Assessing Surveillance Elements of the Zanzibar Malaria Elimination Program to Support Malaria Elimination in Zanzibar

Though significant progress has been made through control efforts in recent years, malaria remains a leading cause of morbidity and mortality throughout the world, with 3.2 billion people at risk of developing the disease. Zanzibar is currently pursuing malaria elimination through the Zanzibar Malaria Elimination Program (ZAMEP), and is working toward a goal of no locally acquired malaria cases by 2018. A comprehensive and well functioning malaria surveillance program is central to achieving this goal. Under ZAMEP’s current surveillance strategy, District Malaria Surveillance Officers (DMSOs) respond to malaria case notifications through the reactive case detection (RACD) system. Three malaria screening and treatment strategies are undertaken in response to this system, including household-level (HSaT), focal-level (FSaT), and mass-level (MSaT). Each strategy is triggered by a different case threshold and tests different-sized populations. The aims of this study were to (1) assess the cost effectiveness of three malaria screening and treatment strategies; (2) assess the timeliness and completeness of ZAMEP’s RACD system; (3) and qualitatively explore the roles of DMSOs.

Screening disposition and budget information for 2014 screening and treatment strategies was analyzed to determine prevalence rates in screened populations and the cost effectiveness of each strategy. Prevalence rates within the screened population varied by strategy: 6.1 percent in HSaT, 1.2 percent in FSaT, and 0.9 percent in MSaT. Of the various costing scenarios considering cost per person screened, MSaT was the most cost-effective, with costs ranging from $9.57 to $12.57 per person screened. Of the various costing scenarios considering cost per case detected, HSaT was the most cost-effective, at $385.51 per case detected.

Case data from 2013 through mid-2015 was used to assess the timeliness and completeness of the RACD system. The average number of RACD activities occurring within 48 hours of notification improved slightly between 2013 and the first half of 2015, from 90.7 percent to 93.1 percent. The average percentage of household members screened during RACD also increased over the same time period, from 84 percent in 2013 to 89.9 percent in the first half of 2015.

Interviews with twenty DMSOs were conducted to gain insights into the challenges to malaria elimination both from the health system and the community perspectives. Major themes discussed in the interviews include the need for additional training, inadequate information capture at health facility, resistance to household testing, transportation difficulties, inadequate personnel during the high transmission season, and community misinformation.

Zanzibar is now considered a low transmission setting, making elimination feasible, but also posing new challenges to achieving this goal. The findings of this study provide insight into how surveillance activities can be improved to support the goal of malaria elimination in Zanzibar. Key changes include reevaluating the use of MSaT activities, improving information capture at health facilities, hiring additional DMSOs during the high transmission season, and improving community communication.

Development of a retroviral strategy that efficiently creates nested chromosomal deletions in mouse embryonic stem cells and its exploitation for functional genomics

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

A compendium of myeloma-associated chromosomal copy number abnormalities and their prognostic value.

To obtain a comprehensive genomic profile of presenting multiple myeloma cases we performed high-resolution single nucleotide polymorphism mapping array analysis in 114 samples alongside 258 samples analyzed by U133 Plus 2.0 expression array (Affymetrix). We examined DNA copy number alterations and loss of heterozygosity (LOH) to define the spectrum of minimally deleted regions in which relevant genes of interest can be found. The most frequent deletions are located at 1p (30%), 6q (33%), 8p (25%), 12p (15%), 13q (59%), 14q (39%), 16q (35%), 17p (7%), 20 (12%), and 22 (18%). In addition, copy number-neutral LOH, or uniparental disomy, was also prevalent on 1q (8%), 16q (9%), and X (20%), and was associated with regions of gain and loss. Based on fluorescence in situ hybridization and expression quartile analysis, genes of prognostic importance were found to be located at 1p (FAF1, CDKN2C), 1q (ANP32E), and 17p (TP53). In addition, we identified common homozygously deleted genes that have functions relevant to myeloma biology. Taken together, these analyses indicate that the crucial pathways in myeloma pathogenesis include the nuclear factor-κB pathway, apoptosis, cell-cycle regulation, Wnt signaling, and histone modifications. This study was registered at http://isrctn.org as ISRCTN68454111.

Total Synthesis of the Antitumor Macrolides, (+)-Brefeldin A and 4‑Epi-Brefeldin A from D‑Glucose: Use of the Padwa Anionic Allenylsulfone [3+2]-Cycloadditive Elimination To Construct Trans-Configured Chiral Cyclopentane Systems

A new synthesis of (+)-brefeldin A is reported via Padwa allenylsulfone [3+2]-cycloadditive elimination. Cycloadduct 13 was initially elaborated into iodide
27, which, following treatment with Zn, gave aldehyde 28 whose C(9) stereocenter was epimerized. Further elaboration into enoate 38 and Julia−Kocienski olefination with 5 subsequently afforded 39, which was deprotected at C(1) and O(15). Yamaguchi macrolactonization of the seco-acid thereafter afforded a macrocycle that underwent O-desilylation and inversion at C(4) to give (+)-brefeldin A following deprotection

Primary Immunodeficiency Associated with Chromosomal Aberration - an ESID Survey

Patients with syndromic features frequently suffer from recurrent respiratory infections, but little is known about the spectrum of immunological abnormalities associated with their underlying chromosomal aberrations outside the well-known examples of Down and DiGeorge syndromes. Therefore, we performed this retrospective, observational survey study.

Solutions of boundary element equations by a flexible elimination process

Abstract not available

A Comparative Study: China’s Water Pollutants Discharge Permit System with Reference to the National Pollutants Discharge Elimination System of the United States of America

China's water pollution control law stipulates the Water Pollution Discharge Permit (WPDP) institution and authorizes the State Council to draft the regulations for its implementation and enforcement. However, until today, national regulations have not been established and the permitting system has been operating according to provincial regulations. in contrast to USA, the effluents permit system has been operated for more than 40 years and received relatively successful results. The CWA/NPDES experience offers a valuable reference for China’s water permit system.

The RGBarrier assay: the parallel study of gene regulatory element performance at defined chromosomal locations

Vertebrate genomes are organised into a variety of nuclear environments and chromatin states that have profound effects on the regulation of gene transcription. This variation presents a major challenge to the expression of transgenes for experimental research, genetic therapies and the production of biopharmaceuticals. The majority of transgenes succumb to transcriptional silencing by their chromosomal environment when they are randomly integrated into the genome, a phenomenon known as chromosomal position effect (CPE). It is not always feasible to target transgene integration to transcriptionally permissive “safe harbour” loci that favour transgene expression, so there remains an unmet need to identify gene regulatory elements that can be added to transgenes which protect them against CPE. Dominant regulatory elements (DREs) with chromatin barrier (or boundary) activity have been shown to protect transgenes from CPE. The HS4 element from the chicken beta-globin locus and the A2UCOE element from a human housekeeping gene locus have been shown to function as DRE barriers in a wide variety of cell types and species. Despite rapid advances in the profiling of transcription factor binding, chromatin states and chromosomal looping interactions, progress towards functionally validating the many candidate barrier elements in vertebrates has been very slow. This is largely due to the lack of a tractable and efficient assay for chromatin barrier activity. In this study, I have developed the RGBarrier assay system to test the chromatin barrier activity of candidate DREs at pre-defined isogenic loci in human cells. The RGBarrier assay consists in a Flp-based RMCE reaction for the integration of an expression construct, carrying candidate DREs, in a pre-characterised chromosomal location. The RGBarrier system involves the tracking of red, green and blue fluorescent proteins by flow cytometry to monitor on-target versus off-target integration and transgene expression. The analysis of the reporter (GFP) expression for several weeks gives a measure of the protective ability of each candidate elements from chromosomal silencing. This assay can be scaled up to test tens of new putative barrier elements in the same chromosomal context in parallel. The defined chromosomal contexts of the RGBarrier assays will allow for detailed mechanistic studies of chromosomal silencing and DRE barrier element action. Understanding these mechanisms will be of paramount importance for the design of specific solutions for overcoming chromosomal silencing in specific transgenic applications.

Elimination of urine in response to water intake is consistent in well-hydrated individuals

A simple method has been recently proposed to assess acute hydration status in humans; however, several questions remain regarding its reliability, validity, and practicality. Objective: Establish reliability of a simple method to assess euhydration, that is, to analyze whether this method can be used as a consistent indicator of a person´s hydration status. In addition, the study sought to assess the effect exercise has on urine volume when euhydration is maintained and a standardized volume of water is ingested. Methods: Five healthy physically active men and five healthy physically active women, 22.5 ± 2.3 years of age (mean ± standard deviation) reported to the laboratory after fasting for 10 hours or more on three occasions, each one week apart. During the two identical resting euhydration conditions (EuA and EuB), participants remained seated for 45 minutes. During the exercise condition (EuExer), participants exercised intermittently in an environmental chamber (average temperature and relative humidity = 32 ± 3°C and 65 ± 7%, respectively) for a period of 45 minutes and drank water to offset loss due to sweating. The order of treatments was randomized. Upon finishing the treatment period, they ingested a volume of water equivalent to 1.43% body mass (BM) within 30 minutes. Urine was collected and measured henceforth every 30 minutes for 3 hours. Results: Urine volume eliminated during EuExer (1205 ± 399.5 ml) was not different from EuB (1072.2±413.1 ml) or EuA (1068 ± 382.87 ml) (p-value = 0.44). Both resting conditions were practically identical (p-value = 0.98) and presented a strong intraclass correlation (r = 0.849, p-value = 0.001). Conclusions: This method, besides simple, proved to be consistent in all conditions; therefore, it can be used with the certainty that measurements are valid and reliable.

Prevalence of SOS-mediated control of integron integrase expression as an adaptive trait of chromosomal and mobile integrons

BACKGROUND Integrons are found in hundreds of environmental bacterial species, but are mainly known as the agents responsible for the capture and spread of antibiotic-resistance determinants between Gram-negative pathogens. The SOS response is a regulatory network under control of the repressor protein LexA targeted at addressing DNA damage, thus promoting genetic variation in times of stress. We recently reported a direct link between the SOS response and the expression of integron integrases in Vibrio cholerae and a plasmid-borne class 1 mobile integron. SOS regulation enhances cassette swapping and capture in stressful conditions, while freezing the integron in steady environments. We conducted a systematic study of available integron integrase promoter sequences to analyze the extent of this relationship across the Bacteria domain. RESULTS Our results showed that LexA controls the expression of a large fraction of integron integrases by binding to Escherichia coli-like LexA binding sites. In addition, the results provide experimental validation of LexA control of the integrase gene for another Vibrio chromosomal integron and for a multiresistance plasmid harboring two integrons. There was a significant correlation between lack of LexA control and predicted inactivation of integrase genes, even though experimental evidence also indicates that LexA regulation may be lost to enhance expression of integron cassettes. CONCLUSIONS Ancestral-state reconstruction on an integron integrase phylogeny led us to conclude that the ancestral integron was already regulated by LexA. The data also indicated that SOS regulation has been actively preserved in mobile integrons and large chromosomal integrons, suggesting that unregulated integrase activity is selected against. Nonetheless, additional adaptations have probably arisen to cope with unregulated integrase activity. Identifying them may be fundamental in deciphering the uneven distribution of integrons in the Bacteria domain.

Lack of geographic variation in Y-chromosomal introns of red deer (Cervus elaphus)

Intra-specific Y-chromosomal sequence variation is useful for analysing the male contribution to a species’ spatial genetic structure. In red deer (Cervus elaphus) this is especially relevant, because geographic dispersal and game translocations occur mainly through the males. However, Y-chromosomal markers for wild organisms are scarce and frequently non-polymorphic within species. We assessed the intra-specific variation of two Y-chromosomal introns in red deer, one in the DBY (or DDX3Y) gene and the other in the UBE1Y gene. The introns were amplified using previously published exonic primers and directly sequenced in individuals of five red deer subspecies from across Eurasia. However, no nucleotide polymorphism was observed, which rebuts the usefulness of these introns for studies of red deer phylogeography and on illegal transport of red deer within this region. Male-based phylogeographic studies should thus be focused on other Y-chromosomal markers for this species.

Bioaccumulation and elimination of Endosulfan in zebra fish (Brachydanio rerio).

The bioaccumulation and elimination of endosulfan in zebra fish (Brachydanio rerio) were investigated in a semi-static bioassay. The pesticide mean concentration in water was 03ug litre(-1) and the level of endosulfan residues (x(alfa)+B(beta)-isomers+endosulfan sulfate) in the exposed fish at day 21 was 0.81 (+-0.12)ug g(-1) body weight. The estimated value of the bioconcentration factor (BCF) was 2650 (+-441), the total endosulfan residues being eliminated with a biological half-life of four days. Histopathological studies showed predominantly lipid accumulation in the liver and necrotic focus in the gills of exposed fish.

Uptake and elimination of endosulfan by zebra fish.

1992

Bioconcentration and elimination of endosulfan by yellow tetra fish under laboratory conditions.

1992