Research in development: the approach of AAS

The CGIAR Research Program on Aquatic Agricultural Systems (AAS) is pursuing a Research in Development approach that emphasizes the importance of embedding research in the development context. Reflecting this emphasis the six elements of this approach are a commitment to people and place, participatory action research, gender transformative research, learning and networking, partnerships, and capacity building. It is through the careful pursuit of these six elements that we believe that the program will achieve the development outcomes we aspire to, and do so at scale

Reply to Comment on “Sloppy models, parameter uncertainty, and the role of experimental design"

available in PMC 2012 November 10.We welcome the commentary from Chachra, Transtrum, and Sethna1 regarding our paper “Sloppy models, parameter uncertainty, and the role of experimental design,”2 as their intriguing work shaped our thinking in this area.3 Sethna and colleagues introduced the notion of sloppy models, in which the uncertainty in the values of some combinations of parameters is many orders of magnitude greater than others.4 In our work we explored the extent to which large parameter uncertainties are an intrinsic characteristic of systems biology network models, or whether uncertainties are instead closely related to the collection of experiments used for model estimation. We were gratified to find the latter result –– that parameters are in principle knowable, which is important for the field of systems biology. The work also showed that small parameter uncertainties can be achieved and that the process can be greatly accelerated by using computational experimental design approaches5–9 deployed to select sets of experiments that effectively exercise the system in complementary directions

Prevention of Group B Streptococcal Disease in the Newborn.

Group B streptococcus (GBS) is a leading cause of morbidity and mortality among newborns. Universal screening for GBS among women at 35 to 37 weeks of gestation is more effective than administration of intrapartum antibiotics based on risk factors. Lower vaginal and rectal cultures for GBS are collected at 35 to 37 weeks of gestation, and routine dindamycin and erythromycin susceptibility testing is performed in women allergic to penicillin. Women with GBS bacteriuria in the current pregnancy and those who previously delivered a GBS-septic newborn are not screened but automatically receive intrapartum antibiotics. Intrapartum chemoprophylaxis is selected based on maternal allergy history and susceptibility of GBS isolates. Intravenous penicillin G is the preferred antibiotic, with ampicillin as an alternative. Penicillin G should be administered at least four hours before delivery for maximum effectiveness. Cefazolin is recommended in women allergic to penicillin who are at low risk of anaphylaxis. Clindamycin and erythromycin are options for women at high risk for anaphylaxis, and vancomycin should be used in women allergic to penicillin and whose cultures indicate resistance to clindamycin and erytbromycin or when susceptibility is unknown. Asymptomatic neonates born to GBS-colonized mothers should be observed for at least 24 hours for signs of sepsis. Newborns who appear septic should have diagnostic work-up including blood culture followed by initiation of ampicillin and gentamicin. Studies indicate that intrapartum prophylaxis of GBS carriers and selective administration of antibiotics to newborns reduce neonatal GBS sepsis by as much as 80 to 95 percent

Building Bridges to an Uncertain Future Lived Now: Lessons from the Use of Participatory Action Research and Theory of Change Towards A Realistic Community-Based Participatory Monitoring and Evaluation System

Building on experience from the CGIAR Research Program on Aquatic Agricultural Systems implemented by WorldFish in the Visayas and Mindanao regions of the Philippines, known as the VisMin Hub, we describe the development and evolution of a monitoring and evaluation (M&E) system emerging from the facilitated action-reflection cycles of testing and adopting theories of change carried out with community partners through participatory action research (PAR). The former guides our community partners and us, as members of the potentially emergent PAR groups, towards the realization of the community’s vision; the latter facilitates learning to understand what, how and why change is unfolding. Unlike the conventional M&E system where indicators are pre-set at the beginning of program implementation, these processes result in an organically-evolved, communitybased participatory M&E system that is continuously revised according to contexts to guide communities towards realizing their visions. Its ultimate outcome is enhanced people’s capacity to own the product and process, giving rise to an internally-driven change. Towards the end, the paper offers an iterative discussion of learnings from implementing such an approach

Using theory of change to achieve impact in AAS

The CGIAR Strategy and Results Framework sets out four system level outcomes (SLOs), namely: reducing rural poverty, improving food security, improving nutrition and health and sustainable management of natural resources. In pursuit of these objectives the CGIAR has developed a set of sixteen CGIAR Research Programs (CRPs), each of which is expected to make specific contributions to a range of intermediate development outcomes (IDOs) linked to the SLOs. As part of this work the CRPs are developing impact pathways and theories of change designed to explain how the programs will achieve IDOs. The purpose of the present paper is to explain the approach that the CRP on Aquatic Agricultural Systems (AAS) is taking to using these programmatic tools to help achieve impact

Bremelanotide for Treatment of Female Hypoactive Sexual Desire

Hypoactive sexual desire disorder (HSDD) is a persistent deficiency or absence of sexual fantasies and desire resulting in significant distress or interpersonal difficulty. Women with this disorder may display a lack of motivation for sexual activity, reduced responsiveness to erotic cues, a loss of interest during sexual activity, and avoidance of situations that could lead to sexual activity. The pathophysiology of HSDD is thought to be centered around inhibitory and excitatory hormones, neurotransmitters, and specific brain anatomy. Due to the multifactorial nature of HSDD, treatment can be complex and must attempt to target the biological and psychosocial aspects of the disorder. Bremelanotide is a melanocortin receptor agonist and has been recently approved by the FDA to treat HSDD. Bremelanotide is administered intranasally or as a subcutaneous injection. The recommended dosage of bremelanotide is 1.75 mg injected subcutaneously in the abdomen or thigh at least 45 min before sexual activity. Studies showed improvements in desire, arousal, and orgasm scores when 1.75 mg of bremelanotide was administered before sexual activity compared to a placebo. Bremelanotide is a promising way to treat HSDD

Sloppy Models, Parameter Uncertainty, and the Role of Experimental Design

Computational models are increasingly used to understand and predict complex biological phenomena. These models contain many unknown parameters, at least some of which are difficult to measure directly, and instead are estimated by fitting to time-course data. Previous work has suggested that even with precise data sets, many parameters are unknowable by trajectory measurements. We examined this question in the context of a pathway model of epidermal growth factor (EGF) and neuronal growth factor (NGF) signaling. Computationally, we examined a palette of experimental perturbations that included different doses of EGF and NGF as well as single and multiple gene knockdowns and overexpressions. While no single experiment could accurately estimate all of the parameters, experimental design methodology identified a set of five complementary experiments that could. These results suggest optimism for the prospects for calibrating even large models, that the success of parameter estimation is intimately linked to the experimental perturbations used, and that experimental design methodology is important for parameter fitting of biological models and likely for the accuracy that can be expected from them.National Institutes of Health (U.S.) (U54 CA112967)MIT-Portugal ProgramSingapore-MIT Alliance for Research and Technolog