7. Proof Of Concept _BEST_
Metabolic syndrome is characterized by a constellation of comorbidities that predispose individuals to an increased risk of developing cardiovascular pathologies as well as type 2 diabetes mellitus1. The gut microbiota is a new key contributor involved in the onset of obesity-related disorders2. In humans, studies have provided evidence for a negative correlation between Akkermansia muciniphila abundance and overweight, obesity, untreated type 2 diabetes mellitus or hypertension3-8. Since the administration of A. muciniphila has never been investigated in humans, we conducted a randomized, double-blind, placebo-controlled pilot study in overweight/obese insulin-resistant volunteers; 40 were enrolled and 32 completed the trial. The primary end points were safety, tolerability and metabolic parameters (that is, insulin resistance, circulating lipids, visceral adiposity and body mass). Secondary outcomes were gut barrier function (that is, plasma lipopolysaccharides) and gut microbiota composition. In this single-center study, we demonstrated that daily oral supplementation of 1010 A. muciniphila bacteria either live or pasteurized for three months was safe and well tolerated. Compared to placebo, pasteurized A. muciniphila improved insulin sensitivity (+28.62 7.02%, P = 0.002), and reduced insulinemia (-34.08 7.12%, P = 0.006) and plasma total cholesterol (-8.68 2.38%, P = 0.02). Pasteurized A. muciniphila supplementation slightly decreased body weight (-2.27 0.92 kg, P = 0.091) compared to the placebo group, and fat mass (-1.37 0.82 kg, P = 0.092) and hip circumference (-2.63 1.14 cm, P = 0.091) compared to baseline. After three months of supplementation, A. muciniphila reduced the levels of the relevant blood markers for liver dysfunction and inflammation while the overall gut microbiome structure was unaffected. In conclusion, this proof-of-concept study (clinical trial no. NCT02637115 ) shows that the intervention was safe and well tolerated and that supplementation with A. muciniphila improves several metabolic parameters.
7. Proof of Concept
Multi-segment foot kinematic analyses have gained enormous popularity in the last ten years since they provide a more detailed analysis of foot kinematics compared to single segment models [1, 2]. Until now, these multi-segment approaches have predominantly been used to assess barefoot foot kinematics [3,4,5]. Non-invasive in-shoe foot kinematics however, remain delicate to quantify as certain challenges arise: the difficulty to apply regular markers due to the fact that the skin is not directly accessible, the necessity for an adequate shoe which fits various foot morphologies and the need for adequate repeatability throughout a repeated measure condition. Several authors tried to overcome these challenges by introducing modified shoes that allow skin-mounted markers for in-shoe multi-segment foot analysis with and without foot orthoses [6,7,8,9,10]. Apart from shoe modification, other challenges occur when measuring in-shoe foot kinematics, as regular markers are complex to place on the foot when in shod condition. Bishop et al. have addressed this challenge by manufacturing a so-called two-part in-shoe marker wand . Being an interesting development, our aim was to expand the applicability of this concept in order to provide a solution for future research investigating shod conditions/orthoses, as an optimal combination between modified shoes and feasible markers needs to be found for repeated measurement designs. The objective of the current study was to develop and assess reliability and repeatability of a thin and solid in-shoe marker wand, consisting of a baseplate and marker-unit, with user-friendly features that allow for repeated in-shoe multi-segment foot analyses using modified shoes.
ME made substantial contributions to conception and design of the study, undertook all clinical data collection, contributed to analysis and interpretation of data and to writing the manuscript. FS made substantial contributions to interpretation of the data and writing the manuscript. TP made substantial contributions to conception and design of the study and writing of the manuscript. KD made substantial contributions to conception and design of the study, undertook some clinical data collection, contributed to analysis and interpretation of data and to writing the manuscript. All authors were involved in drafting of the manuscript or revising it critically for important intellectual content. All authors read and approved the final manuscript.
A software proof of concept (PoC) is designed to demonstrate the feasibility of a proposed software solution. A proof of concept could be as informal as creating a marketing video and gauging interest in the product idea or as formal as creating a simple hand-built version of the software to test its feasibility.
Regardless of the exact approach, proof of concepts are typically low cost and developed very early in the formation of a new business or product idea. They can be used to justify later stages of product development such as a prototype or minimum viable product (MVP).
While not the right fit for everyone, a PoC project is an important step for many startup teams as it can test out one or more business concepts before moving on to develop a full product prototype or raise funding.
Proof of concepts are particularly important for businesses that are entering an unknown market or introducing a new type of product. Depending on your product idea you may find that a proof of concept is helpful to:
As you make a plan to test your business idea with a proof of concept, you should have first thought about what your goals are as well as have defined success criteria for your project. What are you trying to accomplish by building a proof of concept? Some goals might include:
Your high-level goals for the proof of concept will dictate what type of proof of concept you should build, what your budget and timeline should look like, and what team members need to be involved in the process.
Remember, a proof of concept is different from a product prototype or minimum viable product. To help keep costs to a minimum, proof of concept project teams should be as small as possible (often just one person). While some teams choose to hire project managers to help develop the proof of concept, most teams should be able to handle the PoC build internally.
This proof of concept example demonstrates the value in keeping this phase high-level. The aim of the PoC should be to validate the proposed idea, not to provide technical proof of its validity or provide a working model of the end product.
OpenBay also interviewed customers during the proof of concept stage, but their goal was to see what people thought of their idea more generally. As a marketplace platform, they wanted to validate that both sides of the marketplace resonated with their potential product.
Second, the theory proposes that individuals with flatter associative hierarchies outperform those with steeper hierarchies in the RAT, because they are able to access and combine remote ideas (Mednick, 1962). This implies that the solutions of RAT problems have to be sufficiently remote from the cues (i.e., a weak, uncommon, or infrequent relation) that individuals with flatter associative hierarchies will have an advantage over individuals who produce close and common associates. Moreover, the concept of associative hierarchies also implies that item remoteness is the principal determinant of item difficulty, so that high test scores reflect better remote associative abilities (Davelaar, 2015). Following this rationale, it is possible that an optimal threshold and variability of item remoteness may be required in order to ensure the validity and sensitivity of the measure. Although the link between item remoteness and other psychometric properties of the RAT (such as item difficulty and item sensitivity) is essential, it lacks empirical confirmation.
The successful completion of the proof of concept, named the COT, a Carbon Tracing Platform will be critical in helping to ensure traceability of emissions from mine to the final product. With a focus on end-to-end traceability, the COT platform uses distributed ledger technology to track CO2 emissions.
In the June 2019 issue, the journal Peptides published our last work on calcitonin gene-related peptide (CGRP), a review dealing with the anti-CGRP and anti-CGRP receptor monoclonal antibodies (mAbs) recently introduced for migraine treatment . The paper addressed the concerns raised by the potential risks ensuing a long-term inhibition of CGRP functions, and we discussed whether the different action mechanisms of these mAbs (i.e. quenching systemic CGRP vs blocking its receptors) might be associated to different safety profiles. Among other issues, we made a point of measuring plasma CGRP levels during long-term treatments with anti-CGRP mABs . Concerns about the potential risks associated to long-term blockade of CGRP or CGRP receptor are shared by several groups [2,3,4,5], whereas a more optimistic view foresees a remarkable safety profile, based on the concept that anti-CGRP and anti-CGRP receptor mAbs knockdown, but do not knockout CGRP signaling .
Poor outcomes of hepatic resections in the emergency setting and the understanding of the hemorrhagic shock have led us towards the concept of damage control laparotomy with perihepatic packing. This approach, combined with advances in resuscitation and interventional radiology, has delivered a decline in overall mortality rates .
This is a first approach and proof of concept; therefore, it has several limitations. The limited sample size in this first pilot experience and the obvious differences between pigs and humans prevent us from drawing conclusions. However, we establish a first step towards the development of this new device. A new study with different injuries in different parts of the liver and a bigger sample size still in pigs will be conducted. 041b061a72