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Assignment Briefs 12-13-2022

L7 critical literature analysis - Cell Biology 66-706916

Faculty of Health & Wellbeing - Department of Biosciences

L7 critical literature analysis - Cell Biology 66-706916

The coursework (50% module weighting) will be in-depth, critical analysis of a recent Cell Biology article. A critical analysis examines an article to determine how effective it is at making an argument or point. To make this determination, you will need to explore prior work that provides the context for the article, carefully examine the scientific methods and results presented in the article, and consider how the conclusions made relate to the topics covered within the module.

The deadline for the coursework is Monday, December 5th (week 19).

You will be provided with the article in the introductory lecture (week 10), and the article will be available to download from Blackboard at this point. The report should be similar to a "news and views" article found in journals such as Nature and Cell - you can find an example of this kind of article at this end of this brief, and there are other examples on Blackboard for you to use to familiarise yourself with this style of writing.

Support: a tutorial session will be arranged in week 13 where you will be able to ask specific questions about your work to date and I will go over some of the methods. I will upload a summary to summarise key points. We`ll then have a follow-up tutorial in week 16 to address specific questions you may have about the paper. Topics relevant to the coursework will also be highlighted in appropriate lectures, so that the coursework and lecture series complement each other.

Word count: "News and views" articles are concise, focussed reviews of around 1500-2000 words, so there is a 2000 word limit for this coursework. You should provide a word count at the end of your coursework. An important skill in writing this kind of article is being able to write concisely, exceeding this word count will affect your marks in the "communication and structure" component of the marking criteria, as you are not demonstrating an ability to communicate the key points clearly and with focus.

References: The report should be based on the article provided, but in order to provide context you will need to read around the literature to identify the key studies that have lead up to this article. These should be cited and referenced in the SHU-Harvard style. There is no limit on the number or references you can use, but "news and views" articles generally use 12-15 references to support their argument.

Figures: "News and views" articles often include a figure to illustrate the overall message of the article. You do not have to include a figure, however you may wish to consider whether including one would help to explain the concepts in the article.

Submissions: you will need to submit a .doc or .pdf file through the Grade Centre submission point provided on Blackboard, and the same file to the Turnitin submission point provided 

 

Assessment criteria for the report.

You should consider when writing your review:

Background: What is the context for this study? What area of Cell Biology is being addressed, and why was this necessary? What prior work provided important findings which led up to this study?

Hypothesis/aims: Clearly state what the study aimed to identify.

What methods were used: what approaches did the study take? What property of cellular function do these approaches measure? Why were these approaches appropriate?

Findings: What were the key results? What conclusions did the authors draw from these results? How did the experimental data link to the conclusions?

Future work: What was the overall message from this work? Were these conclusions appropriate? What would be these next steps for this work?

An example of this type of article is provided on pages 3-7 as a guide.

The coursework will be assessed according to set criteria which are detailed on page 8-9. In order to achieve a pass in the module you must gain 50% overall, and the coursework is worth 50% of the module. Written feedback will be given on your individual coursework

Example of a "news and views" article:

ECM stiffness paves the way for tumor cells.

Seewalt, V: Nature Medicine volume20, pages332–333 (2014)

Until recently, breast cancer studies focused on signaling that occurred within epithelial cells but did not account for the complex molecular circuits regulated by the breast microenvironment. In particular, ECM collagen was thought to be an inert barrier to tumor invasion and metastasis. Studies over the past seven years, however, provide evidence that ECM collagen has a dynamic role in breast microenvironment and is an active participant that promotes tumor progression (Lu, Weaver and Werb, 2012)

Understanding how ECM collagen influences breast cancer biology has become a pressing issue, given new US state laws requiring radiologists to inform women undergoing screening mammography whether they have high mammographic density (Grady, 2012) - a general measure of the relative ratio of ECM collagen to adipose cell volume (Boyd, Martin, Yaffe and Mikin, 2011) Current US laws rely on the observation in populations—but not individuals—that high mammographic density predicts a two- to sixfold higher risk of breast cancer (Boyd, Martin, Yaffe and Mikin 2011), however, it is a poor predictor of risk in individuals (Cecchini et al., 2012). Moreover, it fails to identify aggressive clinical outcome (Gierach et al., 2012), underscoring the need for mechanistic studies of ECM collagen signaling. A recent study carried out by the US National Cancer Institute with over 9,000 women showed that whereas high mammographic breast density predicted an increased incidence of breast cancer, low mammographic density was linked to increased breast cancer–related deaths (Gierach et al., 2012). In light of the recent US mammographic density notification laws, these data underscore the need for a better understanding of how ECM collagen contributes to breast cancer progression and disease risk.

Since 2005, preclinical studies by Valerie Weaver and her group have shown that the structure, orientation and physical properties of ECM collagen play a key part in regulating aggressive biology of breast cancers (Butcher, Alliston and Weaver, 2009). In this issue of Nature Medicine, Mouw et al (2014) show that ECM collagen–generated tensile forces regulate an epithelial signaling circuit that activates microRNA (miRNA) expression to drive tumor progression. Increased ECM stiffness transcriptionally activated MYC and upregulated the miRNA miR-18a, leading to reduced expression of the tumor suppressor phosphatase and tensin homolog (PTEN) and homeobox A9 (HOXA9) and tumor invasion and metastasis in mice. In women with luminal breast cancer, miR-18a predicted poor survival. These findings not only provide an important link between the physical structure of the ECM microenvironment and the activation of tumor cell signaling pathways that promote aggressive biology but also associate the stiffness of the breast tissue matrix with the survival of women with luminal breast cancer.

The work by Mouw et al (2014) contributes to an emerging picture of how ECM collagen structure and the tumor microenvironment as a whole drive signaling networks that promote breast cancer initiation and progression. In particular, collagen fibers, which are the main components of the ECM, produce physical tension on epithelial cells that activate signaling pathways, which, in turn, regulate invasiveness in mouse models of breast cancer (Butcher, Alliston and Weaver, 2009; Mouw et al, 2014; Sabeh, Shimizu-Hirota and Weiss, 2009). Investigators have shown in mice that cancer cells preferentially invade along stiff collagen fibers into the adjacent stroma, and stiff aligned collagen identifies focal sites of breast cancer cell microinvasion (Sabeh, Shimizu-Hirota and Weiss, 2009; Friedl and Wolf, 2010). In fact, mammary gland involution results in ECM collagen remodeling, and postpartum activation of tissue inflammation seems to induce `scarring` of ECM collagen by converting normal flexible fibers into high-risk stiff aligned collagen (Lyons et al, 2011). These findings indicate that matrix stiffness can induce physical changes in the tissue that can influence the behavior of tumor cells. Moreover, stiff cross-linked collagen has been shown to predict poor survival in women with invasive breast cancer (Conklin et al, 2011), emphasizing the potential clinical relevance of alterations of the ECM structure in the mammary gland.

Previously, Weaver and her group showed that cross-linked ECM collagen increases ECM stiffness and promotes malignancy (Kumar and Weaver, 2012); however, despite the mechanistic insights provided, the role of ECM mechanosignaling and human breast cancer progression is still not well defined. Using nonmalignant human mammary epithelial cells plated in soft or stiff matrices, Mouw et al (2014) found that miRNAs were upregulated in cells plated on stiff substrates, which was also confirmed in a genetically engineered mouse model of breast cancer. In particular, high ECM matrix stiffness drove tumor progression by upregulating miR-18a in both cultured nonmalignant and transformed breast cancer cell lines (Mouw et al, 2014).

miRNAs are post-transcriptional regulators of gene expression that are altered in cancer, having an impact on cell-cell interactions and integrin-dependent adhesion (Valastyan and Weinberg, 2011). As integrin signaling has been previously shown to be increased in tumors and reduced when ECM stiffening is prevented (Butcher, Alliston and Weaver, 2009), this suggests functional links between miRNA expression and ECM mechanosignaling during cancer progression. The authors now delineated how miR-18a fosters tumor progression by showing that its induction by increased matrix stiffness upon integrin engagement results in reduced amounts of the tumor suppressor PTEN (protein and mRNA). Because PTEN is frequently lost in aggressive breast cancers (Gilbert et al, 2010), these studies identify how ECM collagen stiffness can trigger the aggressive biology of breast cancers.

Using human mammary epithelial cells grown on a stiff substrate and in stiff mouse mammary gland tissue, Mouw et al (2014) found that miR-18a expression decreases expression of PTEN both directly and indirectly through the targeting of the homeobox-A gene HOXA9 (Fig. 1). HOXA9, a known regulator of mammary gland homeostasis and mammary tissue regeneration during the menstrual cycle and pregnancy, is frequently lost in aggressive breast cancers (Gilbert et al, 2010). The authors further demonstrated that direct binding of the HOXA9 DNA-binding domain to the PTEN promoter is required for gene expression, which is relevant, as lack of HOXA9 expression has been shown to also lead to loss of BRCA1expression (Gilbert et al, 2010). These data provide a molecular link between ECM mechanosignaling and the epigenetic loss of BRCA1 expression.

Because loss of PTEN and HOXA9 predicts aggressive biology, the mechanosignaling-regulating expression of miR-18a and downstream PTEN and HOXA9 suggests expression of miR-18 could stratify human breast cancers for risk. The clinical relevance of ECM stiffness–induced miR-18a and PTEN repression was investigated by assessing abundance of HOXA9 and PTEN in breast cancer subtypes and in normal tissue (Mouw et al, 2014). Basal-type breast cancer is the clinically most aggressive subtype of breast cancer; accordingly, ECM stiffness and miR-18a expression was the highest in these cancers, and PTEN and HOXA9 mRNA expression lowest. Mouw et al (2014) used publicly available gene expression data sets to test for associations between miR-18a and clinical outcome in all breast cancer subtypes. High miR-18a expression at initial diagnosis was associated with shorter time to distant relapse-free survival, and miR-18a expression was significantly predictive of future disease progression for women with luminal breast cancers (but not basal-type breast cancers).

Figure 1: ECM-generated mechanical force drives an miRNA circuit that promotes malignancy in preclinical models and predicts distal relapse-free survival (DRFS) in luminal breast cancer. Increased ECM stiffness promotes β1 integrin clustering, transcriptionally activates MYC and induces the polycistronic miR-17-92 cluster. This results in the upregulation of a particular miRNA, miR-18a, which, in turn, reduces expression of PTEN and HOXA9. Low PTEN increases signaling through the phosphoinositide 3-kinase (PIP3)–AKT pathway, promoting invasion and metastasis. Increased ECM-generated mechanical force can therefore regulate the expression of PTEN, HOXA9 and also BRCA1 via a miR-18a–dependent signaling network. FAK, focal adhesion kinase; IP3, inositol triphosphate. Image: Katie Vicari

This study has some limitations and uncovers important future directions. Biomarkers are needed to predict risk for all cancers; the finding that miR-18a can stratify luminal breast cancer risk provides the groundwork to identify women who may need aggressive chemotherapy regimens and, conversely, spare those with relatively indolent disease from unnecessary chemotherapy. The investigators found that miR-18a expression predicted prognosis in luminal breast cancers but not in the basal-like subtype of triple-negative breast cancers (Mouw et al, 2014). Dysregulation of PTEN and HOXA9 signaling seems to be crucial in the pathogenesis of basal-like breast cancers (Valastyan and Weinberg, 2011; Gilbert et al, 2010); thus, it would be expected that as miR-18a caused the loss of these two proteins, its expression would predict disease outcome in women with this type of tumor. However, this may not have been observed because the overall prognosis for established basal-like breast cancer, in which miR-18a expression was highest, is poor. The potential of this work may lie in testing whether miR-18a expression can serve as an early-detection and early-risk marker for basal-type breast cancer. Future studies may provide a more precise tool to assess the complex contribution of ECM collagen to the molecular circuitry governing breast cancer risk and aggressive biology.

 

 

 

References:

Boyd, N.F., Martin, L.J., Yaffe, M.J., Minkin, S. Mammographic density and breast cancer risk: current understanding and future prospects. Breast Cancer Res. 13, 223–229 (2011).

Butcher, D.T., Alliston, T. & Weaver, V.M. A tense situation: forcing tumour progression. Nat. Rev. Cancer 9, 108–122 (2009).

Cecchini, R.S., Costantino, J.P., Cauley, J.A., Cronin, W.M., Wickerham, D.L., Bandos, H., Weissfeld, J.L., Wolmark, N. Can. Prev. Res. (Phila.) 5, 1321–1329 (2012).

Conklin, M.W., Eickhoff, J.C., Riching, K.M., Pehlke, C.A., Elicieri, K.W., Provenzano, P.P….Keely, P.J. Aligned collagen is a prognostic signature for survival in human breast carcinoma. Am. J. Pathol. 178, 1221–1232 (2011).

Friedl, P. & Wolf, K. J. Plasticity of cell migration: a multiscale tuning model. Cell Biol. 188, 11–19 (2010).

Gierach, G.L., Ichikawa, L., Kerlikowske, K., Brinton, L.A., Farhat, G.N., Vacek, P.M….Sherman, M.E. J. Natl. Cancer Inst. 104, 1218–1227 (2012).

Gilbert, P.M., Mouw, J.K., Unger, M.A., Lakins, J.N., Gbegnon, M.K., Clemmer, V.B….Weaver, V.M. HOXA9 regulates BRCA1 expression to modulate human breast tumor phenotype.J. Clin. Invest. 120, 1535–1550 (2010).

Grady, D. New laws add a divisive component to breast screening. The New York Times. (24 October 2012).

Kumar, S. & Weaver, V.M. Mechanics, malignancy, and metastasis: the force journey of a tumor cell. Cancer Metastasis Rev. 28, 113–127 (2009).

Lu, P., Weaver, V.M. & Werb, Z. The extracellular matrix: a dynamic niche in cancer progression. J. Cell Biol. 196, 395–406 (2012).

Lyons, T.R., O`Brien, J., Borges, V.F., Conklin, M.W., Keely, P.J., Eliceiri, K.W….Schedin, P. Postpartum mammary gland involution drives progression of ductal carcinoma in situ through collagen and COX-2. Nat. Med. 17, 1109–1115 (2011).

Mouw, J.K., Yui, Y., Damiono, L., Bainer, R.O., Lakins, J.N., Acerbi, I….Weaver, V.M. Tissue mechanics modulate microRNA-dependent PTEN expression to regulate malignant progression. Nat. Med. 20, 360–367 (2014).

Sabeh, F., Shimizu-Hirota, R. & Weiss, S.J. Protease-dependent versus -independent cancer cell invasion programs: three-dimensional amoeboid movement revisited. J. Cell Biol. 185, 11–19 (2009).

Valastyan, S. & Weinberg, R.A. Roles for microRNAs in the regulation of cell adhesion molecules. J. Cell Sci. 124, 999–1006 (2011).


Department of Biosciences & Chemistry

L7 Critical Literature Analysis:  Cell Biology

 

Instructions:

1) Complete your name.

2) Save file as: surname_Lit_CW_2019-20.docx   eg Peake_N_Lit _CW_2019-20.docx

3) Insert your work on the final page so that the feedback forms are at the front.

4) Submit your work to Blackboard submission tool on the Blackboard site and Turnitin as a Word-compatible file (not a pdf).

 

Student Name:
Number:

 

Learning contract? Insert details if applicable here.

 

Marker:

 

Grade:

 

Strengths:

 

Areas to improve:

 

Student comments for feed-forward
how will you use this feedback to improve your future work?:

mark

Knowledge and Understanding

Arguments and Evaluation

Communication and Structure

Use of citations and referencing

High
Distinction

Exceptional breadth and depth of knowledge and understanding, evidenced by own independent insight and critical awareness of concepts at the forefront of the discipline

Cogent arguments and explanations are consistently provided. A sustained academic approach to all aspects of the tasks is evidenced.

Effectively and competent communication in a style very close to publishable or commercial standard. English language is presented in an eloquent and professional manner.

Evidence of extensive and appropriate independent inquiry operating with advanced concepts, methods and techniques at the forefront of the discipline.

Distinction

Excellent knowledge and understanding evidenced by some clear independent insight and critical awareness of relevant concepts some of which are at the forefront of the discipline.

Arguments and explanations show a competent understanding of all of the relevant content. A sustained academic approach to most aspects of the tasks is evidenced.

Effectively and competent communication and structure in a style that is suited to a technical audience.

Evidence of independent inquiry. Arguments and explanations are provided that are well - supported by the literature at the forefront of the discipline. APA style referencing throughout. 

Merit

Very good knowledge and understanding is evidenced through facts and concepts that are related together.

Arguments and explanations are provided that are typically supported by the literature and in some cases may challenge some received wisdoms.

Effectively and competent communication and structure.

Evidence of some competent independent inquiry. Able to relate taught facts/concepts together some of which are at the forefront of the discipline. APA style referencing throughout.  .

Pass

Good knowledge and understanding of the area of study balanced towards the descriptive rather than critical or analytical and mostly confined to concepts that are not at the forefront of the discipline

Arguments and explanations are limited in range and depth although some are adequately supported by the literature albeit descriptively rather than critically.

Communication shows clarity but structure may not always be coherent.

Evidence of some independent reading and research to advance work and inform arguments and approaches. APA style referencing throughout may have minor errors. 

Fail

 

Knowledge and understanding is marginally insufficient as the text  typically deals with terminology, basic facts and concepts

 

 

 

Adequate knowledge of concepts but fails to add meaningful detail or make sufficient links between concepts and facts.

 

Communication/presentation fails to  demonstrate clarity and focus; inability to adequately define problems and make reasoned judgements.

 

Some ability to  independently select and evaluate reading/research however there is a strong reliance on set sources and to provide descriptive and unsubstantiated arguments/method. APA style referencing throughout may have major errors. 

Fail

Knowledge and understanding is highly insufficient as the text is unable to evidence any meaningful understanding of theory,

 concepts or methods.

Very limited evidence of reading and research to advance work. Limited or lack of understanding of the boundaries of the discipline

May not have clearly distinguished sections, poor structure. Lacks connections between sections and little evidence of a developing argument

Inability to communicate coherently

English may be confused and inappropriate. Main data are poorly presented. APA style referencing throughout may have major errors. 

 

Zero

Work of no merit OR absent, work not submitted, penalty in some misconduct cases.

Class

CG

General Characteristics

DISTINCTION

 

 

96

Exceptionalbreadthanddepthofknowledgeandunderstandingevidencedbyownindependentinsightandcriticalawarenessof relevant literature and concepts at the forefront of the discipline; evidence of extensive and appropriate independent inquiry operating with advanced concepts, methods and techniques to solve problems in unfamiliar contexts; Cogent arguments and explanationsareconsistentlyprovidedusingarangeofmediademonstratinganabilitytocommunicateeffectivelyinavarietyof formats using a sophisticated level of the English language in an eloquent and professional manner to both technical and non- technicalaudiences;asustainedacademicapproachtoallaspectsof thetasksisevidenced;academicworkextendsboundariesof

the disciplines and is beyond expectation of the level and may achieve or be very close to publishable or commercial standard.

89

Excellent knowledge and understanding evidenced by some clear independent insight and critical awareness of relevant concepts some of which are at the forefront of the discipline; evidence of appropriate independent inquiry operating with core concepts, methods and techniques to solve complex problems in mostly familiar contexts; Arguments and explanations are provided that is well- supported by the literature and in some cases uses a range of media demonstrating an ability to communicate effectively in a limited number  of formats using own style that is suited to  both technical and non-technical audiences;  a sustained academic approach to mostaspectsofthetasksisevidenced;oneormoreaspectsoftheacademicworkisbeyondtheprescribedrangeandevidencesa competent understanding of all of the relevant taught content.

81

74

MERIT

 

 

68

Verygoodknowledgeandunderstandingisevidencedasthestudentistypicallyabletoindependentlyrelatetaughtfacts/concepts together some of which are at the forefront of the discipline; evidence of some competent independent inquiry operating with core concepts,methodsandtechniquestosolvefamiliarproblems;Argumentsandexplanationsareprovidedthataretypicallysupported bytheliteratureandinsomecasesmaychallengesomereceivedwisdoms;competentlyusesalltaughtmediaandcommunication methodstocommunicateeffectivelyinafamiliarsettings;anacademicallyrigorousapproachappliedtosomeaspectsofthetasksis evidenced;somebeyondtheprescribedrange,mayrelyonsetsourcestoadvancework/directarguments;demonstratesautonomy in approach to learning.

65

62

PASS

 

 

58

Goodknowledgeandunderstandingoftheareaofstudybalancedtowardsthedescriptiveratherthancriticaloranalyticaland mostlyconfinedtoconceptsthatarenotattheforefrontofthediscipline;evidenceofsomeindependentreadingandresearchto advanceworkandinformargumentsandapproaches;Argumentsandexplanationsarelimitedinrangeanddepthalthoughsomeare adequately supported by the literature albeit descriptively rather than critically; competently uses at least one taught media and communication method to communicate appropriately in familiar settings; although the approach applied to some aspects of the tasksmaylackacademicrigour,therearesomeclearareasofcompetencewithintheprescribedrange.Reliesonsetsourcesto

advance work/direct arguments and communicated in a way which shows clarity but structure may not always be coherent.

55

52

FAIL

 

 

45

Knowledge and understanding is marginally insufficient as the student is typically only able to deal with terminology, basic facts and concepts; Adequate knowledge of concepts within the prescribed range but fails to add meaningful detail or make sufficient links between concepts and facts to  adequately solve problems posed by the  assessment; some ability to  independently select and evaluate reading/research however there is a strong reliance on set sources and to provide descriptive and unsubstantiated arguments/methods; communication/presentation is competent in places and at a threshold  level  as  it  fails to  demonstrate  clarity and focus; inability to adequately define problems and make reasoned judgements; The general approach to tasks lacks rigor and where there is competence and rigor, it is not sustained.

35

25

Knowledge and understanding is highly insufficient as the student is unable to evidence any meaningful understanding of two or more taught concepts or methods; very limited evidence of reading and research to advance work; inadequate technical and practical skills as the student is unable to use and apply such skills to address problems or make judgements; limited or lack of understanding of the boundaries of the discipline and does not question received wisdom; approach to learning lacks autonomy and approach to tasks is not sustained; inability to communicate coherently.

15

5

ZERO

0

Work of no merit OR absent, work not submitted, penalty in some misconduct cases.

mark

Knowledge and Understanding

Arguments and Evaluation

Communication and Structure

Use of citations and referencing

High
Distinction

Exceptional breadth and depth of knowledge and understanding, evidenced by own independent insight and critical awareness of concepts at the forefront of the discipline

Cogent arguments and explanations are consistently provided. A sustained academic approach to all aspects of the tasks is evidenced.

Effectively and competent communication in a style very close to publishable or commercial standard. English language is presented in an eloquent and professional manner.

Evidence of extensive and appropriate independent inquiry operating with advanced concepts, methods and techniques at the forefront of the discipline.

Distinction

Excellent knowledge and understanding evidenced by some clear independent insight and critical awareness of relevant concepts some of which are at the forefront of the discipline.

Arguments and explanations show a competent understanding of all of the relevant content. A sustained academic approach to most aspects of the tasks is evidenced.

Effectively and competent communication and structure in a style that is suited to a technical audience.

Evidence of independent inquiry. Arguments and explanations are provided that are well - supported by the literature at the forefront of the discipline. APA style referencing throughout. 

Merit

Very good knowledge and understanding is evidenced through facts and concepts that are related together.

Arguments and explanations are provided that are typically supported by the literature and in some cases may challenge some received wisdoms.

Effectively and competent communication and structure.

Evidence of some competent independent inquiry. Able to relate taught facts/concepts together some of which are at the forefront of the discipline. APA style referencing throughout.  .

Pass

Good knowledge and understanding of the area of study balanced towards the descriptive rather than critical or analytical and mostly confined to concepts that are not at the forefront of the discipline

Arguments and explanations are limited in range and depth although some are adequately supported by the literature albeit descriptively rather than critically.

Communication shows clarity but structure may not always be coherent.

Evidence of some independent reading and research to advance work and inform arguments and approaches. APA style referencing throughout may have minor errors. 

Fail

 

Knowledge and understanding is marginally insufficient as the text  typically deals with terminology, basic facts and concepts

 

 

 

Adequate knowledge of concepts but fails to add meaningful detail or make sufficient links between concepts and facts.

 

Communication/presentation fails to  demonstrate clarity and focus; inability to adequately define problems and make reasoned judgements.

 

Some ability to  independently select and evaluate reading/research however there is a strong reliance on set sources and to provide descriptive and unsubstantiated arguments/method. APA style referencing throughout may have major errors. 

Fail

Knowledge and understanding is highly insufficient as the text is unable to evidence any meaningful understanding of theory,

 concepts or methods.

Very limited evidence of reading and research to advance work. Limited or lack of understanding of the boundaries of the discipline

May not have clearly distinguished sections, poor structure. Lacks connections between sections and little evidence of a developing argument

Inability to communicate coherently

English may be confused and inappropriate. Main data are poorly presented. APA style referencing throughout may have major errors. 

 

Zero

Work of no merit OR absent, work not submitted, penalty in some misconduct cases.

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