Evaluation of Indirect Fluorescent Antibody Assays Compared to Rapid Influenza Diagnostic Tests for the Detection of Pandemic Influenza A (H1N1) pdm09

Performance of indirect fluorescent antibody (IFA) assays and rapid influenza diagnostic tests (RIDT) during the 2009 H1N1 pandemic was evaluated, along with the relative effects of age and illness severity on test accuracy. Clinicians and laboratories submitted specimens on patients with respiratory illness to public health from April to mid October 2009 for polymerase chain reaction (PCR) testing as part of pandemic H1N1 surveillance efforts in Orange County, CA; IFA and RIDT were performed in clinical settings. Sensitivity and specificity for detection of the 2009 pandemic H1N1 strain, now officially named influenza A(H1N1)pdm09, were calculated for 638 specimens. Overall, approximately 30% of IFA tests and RIDTs tested by PCR were falsely negative (sensitivity 71% and 69%, respectively). Sensitivity of RIDT ranged from 45% to 84% depending on severity and age of patients. In hospitalized children, sensitivity of IFA (75%) was similar to RIDT (84%). Specificity of tests performed on hospitalized children was 94% for IFA and 80% for RIDT. Overall sensitivity of RIDT in this study was comparable to previously published studies on pandemic H1N1 influenza and sensitivity of IFA was similar to what has been reported in children for seasonal influenza. Both diagnostic tests produced a high number of false negatives and should not be used to rule out influenza infection

Left-Right Function of dmrt2 Genes Is Not Conserved between Zebrafish and Mouse

Background: Members of the Dmrt family, generally associated with sex determination, were shown to be involved in several other functions during embryonic development. Dmrt2 has been studied in the context of zebrafish development where, due to a duplication event, two paralog genes dmrt2a and dmrt2b are present. Both zebrafish dmrt2a/terra and dmrt2b are important to regulate left-right patterning in the lateral plate mesoderm. In addition, dmrt2a/terra is necessary for symmetric somite formation while dmrt2b regulates somite differentiation impacting on slow muscle development. One dmrt2 gene is also expressed in the mouse embryo, where it is necessary for somite differentiation but with an impact on axial skeleton development. However, nothing was known about its role during left-right patterning in the lateral plate mesoderm or in the symmetric synchronization of somite formation. Methodology/Principal Findings: Using a dmrt2 mutant mouse line, we show that this gene is not involved in symmetric somite formation and does not regulate the laterality pathway that controls left-right asymmetric organ positioning. We reveal that dmrt2a/terra is present in the zebrafish laterality organ, the Kupffer’s vesicle, while its homologue is excluded from the mouse equivalent structure, the node. On the basis of evolutionary sub-functionalization and neo-functionalization theories we discuss this absence of functional conservation. Conclusions/Significance: Our results show that the role of dmrt2 gene is not conserved during zebrafish and mous

The influenza pandemic preparedness planning tool InfluSim

BACKGROUND: Planning public health responses against pandemic influenza relies on predictive models by which the impact of different intervention strategies can be evaluated. Research has to date rather focused on producing predictions for certain localities or under specific conditions, than on designing a publicly available planning tool which can be applied by public health administrations. Here, we provide such a tool which is reproducible by an explicitly formulated structure and designed to operate with an optimal combination of the competing requirements of precision, realism and generality. RESULTS: InfluSim is a deterministic compartment model based on a system of over 1,000 differential equations which extend the classic SEIR model by clinical and demographic parameters relevant for pandemic preparedness planning. It allows for producing time courses and cumulative numbers of influenza cases, outpatient visits, applied antiviral treatment doses, hospitalizations, deaths and work days lost due to sickness, all of which may be associated with economic aspects. The software is programmed in Java, operates platform independent and can be executed on regular desktop computers. CONCLUSION: InfluSim is an online available software which efficiently assists public health planners in designing optimal interventions against pandemic influenza. It can reproduce the infection dynamics of pandemic influenza like complex computer simulations while offering at the same time reproducibility, higher computational performance and better operability

Institutionalizing Provider-Initiated HIV Testing and Counselling for Children: An Observational Case Study from Zambia

Background: Provider-initiated testing and counselling (PITC) is a priority strategy for increasing access for HIV-exposed children to prevention measures, and infected children to treatment and care interventions. This article examines efforts to scale-up paediatric PITC at a second-level hospital located in Zambia’s Southern Province, and serving a catchment area of 1.2 million people. Methods and Principal Findings: Our retrospective case study examined best practices and enabling factors for rapid institutionalization of PITC in Livingstone General Hospital. Methods included clinical observations, key informant interviews with programme management, and a desk review of hospital management information systems (HMIS) uptake data following the introduction of PITC. After PITC roll-out, the hospital experienced considerably higher testing uptake. In a 36-month period following PITC institutionalization, of total inpatient children eligible for PITC (n = 5074), 98.5 % of children were counselled, and 98.2 % were tested. Of children tested (n = 4983), 15.5 % were determined HIVinfected; 77.6 % of these results were determined by DNA polymerase chain reaction (PCR) testing in children under the age of 18 months. Of children identified as HIV-infected in the hospital’s inpatient and outpatient departments (n = 1342), 99.3 % were enrolled in HIV care, including initiation on co-trimoxazole prophylaxis. A number of good operational practices and enabling factors in the Livingstone General Hospital experience can inform rapid PIT

Genome-wide Association Studies in Ancestrally Diverse Populations: Opportunities, Methods, Pitfalls, and Recommendations

Genome-wide association studies (GWASs) have focused primarily on populations of European descent, but it is essential that diverse populations become better represented. Increasing diversity among study participants will advance our understanding of genetic architecture in all populations and ensure that genetic research is broadly applicable. To facilitate and promote research in multi-ancestry and admixed cohorts, we outline key methodological considerations and highlight opportunities, challenges, solutions, and areas in need of development. Despite the perception that analyzing genetic data from diverse populations is difficult, it is scientifically and ethically imperative, and there is an expanding analytical toolbox to do it well

Behavior and Impact of Zirconium in the Soil–Plant System: Plant Uptake and Phytotoxicity

Because of the large number of sites they pollute, toxic metals that contaminate terrestrial ecosystems are increasingly of environmental and sanitary concern (Uzu et al. 2010, 2011; Shahid et al. 2011a, b, 2012a). Among such metals is zirconium (Zr), which has the atomic number 40 and is a transition metal that resembles titanium in physical and chemical properties (Zaccone et al. 2008). Zr is widely used in many chemical industry processes and in nuclear reactors (Sandoval et al. 2011; Kamal et al. 2011), owing to its useful properties like hardness, corrosion-resistance and permeable to neutrons (Mushtaq 2012). Hence, the recent increased use of Zr by industry, and the occurrence of the Chernobyl and Fukashima catastrophe have enhanced environmental levels in soil and waters (Yirchenko and Agapkina 1993; Mosulishvili et al. 1994 ; Kruglov et al. 1996)

The Cyclostratigraphy Intercomparison Project (CIP): consistency, merits and pitfalls

Cyclostratigraphy is an important tool for understanding astronomical climate forcing and reading geological time in sedimentary sequences, provided that an imprint of insolation variations caused by Earth’s orbital eccentricity, obliquity and/or precession is preserved (Milankovitch forcing). Numerous stratigraphic and paleoclimate studies have applied cyclostratigraphy, but the robustness of the methodology and its dependence on the investigator have not been systematically evaluated. We developed the Cyclostratigraphy Intercomparison Project (CIP) to assess the robustness of cyclostratigraphic methods using an experimental design of three artificial cyclostratigraphic case studies with known input parameters. Each case study is designed to address specific challenges that are relevant to cyclostratigraphy. Case 1 represents an offshore research vessel environment, as only a drill-core photo and the approximate position of a late Miocene stage boundary are available for analysis. In Case 2, the Pleistocene proxy record displays clear nonlinear cyclical patterns and the interpretation is complicated by the presence of a hiatus. Case 3 represents a Late Devonian proxy record with a low signal-to-noise ratio with no specific theoretical astronomical solution available for this age. Each case was analyzed by a test group of 17-20 participants, with varying experience levels, methodological preferences and dedicated analysis time. During the CIP 2018 meeting in Brussels, Belgium, the ensuing analyses and discussion demonstrated that most participants did not arrive at a perfect solution, which may be partly explained by the limited amount of time spent on the exercises (∼4.5 hours per case). However, in all three cases, the median solution of all submitted analyses accurately approached the correct result and several participants obtained the exact correct answers. Interestingly, systematically better performances were obtained for cases that represented the data type and stratigraphic age that were closest to the individual participants’ experience. This experiment demonstrates that cyclostratigraphy is a powerful tool for deciphering time in sedimentary successions and, importantly, that it is a trainable skill. Finally, we emphasize the importance of an integrated stratigraphic approach and provide flexible guidelines on what good practices in cyclostratigraphy should include. Our case studies provide valuable insight into current common practices in cyclostratigraphy, their potential merits and pitfalls. Our work does not provide a quantitative measure of reliability and uncertainty of cyclostratigraphy, but rather constitutes a starting point for further discussions on how to move the maturing field of cyclostratigraphy forward

Deconstruction of the (Paleo)Polyploid Grapevine Genome Based on the Analysis of Transposition Events Involving NBS Resistance Genes

Plants have followed a reticulate type of evolution and taxa have frequently merged via allopolyploidization. A polyploid structure of sequenced genomes has often been proposed, but the chromosomes belonging to putative component genomes are difficult to identify. The 19 grapevine chromosomes are evolutionary stable structures: their homologous triplets have strongly conserved gene order, interrupted by rare translocations. The aim of this study is to examine how the grapevine nucleotide-binding site (NBS)-encoding resistance (NBS-R) genes have evolved in the genomic context and to understand mechanisms for the genome evolution. We show that, in grapevine, i) helitrons have significantly contributed to transposition of NBS-R genes, and ii) NBS-R gene cluster similarity indicates the existence of two groups of chromosomes (named as Va and Vc) that may have evolved independently. Chromosome triplets consist of two Va and one Vc chromosomes, as expected from the tetraploid and diploid conditions of the two component genomes. The hexaploid state could have been derived from either allopolyploidy or the separation of the Va and Vc component genomes in the same nucleus before fusion, as known for Rosaceae species. Time estimation indicates that grapevine component genomes may have fused about 60 mya, having had at least 40–60 mya to evolve independently. Chromosome number variation in the Vitaceae and related families, and the gap between the time of eudicot radiation and the age of Vitaceae fossils, are accounted for by our hypothesis

Deviation of eyes and head in acute cerebral stroke

BACKGROUND: It is a well-known phenomenon that some patients with acute left or right hemisphere stroke show a deviation of the eyes (Prévost's sign) and head to one side. Here we investigated whether both right- and left-sided brain lesions may cause this deviation. Moreover, we studied the relationship between this phenomenon and spatial neglect. In contrast to previous studies, we determined not only the discrete presence or absence of eye deviation with the naked eye through clinical inspection, but actually measured the extent of horizontal eye-in-head and head-on-trunk deviation. In further contrast, measurements were performed early after stroke onset (1.5 days on average). METHODS: Eye-in-head and head-on-trunk positions were measured at the bedside in 33 patients with acute unilateral left or right cerebral stroke consecutively admitted to our stroke unit. RESULTS: Each single patient with spatial neglect and right hemisphere lesion showed a marked deviation of the eyes and the head to the ipsilesional, right side. The average spontaneous gaze position in this group was 46° right, while it was close to the saggital body midline (0°) in the groups with acute left- or right-sided stroke but no spatial neglect as well as in healthy subjects. CONCLUSION: A marked horizontal eye and head deviation observed ~1.5 days post-stroke is not a symptom associated with acute cerebral lesions per se, nor is a general symptom of right hemisphere lesions, but rather is specific for stroke patients with spatial neglect. The evaluation of the patient's horizontal eye and head position thus could serve as a brief and easy way helping to diagnose spatial neglect, in addition to the traditional paper-and-pencil tests