Personalised and Precision Medicine in Cancer Clinical Trials: Panacea for Progress or Pandora's Box?

Cancer clinical trials have been one of the key foundations for significant advances in oncology. However, there is a clear recognition within the academic, care delivery and pharmaceutical/biotech communities that our current model of clinical trial discovery and development is no longer fit for purpose. Delivering transformative cancer care should increasingly be our mantra, rather than maintaining the status quo of, at best, the often miniscule incremental benefits that are observed with many current clinical trials. As we enter the era of precision medicine for personalised cancer care (precision and personalised medicine), it is important that we capture and utilise our greater understanding of the biology of disease to drive innovative approaches in clinical trial design and implementation that can lead to a step change in cancer care delivery. A number of advances have been practice changing (e.g. imatinib mesylate in chronic myeloid leukaemia, Herceptin in erb-B2-positive breast cancer), and increasingly we are seeing the promise of a number of newer approaches, particularly in diseases like lung cancer and melanoma. Targeting immune checkpoints has recently yielded some highly promising results. New algorithms that maximise the effectiveness of clinical trials, through for example a multi-stage, multi-arm type design are increasingly gaining traction. However, our enthusiasm for the undoubted advances that have been achieved are being tempered by a realisation that these new approaches may have significant cost implications. This article will address these competing issues, mainly from a European perspective, highlight the problems and challenges to healthcare systems and suggest potential solutions that will ensure that the cost/value rubicon is addressed in a way that allows stakeholders to work together to deliver optimal cost-effective cancer care, the benefits of which can be transferred directly to our patients.

Potential impacts of climate change on agriculture and food safety within the island of Ireland

Climate and other environmental change presents a number of challenges for effective food safety. Food production, distribution and consumption takes place within functioning ecosystems but this backdrop is often ignored or treated as static and unchanging. The risks presented by environmental change include novel pests and diseases, often caused by problem species expanding their spatial distributions as they track changing conditions, toxin generation in crops, direct effects on crop and animal production, consequences for trade networks driven by shifting economic viability of production methods in changing environments and finally, wholesale transformation of ecosystems as they respond to novel climatic regimes.

An evaluation of portion size estimation aids precision, ease of use and likelihood of future use

OBJECTIVE: The present study aimed to evaluate the precision, ease of use and likelihood of future use of portion size estimation aids (PSEA).

DESIGN: A range of PSEA were used to estimate the serving sizes of a range of commonly eaten foods and rated for ease of use and likelihood of future usage.

SETTING: For each food, participants selected their preferred PSEA from a range of options including: quantities and measures; reference objects; measuring; and indicators on food packets. These PSEA were used to serve out various foods (e.g. liquid, amorphous, and composite dishes). Ease of use and likelihood of future use were noted. The foods were weighed to determine the precision of each PSEA.

SUBJECTS: Males and females aged 18-64 years (n 120).

RESULTS: The quantities and measures were the most precise PSEA (lowest range of weights for estimated portion sizes). However, participants preferred household measures (e.g. 200 ml disposable cup) - deemed easy to use (median rating of 5), likely to use again in future (all scored either 4 or 5 on a scale from 1='not very likely' to 5='very likely to use again') and precise (narrow range of weights for estimated portion sizes). The majority indicated they would most likely use the PSEA preparing a meal (94 %), particularly dinner (86 %) in the home (89 %; all P<0·001) for amorphous grain foods.

CONCLUSIONS: Household measures may be precise, easy to use and acceptable aids for estimating the appropriate portion size of amorphous grain foods.

A decision support system for managing irrigation in agriculture

In this paper, an automatic Smart Irrigation Decision Support System, SIDSS, is proposed to manage irrigation in agriculture. Our system estimates the weekly irrigations needs of a plantation, on the basis of both soil measurements and climatic variables gathered by several autonomous nodes deployed in field. This enables a closed loop control scheme to adapt the decision support system to local perturbations and estimation errors. Two machine learning techniques, PLSR and ANFIS, are proposed as reasoning engine of our SIDSS. Our approach is validated on three commercial plantations of citrus trees located in the South-East of Spain. Performance is tested against decisions taken by a human expert.

Valuing water in irrigated agriculture and fisheries in a reservoir of Sri Lanka

Dissertação de Mestrado, Gestão da Água e da Costa, Faculdade de Ciências e Tecnologia, Universidade do Algarve, 2007

Medium-term prospects for portuguese agriculture under health check Proposals: a quantitative analysis with the CAPRI modelling system

The challenges of Common Agricultural Policy are driven by internal and external factors, such as the budgetary constraints, the budget reform, the globalization and the world financial crisis. According to this work results, CAP will continue its evolution from a sectorial to a territorial approach, with a slow re-balance of its two pillars. The Portuguese agriculture will slowly adjust itself to the disappearance of prices and markets policy and the reinforcement of rural development policy. As in the past, agriculture will accommodate the reform effects and adjust to a new framework without sudden brakes or disclosers.

Control of a high Precision Double Drive

The speed control system for a concept for cost effective drives with high precision is presented. The drive concept consists of two parallel working drives. The concept is an alternative to direct drives. One big advantage is the use of standard gear boxes with economical components. This paper deals with the control of the drive system consisting of two parts: one drive produces the power for the machine, another drive makes the motion precice and dynamic. Both drives are combined to one double drive by a control system. The drive system is usefull for printing machines and other machines with high power consumption at a nearly constant speed and high accuracy requirements. The calculation for a drive system with 37 kW shows, that the control drive has to supply only about 20 % of the total torque and power needed to compensate the errors of the power drive. The stability of the system is shown by a simulation of the double drive.

Control of a high Precision Double Drive

The speed control system for a concept for cost effective drives with high precision is presented. The drive concept consists of two parallel working drives. The concept is an alternative to direct drives. One big advantage is the use of standard gear boxes with economical components. This paper deals with the control of the drive system consisting of two parts: one drive produces the power for the machine, another drive makes the motion precice and dynamic. Both drives are combined to one double drive by a control system. The drive system is usefull for printing machines and other machines with high power consumption at a nearly constant speed and high accuracy requirements. The calculation for a drive system with 37 kW shows, that the control drive has to supply only about 20 % of the total torque and power needed to compensate the errors of the power drive. The stability of the system is shown by a simulation of the double drive.

New perspectives on the history of brazilian agriculture.

One of the objectives of this book has been to highlight the importance of the history of agriculture in today's food production and consumption patterns, recovering parts of this history which are not easily found or which have been forgotten or neglected, but which have had a large impact on what we are today.

The global radar applied to the precision farming sector

The case describes the development of MyFARM’s internationalization plan, a service of Deimos Engenharia, under the GloCal Radar. This space engineering company hired Lisbon Consulting Company to undertake the project to overcome its lack of market orientation. The consultants’ analysis revealed Stevens County, Kansas, as the market with the highest potential for MyFARM. A suitable entry strategy and adaptation of the service for the local market was proposed. The case culminates with the Board of Directors discussing the viability of implementing the consultants’ recommendations to start diversifying their sources of revenue streams.

Liquid chromatography-tandem mass spectrometry (LC/APCI-MS/MS) methods for the quantification of captan and folpet phthalimide metabolites in human plasma and urine.

Captan and folpet are fungicides largely used in agriculture. They have similar chemical structures, except that folpet has an aromatic ring unlike captan. Their half-lives in blood are very short, given that they are readily broken down to tetrahydrophthalimide (THPI) and phthalimide (PI), respectively. Few authors measured these biomarkers in plasma or urine, and analysis was conducted either by gas chromatography coupled to mass spectrometry or liquid chromatography with UV detection. The objective of this study was thus to develop simple, sensitive and specific liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry (LC/APCI-MS/MS) methods to quantify both THPI and PI in human plasma and urine. Briefly, deuterated THPI was added as an internal standard and purification was performed by solid-phase extraction followed by LC/APCI-MS/MS analysis in negative ion mode for both compounds. Validation of the methods was conducted using spiked blank plasma and urine samples at concentrations ranging from 1 to 250 μg/L and 1 to 50 μg/L, respectively, along with samples of volunteers and workers exposed to captan or folpet. The methods showed a good linearity (R (2) > 0.99), recovery (on average 90% for THPI and 75% for PI), intra- and inter-day precision (RSD, <15%) and accuracy (<20%), and stability. The limit of detection was 0.58 μg/L in urine and 1.47 μg/L in plasma for THPI and 1.14 and 2.17 μg/L, respectively, for PI. The described methods proved to be accurate and suitable to determine the toxicokinetics of both metabolites in human plasma and urine.

Continuous quantification of HER2 expression by microfluidic precision immunofluorescence estimates HER2 gene amplification in breast cancer.

Chromogenic immunohistochemistry (IHC) is omnipresent in cancer diagnosis, but has also been criticized for its technical limit in quantifying the level of protein expression on tissue sections, thus potentially masking clinically relevant data. Shifting from qualitative to quantitative, immunofluorescence (IF) has recently gained attention, yet the question of how precisely IF can quantify antigen expression remains unanswered, regarding in particular its technical limitations and applicability to multiple markers. Here we introduce microfluidic precision IF, which accurately quantifies the target expression level in a continuous scale based on microfluidic IF staining of standard tissue sections and low-complexity automated image analysis. We show that the level of HER2 protein expression, as continuously quantified using microfluidic precision IF in 25 breast cancer cases, including several cases with equivocal IHC result, can predict the number of HER2 gene copies as assessed by fluorescence in situ hybridization (FISH). Finally, we demonstrate that the working principle of this technology is not restricted to HER2 but can be extended to other biomarkers. We anticipate that our method has the potential of providing automated, fast and high-quality quantitative in situ biomarker data using low-cost immunofluorescence assays, as increasingly required in the era of individually tailored cancer therapy.

Image guided critical screw placement precision in the cervical spine : important or incidental? : results of a series of 91 consecutive cases using OVEM

Study design: A retrospective study of image guided cervical implant placement precision. Objective: To describe a simple and precise classification of cervical critical screw placement. Summary of Background Data: "Critical" screw placement is defined as implant insertion into a bone corridor which is surrounded circumferentially by neurovascular structures. While the use of image guidance has improved accuracy, there is currently no classification which provides sufficient precision to assess the navigation success of critical cervical screw placement. Methods: Based on postoperative clinical evaluation and CT imaging, the orthogonal view evaluation method (OVEM) is used to classify screw accuracy into grade I (no cortical breach), grade la (screw thread cortical breach), grade II (internal diameter cortical breach) and grade III (major cortical breach causing neural or vascular injury). Grades II and III are considered to be navigation failures, after accounting for bone corridor / screw mismatch (minimal diameter of targeted bone corridor being smaller than an outer screw diameter). Results: A total of 276 screws from 91 patients were classified into grade I (64.9%), grade la (18.1%), and grade II (17.0%). No grade III screw was observed. The overall rate of navigation failure was 13%. Multiple logistic regression indicated that navigational failure was significantly associated with the level of instrumentation and the navigation system used. Navigational failure was rare (1.6%) when the margin around the screw in the bone corridor was larger than 1.5 mm. Conclusions: OVEM evaluation appears to be a useful tool to assess the precision of critical screw placement in the cervical spine. The OVEM validity and reliability need to be addressed. Further correlation with clinical outcomes will be addressed in future studies.

Statistique agricole annuelle / Ministère de l'agriculture, Direction de l'agriculture, Bureau des subsistances, des secours et de la statistique agricole

1889.

Statistique agricole annuelle / Ministère de l'agriculture, Direction de l'agriculture, Bureau des subsistances, des secours et de la statistique agricole

1886.