance au
SP
ont été analysées par pyroséquençage dans 861 échantillons positifs pour le parasite.
Résultats
La prévalence de la résistance au
SP
associée à une triple mutation
dhfr
(51I, 59R, 108N) a augmenté de 1,3% au cours de la saison des pluies de l'année 2000 à 35,3% en 2009 et à 54,3% en 2011 (p < = 0,001). En comparant la saison des pluies et la saison sèche, nous avons observé un profil d'augmentation par étape avec une prévalence plus élevée des triples mutants
dhfr
en saison sèche par rapport aux saisons des pluies respectives. La proportion des mutations 437Gly dans
dhps
dans la saison des pluies de 2000 était de 53,2% et a par la suite augmenté à 77,6% en 2009 (p < = 0,001).
Conclusion
L'augmentation des marqueurs moléculaires liés à la résistance au
SP
met en péril l'efficacité du programme
TPI
et des interventions
TPI
prévues au Burkina‐Faso, appelant à une surveillance attentive des marqueurs génotypiques de résistance et à la validation in vivo de l'efficacité du
TPI
.
Objetivo
La sulfadoxina‐pirimetamina (
SP
) se utiliza de forma amplia como tratamiento preventivo intermitente (
IPT
) para la malaria en mujeres embarazadas en África subsahariana. Hay informes sobre la amplia diseminación de la resistencia a
SP
en países en donde se había utilizado alguna vez como primera línea de tratamiento. No está claro si el desarrollo de la resistencia a
SP
también afecta a países en donde la
SP
se utiliza principalmente dentro del contexto del
IPT
, como es el caso de Burkina Faso. Para evaluar la eficacia del
IPT
basado en
SP
, hemos monitorizado la prevalencia de mutaciones genéticas inducidas por
SP
en los genes
dhfr
y
dhps
en poblaciones de
Plasmodium falciparum
en un área rural de Burkina Faso en los últimos 13 años.
Métodos
Estudio de epidemiología molecular que consistió en seis estudios croseccionales consecutivos, durante épocas de lluvia y secas (2009‐2012). Los datos de la época de lluvias en el 2000 sirvieron de base. Las mutaciones en
dhfr
y
dhps
asociadas con resistencia a
SP
se analizaron mediante pirosecuenciación en 861 muestras positivas para parásitos.
Resultados
La prevalencia de resistencia a
SP
por una triple mutación en
dhfr
51I, 59R, 108N aumentó del 1.3% en la época de lluvias del 2000 al 35.3% en 2009, y 54.3% en el 2011 (p<= 0.001). Comparando la época de lluvias y la época seca hemos observado un patrón incremental escalonado con una mayor prevalencia del triple mutante
dhfr
en la época seca respectiva, comparado con la época lluviosa precedente. La proporción de la mutación
dhps
437Gly durante la época lluviosa del 2000 era del 53.2% y aumentó después al 77.6% en el 2009 (p< =0.001).
Conclusión
El aumento en marcadores moleculares relacionado con la resistencia al
SP
pone en peligro la eficacia del
IPT
p y las intervenciones de
IPT
i planeadas en Burkina Faso, requiriendo una monitorización cuidadosa de los marcadores genotípicos de resistencia y la validación
in vivo
de la eficacia del
IPT
.
Full text
Available for:
FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The prevalence of calcified cysts and the significance of calcification as a sign of cyst inactivity in cystic echinococcosis (CE) was evaluated. Seventy-eight patients (36 females, 42 males, mean ...age 40.8 +/- 16.9 years) with CE, having a total of 137 abdominal cysts (116 hepatic, three splenic, one renal and 17 peritoneal cysts), were diagnosed and followed-up by ultrasound during and after albendazole treatment or as part of the watch-and-wait approach recording changes in the cyst wall and content. In 48 patients with 94 cysts, computed tomography (CT) imaging was additionally available and was correlated with ultrasound findings. Cyst wall calcification was classified into (1) "sprinkled", (2) "eggshell-like", and (3) "circular". Calcification of the cyst wall and/or cyst content was detected in 67 echinococcal cysts (48.9% of all cysts) in 39 patients (15 females, 24 males, mean age 40.8 +/- 14.8 years). Of the total of 67 calcified cysts, only 23 were compatible with WHO type CE5, 18 with WHO type CE4. Judged by cyst content, the remaining 26 were of WHO type CE1, CE2 and CE3 (n = 1, n = 8, and n = 17, respectively). During a mean period of 34.3 months (+/- 21.3 months) the majority of cysts (n = 32) did not exhibit any change in cyst content and wall properties. Fourteen cysts showed signs of progressive involution, five cysts (all of WHO type CE3) of renewed activity defined by recurring fluid collection. In 16 cysts, no follow-up was available due to surgery or drop out. Calcification of the cyst is not restricted to the inactive WHO cyst types CE4 and CE5, but occurs in all stages and in up to 50% of cysts. The completeness and, most importantly, the stability of consolidation of cyst content over time predicts cyst inactivity more reliably.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract Objective To evaluate the sensitivity and specificity of magnetic resonance imaging (MR imaging) including MR cholangiography for the identification of cysto-biliary fistulas in patients ...with hepatic hydatid disease. Patients and methods Retrospective analysis of 3 groups of patients (20 patients with 51 echinococcal cysts) in a cohort of 103 patients with cystic echinococcosis with different pretest probabilities for cysto-biliary fistulas. Patients who had MR imaging/MR cholangiography with symptoms and signs of biliary obstruction (5 patients with 16 cysts, group I), before surgery for other reasons than biliary obstruction (9 patients with 14 cysts, group II) and for cyst staging (6 patients with 21 cysts, group III). All MR images were evaluated before surgery for the presence of cyst wall defects and hydatid debris in bile ducts. In groups I and II MR results were compared with surgical, parasitological, and biochemical findings of each individual cyst. Results Based on direct (i.e. defects in the cyst wall and continuity of dilated biliary ducts into adjacent cysts), and indirect MR imaging/MR cholangiography imaging signs (i.e. intraluminal debris) our best estimate of sensitivity and specificity (stage-specific, WHO type CE3 and CE4) for cysto-biliary fistulas was 75% and 95%, respectively. Conclusions MR imaging with MR cholangiography is a valuable non-invasive imaging technique to assess the risk of cysto-biliary fistula-related complications and for planning of surgery.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Objective: To evaluate the existing WHO dengue classification across all age groups and a wide geographical range and to develop a revised evidence-based classification that would better reflect ...clinical severity. Methods: We followed suspected dengue cases daily in seven countries across South-east Asia and Latin America and then categorized them into one of three intervention groups describing disease severity according to the overall level of medical and nursing support required. Using a pre-defined analysis plan, we explored the clinical and laboratory profiles characteristic of these intervention categories and presented the most promising options for a revised classification scheme to an independent group of WHO dengue experts for consideration. Potential warning signs were also evaluated by comparing contemporaneous data of patients who progressed to severe disease with the data of those who did not. Results: A total of 2259 patients were recruited during 2006-2007 and 230 (13%) of the 1734 laboratory-confirmed patients required major intervention. Applying the existing WHO system, 47/210 (22%) of patients with shock did not fulfil all the criteria for dengue hemorrhagic fever. However, no three-tier revision adequately described the different severity groups either. Inclusion of readily discernible complications (shock/severe vascular leakage and/or severe bleeding and/or severe organ dysfunction) was necessary to devise a system that identified patients requiring major intervention with sufficient sensitivity and specificity to be practically useful. Only a small number of subjects (5%) progressed to severe disease while under observation; several warning signs were identified, but much larger studies are necessary to fully characterize features associated with disease progression. Conclusions: Based on these results, a revised classification system comprised of two entities, 'Dengue' and 'Severe Dengue', was proposed and has now been incorporated into the new WHO guidelines. PUBLICATION ABSTRACT
Full text
Available for:
FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
A key challenge in estimating the infection fatality rate (IFR) -- and its relation with various factors of interest -- is determining the total number of cases. The total number of cases is not ...known because not everyone is tested, but also, more importantly, because tested individuals are not representative of the population at large. We refer to the phenomenon whereby infected individuals are more likely to be tested than non-infected individuals, as "preferential testing." An open question is whether or not it is possible to reliably estimate the IFR without any specific knowledge about the degree to which the data are biased by preferential testing. In this paper we take a partial identifiability approach, formulating clearly where deliberate prior assumptions can be made and presenting a Bayesian model which pools information from different samples. When the model is fit to European data obtained from seroprevalence studies and national official COVID-19 statistics, we estimate the overall COVID-19 IFR for Europe to be 0.53%, 95% C.I. = 0.39%, 0.69%.
This qualitative study investigated the experiences of five term contract employed instructors at Saskatchewan Polytechnic using the constructivist grounded theory methodology as discussed by Charmaz ...(2014). The theoretical framework for the study was informed by a review of theories pertaining to organizational behavior and contingent employment as well as the economic and professional development theoretical perspectives on contingent employment.Five participants were interviewed individually using open-ended interviews to elicit their views regarding their contingent employment arrangements. Grounded theory was chosen in an attempt to derive a theory based on the experiences of these five participants rather than trying to fit the experiences into existing theories.The findings showed six core theoretical concepts accounted for the experiences of the contingently employed staff: System Factors, Interaction With Others, Work Conditions, Internal Motivations and Assessments, Doing the Work, and Deriving Personal Benefit (Internal). Each of these core concepts consisted of a number of categories that interacted with each other in either a positive or a negative way, resulting in an overall impact on the participants’ experiences of the work situation. This interaction was examined through the lens of system dynamics (Sterman, 2000). These core concepts and their substantive categories suggest that supervisors, managers, and other organizational figures may have points of intervention to support and even to enhance contingently employed people’s work experiences. A number of possible recommendations for managers, organizations and employees were outlined. Suggestions for possible future research were also provided.
Sehnsuchtsstädte Marco Thomas Bosshard, Jan-Dirk Döhling, Rebecca Janisch, Mona Motakef, Angelika Münter, Alexander Pellnitz / Marco Thomas Bosshard, Jan-Dirk Döhling, Rebecca Janisch, Mona Motakef, Angelika Münter, Alexander Pellnitz
2014
eBook
Auf der Suche nach lebenswerten urbanen Räumen: Wie werden Sehnsuchtsstädte medial konstruiert und kommuniziert? Wie eignen Menschen sich ihren Lebensraum im Alltag an? Welche Sehnsüchte stehen ...hinter technologischen und planerischen Zukunftskonzepten?Die interdisziplinären Beiträge des Bandes thematisieren diese Fragen aus den Blickwinkeln der Kulturwissenschaften, der Soziologie sowie der Stadtplanung und der Ingenieurswissenschaften.
Silicon and silica optical systems have become the primary materials of choice for visible and near-infrared optical devices. However, these materials inherently lack a direct band gap and their ...crystal symmetry limits second-order optical nonlinearity. In order to make next-generation system-on-a-chip devices, other materials must be incorporated into the system to integrate these properties into the system. To minimize propagating wave perturbations in the pre-existing system, these materials should be made as small as possible, fundamentally limiting light-matter interaction. However, new classes of two-dimensional materials that have been recently been discovered possessing both excellent optical properties, such as extraordinary nonlinear susceptibility, and an atomic thickness, making them excellent candidate materials to integrate into optical systems lacking these properties. This dissertation covers work done to characterize and engineer the optical properties in two-dimensional (2D) materials in an effort to integrate them in optical systems. First, a brief introduction is provided in Chapter 1. Chapter 2 discusses the extraordinary second harmonic generation (SHG) in mono- and few-layered Transition Metal Dichalcogenides (TMDs). It is discovered that monolayer TMDs have susceptibilities over three orders of magnitude larger than typical nonlinear crystals. This work is expanded in Chapter 3, where by synthesizing alloy TMD monolayers, we can tune the monolayer nonlinear susceptibility, allowing further opportunities for engineering 2D materials for optical applications. Chapter 4 covers a method to enhance the light-matter interaction in 2D materials by utilizing a simple nanocavity substrate. Using this simple MoS2/Al2O3/Al substrate, we can optimize the monolayer absorption and emission by tuning the oxide thickness layer, increasing the exclusive MoS2 absorption. In order to further increase this light-matter interaction with 2D materials, monolayers must be integrated into higher Q cavities. To demonstrate stronger light-matter enhancement capabilities of ultra-high-Q microresonators, Chapter 5 describes a method to enhance the particle detection capabilities of microresonators using Raman spectroscopy, demonstrating particle detection and characterization capabilities that could become an excellent platform to further increase the light-matter interaction with 2D materials. Finally, Chapter 6 concludes the dissertation by looking forward to future capabilities of 2D and microresonator systems.
PDF
