Syntax of the Hittite “Supine” Construction

As is well-known, the Hittite verbal form ending in -(u)wan, labeled now for more than half a century the “supine”, occurs only in a construction with either dai- ‘to put’ or tiya- ‘to step’ that expresses the notion ‘begin/undertake to do X’: (1) KBo 5.8 iii 3-5 (CTH 61, Annals of Muršili; NH)namma=šmaš=kan ÉRIN.MEŠ išḫiḫḫun nu=mu ÉRIN.MEŠ piškewan dāir n=at=mu laḫḫi kattan paišgauwan tiyēr “Then I imposed (a commitment for) troops on them, and they began to give me troops and began to go o..

Rapid screening of MDR-TB using molecular Line Probe Assay is feasible in Uganda

<p>Abstract</p> <p>Background</p> <p>About 500 new smear-positive Multidrug-resistant tuberculosis (MDR-TB) cases are estimated to occur per year in Uganda. In 2008 in Kampala, MDR-TB prevalence was reported as 1.0% and 12.3% in new and previously treated TB cases respectively. Line probe assays (LPAs) have been recently approved for use in low income settings and can be used to screen smear-positive sputum specimens for resistance to rifampicin and isoniazid in 1-2 days.</p> <p>Methods</p> <p>We assessed the performance of a commercial line probe assay (Genotype MTBDR<it>plus</it>) for rapid detection of rifampicin and isoniazid resistance directly on smear-positive sputum specimens from 118 previously treated TB patients in a reference laboratory in Kampala, Uganda. Results were compared with MGIT 960 liquid culture and drug susceptibility testing (DST). LPA testing was also performed in parallel in a University laboratory to assess the reproducibility of results.</p> <p>Results</p> <p>Overall, 95.8% of smear-positive specimens gave interpretable results within 1-2 days using LPA. Sensitivity, specificity, positive and negative predictive values were 100.0%, 96.1%, 83.3% and 100.0% for detection of rifampicin resistance; 80.8%, 100.0%, 100.0% and 93.0% for detection of isoniazid resistance; and 92.3%, 96.2%, 80.0% and 98.7% for detection of multidrug-resistance compared with conventional results. Reproducibility of LPA results was very high with 98.1% concordance of results between the two laboratories.</p> <p>Conclusions</p> <p>LPA is an appropriate tool for rapid screening for MDR-TB in Uganda and has the potential to substantially reduce the turnaround time of DST results. Careful attention must be paid to training, supervision and adherence to stringent laboratory protocols to ensure high quality results during routine implementation.</p

Extensive transmission of isoniazid resistant M. tuberculosis and its association with increased multidrug-resistant TB in two rural counties of eastern China: A molecular epidemiological study

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to investigate the molecular characteristics of isoniazid resistant <it>Mycobacterium tuberculosis </it>(MTB), as well as its contribution to the dissemination of multi-drug resistant TB (MDR-TB) in rural areas of eastern China.</p> <p>Methods</p> <p>A population-based epidemiological study was conducted in two rural counties of eastern China from 2004 to 2005. In total, 131 isoniazid resistant MTB isolates were molecularly characterized by DNA sequencing and genotyped by IS<it>6110 </it>restriction fragment length polymorphism (RFLP) and spoligotyping.</p> <p>Results</p> <p>The <it>katG</it>315Thr mutation was observed in 74 of 131 isoniazid resistant isolates and more likely to be MDR-TB (48.6%) and have mutations in <it>rpoB </it>gene (47.3%). Spoligotyping identified 80.2% of isoniazid resistant MTB isolates as belonging to the Beijing family. Cluster analysis by genotyping based on IS<it>6110 </it>RFLP, showed that 48.1% isoniazid resistant isolates were grouped into 26 clusters and <it>katG</it>315Thr mutants had a significantly higher clustering proportion compared to those with <it>katG </it>wild type (73%.vs.18%; OR, 12.70; 95%CI, 6.357-14.80). Thirty-one of the 53 MDR-TB isolates were observed in 19 clusters. Of these clusters, isoniazid resistance in MDR-TB isolates was all due to the <it>katG</it>315Thr mutation; 18 clusters also contained mono-isoniazid resistant and other isoniazid resistant isolates.</p> <p>Conclusions</p> <p>These results highlighted that isoniazid resistant MTB especially with <it>katG</it>315Thr is likely to be clustered in a community, develop extra resistance to rifampicin and become MDR-TB in Chinese rural settings.</p

Californian Science Students' Perceptions of their Classoom Learning Environments.

This study utilised the What Is Happening In this Class (WIHIC) questionnaire to examine factors that influence Californian student perceptions of their learning environment. Data were collected from 665 USA middle school science students in 11 Californian schools. Several background variables were included in the study to investigate their effects on students’ perceptions, such as student and teacher gender, student ethnic background and socio-economic status (SES), and student age. Class and school variables, such as class ethnic composition, class size and school socioeconomic status were also collected. A hierarchical analysis of variance was conducted to investigate separate and joint effects of these variables. Results from this study indicate that some scales of the WIHIC are more inclined to measure personal or idiosyncratic features of student perceptions of their learning environment whereas other scales contain more variance at the class level. Also, it was found that different variables affect different scale scores. A variable that consistently affected students' perceptions, regardless of the element of interest in the learning environment was student gender. Generally speaking girls perceived their learning environment more positively than did boys

Direct Nitrate Reductase Assay versus Microscopic Observation Drug Susceptibility Test for Rapid Detection of MDR-TB in Uganda

The most common method for detection of drug resistant (DR) TB in resource-limited settings (RLSs) is indirect susceptibility testing on Lowenstein-Jensen medium (LJ) which is very time consuming with results available only after 2–3 months. Effective therapy of DR TB is therefore markedly delayed and patients can transmit resistant strains. Rapid and accurate tests suitable for RLSs in the diagnosis of DR TB are thus highly needed. In this study we compared two direct techniques - Nitrate Reductase Assay (NRA) and Microscopic Observation Drug Susceptibility (MODS) for rapid detection of MDR-TB in a high burden RLS. The sensitivity, specificity, and proportion of interpretable results were studied. Smear positive sputum was collected from 245 consecutive re-treatment TB patients attending a TB clinic in Kampala, Uganda. Samples were processed at the national reference laboratory and tested for susceptibility to rifampicin and isoniazid with direct NRA, direct MODS and the indirect LJ proportion method as reference. A total of 229 specimens were confirmed as M. tuberculosis, of these interpretable results were obtained in 217 (95%) with either the NRA or MODS. Sensitivity, specificity and kappa agreement for MDR-TB diagnosis was 97%, 98% and 0.93 with the NRA; and 87%, 95% and 0.78 with the MODS, respectively. The median time to results was 10, 7 and 64 days with NRA, MODS and the reference technique, respectively. The cost of laboratory supplies per sample was low, around 5 USD, for the rapid tests. The direct NRA and MODS offered rapid detection of resistance almost eight weeks earlier than with the reference method. In the study settings, the direct NRA was highly sensitive and specific. We consider it to have a strong potential for timely detection of MDR-TB in RLS

The Frenchness of Marcel Lefebvre and the Society of St Pius X:a new reading

The case of Marcel Lefebvre and the Society of St Pius X (SSPX) deserves fresh perspectives. The current historiography is too franco-centric, focused on selective aspects of Lefebvre’s biography and the actions of isolated individuals, rather than with the life of the SSPX itself. After evaluating the current state of the historiography, this article proposes a new analysis of the SSPX’s political discourses in France and internationally and undertakes to reframe the relationship between Lefebvre’s life and his congregation by re-examining his African missionary experiences. Such new perspectives will be helpful as the SSPX moves towards regularisation under the pontificate of Pope Francis

Limited effect of chronic valproic acid treatment in a mouse model of Machado-Joseph disease

Machado-Joseph disease (MJD) is an inherited neurodegenerative disease, caused by a CAG repeat expansion within the coding region of ATXN3 gene, and which currently lacks effective treatment. In this work we tested the therapeutic efficacy of chronic treatment with valproic acid (VPA) (200mg/kg), a compound with known neuroprotection activity, and previously shown to be effective in cell, fly and nematode models of MJD. We show that chronic VPA treatment in the CMVMJD135 mouse model had limited effects in the motor deficits of these mice, seen mostly at late stages in the motor swimming, beam walk, rotarod and spontaneous locomotor activity tests, and did not modify the ATXN3 inclusion load and astrogliosis in affected brain regions. However, VPA chronic treatment was able to increase GRP78 protein levels at 30 weeks of age, one of its known neuroprotective effects, confirming target engagement. In spite of limited results, the use of another dosage of VPA or of VPA in a combined therapy with molecules targeting other pathways, cannot be excluded as potential strategies for MJD therapeuticsPM received funding from Ataxia UK Grant (Project: Pharmacologic therapy for Machado-Joseph disease: from a C. elegans drug screen to a mouse model validation). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.info:eu-repo/semantics/publishedVersio

Lack of Protection following Passive Transfer of Polyclonal Highly Functional Low-Dose Non-Neutralizing Antibodies

Recent immune correlates analysis from the RV144 vaccine trial has renewed interest in the role of non-neutralizing antibodies in mediating protection from infection. While neutralizing antibodies have proven difficult to induce through vaccination, extra-neutralizing antibodies, such as those that mediate antibody-dependent cellular cytotoxicity (ADCC), are associated with long-term control of infection. However, while several non-neutralizing monoclonal antibodies have been tested for their protective efficacy in vivo, no studies to date have tested the protective activity of naturally produced polyclonal antibodies from individuals harboring potent ADCC activity. Because ADCC-inducing antibodies are highly enriched in elite controllers (EC), we passively transferred highly functional non-neutralizing polyclonal antibodies, purified from an EC, to assess the potential impact of polyclonal non-neutralizing antibodies on a stringent SHIV-SF162P3 challenge in rhesus monkeys. Passive transfer of a low-dose of ADCC inducing antibodies did not protect from infection following SHIV-SF162P3 challenge. Passively administered antibody titers and gp120-specific, but not gp41-specific, ADCC and antibody induced phagocytosis (ADCP) were detected in the majority of the monkeys, but did not correlate with post infection viral control. Thus these data raise the possibility that gp120-specific ADCC activity alone may not be sufficient to control viremia post infection but that other specificities or Fc-effector profiles, alone or in combination, may have an impact on viral control and should be tested in future passive transfer experiments