InfuShield: a shielded enclosure for administering therapeutic radioisotope treatments using standard syringe pumps.

The administration of radionuclide therapies presents significant radiation protection challenges. The aim of this work was to develop a delivery system for intravenous radioisotope therapies to substantially moderate radiation exposures to staff and operators. A novel device (InfuShield) was designed and tested before being used clinically. The device consists of a shielded enclosure which contains the therapeutic activity and, through the hydraulic action of back-to-back syringes, allows the activity to be administered using a syringe pump external to the enclosure. This enables full access to the pump controls while simultaneously reducing dose to the operator. The system is suitable for use with all commercially available syringe pumps and does not require specific consumables, maximising both the flexibility and economy of the system. Dose rate measurements showed that at key stages in an I mIBG treatment procedure, InfuShield can reduce dose to operators by several orders of magnitude. Tests using typical syringes and infusion speeds show no significant alteration in administered flow rates (maximum of 1.2%). The InfuShield system provides a simple, safe and low cost method of radioisotope administration

Kestenbaum procedure with posterior fixation suture for anomalous head posture in infantile nystagmus

The purpose of this study was to report the effect of combining the Kestenbaum procedure with posterior fixation suture for infantile horizontal nystagmus with anomalous head posture (AHP) in children. Nine consecutive patients who underwent combined Kestenbaum procedure plus posterior fixation suture to the recessed muscles at the same time were retrospectively studied. All patients were orthotropic before surgery and were followed for at least 6 months. Pre- and postoperative AHP and binocular corrected visual acuity (BCVA), and ocular alignment were assessed. Mean age at surgery was 4.8 ± 1.5 years. The average follow-up was 29.7 months. The average head turn preoperatively was 27.4° and postoperatively 7.2°. The average net change in AHP was 24.8° (P = 0.008). Seven of 9 patients (78%) achieved a residual head turn of 10° or less. The average Log Mar BCVA was 0.33 preoperatively and 0.31 postoperatively (P = 0.68). Only 1 patient needed additional surgery for residual horizontal AHP. No patient developed strabismus. Combined Kestenbaum procedure with posterior fixation suture was an effective and stable procedure in reducing AHP of the range of 20° to 35° in children with infantile nystagmus

A Minimal Threshold of c-di-GMP Is Essential for Fruiting Body Formation and Sporulation in Myxococcus xanthus

Generally, the second messenger bis-(3’-5’)-cyclic dimeric GMP (c-di-GMP) regulates the switch between motile and sessile lifestyles in bacteria. Here, we show that c-di-GMP is an essential regulator of multicellular development in the social bacterium Myxococcus xanthus. In response to starvation, M. xanthus initiates a developmental program that culminates in formation of spore-filled fruiting bodies. We show that c-di-GMP accumulates at elevated levels during development and that this increase is essential for completion of development whereas excess c-di-GMP does not interfere with development. MXAN3735 (renamed DmxB) is identified as a diguanylate cyclase that only functions during development and is responsible for this increased c-di-GMP accumulation. DmxB synthesis is induced in response to starvation, thereby restricting DmxB activity to development. DmxB is essential for development and functions downstream of the Dif chemosensory system to stimulate exopolysaccharide accumulation by inducing transcription of a subset of the genes encoding proteins involved in exopolysaccharide synthesis. The developmental defects in the dmxB mutant are non-cell autonomous and rescued by co-development with a strain proficient in exopolysaccharide synthesis, suggesting reduced exopolysaccharide accumulation as the causative defect in this mutant. The NtrC-like transcriptional regulator EpsI/Nla24, which is required for exopolysaccharide accumulation, is identified as a c-diGMP receptor, and thus a putative target for DmxB generated c-di-GMP. Because DmxB can be—at least partially—functionally replaced by a heterologous diguanylate cyclase, these results altogether suggest a model in which a minimum threshold level of c-di-GMP is essential for the successful completion of multicellular development in M. xanthus

Multi-photon ionisation spectroscopy for rotational state preparation of N+2

In this paper we investigate the 2 + 1′ resonance enhanced multi-photon ionisation (REMPI) of molecular nitrogen via the a1Πg(v = 6) intermediate state and analyse its feasibility to generate molecular nitrogen ions in a well defined ro-vibrational state. This is an important tool for high precision experiments based on trapped molecular ions, and is crucial for studying the time variation of the fundamental constant mp/me using N+2. The transition is not reported in the literature and detailed spectral analysis has been conducted to extract the molecular constants of the intermediate state. By carefully choosing the intermediate ro-vibrational state, the ionisation laser wavelength and controlling the excitation laser pulse energy, unwanted formation of rotationally excited molecular ions can be suppressed and ro-vibrational ground state ions can be generated with high purity

Redrawing Boundaries: WITNESS and the Politics of Citizen Videos

This article engages with several pressing issues revolving around ‘citizen witnessing’, with specific reference to the human rights advocacy group, WITNESS. In the course of tracing WITNESS’ development over the past two decades, it offers an evaluative assessment of the challenges its members have faced in promoting a grassroots, citizen-centred approach to video reportage. More specifically, this advocacy is informed by an ethical commitment to advancing human rights causes by equipping citizens in crisis situations with cameras, and the training to use them, so that they might bear witness to the plight of others. In so doing, this article argues, WITNESS offers a tactical reformulation of the guiding tenets of peace journalism, one with considerable potential for recasting anew its strategic priorities

Influence of HLA-DRB1 and HLA-DQB1 Alleles on IgG Antibody Response to the P. vivax MSP-1, MSP-3α and MSP-9 in Individuals from Brazilian Endemic Area

Background: the antibody response generated during malaria infections is of particular interest, since the production of specific IgG antibodies is required for acquisition of clinical immunity. However, variations in antibody responses could result from genetic polymorphism of the HLA class II genes. Given the increasing focus on the development of subunit vaccines, studies of the influence of class II alleles on the immune response in ethnically diverse populations is important, prior to the implementation of vaccine trials.Methods and Findings: in this study, we evaluated the influence of HLA-DRB1* and -DQB1* allelic groups on the naturally acquired humoral response from Brazilian Amazon individuals (n = 276) against P. vivax Merozoite Surface Protein-1 (MSP-1), MSP-3 alpha and MSP-9 recombinant proteins. Our results provide information concerning these three P. vivax antigens, relevant for their role as immunogenic surface proteins and vaccine candidates. Firstly, the studied population was heterogeneous presenting 13 HLA-DRB1* and 5 DQB1* allelic groups with a higher frequency of HLA-DRB1*04 and HLA-DQB1*03. the proteins studied were broadly immunogenic in a naturally exposed population with high frequency of IgG antibodies against PvMSP1-19 (86.7%), PvMSP-3 (77%) and PvMSP-9 (76%). Moreover, HLA-DRB1*04 and HLA-DQB1*03 alleles were associated with a higher frequency of IgG immune responses against five out of nine antigens tested, while HLA-DRB1* 01 was associated with a high frequency of non-responders to repetitive regions of PvMSP-9, and the DRB1*16 allelic group with the low frequency of responders to PvMSP3 full length recombinant protein.Conclusions: HLA-DRB1*04 alleles were associated with high frequency of antibody responses to five out of nine recombinant proteins tested in Rondonia State, Brazil. These features could increase the success rate of future clinical trials based on these vaccine candidates.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Yerkes National Primate Research Center BaseNational Center for Research Resources of the National Institutes of HealthNIHCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Inst Oswaldo Cruz, Lab Immunoparasitol, BR-20001 Rio de Janeiro, BrazilOswaldo Cruz Fdn Fiocruz, Ctr Technol Dev Hlth CDTS, Rio de Janeiro, BrazilInst Oswaldo Cruz, Lab Simulideos & Oncocercose, BR-20001 Rio de Janeiro, BrazilEmory Univ, Emory Vaccine Ctr, Atlanta, GA 30322 USAUniv Estado Rio de Janeiro, Histocompatibil & Cryopreservat Lab, Rio de Janeiro, BrazilUniversidade Federal de São Paulo, Ctr Terapia Celular & Mol CTCMol, Escola Paulista Med, São Paulo, BrazilEmory Univ, Sch Med, Div Infect Dis, Atlanta, GA USACDC Natl Ctr Infect Dis, Div Parasit Dis, Atlanta, GA USAUniversidade Federal de São Paulo, Ctr Terapia Celular & Mol CTCMol, Escola Paulista Med, São Paulo, BrazilFAPESP: 2009/15132-4Yerkes National Primate Research Center Base: RR00165NIH: RO1 AI0555994Web of Scienc

Evidence That Descending Cortical Axons Are Essential for Thalamocortical Axons to Cross the Pallial-Subpallial Boundary in the Embryonic Forebrain

Developing thalamocortical axons traverse the subpallium to reach the cortex located in the pallium. We tested the hypothesis that descending corticofugal axons are important for guiding thalamocortical axons across the pallial-subpallial boundary, using conditional mutagenesis to assess the effects of blocking corticofugal axonal development without disrupting thalamus, subpallium or the pallial-subpallial boundary. We found that thalamic axons still traversed the subpallium in topographic order but did not cross the pallial-subpallial boundary. Co-culture experiments indicated that the inability of thalamic axons to cross the boundary was not explained by mutant cortex developing a long-range chemorepulsive action on thalamic axons. On the contrary, cortex from conditional mutants retained its thalamic axonal growth-promoting activity and continued to express Nrg-1, which is responsible for this stimulatory effect. When mutant cortex was replaced with control cortex, corticofugal efferents were restored and thalamic axons from conditional mutants associated with them and crossed the pallial-subpallial boundary. Our study provides the most compelling evidence to date that cortical efferents are required to guide thalamocortical axons across the pallial-subpallial boundary, which is otherwise hostile to thalamic axons. These results support the hypothesis that thalamic axons grow from subpallium to cortex guided by cortical efferents, with stimulation from diffusible cortical growth-promoting factors

Functional Assessment of EnvZ/OmpR Two-Component System in Shewanella oneidensis

EnvZ and OmpR constitute the bacterial two-component signal transduction system known to mediate osmotic stress response in a number of Gram-negative bacteria. In an effort to understand the mechanism through which Shewanella oneidensis senses and responds to environmental osmolarity changes, structure of the ompR-envZ operon was determined with Northern blotting assay and roles of the EnvZ/OmpR two-component system in response to various stresses were investigated with mutational analysis, quantitative reverse transcriptase PCR (qRT-PCR), and phenotype microarrays. Results from the mutational analysis and qRT-PCR suggested that the EnvZ/OmpR system contributed to osmotic stress response of S. oneidensis and very likely engaged a similar strategy employed by E. coli, which involved reciprocal regulation of two major porin coding genes. Additionally, the ompR-envZ system was also found related to cell motility. We further showed that the ompR-envZ dependent regulation of porin genes and motility resided almost completely on ompR and only partially on envZ, indicating additional mechanisms for OmpR phosphorylation. In contrast to E. coli lacking ompR-envZ, however, growth of S. oneidensis did not show a significant dependence on ompR-envZ even under osmotic stress. Further analysis with phenotype microarrays revealed that the S. oneidensis strains lacking a complete ompR-envZ system displayed hypersensitivities to a number of agents, especially in alkaline environment. Taken together, our results suggest that the function of the ompR-envZ system in S. oneidensis, although still connected with osmoregulation, has diverged considerably from that of E. coli. Additional mechanism must exist to support growth of S. oneidensis under osmotic stress

Altered cardiac autonomic nervous function in depression

Background:Depression is an independent risk factor for coronary artery disease. Autonomic instability may play a mediating or moderating role in this relationship; however this is not well understood. The objective of this study was to explore cardiac autonomic function and cardiac arrhythmia in depression, the correlation between depression severity and Heart Rate Variability (HRV) related indices, and the prevalence of arrhythmia.Methods:Individuals (n = 53) with major depression as assessed by the Diagnostic and Statistical Manual of Mental Disorders, who had a Hamilton Rating Scale for Depression (HAMD) score ≥20 and a Zung Self-Rating Depression Scale score > 53 were compared to 53 healthy individuals, matched for age and gender. Multichannel Electrocardiograph ECG-92C data were collected over 24 hours. Long-term changes in HRV were used to assess the following vagally mediated changes in autonomic tone, expressed as time domain indices: Standard deviation of the NN intervals (SDNN), standard deviation of 5 min averaged NN intervals (SDANN), Root Mean Square of the Successive Differences (RMSSD) and percentage of NN intervals > 50 ms different from preceding interval (pNN50). Pearson’s correlations were conducted to explore the strength of the association between depression severity (using the SDS and HRV related indices, specifically SDNN and low frequency domain / high frequency domain (LF/HF)).Results:The values of SDNN, SDANN, RMSSD, PNN50 and HF were lower in the depression group compared to the control group (P<.05). The mean value of the LF in the depression group was higher than the in control group (P<.05). Furthermore the ratio of LF/HF was higher among the depression group than the control group (P<.05). A linear relationship was shown to exist between the severity of the depression and HRV indices. In the depression group, the prevalence of arrhythmia was significantly higher than in the control group (P<.05), particularly supraventricular arrhythmias.Conclusions:Our findings suggest that depression is accompanied by dysfunction of the cardiac autonomic nervous system, and further, that depression severity is linked to severity of this dysfunction. Individuals with depression appear to be susceptible to premature atrial and/or ventricular disease

Recombinant Vesicular Stomatitis Virus Vaccine Vectors Expressing Filovirus Glycoproteins Lack Neurovirulence in Nonhuman Primates

The filoviruses, Marburg virus and Ebola virus, cause severe hemorrhagic fever with high mortality in humans and nonhuman primates. Among the most promising filovirus vaccines under development is a system based on recombinant vesicular stomatitis virus (rVSV) that expresses an individual filovirus glycoprotein (GP) in place of the VSV glycoprotein (G). The main concern with all replication-competent vaccines, including the rVSV filovirus GP vectors, is their safety. To address this concern, we performed a neurovirulence study using 21 cynomolgus macaques where the vaccines were administered intrathalamically. Seven animals received a rVSV vector expressing the Zaire ebolavirus (ZEBOV) GP; seven animals received a rVSV vector expressing the Lake Victoria marburgvirus (MARV) GP; three animals received rVSV-wild type (wt) vector, and four animals received vehicle control. Two of three animals given rVSV-wt showed severe neurological symptoms whereas animals receiving vehicle control, rVSV-ZEBOV-GP, or rVSV-MARV-GP did not develop these symptoms. Histological analysis revealed major lesions in neural tissues of all three rVSV-wt animals; however, no significant lesions were observed in any animals from the filovirus vaccine or vehicle control groups. These data strongly suggest that rVSV filovirus GP vaccine vectors lack the neurovirulence properties associated with the rVSV-wt parent vector and support their further development as a vaccine platform for human use