Measuring public-health outcomes of release of transgenic mosquitoes

The transgenic RIDL method could ensure that male mosquitos can be released without biting females and that the males would have no female progeny after mating to wild females. Urban Anopheles or Aedes vector populations, surrounded by different species in rural areas, would seem to be the most appropriate targets for such releases, aiming at eradication. In urban areas intensity of transmission is generally not very high and the public-health outcomes of such urban programmes could be monitored by passive surveillance through health facilities or by active surveillance for infections with or without associated symptoms. The alternative use of transgenic mosquitos would be to produce strains refractory to infection by pathogens such as Plasmodium and to drive such genes into wild populations. In theory, in contrast to sterile-male eradication, such a procedure could "resist" a limited level of immigration and could open up the possibility of using the method against African rural malaria. However, in practice it would seem extremely difficult or impossible to ensure the necessary complete linkage of the refractoriness genes to the driving system. If this problem could be overcome one could monitor the impact of the spreading of the refractoriness genes by its impact on (i) the sporozoite rate in the wild population; (ii) the incidence of re-infection after clearing existing infections with an appropriate drug treatment; (iii) active surveillance for prevalence of malaria fever and anaemia in children; (iv) attacks of severe malaria and deaths monitored though hospitals and village reporters

A New Family of Boundary-Domain Integral Equations for a Mixed Elliptic BVP with Variable Coefficient

A mixed boundary value problem for the stationary heat transfer partial differential equation with variable coefficient is reduced to some systems of direct segregated parametrix-based Boundary-Domain Integral Equations (BDIEs). We use a parametrix different from the one employed by Mikhailov (2002) and Chkadua, Mikhailov, Natroshvili (2009). Mapping properties of the potential type integral operators appearing in these equations are presented in appropriate Sobolev spaces. We prove the equivalence between the original BVP and the corresponding BDIE system. The invertibility and Fredholm properties of the boundary-domain integral operators are also analysed

MacMahon's sum-of-divisors functions, Chebyshev polynomials, and Quasi-modular forms

We investigate a relationship between MacMahon's generalized sum-of-divisors functions and Chebyshev polynomials of the first kind. This determines a recurrence relation to compute these functions, as well as proving a conjecture of MacMahon about their general form by relating them to quasi-modular forms. These functions arise as solutions to a curve-counting problem on Abelian surfaces.Comment: 6 Page

A methodology for comparing design processes

Engineering Design Centre, University of Cambridge; Design and Innovation, Open UniversityWe gain insights into design processes by recognising similarities to other processes, often in radically different industries. The crucial determinants of what happens are characteristics shared with some other design processes. But there is no way to draw on comparisons beyond one's own experience. We are developing a programme of comparative design research that aims to map the similarities and differences between design processes, and develop a deeper understanding of how and why design is done differently in different industries, and how effective practices can be transferred between industries. In this paper we outline a methodology for creating analyses of design processes that facilitates both cross-process comparisons and the integration of different analytical perspectives on design. The analyst draws on a catalogue of previous design process descriptions for useful concepts, to map processes as a network of participants and activities and the relationships between them, and describe the causal relationships between the properties of the participants, activities and relationships.EPSR

The feeding behaviour and Plasmodium infection of Anopheles mosquitoes in southern Ethiopia in relation to use of insecticide-treated livestock for malaria control.

Anopheles arabiensis and An. quadriannulatus species B mosquitoes were collected at sites of human and livestock housing and analysed for blood feeding patterns and infection with malaria sporozoites. A low percentage of human blood meals at some sites suggested that zooprophylaxis could be effective in reducing challenge from Plasmodium falciparum

Investigation of negative cross-resistance as a resistance-management tool for insecticide-treated nets.

Resistance management for insecticide-treated nets (ITNs) remains a challenge. Options are limited, because a safe and highly active insecticide with a persistence of several months is required. These criteria have only been met by pyrethroids, although organophosphates (OPs) and carbamates have been considered as alternatives for impregnation of eave curtains. It has been observed that some pyrethroid-resistant mosquito strains show increased OP susceptibility over pyrethroid-susceptible strains (i.e., negative cross-resistance). The current study investigated whether this phenomenon applies to a range of mosquito species and strains, because a mixture or rotation strategy for resistance management could then be envisaged. Adult female mosquitoes from laboratory strains of Anopheles stephensi Liston, Anopheles gambiae Giles, and Culex quinquefasciatus Say were tested in World Health Organization susceptibility test kits. For An. stephensi, the highly pyrethroid-resistant DUB 234 strain showed the same level of resistance to malathion as the pyrethroid-susceptible DUB S. The malathion-resistant ST MAL strain was as susceptible to pyrethroids as the insecticide-susceptible BEECH. For An. gambiae, the malathion tolerance of the previously pyrethroid-resistant RSP strain was significantly higher than that of the insecticide-susceptible KWA. For Cx. quinquefasciatus, selection of the QUINQ strain with permethrin abolished preexisting resistance to the OP malathion as pyrethroid resistance increased, rendering the strain more susceptible to malathion than PEL SS. Some indication of negative cross-resistance to malathion was found for the permethrin-resistant MUHEZA strain. The occurrence of negative cross-resistance seems dependent on the history of insecticide selection and is not generally applicable. Resistance management for ITNs will need to use mechanisms other than negative cross-resistance to be effective

Phase II evaluation of VDC-1101 in canine cutaneous T-cell lymphoma.

BackgroundCanine cutaneous T-cell lymphoma (CTCL) is an uncommon disease for which efficacious therapies are lacking. The novel anticancer nucleotide prodrug VDC-1101 (formerly known as GS-9219) has shown efficacy in dogs with multicentric lymphoma. One of the observed adverse effects with this drug was a skin change characterized by hair loss, erythema, and pruritus, implying delivery of VDC-1101 to the skin.Hypothesis/objectivesThe primary study objective was to identify the objective response rate (ORR) to VDC-1101 in canine CTCL; secondary objectives included characterization of progression-free survival (PFS) and adverse events (AEs).AnimalsTwelve dogs with chemotherapy-naïve or relapsed, histologically and immunohistochemically confirmed CTCL.MethodsDogs received VDC-1101 as a 30-minute IV infusion once every 21 days. Prednisone (1 mg/kg PO q48h) was administered concurrently.ResultsIn 11 evaluable patients, responses included 1 complete response (CR), 4 partial responses (PR), 2 stable disease (SD), and 4 progressive disease for an ORR of 45% and biologic response rate (CR/PR/SD) of 64%. The median PFS was 37.5 days (26 to >399 days), which includes 1 durable and ongoing CR (>1 year). Gastrointestinal and hematologic AEs were mild; no dogs developed grade 3 or 4 AEs. Three dogs developed dermatopathies and 1 of these dogs was removed from the study as a result of this AE.Conclusions and clinical importanceVDC-1101 has activity against canine CTCL and could provide another treatment option in a disease process with a poor prognosis