Molecular and genomic typing for tuberculosis surveillance: A survey study in 26 European countries

Background: Molecular typing and whole genome sequencing (WGS) information is used for (inter-) national outbreak investigations. To assist the implementation of these techniques for tuberculosis (TB) surveillance and outbreak investigations at European level there is a need for inter-country collaboration and standardization. This demands more information on molecular typing practices and capabilities of individual countries. We aimed to review the use of molecular/genomic typing for TB surveillance in European Union and European Economic Area countries in 2016; assess its public health value; and collect experiences on typing data use for cross-border cluster investigations. / Method: A web-based questionnaire was provided to all TB National Focal Points. The questionnaire consisted of three parts: i) Use and integration of molecular and genomic typing data into TB surveillance; ii) Cross-border cluster investigation and international collaboration, and iii) Perception and evaluation of public health benefits of molecular and genomic typing for TB surveillance. / Results: Of 26 responding countries, 20 used molecular typing for TB surveillance, including nine applying WGS. The level of integration into the national surveillance was heterogeneous. Among six countries not using typing for TB surveillance, more than half planned its implementation soon. Overall, most countries perceived an added public health value of molecular typing for TB control. Concerning international cluster investigations, countries had little experience and did not have standard protocols to exchange typing data. / Conclusion: Our study shows a wide use of molecular and genomic typing data for TB surveillance in EU/EEA countries and reveals that transition to WGS-based typing is ongoing or is considered in most countries. However, our results also show a high heterogeneity in the use and integration of typing data for TB surveillance. Standardization of typing data use for TB surveillance is needed and formal procedures should be developed to facilitate international collaboration

Cancer and thrombosis: Managing the risks and approaches to thromboprophylaxis

Patients with cancer are at increased risk of venous thromboembolism (VTE) compared with patients without cancer. This results from both the prothrombotic effects of the cancer itself and iatrogenic factors, such as chemotherapy, radiotherapy, indwelling central venous devices and surgery, that further increase the risk of VTE. Although cancer-associated thrombosis remains an important cause of morbidity and mortality, it is often underdiagnosed and undertreated. However, evidence is accumulating to support the use of low-molecular-weight heparins (LMWHs) in the secondary prevention of VTE in patients with cancer. Not only have LMWHs been shown to be at least as effective as coumarin derivatives in this setting, but they have a lower incidence of complications, including bleeding, and are not associated with the practical problems of warfarin therapy. Furthermore, a growing number of studies indicate that LMWHs may improve survival among patients with cancer due to a possible antitumor effect. Current evidence suggests that LMWHs should increasingly be considered for the long-term management of VTE in patients with cancer

Interpreting 16S metagenomic data without clustering to achieve sub-OTU resolution

The standard approach to analyzing 16S tag sequence data, which relies on clustering reads by sequence similarity into Operational Taxonomic Units (OTUs), underexploits the accuracy of modern sequencing technology. We present a clustering-free approach to multi-sample Illumina datasets that can identify independent bacterial subpopulations regardless of the similarity of their 16S tag sequences. Using published data from a longitudinal time-series study of human tongue microbiota, we are able to resolve within standard 97% similarity OTUs up to 20 distinct subpopulations, all ecologically distinct but with 16S tags differing by as little as 1 nucleotide (99.2% similarity). A comparative analysis of oral communities of two cohabiting individuals reveals that most such subpopulations are shared between the two communities at 100% sequence identity, and that dynamical similarity between subpopulations in one host is strongly predictive of dynamical similarity between the same subpopulations in the other host. Our method can also be applied to samples collected in cross-sectional studies and can be used with the 454 sequencing platform. We discuss how the sub-OTU resolution of our approach can provide new insight into factors shaping community assembly.Comment: Updated to match the published version. 12 pages, 5 figures + supplement. Significantly revised for clarity, references added, results not change

ESHAP and G-CSF is a superior blood stem cell mobilizing regimen compared to cyclophosphamide 1.5 g m−2 and G-CSF for pre-treated lymphoma patients: a matched pairs analysis of 78 patients

Cyclophosphamide 1.5 g m−2followed by granulocyte colony-stimulating factor (G-CSF) is an effective peripheral blood stem cell (PBSC) mobilizing regimen, but has limited anti-lymphoma activity. We therefore assessed the mobilizing potential of ESHAP (etoposide, ara-C, methylprednisolone and cisplatin), a potent second-line lymphoma regimen followed by G-CSF. The results were compared in 78 patients with relapsed or resistant lymphomas with the use of cyclophosphamide 1.5 g m−2followed by G-CSF in a matched pairs analysis, matching the ESHAP recipients (for predetermined prognostic factors) from a cohort of 178 lymphoma patients mobilized with cyclophosphamide and G-CSF. The total numbers of mononuclear cells collected at apheresis was similar with both regimens but ESHAP plus G-CSF resulted in a significantly higher percentage of CD34+ cells, absolute number of CD34+ cells and GM-CFC (all with P -values < 0.001). The number of patients requiring only one apheresis harvest to achieve a CD34+ cell yield of > 2.0 × 106kg−1was greatly increased in the ESHAP recipients (56/78 vs 17/78, P< 0.001). The total number of progenitor cells collected was not significantly different with the two mobilization regimens because of this higher number of apheresis in the cyclophosphamide group. The proportion of patients who failed to achieve a minimum CD34+ cell target of 1 × 106kg−1with the pooled harvests was less in the ESHAP arm (four patients vs nine patients) despite an increased number of aphereses in the cyclophosphamide recipients. ESHAP plus G-CSF is well tolerated and is an excellent mobilization regimen in patients with pre treated lymphoma. © 2000 Cancer Research Campaig

Gitana: a SQL-based Git Repository Inspector

International audienceSoftware development projects are notoriously complex and difficult to deal with. Several support tools such as issue tracking, code review and Source Control Management (SCM) systems have been introduced in the past decades to ease development activities. While such tools efficiently track the evolution of a given aspect of the project (e.g., bug reports), they provide just a partial view of the project and often lack of advanced querying mechanisms limiting themselves to command line or simple GUI support. This is particularly true for projects that rely on Git, the most popular SCM system today. In this paper, we propose a conceptual schema for Git and an approach that, given a Git repository, exports its data to a relational database in order to (1) promote data integration with other existing SCM tools and (2) enable writing queries on Git data using standard SQL syntax. To ensure efficiency, our approach comes with an incremental propagation mechanism that refreshes the database content with the latest modifications. We have implemented our approach in Gitana, an open-source tool available on GitHub

Lactate Regulates Metabolic and Proinflammatory Circuits in Control of T Cell Migration and Effector Functions

Licensed by the Creative Commons Attribution Licens

High-yield methods for accurate two-alternative visual psychophysics in head-fixed mice

Research in neuroscience relies increasingly on the mouse, a mammalian species that affords unparalleled genetic tractability and brain atlases. Here we introduce high-yield methods for probing mouse visual decisions. Mice are head-fixed, which facilitates repeatable visual stimulation, eye tracking, and brain access. They turn a steering wheel to make two-alternative choices, forced or unforced. Learning is rapid thanks to intuitive coupling of stimuli to wheel position. The mouse decisions deliver high-quality psychometric curves for detection and discrimination, and conform to the predictions of a simple probabilistic observer model. The task is readily paired with two-photon imaging of cortical activity. Optogenetic inactivation reveals that the task requires the visual cortex. Mice are motivated to perform the task by fluid reward or optogenetic stimulation of dopaminergic neurons. This stimulation elicits larger number of trials and faster learning. These methods provide a platform to accurately probe mouse vision and its neural basis

Use of the new World Health Organization child growth standards to describe longitudinal growth of breastfed rural Bangladeshi infants and young children.

BACKGROUND: Although the National Center for Health Statistics (NCHS) reference has been widely used, in 2006 the World Health Organization (WHO) released new standards for assessing growth of infants and children worldwide. OBJECTIVE: To assess and compare the growth of breastfed rural Bangladeshi infants and young children based on the new WHO child growth standards and the NCHS reference. METHODS: We followed 1343 children in the Maternal and Infant Nutrition Intervention in Matlab (MINIMat) study from birth to 24 months of age. Weights and lengths of the children were measured monthly during infancy and quarterly in the second year of life. Anthropometric indices were calculated using both WHO standards and the NCHS reference. The growth pattern and estimates of undernutrition based on the WHO standards and the NCHS reference were compared. RESULTS: The mean birthweight was 2697 +/- 401 g, with 30% weighing <2500 g. The growth pattern of the MINIMat children more closely tracked the WHO standards than it did the NCHS reference. The rates of stunting based on the WHO standards were higher than the rates based on the NCHS reference throughout the first 24 months. The rates of underweight and wasting based on the WHO standards were significantly different from those based on the NCHS reference. CONCLUSIONS: This comparison confirms that use of the NCHS reference misidentifies undernutrition and the timing of growth faltering in infants and young children, which was a key rationale for constructing the new WHO standards. The new WHO child growth standards provide a benchmark for assessing the growth of breastfed infants and children

An investigation into the validity of cervical spine motion palpation using subjects with congenital block vertebrae as a 'gold standard'

BACKGROUND: Although the effectiveness of manipulative therapy for treating back and neck pain has been demonstrated, the validity of many of the procedures used to detect joint dysfunction has not been confirmed. Practitioners of manual medicine frequently employ motion palpation as a diagnostic tool, despite conflicting evidence regarding its utility and reliability. The introduction of various spinal models with artificially introduced 'fixations' as an attempt to introduce a 'gold standard' has met with frustration and frequent mechanical failure. Because direct comparison against a 'gold standard' allows the validity, specificity and sensitivity of a test to be calculated, the identification of a realistic 'gold standard' against which motion palpation can be evaluated is essential. The objective of this study was to introduce a new, realistic, 'gold standard', the congenital block vertebra (CBV) to assess the validity of motion palpation in detecting a true fixation. METHODS: Twenty fourth year chiropractic students examined the cervical spines of three subjects with single level congenital block vertebrae, using two commonly employed motion palpation tests. The examiners, who were blinded to the presence of congenital block vertebrae, were asked to identify the most hypomobile segment(s). The congenital block segments included two subjects with fusion at the C2–3 level and one with fusion at C5-6. Exclusion criteria included subjects who were frankly symptomatic, had moderate or severe degenerative changes in their cervical spines, or displayed signs of cervical instability. Spinal levels were marked on the subject's skin overlying the facet joints from C1 to C7 bilaterally and the motion segments were then marked alphabetically with 'A' corresponding to C1-2. Kappa coefficients (K) were calculated to determine the validity of motion palpation to detect the congenitally fused segments as the 'most hypomobile' segments. Sensitivity and specificity of the diagnostic procedure were also calculated. RESULTS: Kappa coefficients (K) showed substantial overall agreement for identification of the segment of greatest hypomobility (K = 0.65), with substantial (K = 0.76) and moderate (K = 0.46) agreement for hypomobility at C2-3 and C5-6 respectively. Sensitivity ranged from 55% at the C5-6 CBV to 78% at the C2-3 level. Specificity of the procedure was high (91 – 98%). CONCLUSION: This study indicates that relatively inexperienced examiners are capable of correctly identifying inter-segmental fixations (CBV) in the cervical spine using 2 commonly employed motion palpation tests. The use of a 'gold standard' (CBV) in this study and the substantial agreement achieved lends support to the validity of motion palpation in detecting major spinal fixations in the cervical spine

Lack of microbiological concordance between bone and non-bone specimens in chronic osteomyelitis: an observational study

BACKGROUND: Prognosis of chronic osteomyelitis depends heavily on proper identification and treatment of the bone-infecting organism. Current knowledge on selecting the best specimen for culture is confusing, and many consider that non-bone specimens are suitable to replace bone cultures. This paper compares the microbiology of non-bone specimens with bone cultures, taking the last as the diagnostic gold standard. METHODS: Retrospective observational analysis of 50 patients with bacterial chronic osteomyelitis in a 750-bed University-based hospital. RESULTS: Concordance between both specimens for all etiologic agents was 28%, for Staphylococcus aureus 38%, and for organisms other than S. aureus 19%. The culture of non-bone specimens to identify the causative organisms in chronic osteomyelitis produced 52% false negatives and 36% false positives when compared against bone cultures. CONCLUSIONS: Diagnosis and therapy of chronic osteomyelitis cannot be guided by cultures of non-bone specimens because their microbiology is substantially different to the microbiology of the bone