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CGRP Receptor Activation Mechanism and Applications

CGRP Receptor Activation Mechanism and Applications. CGRP Receptor activation Proposal Summary The calcitonin gene-related peptide (CGRP) receptor is a complex of calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 1 (RAMP1). This receptor plays an important role in vasodilation, neurogenic inflammation and is involved in the pathology of migraine. Though mechanisms have been proposed, it is largely unknown how exactly the receptor is activated by its ligand CGRP. Recently a Cryo-EM structure of the human CGRP receptor in complex with CGRP was released, as well as data that displays the key residues within the receptor that are integral for receptor activation. It is known that CGRP forms functionally important interactions with the CLR–RAMP1 complex and so the aim for this project is to review current knowledge on CGRP receptor activation and to utilise data alongside molecular visualisation programs including VMD and SwissPdbViewer to analyse the potential mechanism by which CGRP activates its receptor. Background Introduction to CGRP CGRP is a 37 amino acid neuropeptide with two major isoforms (α and β) which belong to the calcitonin family of peptides. In humans, the two forms differ by three amino acids and so have very similar effects due to their amino acid sequence being alike (Ghatta and Nimmagadda., 2004). The receptor for CGRP is a secretin family receptor GPCR (Family B) known as CLR (Barwell et al., 2013). G-protein coupled receptors (GPCRs) receive a great deal of scientific interest due to being one of the largest targets for pharmaceuticals, however the CGRP receptor is unlike a typical GPCR as there is a requirement for the accessory protein RAMP1, a transmembrane protein which, when dimerised with CLR allows cell surface expression and CGRP binding to occur (Barwell et al., 2013). When alone, CLR will not reach the cell surface and will not respond to any known ligands (Hay et al., 2017). Its been established that CGRP is a highly potent vasodilator and has a definite role in migraine but there is evidence CGRP has a range of actions from cardioprotective effects to pain and itch in arthritis, however, the pathophysiological states that CGRP is involved in is yet to be fully explored (Kee et al., 2018; Russell et al., 2014). As the CGRP pathway appears to be involved in many diseases and disorders, it is important to understand the activation mechanism to gain further knowledge of the CGRP receptor which in turn will lead to the design of emerging medicines. The CGRP Receptor The CGRP receptor consists of an extracellular domain and a transmembrane domain (TM). The extracellular domain is found outside the cell and is connected to the TM found within the cell membrane. CGRP causes the TM to change its conformation by interacting with the two domains. The C‐terminus of the peptide interacts with the N-terminal domain of CLR while the N‐terminus of the peptide interacts with the transmembrane domain of CLR and its associated extracellular loops resulting in activation (Woolley et al., 2013). The details of how CGRP interacts with the TM and extracellular loop regions of the CGRP receptor remains unclear (Barwell et al., 2012) CGRP Binding and Understanding Receptor Activation As of now, a structure of CGRP bound to its receptor has been proposed (Liang et al., 2018). Current literature suggests that 61.5% of CGRP’s surface is buried within the CLR-RAMP1 complex which indicates numerous significant points of contact between the bound peptide-receptor complex (Liang et al., 2018). The second extracellular loop (ECL2) is thought to have an important role in ligand binding and receptor activation as seen in other GPCRs (Woolley et al., 2013). 13 ECL2 residues were identified as influencing CGRP-receptor interaction. ECL2 is highly conserved and the longest ECL so there is certainly it has involvement in the activation of GPCRs (Woolley et l., 2013). ECL 1 has two residues involved in peptide binding and ECL3 has one, which suggests their roles have less influence over CGRP-receptor interactions although they are mandatory for normal functioning of the receptor (Barwell et al., 2011). The only direct contact between CGRP and RAMP1 is limited to the far C terminus of the peptide and a number of RAMP residues (Liang et al., 2018). The N-terminal peptide loop within CGRP forms extensive van der Waals interactions with CLR (Liang et al., 2018). There is also a functionally important interaction between the N terminus of CGRP and the core of CLR involving a hydrogen bond between H295 and CGRP T6. Other hydrogen bonds are present but in little number and are of little importance for CGRP binding (Liang et al., 2018). Below H295 is a peptide binding pocket formed by a series of amino acids, this pocket is of particular interest as it makes for an attractive target for new drugs (Liang et al., 2018). Other important interactions include those between the peptide and TM3/TM5 (Liang et al., 2018). Although the interactions between CGRP and its receptor are well known. It is uncertain how these interactions result in activation of the CGRP receptor. Activation of the CGRP receptor has been associated with an increase in the second messenger cAMP (King and Brain., 2013). There have been a number of mutations and alanine substitutions to residues that have lead to a decrease in CGRP potency on cAMP accumulation, this would indicate that the affected residues have functional importance in receptor activation. Prior research has discovered that CGRP T4, CGRP T6, CGRP T9 among others are important residues for receptor activation (Liang et al., 2018). Recent developments in cryo-electron microscopy have led to the structure of an active CGRP receptor. Figure 1 (Liang et al., 2018). Cryo-EM is a very powerful tool, in this case, it allows researchers to observe the CGRP receptor as a whole and in its active state as opposed to studying individual components of the receptor structure (Diamond Light Source., 2015). The cryo-EM model is now available on the Protein Data Bank (a database for the structural data of proteins and other large biological molecules) and will be used to gain an understanding of CGRP-receptor activation. Figure 1, Complex of a full-length, active-state calcitonin gene-related peptide receptor with calcitonin gene-related peptide ligand (Liang et al., 2018) The Need for New CGRP Agonists and Antagonists Migraine medication has been developed in the form of CGRP receptor antagonists, all of which have shown promising results. The gepant class of drugs which are non-peptide CGRP antagonists, including olcegepant and telcagepant, have high selectivity for CGRP receptors and have shown therapeutic efficacy in migraine induced by CGRP. Despite this, the marketing of these drugs has been halted due to safety and tolerability issues including liver toxicity and poor oral bioavailability (Goadsby, P., 2016). CGRP receptor antibodies could be an appropriate alternative as they have demonstrated similar efficacy and good tolerability without inducing liver toxicity, but the long-term effects of blocking CGRP are unknown and the cost of therapy is an additional problem (Deen et al,. 2017). In recent news, Erunumab, a monoclonal antibody of the CGRP receptor, was licensed for use by the FDA and EMA. It is currently being evaluated by NICE for the preventative treatment of migraine so there is promise that CGRP antagonists could have a place in clinical practice in the UK (NICE., 2018). . There is also a chance for CGRP receptor agonists to have a role in future healthcare. CGRP is a potent vasodilator and as a consequence, its deemed to have cardioprotective effects (Kee et al., 2018). Evidence shows that the peptide helps relieve congestive heart failure, but the degree of benefit is limited because CGRP has a relatively short half-life, and as a peptide, it cannot be delivered orally (Gennari et al., 1990; Shekhar et al., 1991). Analogues of the peptide have been synthesised which improved on the half-life and the beneficial effects in heart failure were demonstrated at a similar potency to the native peptide (Aubdool et al., 2017). To obtain an oral agonist, however, research most probably needs to be done in the area of non-peptide CGRP agonist synthesis. Further work here may uncover new drugs that could be viable for the treatment of cardiovascular disease. Under these circumstances, there is encouragement for further research into the mechanism of CGRP receptor activation to develop drugs that could possibly be advantageous over existing treatments. Aim and Objectives Aim: The aim of this project is to analyse the mechanism by which CGRP activates its receptor, through the use of molecular visualisation programs VMD and SwissPdbViewer Objectives: – Become familiar with VMD and SwissPdbViewer – Identify and record the residues that move during the transition from the inactive to the active state of the receptor – Identify key points of contact between CGRP and the CLR-RAMP1 complex that have importance in receptor activation Research Design and Methodology In this project, the plan is to continue studying how CGRP binds to its receptor and how this causes the receptor to become activated. Learning how the receptor shape will change when CGRP binds to its receptor is achievable via computer modelling. The active-state receptor structure is known for certain, but by using homology modelling, we can make a good guess at the inactive structure. This will be done using molecular dynamics simulations (VMD) and macromolecular modelling (SwissPdbViewer). Molecular dynamics (MD) is a form of computer simulation in which atoms and molecules are allowed to interact for a period of time giving a view of the motion of the atoms. It solves Newton’s equation of motion on a model of a molecule to obtain the trajectory of its motion (Jefferies et al., 2017). Using MD, Dr John Simms has built a model on how the CGRP receptor moves between the two states and by using VMD to analyse this trajectory, we can see what residues are moving frame by frame. A table will be constructed to record what is moving and at what frame this movement occurs. Conformations will also be saved at specific frames and viewed in SwissPdbViewer for analysis. SwissPdbViewer allows viewing of several models simultaneously so the model receptor can be superimposed on the cryo-EM structure allowing for comparisons and as a form of quality control. It can also be used to obtain bond lengths, atom distances and find hydrogen bonds between proteins and ligands (Rhodes, G., 2006). Through this method, the interactions between CGRP and its receptor can be better understood which will add onto the existing body of academic research and potentially be beneficial in the design of new drugs. Gantt Chart Bibliography Aubdool, A. A., Thakore, P., Argunhan, F., Smillie, S.-J., Schnelle, M., Srivastava, S., et al. (2017). A novel α-calcitonin gene-related peptide analogue protects against end-organ damage in experimental hypertension, cardiac hypertrophy, and heart failure. Circulation, 136,pp. 367–383. Evaluation of the therapeutic potential of a CGRP analogue with a longer half-life than the native peptide. Testing its ability to relieve cardiovascular disease in murine models of hypertension and heart failure. Provides details of results in terms of cardioprotection and tolerability. Barwell, J., Conner, A. and Poyner, D. (2011). Extracellular loops 1 and 3 and their associated transmembrane regions of the calcitonin receptor-like receptor are needed for CGRP receptor function. Biochimica et Biophysica Acta (BBA) – Molecular Cell Research, 1813(10), pp.1906-1916. Detailed analysis of the function of ECL1 and ECL3 recognising their importance in binding and cell surface expression. Provides information on the residues in the ECLs that are of importance in receptor expression. Provides some information on the interactions between CGRP and the domains of its receptor Barwell, J., Gingell, J., Watkins, H., Archbold, J., Poyner, D. and Hay, D. (2012). Calcitonin and calcitonin receptor-like receptors: common themes with family B GPCRs?. British Journal of Pharmacology, 166(1), pp.51-65. Reviews how applicable Family B GPCRs are to CTR and CLR receptors. This includes looking into the functional domains, N-terminal domains, C-terminal domains and transmembrane domains of the receptors. Barwell, J., Wheatley, M., Conner, AC., Taddese, B., Vohra, S., Reynolds, CA. and Poyner, DR. (2013), The activation of the CGRP receptor. Biochemical Society Transactions, vol. 41, no. 1, pp. 180-184. Talks about the activation of Family B GPCRs and how it could be applied to the CGRP receptor. Provides detailed background information on the CGRP receptor. Deen, M., Correnti, E., Kamm, K., Kelderman, T., Papetti, L., Rubio-Beltrán, E., Vigneri, S., Edvinsson, L. and Maassen Van Den Brink, A. (2017). Blocking CGRP in migraine patients – a review of pros and cons. The Journal of Headache and Pain, 18(1). A review of the advantages and disadvantages of blocking GCRP in migraine, looking at efficacy and tolerability of drugs including gepants and monoclonal antibodies. Concluding that the benefits of CGRP treatment of migraine outweigh the drawbacks. Provides information on the use of CGRP receptor antibodies for the preventative treatment of migraine. Diamond Light Source. (2015). How it Works: Cryo-Electron Microscopy – Diamond Light Source. [online] Available at: [Accessed 1 Nov. 2018]. A website which includes a guide to how cryo-electron microscopy works. Has information on how it is different from other forms of microscopy and in some scenarios, why it is a more appropriate technique. Gennari, C., Nami, R., Agnusdei, D., and Fischer, J. A. (1990). Improved cardiac performance with human calcitonin gene related peptide in patients with congestive heart failure. Cardiovasc. Res. 24,pp. 239–241. Looks at what cardiovascular effects CGRP has when administered to patients who have congestive heart failure. Provides results on the outcome of using CGRP treatment, as well as issues that would limit its use in a clinical setting. Ghatta S., Nimmagadda D. (2004) Calcitonin gene-related peptide: Understanding its role. Indian Journal of Pharmacology 36: 277-283. A review of the CGRP receptor and its biological significance in different systems of the human body. Includes useful introductory information on the CGRP receptor. Hay, D., Garelja, M., Poyner, D. and Walker, C. (2017). Update on the pharmacology of calcitonin/CGRP family of peptides: IUPHAR Review 25. British Journal of Pharmacology, 175(1), pp.3-17. A review which provides details on the pharmacology on the CGRP family of peptides. Includes information to do with the importance of RAMP1 and what events would not occur without it. Jefferies, D. and Khalid, S. (2018). Modeling of Microscale Transport in Biological Processes. Academic Press, pp.1-18. Talks about recent advances in theoretical and computational modelling. Contains an introductory section about molecular dynamics in great detail. Kee, Z., Kodji, X. and Brain, S. (2018). The Role of Calcitonin Gene Related Peptide (CGRP) in Neurogenic Vasodilation and Its Cardioprotective Effects. Frontiers in Physiology, 9. A review discussing the potential of CGRP as a target in the treatment of cardiovascular diseases. Looking at CGRP antagonists, antibodies and analogues. Has information on the effects that CGRP exhibits including vasodilation, cardioprotection and involvement in migraine. King, R. and Brain, S. (2013). Handbook of Biologically Active Peptides. 2nd ed. San Diego: Academic Press, pp.1394-1401. Discusses all features of biologically active peptides including CGRP. Provides information in relation to CGRP and second messengers in terms of receptor activation. Liang, Y., Khoshouei, M., Deganutti, G., Glukhova, A., Koole, C., Peat, T., Radjainia, M., Plitzko, J., Baumeister, W., Miller, L., Hay, D., Christopoulos, A., Reynolds, C., Wootten, D. and Sexton, P. (2018). Cryo-EM structure of the active, Gs-protein complexed, human CGRP receptor. Nature, 561(7724), pp.492-497. A report of the cryo-EM active-state CGRP receptor structure. Provides detailed information on the interactions between CGRP and the binding site. Liang, Y., Khoshouei, M., Deganutti, G., Glukhova, A., Koole, C., Peat, T., Radjainia, M., Plitzko, J., Baumeister, W., Miller, L., Hay, D., Christopoulos, A., Reynolds, C., Wootten, D. and Sexton, P. (2018). 6E3Y Cryo-EM structure of the active, Gs-protein complexed, human CGRP receptor. [image] Available at: [Accessed 10 Nov. 2018]. Image source for the cryo-EM of the active human CGRP receptor. NICE (2018). Erenumab for preventing migraine [ID1188] | Guidance and guidelines | NICE. [online] Available at: [Accessed 10 Nov. 2018]. NICE evaluation of erenumab for prevention of migraine. It is ongoing and has a timeline of the events that have occurred thus far. Rhodes, G. (2006). Crystallography Made Crystal Clear. 3rd ed. Saint Louis: Elsevier Science. A guide for users of macromolecular models. Provides an introduction to SwissPdbViewer and a tutorial for beginners. Russell, F., King, R., Smillie, S., Kodji, X. and Brain, S. (2014). Calcitonin Gene-Related Peptide: Physiology and Pathophysiology. Physiological Reviews, 94(4), pp.1099-1142. A review of the physiology of CGRP including its synthesis, metabolism, structure, distribution as well as the CGRP receptor. Provides information on the pathophysiological states that CGRP is involved in. Shekhar, Y. C., Anand, I. S., Sarma, R., Ferrari, R., Wahi, P. L., and Poole-Wilson, P. A. (1991). Effects of prolonged infusion of human alpha calcitonin gene-related peptide on hemodynamics, renal blood flow and hormone levels in congestive heart failure. Am. J. Cardiol.67,pp. 732–736. A study looking at the hemodynamic effects of infusion of CGRP over a long period of time. Mentions limitations to treatment including loss of effect within 30 minutes after treatment was stopped. Woolley, M., Watkins, H., Taddese, B., Karakullukcu, Z., Barwell, J., Smith, K., Hay, D., Poyner, D., Reynolds, C. and Conner, A. (2013). The role of ECL2 in CGRP receptor activation: a combined modelling and experimental approach. Journal of The Royal Society Interface, 10(88), pp.20130589-20130589. Investigation of the role of ECL2 in the binding of CGRP to its receptor through the use of mutagenesis and modelling. Has detailed information on ECL2 and its involvement in CGRP receptor-ligand binding. CGRP Receptor Activation Mechanism and Applications
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Last week, you were asked to consider which stage of critical thinking you felt that you were in. This week, building off last week’s assignment and lecture, we know that employers are wanting more critical thinking from their employees. From the perspective of the employer, why is it so important to have employees who can critically think? From your perspective, how has critical thinking helped you in the past, or how do you perceive it helping you as an employee in the future? (Consider your dream job!)Your work should be at least 500 words, but mostly draw from your own personal experience. This should be written in first person and give examples from your life. Be sure if you are using information from the readings that you properly cite your readings in this, and in all assignments.
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Week 4 Reflection the Graduate Film Released in 1967 Discussion.

Instructions: In one to two paragraphs (300-400 words), answer ONLY ONE of the following questions in relation to The Graduate (Nichols, 1967). Your response should include a central thesis/interpretive claim that serves as the central focus of your reflection, supported by formal devices in the scene. TIP: to boost clarity in these short reflections, put a clear and explicit interpretive claim somewhere in the first few sentences of the reflection. Complete this by 11:59PM PST on Sunday, November 1st. There is no time limit and you are allowed one submission before the deadline. Be sure that your submission is entered either using the text box or uploaded as a PDF, DOC, or TXT file.
NOTE: Late reflections are accepted for grading for up to two weeks after the initial due date or by the end of Finals Week, whichever comes first. However, please note that the later the reflection, the greater the grade deduction. The lowest reflection grade (1 out of a total of 6 weekly reflections) will be dropped. Plagiarism—submitting work that is not the student’s own, whether lifted from a printed source or from the internet, or submitting writing by someone else (e.g., a tutor or friend), will warrant a reduced or failing grade, depending on the severity of the plagiarism involved. 
Answer ONE of the following questions in your reflection: 
Question 1:
As noted by Prof. Lim in lecture 4C, the motif of drifting vs. stasis is central to The Graduate (Nichols, 1967). Drawing on examples from only one to two scenes, make a claim regarding this motif, supported by two formal devices of cinematography and/or editing.
Question 2:
The Graduate (Nichols, 1967) follows the interior struggle of a recent college graduate, Benjamin Braddock, who remarks, “I’m worried about my future.” Drawing on specific examples from only one to two scenes, make an interpretive claim about how two formal devices of cinematography and/or editing function as a means of expressing Benjamin’s subjective state. 
Question 3:
Imagine the year is 1967 and your good friend Mike Nichols phones you for advice on how to market his forthcoming film, The Graduate. Nichols is torn between promoting his film as a sex comedy about seduction and desire or as a melodrama about anxiety and failure. He calls you because of your reputation as a brutally honest film critic. Respond to Nichols’ dilemma by developing an interpretive claim about genre hybridity in The Graduate. Support your argument by referencing one or two specific scenes and two formal devices of cinematography and/or editing (such as mobile framing, selective focus, deep focus, or shot transitions).
Question 4:
In Lecture 4C, Professor Lim discusses the “Scarborough Fair” leitmotif in The Graduate, which occurs 4 times in the film (1. After Elaine finds out about the affair; 2. After Ben decides to marry Elaine, following her to Berkeley; 3. Ben following Elaine from the bookstore to the bus; and 4. Ben and Elaine at the zoo).  Craft an interpretive claim about how the leitmotif establishes a relationship (of similarity or contrast) between two of these scenes or shapes the audience’s emotional response or their expectations about narrative events.
https://www. .com/discuss/25402696/300-400…

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Week 4 Reflection the Graduate Film Released in 1967 Discussion

Belhaven University Appreciation the Employers Show to The Employees at Work Essay.

write a 3-page minimum (750 words) paper describing your understanding of appreciation where you work? How is appreciation communicated? As a future leader how would you show appreciation of your employees in an effort to motivate them? Using Hebrews 12: 1-2 responded on how the Bible guides us in the area of leading others. Provide and explain workplace examples.Requirements: Each paper submitted in this course must have a title page and a reference page. You are expected to reference and cite a minimum of two scholarly sources in each paper. Proper APA format must be followed.
Belhaven University Appreciation the Employers Show to The Employees at Work Essay

FIN 307 IAU University Finance Money and Banking Cryptocurrency Questions

FIN 307 IAU University Finance Money and Banking Cryptocurrency Questions.

Course : FIN 307 – MONEY AND BANKING1. Explain why Bitcoin, a cryptocurrency, cannot function as Money within 400 words. (Hint: Functions of Money)2. Explain the development of Shadow Banking System within 400 words. (Hint; Securitization)……….Another Question :Cryptocurrencies: Does it likely to replace traditional fiat currency? Cryptocurrency, an encrypted, peer-to-peer network for facilitating digital barter, is a technology developed eight years ago. Bitcoin, the first and most popular cryptocurrency, is paving the way as a disruptive technology to long standing and unchanged financial payment systems that have been in place for many decades. While cryptocurrencies are not likely to replace traditional fiat currency, they could change the way Internet-connected global markets interact with each other, clearing away barriers surrounding normative national currencies and exchange rates. Technology advances at a rapid rate, and the success of a given technology is almost solely dictated by the market upon which it seeks to improve. Cryptocurrencies may revolutionize digital trade markets by creating a free flowing trading system without fees.Note: Please use the shared Research Papers and other online sources to provide answers to the following questions. Question : Risk involved investing in cryptocurrencies and the future of cryptocurrency according to the available information? Please do your best doctor Answer will be checked plagiarism software therefore, avoid from copy and paste and must include references in text and end references.
FIN 307 IAU University Finance Money and Banking Cryptocurrency Questions

Methods of Environmental Assessment

assignment writing services Methods of Environmental Assessment. Rapid Environmental Impact Assessment Tool – This method of environmental assessment was designed to help local councils as well as various organizations to create a preliminary assessment and environmental screening of a proposed project or activity in order to determine whether it has a negative, neutral or positive environmental impact (Schianetz et al., 2007). Leopold Matrix -Similar to the Rapid Environmental Impact Assessment Tool, the Leopold matrix is similarly utilized to measure the impact of a project on the environment (Safont et al., 2012). What differentiates the Leopold Matrix from other methods of environmental assessment is the way in which it utilizes measures of importance (i.e. from a measure of 1 to 10) to magnitude (i.e. from -10 to 10) in order to determine the overall impact of a particular activity (Safont et al., 2012). Fuzzy logic – Often utilizing quantitative data as a means of assessment, Fuzzy logic can be considered a means of processing data so as to extend classical set theory to the extent that it can handle partial membership. In other words, fuzzy logic is used as a means of clarifying concepts related to “safety”, “health” and “acceptable” to the extent that it can be clearly understood based on quantitative analysis of data sets involving appropriate measures that deal with such abstract concepts (Ridgway, 2005). It should be noted though that due to the complications involved in fuzzy logic applications and methods of utilization, it is rarely utilized in risk assessment or environmental policy due to the presence of better tools of assessment (Ridgway, 2005). Flash Environmental Assessment Tool (FEAT) While not utilized on a daily basis, the Flash Environmental Assessment Tool is one the best methods of assessing any existing or potential environmental impact risks that can be considered as a “significant” risk to locals and the environment through the release of unnatural or exotic chemical compounds into the surrounding environment (Saeed et al., 2012). FEAT is normally seen in use when a tanker ship, a truck or other vehicle has accidentally let loose its shipment of chemicals. During such incidents, it is important to determine the level of danger involved so that proper cleanup procedures can be implemented (Saeed et al., 2012). Differences in Methodologies The Rapid Environmental Impact Assessment Tool utilizes 14 potential environmental factors in a checklist format as a means of assessing the impact of a particular project or activity (Chang et al., 2013). Utilizing a color code scheme, it is able to determine whether an activity would be positive for the environment or not. The Leopold Matrix on the other hand utilizes a set of columns which show the various activities of a project with each being measured on a scale of -10 to 10 as to whether or not they are good or bad for the environment (Chang et al., 2013). Fuzzy logic assessment differs from the previous examples in that it utilizes a theoretical framework in order to utilize imprecise and uncertain factors in a way that generates an output that is logical. Examples of this can consist of determining how the amount of trees cut on a daily basis impacts the amount of carbon dioxide in the hair which can adversely affect people and the environment. FEAT on the other hand utilizes a large array of information on compounds and their impact on local environments in order to create its method of assessment. Similarities Differences Rapid Environmental Impact Assessment Tool Both utilize a ranking system to create an environmental assessment Utilizes a 14 point check list to assess the environmental impact of projects Leopold Matrix Examines individual activities on their potential environmental impact Fuzzy logic Utilizes statistical data on imprecise factors to create a conclusion Flash Environmental Assessment Tool (FEAT) Utilizes prior scientific information on chemicals to conduct an analysis Reference List Chang, T., Nielsen, E., Auberle, W.,Methods of Environmental Assessment

WU Advanced Levels of Clinical Inquiry and Systematic Reviews Presentation

WU Advanced Levels of Clinical Inquiry and Systematic Reviews Presentation.

Assignment: Evidence-Based Project, Part 2: Advanced Levels of Clinical Inquiry and Systematic Reviews
Your quest to purchase a new car begins with an identification of the factors important to you. As you conduct a search of cars that rate high on those factors, you collect evidence and try to understand the extent of that evidence. A report that suggests a certain make and model of automobile has high mileage is encouraging. But who produced that report? How valid is it? How was the data collected, and what was the sample size?
In this Assignment, you will delve deeper into clinical inquiry by closely examining your PICO(T) question. You also begin to analyze the evidence you have collected.
To Prepare:

Review the Resources and identify a clinical issue of interest that can form the basis of a clinical inquiry.
Develop a PICO(T) question to address the clinical issue of interest you identified in Module 2 for the Assignment. This PICOT question will remain the same for the entire course.
Use the key words from the PICO(T) question you developed and search at least four different databases in the Walden Library. Identify at least four relevant systematic reviews or other filtered high-level evidence, which includes meta-analyses, critically-appraised topics (evidence syntheses), critically-appraised individual articles (article synopses). The evidence will not necessarily address all the elements of your PICO(T) question, so select the most important concepts to search and find the best evidence available.
Reflect on the process of creating a PICO(T) question and searching for peer-reviewed research.

The Assignment (Evidence-Based Project)
Part 2: Advanced Levels of Clinical Inquiry and Systematic Reviews
Create a 6- to 7-slide PowerPoint presentation in which you do the following:

Identify and briefly describe your chosen clinical issue of interest.
Describe how you developed a PICO(T) question focused on your chosen clinical issue of interest.
Identify the four research databases that you used to conduct your search for the peer-reviewed articles you selected.
Provide APA citations of the four relevant peer-reviewed articles at the systematic-reviews level related to your research question. If there are no systematic review level articles or meta-analysis on your topic, then use the highest level of evidence peer reviewed article.
Describe the levels of evidence in each of the four peer-reviewed articles you selected, including an explanation of the strengths of using systematic reviews for clinical research. Be specific and provide examples.

Article 1
I choose the article “Client retention in community treatment: completer and non-completer experiences of an individualized, needs-based partner abuse intervention program.” since it relates to the clinical issue of interest which is understanding the issues that influenced late recovery of the client. The peer reviewed article was used to highlight the importance of incorporating therapeutic alliance and providing structured individualized treatment to participants of partner abuse intervention programs (Pearson et al., 2020). The research methodology applied was qualitative which focused on elaborating the target issue through data collected from books and other internet sources or materials. Qualitative research helps maintain good relationships between researchers and study participants hence the delivery of quality information. Data was collected using semi-structured interviews which were completed by 14 participants. The interviews added a strength for the research since information shared by the participants was valid based on their subjective experiences.
Article 2
I selected the article “High risk situations predicting relapse in self-referred addicts to Bushehr province substance abuse treatment centres” since it provides a deeper explanation of the effective strategies for relapse prevention which is a major clinical issue of interest. The study was used to evaluate high risk situations for relapse self-referred drug addicts. Researchers used IDTS Marlatt questionnaires to conduct analytical and descriptive statistics. The questionnaires added a strength to the study since they assessed high risk situations that influence relapse on self-referred addicts in substance abuse centres (Shafiei et al., 2014). Questionnaires are more practical and easier to analyse which is a major strength when using them to collect data for quantitative studies. The qualitative study helped highlight major clinical and psychological strategies used to minimize the high rates of relapse.
Article 3
I selected the article “Relapse Coping Strategies in Young Adults Addicts: A Quantitative Study in Iran” since it provides a highlight of the cognitive-behavioural coping approach used to prevent relapse among young adult addicts. The coping strategies are used to replace incompatible behavior with compatible answers. Research was conducted through a quantitative study whereby a sample of 70 self-referred drug addicts were examined (Shafiei et al., 2016). The participants shared information about relapse coping strategies through questionnaires. Quantitative research enables generalization of research findings through objective and accurate information shared by the study participants. The data collection method was efficient since it helped highlight coping skills effective for young adults. Information shared through the questionnaire was valid and efficient, a factor that influenced successful research.
Article 4
I selected the article “A qualitative exploration of social support during treatment for severe alcohol use disorder and recovery” since it relates to the clinical issue of social support required for recovering addicts. Data collected through the study explains complex issues and barriers experienced by individuals recovering. Qualitative research was conducted to help incorporate the human experience when undergoing treatment for severe alcohol use disorder. Researchers conducted interviews in 2014 and 2015 and an in-depth thematic analysis of topics related to social support (Brooks et al., 2017). The interviews presented a strength in the study since they highlighted the relationship between quality and nature of sustained sobriety when patients transition from the research facilities in charge of rehabilitation treatment in the community.
Brooks, A. T., Lòpez, M. M., Ranucci, A., Krumlauf, M., & Wallen, G. R. (2017). A qualitative exploration of social support during treatment for severe alcohol use disorder and recovery. Addictive behaviors reports, 6, 76-82.
Pearson, D. A., Steward, C. D., & Ford, A. K. (2020). Client retention in community treatment: completer and noncompleter experiences of an individualized, needs-based partner abuse intervention program. Journal of interpersonal violence, 0886260520907356.
Shafiei, E., Hoseini, A. F., Bibak, A., & Azmal, M. (2014). High risk situations predicting relapse in self-referred addicts to bushehr province substance abuse treatment centers. International journal of high risk behaviors & addiction, 3(2).
Shafiei, E., Hoseini, A. F., Parsaeian, F., Heidarinejad, A., & Azmal, M. (2016). Relapse coping strategies in young adults addicts: A quantitative study in Iran. Indian journal of psychological medicine, 38(1), 46-49.
WU Advanced Levels of Clinical Inquiry and Systematic Reviews Presentation

Health Sciences homework help

Health Sciences homework help. This is an assignment that focuses on the fraud protection measures and recommendations for Doha Carpets.The paper also investigates the training of new software.,The fraud protection measures and recommendations for Doha Carpets,NOTE: • This is an individual assignment. • Any copying, sharing, plagiarizing of content will result in a grade of 0. • Please review the marking rubric on pages 2-4. • This assignment is worth 15% of the final grade. •Doha Gold Doha Gold is a successful and fast growing high end jewelry retail chain in the Middle East. Recently, several smaller shops and boutiques were acquired to expand its operations. The new company is much larger than the original company and it has outgrown its accounting software. The original accounting system was a package from ,Peachtree Software,, which initially ran on a stand-alone PC and later on a network. Now, the firm is preparing to install a powerful, scalable accounting package that can support the company’s current and future operations. You have been hired to implement the new system.,Tasks 1. Firstly, what types of fraud protection measures would you recommend for Doha Carpets? Explain each recommendation. 2. Secondly, who should receive training on the new software, and what topics should the training cover? 3. Thirdly, what changeover strategy would you suggest for the new accounting system? Also, explain your answer. 4. The owner of Doha Gold does not believe it is necessary to perform testing of the new software. Explain testing and also why it is important to systems development. What types of tests would you recommend be complete for this project?,The paper should be at least three pages long exclusive of the reference and the cover page. Subsequently, ensure that you include all the references from the sources that you are to use in the assignment. Lastly, use the APA format and style in writing and citing.Health Sciences homework help