Controlled Release Spatial Repellent Devices (CRDS) as Novel Tools Against Malaria Transmission: A Semi-Field Study in Macha, Zambia

Background: The emergence of mosquitoes that can avoid indoor-deployed interventions, such as treated bed nets and indoor residual spraying, threatens the mainstay of malaria control in Zambia. Furthermore, the requirement for high coverage of these tools poses operational challenges. Spatial repellents are being assessed to supplement these vector control tools, but limitations exist in the residual effect of the repellent and the need for external power or heat for diffusion of the volatiles. Methods: A semi-field evaluation of a novel controlled release spatial repellent device (CRD) was conducted in Macha, Zambia. These devices emanate metofluthrin with no need for external power. Devices were deployed in huts within the semi-field system (SFS). Female Anopheles gambiae sensu stricto released within the SFS were trapped overnight by light traps and collected by aspiration the next morning inside and outside of huts to determine the extent of mosquito repellency and the impact on host-seeking and survival. Experiments studied the impact of number of devices as well as the presence of hut occupants. The study was complemented with numerical methods based on computational fluid dynamics to simulate spatial distribution of metofluthrin. Results: Presence of CRDs was associated with significant reductions in indoor counts of mosquitoes, regardless of whether huts were occupied or not. Repellency ranged from 15 to 60% compared to huts with no devices. Reducing the number of devices from 16 to 4 had little impact on repellency. When huts were occupied, indoor mosquito host-seeking was higher in the presence of CRDs, whilst survival was significantly reduced. Conclusions: This study demonstrated that deployment of as few as four CRDs within a hut was associated with reduced indoor mosquito densities. As would be expected, presence of occupants within huts, resulted in greater indoor catches (both with and without devices). The increased indoor mosquito host-seeking and mortality in huts when devices were present may be explained by the excito-repellency activity of metofluthrin. These semi-field experiments provide preliminary data on the utility of CRD spatial repellents to reduce indoor densities of An. gambiae mosquitoes. Studies will further investigate the impact of CRDs on mosquito behaviour as well as epidemiological protective efficacy

Mutuality of Rogers's therapeutic conditions and treatment progress in the first three psychotherapy sessions

Abstract Objective: Research on the effects of Rogers’s therapeutic relationship conditions has typically focused on the unilateral provision of empathy, unconditional positive regard, and congruence from therapist to client. Method: This study looked at both client and therapist mutuality of the Rogerian therapeutic conditions and the association between mutuality and treatment progress in the first three psychotherapy sessions. Clients (N = 62; mean age = 24.32; 77% female, 23% male) and therapists (N = 12; mean age = 34.32; nine female and three male) rated one another using the Barrett-Lennard Relationship Inventory after the first and third session. Results: Both clients and therapists perceived the quality of the relationship as improved over time. Client rating of psychological distress (CORE-OM) was lower after session 3 than at session 1 (es = .85, [95% CIs: .67, 1.03]). Hierarchical multiple regression was used to test the predictive power of mutually high levels of the therapeutic conditions on treatment progress. The association between client rating of therapist-provided conditions and treatment progress at session 3 was higher when both clients and therapists rated each other as providing high levels of the therapeutic conditions (R2 change = .073, p < .03). Conclusions: The findings suggest mutuality of Rogers’s therapeutic conditions is related to treatment progress. Keywords: therapeutic relationship; psychotherapy; mutuality; treatment progres

A case of polyarteritis nodosa limited to the right calf muscles, fascia, and skin: a case report

<p>Abstract</p> <p>Introduction</p> <p>Limited polyarteritis nodosa is a rare benign disease that usually responds well to systemic corticosteroid treatment. We report a case limited to calf muscles, fascia, and skin treated with local corticosteroid therapy directed to the affected areas by ultrasound guidance.</p> <p>Case presentation</p> <p>A 36-year-old Caucasian woman presented with a 10-month history of progressive right calf pain and swelling, which were unresponsive to treatment with non-steroidal anti-inflammatory drugs and physiotherapy. An examination revealed a swollen tender right calf with indurated overlying skin. Laboratory investigations showed an erythrocyte sedimentation rate of 24 mm/hour and a C-reactive protein of 15 mg/dl. Full blood count, renal profile, and creatinine kinase level were normal. A full autoantibody screen and hepatitis B and C serology results were negative. A chest X-ray was unremarkable. Magnetic resonance imaging of the right leg revealed increased signal intensity in T2-weighted images and this was suggestive of extensive inflammatory changes of the gastrocnemius muscle and, to a lesser extent, the soleus muscle. There were marked inflammatory changes throughout the gastrocnemius muscle and the subcutaneous tissue circumferentially around the right lower leg. A biopsy of affected skin, muscle, and fascia showed histopathological features consistent with polyarteritis nodosa, including small-vessel vasculitis with fibrinoid changes in the vessel wall and intense perivascular and focal mural chronic inflammatory changes. Our patient declined treatment with oral steroids. She received a course of ultrasound-guided injections of steroid (Depo-Medrone, methylprednisolone) in the involved muscle area and commenced maintenance azathioprine with a good response.</p> <p>Conclusions</p> <p>Limited polyarteritis nodosa is rare and affects middle-aged individuals. In most cases, treatment with moderate- to high-dose corticosteroids gives symptomatic relief within one week. Resistant cases require treatment with cytotoxics or intravenous immunoglobulins. This case demonstrates response to local targeted steroid therapy as an alternative to systemic steroids.</p

Non-linear numerical simulations of magneto-acoustic wave propagation in small-scale flux tubes

We present results of non-linear, 2D, numerical simulations of magneto-acoustic wave propagation in the photosphere and chromosphere of small-scale flux tubes with internal structure. Waves with realistic periods of three to five minutes are studied, after applying horizontal and vertical oscillatory perturbations to the equilibrium model. Spurious reflections of shock waves from the upper boundary are minimized thanks to a special boundary condition. This has allowed us to increase the duration of the simulations and to make it long enough to perform a statistical analysis of oscillations. The simulations show that deep horizontal motions of the flux tube generate a slow (magnetic) mode and a surface mode. These modes are efficiently transformed into a slow (acoustic) mode in the vA < cS atmosphere. The slow (acoustic) mode propagates vertically along the field lines, forms shocks and remains always within the flux tube. It might deposit effectively the energy of the driver into the chromosphere. When the driver oscillates with a high frequency, above the cut-off, non-linear wave propagation occurs with the same dominant driver period at all heights. At low frequencies, below the cut-off, the dominant period of oscillations changes with height from that of the driver in the photosphere to its first harmonic (half period) in the chromosphere. Depending on the period and on the type of the driver, different shock patterns are observed.Comment: 22 pages 6 color figures, submitted to Solar Physics, proceeding of SOHO 19/ GONG 2007 meeting, Melbourne, Australi

The copper centers of tyramine β-monooxygenase and its catalytic-site methionine variants: an X-ray absorption study

Tyramine β-monooxygenase (TBM) is a member of a family of copper monooxygenases containing two noncoupled copper centers, and includes peptidylglycine monooxygenase and dopamine β-monooxygenase. In its Cu(II) form, TBM is coordinated by two to three His residues and one to two non-His O/N ligands consistent with a [CuM(His)2(OH2)2–CuH(His)3(OH2)] formulation. Reduction to the Cu(I) state causes a change in the X-ray absorption spectroscopy (XAS) spectrum, consistent with a change to a [CuM(His)2S(Met)–CuH(His)3] environment. Lowering the pH to 4.0 results in a large increase in the intensity of the Cu(I)–S extended X-ray absorption fine structure (EXAFS) component, suggesting a tighter Cu–S bond or the coordination of an additional sulfur donor. The XAS spectra of three variants, where the CuM Met471 residue had been mutated to His, Cys, and Asp, were examined. Significant differences from the wild-type enzyme are evident in the spectra of the reduced mutants. Although the side chains of His, Cys, and Asp are expected to substitute for Met at the CuM site, the data showed identical spectra for all three reduced variants, with no evidence for coordination of residue 471. Rather, the K-edge data suggested a modest decrease in coordination number, whereas the EXAFS indicated an average of two His residues at each Cu(I) center. These data highlight the unique role of the Met residue at the CuM center, and pose interesting questions as to why replacement by the cuprophilic thiolate ligand leads to detectable activity whereas replacement by imidazole generates inactive TBM

Frequency drifts of 3-min oscillations in microwave and EUV emission above sunspots

We analyse 3-min oscillations of microwave and EUV emission generated at different heights of a sunspot atmosphere, studying the amplitude and frequency modulation of the oscillations, and its relationship with the variation of the spatial structure of the oscillations. High-resolution data obtained with the Nobeyama Radioheliograph, TRACE and SDO/AIA are analysed with the use of the Pixelised Wavelet Filtering and wavelet skeleton techniques. 3-min oscillations in sunspots appear in the form of repetitive trains of the duration 8-20 min (13 min in average). The typical interval between the trains is 30-50 min. The oscillation trains are transient in frequency and power. We detected a repetitive frequency drifts of 3-min oscillations during the development of individual trains. Wavelet analysis shows three types of the frequency drift: positive, negative and fluctuations without drift. The start and end of the drifts coincide with the start time and end of the train. The comparative study of 3-min oscillations in the sequences of microwave and EUV images show the appearance of new sources of the oscillations in sunspots during the development of the trains. These structures can be interpreted as waveguides that channel upward propagating waves, responsible for 3-min oscillations. A possible explanation of the observed properties is the operation of two simultaneous factors: dispersive evolution of the upwardly-propagating wave pulses and the non-uniformity of the distribution of the oscillation power over the sunspot umbra with different wave sources corresponding to different magnetic flux tubes with different physical conditions and line-of-sight angles.Comment: 12 pages, 11 figures, submitted to A&A, 201

Modeling the Subsurface Structure of Sunspots

While sunspots are easily observed at the solar surface, determining their subsurface structure is not trivial. There are two main hypotheses for the subsurface structure of sunspots: the monolithic model and the cluster model. Local helioseismology is the only means by which we can investigate subphotospheric structure. However, as current linear inversion techniques do not yet allow helioseismology to probe the internal structure with sufficient confidence to distinguish between the monolith and cluster models, the development of physically realistic sunspot models are a priority for helioseismologists. This is because they are not only important indicators of the variety of physical effects that may influence helioseismic inferences in active regions, but they also enable detailed assessments of the validity of helioseismic interpretations through numerical forward modeling. In this paper, we provide a critical review of the existing sunspot models and an overview of numerical methods employed to model wave propagation through model sunspots. We then carry out an helioseismic analysis of the sunspot in Active Region 9787 and address the serious inconsistencies uncovered by \citeauthor{gizonetal2009}~(\citeyear{gizonetal2009,gizonetal2009a}). We find that this sunspot is most probably associated with a shallow, positive wave-speed perturbation (unlike the traditional two-layer model) and that travel-time measurements are consistent with a horizontal outflow in the surrounding moat.Comment: 73 pages, 19 figures, accepted by Solar Physic

Effects and safety of rituximab in systemic sclerosis: An analysis from the European Scleroderma Trial and Research (EUSTAR) group

Objectives: To assess the effects of Rituximab (RTX) on skin and lung fibrosis in patients with systemic sclerosis (SSc) belonging to the European Scleroderma Trial and Research (EUSTAR) cohort and using a nested case-control design. Methods: Inclusion criteria were fulfilment of American College of Rheumatology classification criteria for SSc, treatment with RTX and availability of follow-up data. RTX-treated patients were matched with control patients from the EUSTAR database not treated with RTX. Matching parameters for skin/lung fibrosis were the modified Rodnan Skin Score (mRSS), forced vital capacity (FVC), follow-up duration, scleroderma subtype, disease duration and immunosuppressive co-treatment. The primary analysis was mRSS change from baseline to follow-up in the RTX group compared with the control group. Secondary analyses included change of FVC and safety measures. Results: 63 patients treated with RTX were included in the analysis. The case-control analysis in patients with severe diffuse SSc showed that mRSS changes were larger in the RTX group versus matched controls (N=25; -24.0±5.2% vs-7.7±4.3%; p=0.03). Moreover, in RTX-treated patients, the mean mRSS was significantly reduced at follow-up compared with baseline (26.6±1.4 vs 20.3±1.8; p=0.0001). In addition, in patients with interstitial lung disease, RTX prevented significantly the further decline of FVC compared with matched controls (N=9; 0.4±4.4% vs-7.7±3.6%; p=0.02). Safety measures showed a good profile consistent with previous studies in autoimmune rheumatic diseases. Conclusions: The comparison of RTX treated versus untreated matched-control SSc patients from the EUSTAR cohort demonstrated improvement of skin fibrosis and prevention of worsening lung fibrosis, supporting the therapeutic concept of B cell inhibition in SSc

Inhibition of Toxic Shock by Human Monoclonal Antibodies against Staphylococcal Enterotoxin B

BACKGROUND: Staphylococcus aureus is implicated in many opportunistic bacterial infections around the world. Rising antibiotic resistance and few alternative methods of treatment are just two looming problems associated with clinical management of S. aureus. Among numerous virulence factors produced by S. aureus, staphylococcal enterotoxin (SE) B is a secreted protein that binds T-cell receptor and major histocompatibility complex class II, potentially causing toxic shock mediated by pathological activation of T cells. Recombinant monoclonal antibodies that target SEB and block receptor interactions can be of therapeutic value. METHODOLOGY/PRINCIPAL FINDINGS: The inhibitory and biophysical properties of ten human monoclonal antibodies, isolated from a recombinant library by panning against SEB vaccine (STEBVax), were examined as bivalent Fabs and native full-length IgG (Mab). The best performing Fabs had binding affinities equal to polyclonal IgG, low nanomolar IC(50)s against SEB in cell culture assays, and protected mice from SEB-induced toxic shock. The orthologous staphylococcal proteins, SEC1 and SEC2, as well as streptococcal pyrogenic exotoxin C were recognized by several Fabs. Four Fabs against SEB, with the lowest IC(50)s, were converted into native full-length Mabs. Although SEB-binding kinetics were identical between each Fab and respective Mab, a 250-fold greater inhibition of SEB-induced T-cell activation was observed with two Mabs. CONCLUSIONS/SIGNIFICANCE: Results suggest that these human monoclonal antibodies possess high affinity, target specificity, and toxin neutralization qualities essential for any therapeutic agent