A Three Monoclonal Antibody Combination Potently Neutralizes Multiple Botulinum Neurotoxin Serotype E Subtypes.

Human botulism is most commonly caused by botulinum neurotoxin (BoNT) serotypes A, B, and E. For this work, we sought to develop a human monoclonal antibody (mAb)-based antitoxin capable of binding and neutralizing multiple subtypes of BoNT/E. Libraries of yeast-displayed single chain Fv (scFv) antibodies were created from the heavy and light chain variable region genes of humans immunized with pentavalent-toxoid- and BoNT/E-binding scFv isolated by Fluorescence-Activated Cell Sorting (FACS). A total of 10 scFv were isolated that bound one or more BoNT/E subtypes with nanomolar-level equilibrium dissociation constants (KD). By diversifying the V-regions of the lead mAbs and selecting for cross-reactivity, we generated three scFv that bound all four BoNT/E subtypes tested at three non-overlapping epitopes. The scFvs were converted to IgG that had KD values for the different BoNT/E subtypes ranging from 9.7 nM to 2.28 pM. An equimolar combination of the three mAbs was able to potently neutralize BoNT/E1, BoNT/E3, and BoNT/E4 in a mouse neutralization assay. The mAbs have potential utility as therapeutics and as diagnostics capable of recognizing multiple BoNT/E subtypes. A derivative of the three-antibody combination (NTM-1633) is in pre-clinical development with an investigational new drug (IND) application filing expected in 2018

Terrestrial Myriametric Radio Burst Observed by IMAGE and Geotail Satellites

We report IMAGE and Geotail simultaneous observations of a terrestrial myriametric radio burst (TMRB) detected on August 19, 2001. The TMRB was confined in time (0830-1006 UT) and frequency (12-50 kHz), suggesting a fan beam-like emission pattern from a single discrete source. Analysis and comparisons with existing TMR radiations strongly suggest that the TMRB is a distinct emission perhaps resulting from dayside magnetic reconnection instigated by northward interplanetary field condition

Terrestrial Myriametric Radio Burst Observed by IMAGE and Geotail Satellites

We report the simultaneous detection of a terrestrial myriametric radio burst (TMRB) by IMAGE and Geotail on 19 August 2001. The TMRB was confined in time (0830-1006 UT) and frequency (12-50kHz). Comparisons with all known nonthermal myriametric radiation components reveal that the TMRB might be a distinct radiation with a source that is unrelated to the previously known radiation. Considerations of beaming from spin-modulation analysis and observing satellite and source locations suggest that the TMRB may have a fan beamlike radiation pattern emitted by a discrete, dayside source located along the poleward edge of magnetospheric cusp field lines. TMRB responsiveness to IMF Bz and By orientations suggests that a possible source of the TMRB could be due to dayside magnetic reconnection instigated by northward interplanetary field condition

Ethnobotanical knowledge and crop diversity in swidden fields: a study in a native Amazonian society

Crop diversity protects food consumption in poor households within developing nations. Here we estimate the association between crop diversity on swidden fields and ethnobotanical knowledge. We conducted research among 215 male household heads from a native Amazonian society. Using multivariate regressions, we found higher crop diversity among households that depend on agricultural production for household consumption. We also found a statistically significant and positive, but low, association between the ethnobotanical knowledge of the male household head and crop diversity. Doubling the stock of ethnobotanical knowledge of the male household head is associated with a 9% increase in the number of crops sown by a household. The association remained after we controlled for the household level of market exposure, but vanished after we controlled for the social capital of the male household head. Future research should compare the association between ethnobotanical knowledge and crop diversity across different agricultural systems (i.e., home gardens, fallow fields)

Extraction and inhibition of enzymatic activity of botulinum neurotoxins /B1, /B2, /B3, /B4, and /B5 by a panel of monoclonal anti-BoNT/B antibodies

<p>Abstract</p> <p>Background</p> <p>Botulism is caused by botulinum neurotoxins (BoNTs), extremely toxic proteins which can induce respiratory failure leading to long-term intensive care or death. Treatment for botulism includes administration of antitoxins, which must be administered early in the course of the intoxication; therefore, rapid determination of human exposure to BoNT is an important public health goal. In previous work, our laboratory reported on Endopep-MS, a mass spectrometry-based activity method for detecting and differentiating BoNT/A, /B, /E, and /F in clinical samples. We also demonstrated that antibody-capture is effective for purification and concentration of BoNTs from complex matrices such as clinical samples. However, some antibodies inhibit or neutralize the enzymatic activity of BoNT, so the choice of antibody for toxin extraction is critical.</p> <p>Results</p> <p>In this work, we evaluated 24 anti-BoNT/B monoclonal antibodies (mAbs) for their ability to inhibit the <it>in vitro </it>activity of BoNT/B1, /B2, /B3, /B4, and /B5 and to extract those toxins. Among the mAbs, there were significant differences in ability to extract BoNT/B subtypes and inhibitory effect on BoNT catalytic activity. Some of the mAbs tested enhanced the <it>in vitro </it>light chain activity of BoNT/B, suggesting that BoNT/B may undergo conformational change upon binding some mAbs.</p> <p>Conclusions</p> <p>In addition to determining <it>in vitro </it>inhibition abilities of a panel of mAbs against BoNT/B1-/B5, this work has determined B12.2 and 2B18.2 to be the best mAbs for sample preparation before Endopep-MS. These mAb characterizations also have the potential to assist with mechanistic studies of BoNT/B protection and treatment, which is important for studying alternative therapeutics for botulism.</p

Effects of galactic dark halo rotation on WIMP direct detection

The effects of a possible rotation of the galactic dark halo on the calculation of the direct detection rates for particle dark matter are analyzed, with special attention to the extraction of the upper limits on the WIMP--nucleon scalar cross section from the experimental data. We employ a model of dark halo rotation which describes the maximal possible effects. For WIMP masses above 50 GeV, the upper limit exclusion plot is modified by less than a factor of two when rotation is included. For lighter masses the effect can be stronger, suggesting the necessity to develop specific models of halo rotation in order to provide more accurate conclusions.Comment: 14 pages, 7 figures included as PS file

Paediatric obsessive-compulsive disorder and depressive symptoms: clinical correlates and CBT treatment outcomes.

Depression frequently co-occurs with paediatric obsessive-compulsive disorder (OCD), yet the clinical correlates and impact of depression on CBT outcomes remain unclear. The prevalence and clinical correlates of depression were examined in a paediatric specialist OCD-clinic sample (N = 295; Mean = 15 [7 - 18] years, 42 % female), using both dimensional (Beck Depression Inventory-youth; n = 261) and diagnostic (Development and Wellbeing Assessment; n = 127) measures of depression. The impact of depressive symptoms and suspected disorders on post-treatment OCD severity was examined in a sub-sample who received CBT, with or without SSRI medication (N = 100). Fifty-one per-cent of patients reported moderately or extremely elevated depressive symptoms and 26 % (95 % CI: 18 - 34) met criteria for a suspected depressive disorder. Depressive symptoms and depressive disorders were associated with worse OCD symptom severity and global functioning prior to CBT. Individuals with depression were more likely to be female, have had a psychiatric inpatient admission and less likely to be attending school (ps < 0.01). OCD and depressive symptom severity significantly decreased after CBT. Depressive symptoms and depressive disorders predicted worse post-treatment OCD severity (βs = 0.19 and 0.26, ps < 0.05) but became non-significant when controlling for pre-treatment OCD severity (βs = 0.05 and 0.13, ns). Depression is common in paediatric OCD and is associated with more severe OCD and poorer functioning. However, depression severity decreases over the course of CBT for OCD and is not independently associated with worse outcomes, supporting the recommendation for treatment as usual in the presence of depressive symptoms

What factors are associated with recent intimate partner violence? findings from the WHO multi-country study on women's health and domestic violence

<p>Abstract</p> <p>Background</p> <p>Intimate partner violence (IPV) against women is a global public health and human rights concern. Despite a growing body of research into risk factors for IPV, methodological differences limit the extent to which comparisons can be made between studies. We used data from ten countries included in the WHO Multi-country Study on Women's Health and Domestic Violence to identify factors that are consistently associated with abuse across sites, in order to inform the design of IPV prevention programs.</p> <p>Methods</p> <p>Standardised population-based household surveys were done between 2000 and 2003. One woman aged 15-49 years was randomly selected from each sampled household. Those who had ever had a male partner were asked about their experiences of physically and sexually violent acts. We performed multivariate logistic regression to identify predictors of physical and/or sexual partner violence within the past 12 months.</p> <p>Results</p> <p>Despite wide variations in the prevalence of IPV, many factors affected IPV risk similarly across sites. Secondary education, high SES, and formal marriage offered protection, while alcohol abuse, cohabitation, young age, attitudes supportive of wife beating, having outside sexual partners, experiencing childhood abuse, growing up with domestic violence, and experiencing or perpetrating other forms of violence in adulthood, increased the risk of IPV. The strength of the association was greatest when both the woman and her partner had the risk factor.</p> <p>Conclusions</p> <p>IPV prevention programs should increase focus on transforming gender norms and attitudes, addressing childhood abuse, and reducing harmful drinking. Development initiatives to improve access to education for girls and boys may also have an important role in violence prevention.</p