Development Of Rapid Protocols Research Articles

Rapid Protocol Development, Study Startup and Enrolment of a Prospective Study of COVID-19 Vaccination for Patients with Cancer: A Collaborative Approach.

COVID-19 is an unprecedented global health emergency. It has been highly disruptive for patients with cancer, both due to an increased burden of severe illness and due to pressure on healthcare systems. COVID-19 vaccination has been an important public health measure for this patient group. The aim of this study was to describe the rapid design and startup of a multicentre study of COVID-19 vaccine response for vulnerable patients with cancer. Study startup: We set up a multicentre prospective observational study of COVID-19 vaccination response for Australian patients with cancer. Due to intensive collaboration between health services, the funding body and laboratories, we were able to develop a protocol and enrol the first patient within 52 days of the initial study proposal. Rapid startup was further enabled by prompt availability of funding and by high-level engagement of institutional review boards, allowing expedited review. Study enrolment: We rapidly enroled more than 500 patients, 80% within 4 months of study opening. Engagement and follow-up were maintained throughout the course of up to five serial vaccination doses. Our study is an example of intensive collaboration inspired by the COVID-19 pandemic and may serve as an example of an agile research response to real-time public health challenges.

A Framework to Simplify Combined Sampling Strategies in Rosetta.

A core task in computational structural biology is the search of conformational space for low energy configurations of a biological macromolecule. Because conformational space has a very high dimensionality, the most successful search methods integrate some form of prior knowledge into a general sampling algorithm to reduce the effective dimensionality. However, integrating multiple types of constraints can be challenging. To streamline the incorporation of diverse constraints, we developed the Broker: an extension of the Rosetta macromolecular modeling suite that can express a wide range of protocols using constraints by combining small, independent modules, each of which implements a different set of constraints. We demonstrate expressiveness of the Broker through several code vignettes. The framework enables rapid protocol development in both biomolecular design and structural modeling tasks and thus is an important step towards exposing the rich functionality of Rosetta’s core libraries to a growing community of users addressing a diverse set of tasks in computational biology.

Strategies to increase efficiency in protocol development.

e16508 Background: In 2010, the NCI’s Operational Efficiency Working Group recommended changes aimed at compressing the timeline for cancer clinical trial activation. SWOG implemented multiple changes prior to and since that report, intended to increase protocol development efficiency. Two protocol development interventions were piloted; weekly meetings of SWOG leadership and the study team, or SWOG Activation Team (“SWAT”), which began in 2007, and intensive RaPID Protocol Development Meetings, beginning in 2010. Methods: The highest priority developing trial was selected for SWAT, with only one trial using this mechanism at a time. RaPID trials were chosen based on trial complexity and urgency. We reviewed all protocol development milestones across SWOG protocols activated between 2007 and 2011. Results of the review were compared and contrasted for 1) the two piloted interventions 2) pre- and post-OEWG implementation and 3) time from trial activation to first patient entered. Results: Time to activation results are outlined in the table. Within SWAT, the median time to activation was 400 days, 190 days sooner that all trials developed in the same time period. RaPID trials median time to activation was 225 days, 365 days sooner than others developed in the same timeframe. Regardless of intervention type, median time from concept submission to trial activation was 724 days pre-OEWG and 286 days post-OEWG. The median time from trial activation to first patient accrued was 106 days pre-OEWG implementation and 75 days post-OEWG. Conclusions: While barriers to timely trial activation still exist, SWOG programs aimed at enhancing the efficiency of protocol development, in partnership with the implemented OEWG recommendations, have been successful. SWOG has developed effective and timely protocol develop strategies among diverse, and geographically dispersed, study teams with only modest increases in effort and cost. Supported in part by PHS Cooperative Agreement grant awarded by the National Cancer Institute, DHHS: CA032102. [Table: see text]

A dynamic reconfigurable routing framework for wireless sensor networks

Sensornet deployments of the future are expected to deliver a multitude of services, ranging from reliable sensing, real time streams, mission critical support, network reprogramming and so on. Naturally, no one routing protocol can sufficiently cater to the network layer functionalities expected. Severe resource constraints further limit the possibility of multiple routing protocols to be implemented. Further, vertically integrated designs of present protocols hinder synergy and code-reuse among implementations. In this paper, we present an architecture that allows applications to send different types of flows, often with conflicting communication requirements. A flow’s requirements are made visible to our framework by using just 3 bits in the packet header. The core architecture is a collection of highly composable modules that allows rapid protocol development and deployment. We show that our framework can provide: (i) flow based network functionality that ensures each flow gets an application specific network layer which is dynamically knit as per the flow’s needs, (ii) modular organization that promotes code-reuse, run time sharing, synergy and rapid protocol development and (iii) pull processing that allows flows to dictate their traffic rate in the network, and implement flexible scheduling policies. This creates a framework for developing, testing, integrating, and validating protocols that are highly portable from one deployment to another. Using our framework, we show that virtually any communication pattern can be described to the framework. We validate this by gathering requirements for one real world application scenario: predictive maintenance (PdM). The requirements are used to generate a fairly complete and realistic traffic workload to drive our evaluation. Using simulations and 40 node MicaZ testbed experiments, we show that our framework can meet the deployments demands at granularities not seen before in sensornets. We measure the costs of using this framework in terms of code size, memory footprints and forwarding costs on MicaZ motes.

Efficiency of Primed In Situ Labeling (PRINS) Method for Interphasic Chromosomal Screening: a Review.

The advent of molecular genetic techniques has brought forth new procedures for in situ chromosomal analysis. One of these techniques is the primed in situ labeling (PRINS) procedure which constitutes a fast and efficient alternative to conventional fluorescence in situ hybridization (FISH) for chromosomal detection. Based on the use of chromosome-specific primers, the PRINS method combines the high sensitivity of the PCR reaction with the cytological localization of DNA sequences. Using this approach, numerous cytogenetic applications have been successfully developed on various types of cells. With the development of rapid protocols producing reliable and reproductible results, the PRINS procedure has an enormous potential for cytogenetic investigations.

The use of monoclonal antibody affinity columns for assessing DNA damage and repair following exposure to aflatoxin B 1

Primary hepatocellular carcinoma is one of the most lethal and common cancers in the world. It is particularly prevalent on the continents of Africa and Asia. A number of epidemiological studies have associated the exposure status of people to aflatoxin B 1 as being important in the etiology of liver cancer. However, to date these studies have relied upon the criteria of presumptive intake data, rather than relying upon quantitative analyses of aflatoxin—DNA adduct and metabolite content obtained by monitoring biological fluids from exposed people. Information obtained by monitoring exposed individuals for specific DNA adducts and metabolites will define the pharmacokinetics of aflatoxin B 1 in people, thereby facilitating risk assessments. We have developed monoclonal antibodies specific for aflatoxin metabolites, especially the DNA adducts. These monoclonal antibodies are used in solid phase immunoassays for the preparative purification of these aflatoxin derivatives from biological fluids. These methods in conjunction with other analytical procedures have resulted in the development of rapid protocols used to quantitatively measure aflatoxins in urine obtained from people dietarily exposed to this carcinogen. The people examined live in the Gambia and high liver cancer regions in the People's Republic of China. We have recently completed a pilot study in China where we have now begun to identify the pharmacokinetic parameters associated with chronic exposure of aflatoxin B 1 in the diet. Despite the development of these new technologies, we must continue to define animal model systems which can be used to interpret the human data. Our work using animal models based on the differential effects of ethoxyquin on the kinetics of aflatoxin—DNA adducts and gamma glutamyl transpeptidase-positive foci formation indicate that the direct linear extrapolation of total adduct content in target tissues to dose may be inappropriate to assign risk to people (or rats). However, our findings do support the concept that measurement of the major, rapidly excised AFB 1- N 7-Gua adduct in tissues and fluids is an appropriate dosimeter for estimating exposure status and risk in individuals consuming this mycotoxin. Further studies employing different classes of modifiers of aflatoxin carcinogenesis in rodent models should better define the relationships between hepatic and urinary levels of AFB 1- N 7-Gua and susceptibility to neoplasia.