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21-22. doi: 10.1101/2.354. doi: 10.11011/j.1365-2133.2006.07646.x.
## Ethics approval and consent to participate
The study was conducted in accordance with the ethical principles of the Declaration of Helsinki (2013). Ethical approval was obtained from Sakhiya Skin Clinic, Surat, Gujarat, India. (Approval No: 2023/06). Consent forms were signed by patient. He was informed that he had the right to withdraw from the study at any time without any consequences. All pictures reported in this case- report study belong to Sakhiya Skin Clinic, Surat- 395003, Gujarat, India.
## Consent for publication
Not applicable
## Competing interest
The authors declare that they have no competing interests.
## Open Access
This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article unless otherwise stated.
## Author Details
1Department of Dermatology, Sakhiya Skin Clinic, Surat, Gujarat, India. 2Department of Medical Writing, Sakhiya Skin Clinic, Surat, Gujarat, India
## Article Info
Received: 21 April 2023 Accepted: 03 June 2023 Published: 07 June 2023
## References
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5. Heizmann M, Itin P, Wernli M, Borradori L, Bargetzi MJ. Successful treatment of paraneoplastic pemphigus in follicular NHL with rituximab: report of a case and review of treatment for paraneoplastic pemphigus in NHL and CLL. Am J Hematol. Feb 2001;66(2):142-4. doi: 10.1002/1096-8652(200102)66:2<142::AID-AJH1032>3.0. CO;2-0.
6. Food and Drug Administration. Rituxan label; 2012 [cited Feb 2, 2021]. Available from: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/103705s5373lbl.pdf.
7. Belgi AS, Azeez M, Hoyle C, Williams REA. Response of pemphigus vulgaris to anti-CD20 antibody therapy (rituximab) may be delayed. Clin Exp Dermatol. 2006 Jan;31(1):143. doi: 10.1111/j.1365-2230.2005.01941.x.
8. Schmidt E, Seitz CS, Benoit S, Brocker EB, Goebeler M. Rituximab in autoimmune bullous diseases: mixed responses and adverse effects. Br J Dermatol. 2007 Feb;156(2):352-6. doi: 10.1111/j.1365-2133.2006.07646.x.
9. Barrera MV, Mendiola MV, Bosch RJ, Herrera E. Prolonged treatment with rituximab in patients with refractory pemphigus vulgaris. J Dermatolog Treat. 2007 Jan;18(5):312-4. doi: 10.1080/09546630701323988.
10. Faurschou A, Gniadecki R. Two courses of rituximab (anti-CD20 monoclonal antibody) for recalcitrant pemphigus vulgaris. Int J Dermatol. 2008 Mar;47(3):292-4. doi: 10.1111/j.1365-4632.2008.03423. x.
11. Craythome EE, Mufti G, DuVivier AW. Rituximab used as a first-line single agent in the treatment of pemphigus vulgaris. J Am Acad Dermatol. 2011 Nov;65(5):1064-5. doi: 10.1016/j.jaad.2010.06.033.
12. Horváth B, Huizinga J, Pas HH, Mulder AB, Jonkman MF. Low-dose rituximab is effective in pemphigus. Br J Dermatol. 2012 Feb;166(2):405-12. doi: 10.1111/j.1365-2133.2011.10663. x.
13. Craythome E, Du Vivier A, Mufti GJ, Warnakulasuriya S. Rituximab for the treatment of corticosteroid—refractory pemphigus vulgaris with oral and skin manifestations. J Oral Pathol Med. 2011 Sep;40(8):616-20. doi: 10.1111/j.1600-0714.2011.01017. x
14. Kim JH, Kim YH, Kim MR, Kim SC. Clinical efficacy of different doses of rituximab in the treatment of pemphigus: a retrospective study of 27 patients. Br J Dermatol. 2011 Sep;165(3):646-51. doi: 10.1111/j.1365-2133.2011.10411. x
15. Kasperkiewicz M, Shimanovich I, Ludwig RJ, Rose C, Zillikens D, Schmidt E. Rituximab for treatment-refractory pemphigus and pemphigoid: a case series of 17 patients. J Am Acad Dermatol. 2011 Sep;65(3):552-8. doi: 10.1016/j.jaad.2010.07.032
16. Investor update. Basel; June 12, 2019. [cited Feb 5, 2021]. Available from: https://www.roche.com/investors/updates/inv-update-2019-06-12. htm.
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2645-9248 Journal homepage: www.jidhealth.com Open A ccess Original Article
# A case report on generalized pemphigus vulgaris treated with rituximaba
J agdish J adavbhai Sakhiya \(^{1*}\) , Dhruv J agdish Sakhiya \(^{1}\) , J ashmine Mukeshbhai Gandhi \(^{1}\) , Feral Ravi Daruwala \(^{2}\)
## Abstract
Background: Pemphigus vulgaris has an obscure etiology; the presence of autoantibodies is coherent with an autoimmune disease. Rituximab a monoclonal antibody that specifically targets the CD20 antigen of B lymphocytes, has arisen as a novel treatment approach for pemphigus vulgaris.
Case presentation: A 39- year- old male patient presented with a three- month history of mouth ulcers, poor oral hygiene accompanied with heavy tobacco smoking and alcohol consumption. He was diagnosed with pemphigus vulgaris. The disease gradually progressed to involve other body parts. The patient had shown partial improvement after conventional therapy (oral cefuroxime, oral prednisolone with azathioprine) and was later on successfully treated with rituximab. After 90 days of follow- up, no future recurrence was observed.
Conclusion: With this case, the authors would like to aware other clinicians of the potential use of rituximab in treating pemphigus vulgaris, especially when the conventional therapy fails.
Keywords: Autoantibodies; Pemphigus, Rituximab, Oral Hygiene, Ulceration, Tobacco Smoking, Alcohol
consumption, India
## Background
text[[92, 611, 485, 835], [512, 596, 905, 903]]
The term pemphigus implies a group of autoimmune, mucocutaneous blistering diseases, in which the keratinocyte antigens are the target of the autoantibodies, prompting acantholysis and the formation of blisters. Main variants of pemphigus include pemphigus vulgaris (PV) and pemphigus folicaceus (PF). PV is the most common subtype and represents well over \(80\%\) of cases. As being a serious and potentially lifethreatening condition, early treatment is of utmost importance [1]. The advent of corticosteroids in the amelioration of pemphigus has dramatically changed the outlook of this perpetually disastrous disease; thus, corticosteroids have become the cornerstone of pemphigus therapy. One case reported favorable outcomes with combined therapy of highdose corticosteroids and other immunosuppressants. However, such a high dose of corticosteroids can cause serious adverse events such as several metabolic problems, global reduction of immune system efficacy, antecedent risk of serious infections, and mortality [2]. To overcome these long- term events, Pasricha and Gupta introduced dexamethasone cyclophosphamide pulse (DCP) therapy in 1984 [3]. Later on, DCP and oral corticosteroids with or without adjuvant immunosuppressants (azathioprine, cyclophosphamide, mycophenolate mofetil, and cyclosporine) have emerged as the backbone of pemphigus treatment, however, they are associated with the high death rate in pemphigus [4]. With these conventional treatments, some patients fail to improve or some have contraindications for their usage, or some encounter relapse. Hence, advanced research has continuously been going on for finding newer molecules in pemphigus. In 2001, Heizmann et al. [5] first used rituximab for the therapy of autoimmune bullous diseases. He reported a case of paraneoplastic pemphigus favorably managed with rituximab, since then there was a drastic development in the pemphigus treatment era. Rituximab chimeric monoclonal antibody selectively acts on the CD20 expressing B cells, which are known to secrete auto- antibodies targeting the epidermal desmogleins (DSG). It has been used nearly in one million patients for treating lymphoma worldwide. Recently, rituximab has been approved for rheumatoid arthritis that is unresponsive
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The parametric equations for a projectile with constant gravity g:
\[x = v_0 t \cos \theta + x_0\]
\[y = -\frac{1}{2} gt^2 + v_0 t \sin \theta + y_0\]
ex. A shell is fired from ground level with an initial speed of 768 ft/sec. at an angle of 30°. Find:
\[1. \vec{r}(t)\]
2. the maximum altitude attained
3. the range of the shell
4. the speed on impact
5. the horizontal distance when \(y = 2240 \, \text{ft}\).
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Do: An electron in a TV tube is beamed horizontally at a speed of 5 x \(10^{6}\) m/sec. toward the face of the tube 40 cm away. To determine how far the electron drops before it hits, which equation would be used?
a. \(y = -4.9t^{2}\) b. \(y = -4.9t^{2} - 5x10^{6}t\) c. \(5x10^{6}t = 4\) d. \(5x10^{6}t = 40\)
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4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4. 4.
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1)
# The Arab Family in Kuwait: Size and Structure (1)
Recent studies dealing with family status in the Arab world are few and sometimes contradictory. While some researchers, such as Dr. Madeeha Naser (1972), assume that \(75\%\) of Iraqi families belong to the extended type grouping three generations living under one roof \((2)\) , Dr. Sana Khawli's investigation, condensed in Al- Raida (no. 9, vol. II, p. 15), leads her to conclude that the Arab family is evolving into a non- isolated nuclear family.
Some researchers adopt a middle course by recognizing the existence of differences between country and town regarding family type and affirming that the extended family exists in a larger proportion in the country than in town and city. Good, another sociologist, asserts that for economic and other reasons, the extended family has not been the rule in Arab countries. Peterson says that demographic factors have prevented the extensive spread of the extended family in Egypt and that the large family of six members or more formed \(40\%\) of Egyptian families since the beginning of the twentieth century.
A study prepared by Dr. Fahd al- Thaqeb aims to show that even if economic and demographic conditions should favor the spread of the extended family, as is the case in Kuwait, this family type is bound to remain a minority.
This study is based on statistics derived from interviews between 1965 and 1970 with a random sample of Kuwaiti families representing various social levels.
## Family Size
Between 1965 and 1970, the majority of families in Kuwait were made up of six or more members per family. This proportion decreased among university graduates from \(67.4\%\) in 1965 to \(56.9\%\) in 1970. The data reveal that the number of family members tends to decrease in proportion with the cultural, economic and social status of the family. For example, while \(33\%\) of family heads with secondary education have limited the number of their families to five or less, only \(12\%\) of illiterate family heads have adhered to this number.
Large- sized families are characteristic of higher middle and lower middle classes. Small- sized families of 1- 5 members exist at the rate of \(38\%\) in less privileged classes, while \(72\%\) of the lower middle class are made up of eight or more each.
## Family Structure
Three family types have been singled out: the nuclear, the quasi- extended and the extended family. The first
(1) Condensed from Dr. Fahd Al-Thaqeb, "Size and Structure of the Arab and Kuwaiti Family," Journal of Social Sciences, No 12, Year IV, July 1976 (Arabic), pp. 81-91.
(2) Ibid. p. 81.
comprises the parents and children; the third includes two or more families living in the same house, joined by blood ties. The quasi- extended family is a small sized extended family.
In Kuwait, the nuclear family forms \(59.2\%\) , the quasi- extended \(18.4\%\) , and the extended family \(22.4\%\) .
The size of the family is not a sound indicator of its type, though it may have some connection with it. It was found that only \(26\%\) of the nuclear families interviewed were made up of six members each, while \(70\%\) of them had 6- 12 members per unit.
The study has shown that the nuclear family, while it is not the ideal type, is most common among urban, educated, young people and among the middle class. This type is less common in lower and lower middle class. About \(31\%\) of families of the lower class are quasi- extended while in the upper socio- economic group, the quasi- extended type reaches only \(15\%\) .
The proportion of the extended family type is higher among illiterate groups: \(30\%\) for illiterate against \(17\%\) for university people.
## Age of Respondents
The family type differed according to the age of people interviewed. Around \(50\%\) of the young lived in nuclear families. Many of them lived in quasi- nuclear ones and did not break communication with their relatives. The ages of \(65\%\) of nuclear family people ranged between 30 and 39 years, while the highest proportion of the extended family type existed among those who were 50 years of age or above.
## Conclusion
The majority of families forming the random sample of this survey belonged to the nuclear family type. The extended family, though it should be favored by social and demographic conditions in a country like Kuwait, is likely to form a minority.
The data show a steady increase in the average number of family members during the last few years. In 1957 the average was 6.8 per family; in 1965 it rose to 7.3; and in 1970, to 7.6. The rise is due to improved economic and demographic conditions in Kuwait. Also, the proportion of families numbering 6 or more each, rose from \(66.4\%\) in 1965 to \(70.2\%\) in 1970.
The family size is also an indicator of the fertility rate and bears no relation to family structure. It is noteworthy that extended families joining together three generations formed only \(17\%\) of the bulk of extended families. This result coincides with Good's theory that traditional, extended families have been and remain a minority in the Arab world.
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24 baseline demographics and disease characteristics. Significant ( \(p<0.1\) ) variables in univariate were included in multivariate models. Last, multivariate models were selected based on model fit statistics (Akaike information criterion and \(r^2\) ) and clinical significance. Adjusted OR and \(95\%\) CIs for selected baseline variables were calculated.
# RESULTS
Overall, 334 patients were randomised to treatment and received adalimumab+MTX ( \(n=171\) ) or MTX alone ( \(n=163\) ), and 148 (86.5%) and 128 (78.5%) patients completed the double-blind portion of the study, respectively (figure 1). Demographics and baseline characteristics were well matched between treatment groups (table 1). The mean RA disease duration was 0.3 years, and the majority of patients had \(\geq 1\) erosion at baseline and high disease activity. The mean MTX dose during the 26-week study was \(6.2\pm 0.8\) mg/week in the adalimumab+MTX group and \(6.6\pm 0.6\) mg/week in the MTX alone group ( \(p<0.001\) ). After 26 weeks of treatment, 34.5% (59/171) of adalimumab+MTX patients were receiving MTX 8 mg/week versus 65.0% (106/163) of MTX alone patients ( \(p<0.001\) ).
# Radiographic progression
Treatment with adalimumab+MTX significantly inhibited radiographic progression (figure 2A) at week 26 versus MTX alone (mean change±SD, \(1.5\pm 6.1\) vs \(2.4\pm 3.2\) , respectively; \(p<0.001\) ). Results were confirmed by an LE analysis (figure 2A). Changes in radiographic progression during 26 weeks of treatment were also assessed by a cumulative probability plot of \(\Delta mTSS\) (figure 2B). Fewer adalimumab+MTX patients exhibited radiographic progression (\(\Delta mTSS>0.5\) ), with 62.0% (106/171) of patients showing no radiographic progression versus 35.4% (57/161) of MTX alone patients ( \(p<0.001\) ). Furthermore, only 14.0% (24/171) of adalimumab+MTX patients exhibited clinically relevant radiographic progression (\(\Delta mTSS>3\) ) versus 37.3% (60/161) of MTX alone patients ( \(p<0.001\) ). In addition, a significantly higher percentage of adalimumab+MTX patients did not experience worsening (\(\leq 0.5\) ) in erosion score (73.7% (126/171)) versus MTX alone patients (42.2% (68/161); \(p<0.001\) ). In patients who lacked baseline erosive damage, the continued absence of erosions was reported in more adalimumab+MTX patients versus MTX alone patients (9/9 vs 2/6 patients, respectively; \(p=0.01\) ).
# Clinical response
A significantly higher percentage of adalimumab+MTX patients achieved ACR responses versus MTX alone patients at each assessment (figure 3A-C). Significant differences between treatment groups, observed as early as week 2, were maintained through week 26. At week 26, a significantly larger percentage of adalimumab+MTX patients versus MTX alone patients achieved ACR20, ACR50 and ACR70 (figure 3A-C) and ACR90 (12.9% vs 5.5%; \(p=0.02\) ) responses. Significant differences in favour of adalimumab+MTX were also observed from week 2 to 26 for DAS28-ESR, DAS28-CRP, SDAI and CDAI (see online supplementary figure 1A-D). A larger percentage of adalimumab+MTX patients than MTX alone patients demonstrated good or moderate European League Against Rheumatism responses (figure 3D) and were in states of low disease activity or remission after 26 weeks of treatment (figure 3E). Furthermore, a significantly larger percentage of adalimumab+MTX patients versus MTX alone patients satisfied Boolean remission criteria (19.3% vs 8.6%, \(p=0.007\) ). Adalimumab+MTX achieved a 1.8-
Table 1 Demographics and baseline characteristics
<table>Parameter*Adalimumab+MTX<br>(n=171)MTX (n=163)Age±SD (year)54.0±13.154.0±13.2Females (n \((\%)\)144 (84.2)128 (78.5)RA duration±SD (year)0.3±0.40.3±0.4Weight±SD (kg)54.4±9.756.1±12.3Previous DMARD use (n \((\%)\)74 (43.3)87 (53.4)1 DMARD57 (33.3)69 (42.3)2 DMARDs17 (9.9)18 (11.0)Corticosteroid use at baseline (n \((\%)\)58 (33.9)49 (30.1)RF positive (n \((\%)\)146 (85.4)136 (83.4)Mean titre±SD (IU/ml)154.5±202.3163.7±362.8Anti-CCP positive (n \((\%)\)145 (84.8)136 (83.4)Mean titre±SD (IU/ml)386.2±694.2241.3±367.2ESR (mm/h)59.9±30.161.8±29.0CRP (mg/dl)2.9±3.03.1±3.3Swollen joint count (n±SD)0-2811.5±4.711.8±5.30-6616.5±6.217.3±7.7Tender joint count (n±SD)0-2813.2±5.813.2±6.10-6820.7±9.421.1±10.2mTSS13.6±22.313.6±17.4Erosion score7.5±11.67.3±9.2Joint space narrowing score6.2±11.46.2±9.4DAS28-ESR6.6±0.96.6±1.0DAS28-CRP5.8±1.05.9±1.0HAQ-DI score1.1±0.71.3±0.8SDAI score40.7±12.041.4±13.8CDAI score37.8±10.938.3±12.4Physician's global assessment of disease activity±SD (mm)65.8±18.466.2±18.8Patient's global assessment of disease activity±SD (mm)64.1±24.866.4±23.7</table>
*Data are mean±SD unless otherwise indicated.CCP, cyclic citrullinated peptide; CDAI, clinical disease activity index; CRP, C reactive protein; DAS28-CRP, disease activity score using a 28-joint count and CRP level; DAS28-ESR, disease activity score using a 28-joint count and ESR; DMARD, disease-modifying antirheumatic drug; ESR, erythrocyte sedimentation rate; HAQ-DI, Health Assessment Questionnaire disability index; mTSS, modified total Sharp score; MTX, methotrexate; RA, rheumatoid arthritis; RF, rheumatoid factor; SDAI, simplified disease activity index.
to 2.2-fold increase in the percentage of patients achieving clin-ical remission, across all definitions of clinical remission evalu-ated, versus MTX alone.
A significantly larger decrease from baseline in mean HAQ-DI score, indicative of an improvement in physical function, was observed for adalimumab+MTX patients versus MTX alone patients at week 26 (-0.6±0.6 vs -0.4±0.6; \(p<0.001\) ). Although the significant difference between the two groups was small (0.2 units), the percentage of patients achieving normal functional-ity (HAQ-DI score<0.5) after 26 weeks of treatment was also sig-nificantly higher with adalimumab+MTX (figure 3F).
# Factors associated with the absence of radiographic progression or with clinical remission
Disease activity or function baseline variables generally were associated with the absence of radiographic progression ( \(\Delta mTSS\leq 0.5\) ) and with clinical remission (DAS28-ESR<2.6) in both treatment groups (see online supplementary text and online supplementary table 1).
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1995;38:44-8. 22 Fries JF, Spitz P, Kraines RG, et al. Measurement of patient outcome in arthritis. Arthritis Rheum 1980;23:137-45. 23 Smolen JS, Breedveld FC, Schiff MH, et al. A simplified disease activity index for rheumatoid arthritis for use in clinical practice. Rheumatology (Oxford) 2003;42:244-57. 24 Aletaha D, Nell VPK, Stamm T, et al. Acute phase reactants add little to composite disease activity indices for rheumatoid arthritis: validation of a clinical activity score. Arthritis Res Ther 2005;7:R796-806. 25 van Gestel AM, Prevoo MLL, van't Hof MA, et al. Development and validation of the European League Against Rheumatism response criteria for rheumatoid arthritis. Comparison with the preliminary American College of Rheumatology and the World Health Organization/International League Against Rheumatism criteria. Arthritis Rheum 1996;39:34-40. 26 Wells G, Becker J-C, Teng J, et al. Validation of the 28-joint Disease Activity Score (DAS28) and European League Against Rheumatism response criteria based on C-reactive protein against disease progression in patients with rheumatoid arthritis, and comparison with the DAS28 based on erythrocyte sedimentation rate. Ann Rheum Dis 2009;68:954-60. 27 Felson DT, Smolen JS, Wells G, et al. American College of Rheumatology/European League Against Rheumatism provisional definition of remission in rheumatoid arthritis for clinical trials. Ann Rheum Dis 2011;70:404-13. 28 Aletaha D, Smolen J. The Simplified Disease Activity Index (SDAI) and the Clinical Disease Activity Index (CDAI): a review of their usefulness and validity in rheumatoid arthritis. Clin Exp Rheumatol 2005;23(5 suppl 39):S100-8.
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Local transportation for the participating teams shall be the responsibility of the participating institutions.
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75-150 volunteers on competition day will be needed for assignments, including course safety, finish chute, concessions, parking, media and merchandise sales.
The prospective host that is bidding on this championship agrees to all terms and conditions as outlined above in this Championship Bid Specifications Agreement. We agree to comply with all the requirements listed in this document and to administer the designated championship in accordance with the policies of the NCAA and the applicable NCAA sports committee. Prospective hosts that agree with all the requirements listed in this document for the designated championship shall signify agreement by selecting "Yes" below.
*Figure sample_00014_fig01: 1. The image is entirely white, with no discernible objects or scenery.
2. There are no people, animals, or characters in the image, and thus no emotions are being conveyed.
3. The image is a simple, flat color, with no shading or texture.
The style of the image is simple and minimalist.*
Prospective hosts who do not agree with all requirements in this document shall select either "No" or "No with Exception" and declare any issues and/or exceptions regarding the aforementioned terms. Please note: any proposed revisions to the language in this document must be specified in the bidding portal to be considered.
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[
{
"description": "1. The image is entirely white, with no discernible objects or scenery.\n2. There are no people, animals, or characters in the image, and thus no emotions are being conveyed.\n3. The image is a simple, flat color, with no shading or texture.\nThe style of the image is simple and minimalist.",
"figure_id": "sample_00014_fig01",
"image_path": "sample_00014/figures/sample_00014_fig01.png"
}
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145 (Fig. 6B), which over-express EGFR (Fig. 6C).
*Figure sample_00015_fig01: 145 (Fig. 6B), which over-express EGFR (Fig. 6
<table>Surviving FractionA1B0.9C0.7D0.5E0.4F0.3G0.2H0.15I0.1J0.08K0.06L0.05M0.04N0.03O0.02P0.015Q0.01R0.008S0.006T0.005W0.004X0.003Y0.002Z0.0015V0.001W0.0008X0.0006Y0.0005Z0.0004V0.0003W0.0002X0.00015Y0.0001Z0.00008V0.00006W0.00004X0.00003Y0.00002Z0.000015V0.00001W0.000008X0.000006Y0.000004Z0.000003V0.000002W0.0000015*
<center>Figure 6. SR48692 radiosensitizes human prostate cancer cells expressing low levels of EGFR (A, PC-3M) but not prostate cancer cells overexpressing EGFR (B, DU-145). (C) Expression of EGFR in normal (RWPE-1) and PC cell lines (LNCaP, C4-2, DU-145, PC-3 and PC-3M).</center>
In summary, our data show that SR48692 selectively sensitizes PC cells to ionizing radiation. Our results also show that NT stimulation (a) activates a novel EGFR/Src/Stat5b signaling pathway and enhances PC cell proliferation and (b) stabilizes the androgen receptor (AR) through EGFR/Src -dependent phosphorylation; both of which can be inhibited by SR48692. Activation of the EGFR, Src and AR pathway(s) has been implicated, not only in the development of androgen-independent disease, but also in tumor metastasis, especially in bones. Future research, planned for the third and final year of this project, will concentrate on animal studies (completing Task 2 and 3), the role(s) of neuroendocrine cell secretions (Task 1c), and will finalize studies on molecular mechanisms of SR48692 radiosensitizing activity (Task 4). In addition, Cetuximab (C-225/Erbitux, ImClone), a clinically used EGFR inhibitor, will be used to study the role of EGFR in SR-induced radiosensitization. We speculate that inhibitors, such as Cetuximab or Dasatinib (Bristol-Myers-Squibb; a Src family inhibitor), will significantly improve experimental radiotherapy outcome and could establish the basis for future combined treatment therapy in humans.
## KEY RESEARCH ACCOMPLISHMENTS
- We have demonstrated that radiosensitizing activity of SR48692 depends on the expression of NTR1 receptor in prostate cells. This establishes the foundation of cancer-specificity of SR48692 radiosensitizing activity.
- We have demonstrated that radiosensitizing activity of SR48692 is not dependent on androgen receptor (AR) expression levels in prostate cells. However, SR48692 blocks neurotensin-induced AR phosphorylation/stabilization. Therefore, blocking NTR1 receptor could provide additional benefits to anti-tumor therapy.
- We have demonstrated that the radiosensitizing activity of SR48692 is affected by the EGFR receptor levels in prostate cells.
|
[
{
"description": "145 (Fig. 6B), which over-express EGFR (Fig. 6\n\n<table>Surviving FractionA1B0.9C0.7D0.5E0.4F0.3G0.2H0.15I0.1J0.08K0.06L0.05M0.04N0.03O0.02P0.015Q0.01R0.008S0.006T0.005W0.004X0.003Y0.002Z0.0015V0.001W0.0008X0.0006Y0.0005Z0.0004V0.0003W0.0002X0.00015Y0.0001Z0.00008V0.00006W0.00004X0.00003Y0.00002Z0.000015V0.00001W0.000008X0.000006Y0.000004Z0.000003V0.000002W0.0000015",
"figure_id": "sample_00015_fig01",
"image_path": "sample_00015/figures/sample_00015_fig01.png"
}
] |
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4
Introduction 4
**Body** 4
**Key Research Accomplishments** 7
**Reportable Outcomes** 8
**Conclusion** 8
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W81XWH-08-1-0114
TITLE: Mechanisms of Radiosensitization by the Neurotensin Receptor Antagonist SR48692 in Prostate Cancer Models
PRINCIPAL INVESTIGATOR: Jaroslaw Dziegielewski, Ph.D.
CONTRACTING ORGANIZATION: University of Virginia Charlottesville, VA 22904
REPORT DATE: April 2010
TYPE OF REPORT: Annual
PREPARED FOR: U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012
DISTRIBUTION STATEMENT:
- Approved for public release; distribution unlimited
The views, opinions and/or findings contained in this report are those of the author(s) and should not be construed as an official Department of the Army position, policy or decision unless so designated by other documentation.
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A basic requirement of this course is that you will participate in all class meetings and conscientiously complete all required course activities and/or assignments. Keep in touch with me if you are unable to attend, participate, or complete an assignment on time. If you miss more than half of the required activities within the first 25% of the course without contacting me, you may be administratively withdrawn from this course. Administrative withdrawal may have academic, financial, and financial aid implications. Administrative withdrawal will take place after the full refund period, and if you are administratively withdrawn from the course you will not be eligible for a tuition refund. If you have questions about the administrative withdrawal policy at any point during the semester, please contact your instructor.
LAST WITHDRAW DATE: Last day to withdraw with automatic grade of W is Sunday, October 21, 2018. Requires advisor approval via the late drop/add classes link in One.IU. UCOL students or Engineering/Technology freshmen must see advisor by 5:00PM on the prior Friday. In person transactions must be processed by 5:00P on the prior Friday (October 19, 2018).
Beginning October 22, 2018, drops will be approved only in serious, extenuating circumstances and requires the approval of the student's advisor, instructor, Chair or Associate Chair in Mathematics, and the School of Science Dean's Office. If you stop attending class without officially withdrawing by the last withdraw date, your grade will be an F for the course. If you find it necessary to withdraw from the course, we encourage you to first talk to your instructor or to your advisor so that they can assist you in deciding what alternative options best fit your needs. Students should read carefully the withdraw information found on the Registrar's website (registrar.iupui.edu) under the Academic Calendar.
INCOMPLETES: A grade of "Incomplete" (I) will only be given in accordance with the Department of Mathematical Sciences Grade of Incomplete Policy. An incomplete (grade of I) is only allowed for special circumstances: the student must have a passing grade in \(75\%\) of the course work. Specifically, students must be passing at the \(3 / 4\) mark of the session to qualify for assigning an incomplete. The instructor must agree that an incomplete is appropriate and it must be approved by the Associate Chair of the Department of Mathematical Sciences.
IUPUI POLICY ON DISABILITY ACCOMMODATIONS Students needing accommodations because of disability will need to register with Adaptive Educational Services (AES) and complete the appropriate forms issued by AES before accommodations will be given. The AES office is located in Taylor Hall, UC 100. You can also reach the office by calling 317- 274- 3241.
IUPUI POLICY ON RELIGIOUS HOLIDAYS IUPUI respects the right of all students to observe their religious holidays and will make reasonable accommodation, upon request, for such observances. Students seeking accommodation for religious observances MUST submit a request in writing to the course instructor by the end of the second week of the semester and should use the Request for Course Accommodation Due to Religious Observance Form. More information on the IUPUI Policy on Religious Holidays is available here: registrar.iupui.edu/religious.html. Failure to comply with the university policy will result in no accommodations given later in the semester.
IUPUI POLICY ON ACADEMIC INTEGRITY: The IU Code of Student Rights, Responsibilities, and Conduct states that students must uphold and maintain academic and professional honesty and integrity; the code defines academic misconduct as any activity that tends to undermine the academic integrity of the institution. Students engaging in academic misconduct may therefore receive penalties from their course instructor and disciplinary action from the university. Policies against academic misconduct apply to all course-, department-, school-, and university- related activities. Academic misconduct may involve human, hard- copy, or electronic resources and includes but is not limited to the following: cheating, fabrication, plagiarism, interference, violation of course rules, and facilitating academic dishonesty. For definitions of these activities, visit studentcode.iu.edu/responsibilities/academic- misconduct.html. Additional information about the rights and responsibilities of IU students is available at studentcode.iu.edu/.
STUDENT ENGAGEMENT ROSTER: This semester your instructor will be using the Student Engagement Roster (SER) to provide real- time feedback on your performance in this course. Periodically throughout the semester the instructor will be entering data on factors such as your class attendance, participation, and success with coursework, among other things. This information will provide feedback on how you are faring in the course and offer you suggestions on how you might be able to improve your performance. Students can view their submitted SER data through the One.IU tile, Student Engagement Roster (Student).
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15400 Trigonometric Fall 2018 Course Policy
**See instructor for section-specific course materials**
**INSTRUCTOR:**
**OFFICE:**
**E-MAIL:**
A working knowledge of the concepts of college algebra and trigonometry is essential for all parts of science, engineering, and technology. Many other courses, (e.g. business, economics, health sciences, and more), will require you to apply the mathematical tools you learn in your college algebra and trigonometry courses, so keep in mind that success in future courses may depend heavily on your ability to apply the material from MATH 15400.
**OFFICIAL IUPUI COURSE DESCRIPTION: MATH 15400** **Trigonometry (3 cr.)**: P: MATH 15300 (with a minimum grade of C). MATH 15300-15400 is a two-semester version of MATH 15900. Not open to students with credit in MATH 15900. This course covers college-level trigonometry and, together with MATH 15300, provides preparation for MATH 16500, MATH 22100, and MATH 23100.
**MORE ON PREREQUISITES:** It is assumed that you have recently mastered the material of MATH 15300 (College Algebra) with a grade of C or better within the last year. If this is not the case then you should talk to your instructor as soon as possible to decide if this is the correct class for you. The main reason people have difficulty with MATH 15400 is because of insufficient background. A gain, if you are not sure if this is the right class for you, talk to your instructor early. It is not difficult to determine which class you should be in.
**TEXTBOOK:** The correct textbook for all sections of MATH 15400 is, Algebra and Trigonometry with Analytic Geometry, Classic 12th Edition, by Swokowski and Cole, with Enhanced WebAssign Access Card, ISBN: 9781305525849, Loose-leaf 3-ring textbook, Cengage Publisher. There are over a dozen different editions and formats of this textbook so it is important that you get the correct one. The required textbook may be purchased at the IUPUI Barnes & Noble Bookstore.
# IUPUI DEPARTMENT OF MATHEMATICAL SCIENCES CALCULATOR POLICY:
· In all developmental and introductory courses at IUPUI numbered below MATH 16500, the only technology that can be used on in-class, closed-book assessments (quizzes, tests, final exam) is the Texas Instruments TI-30XA scientific calculator.
· In all calculus and calculus-related courses at IUPUI with numbers MATH 16500 or above, no calculators or other forms of technology can be used on in-class, closed-books assessments (quizzes, tests, final)
· For math/stat courses with numbers above MATH 26600, it is up to the instructor's discretion as to what forms of technology may be used on in-class, closed-book assessments.
**MORE ON CALCULATOR POLICY:** The TI-30XA is the only calculator allowed on quizzes and exams. No other calculator is allowed in the classroom. It does not matter what you were allowed to use in your previous math course. Bring your TI-30XA scientific calculator with you to every class period. The calculator slide cover must be removed and put away when taking an exam or quiz.
**ATTENDANCE:** Attendance is required of all students without exception. A student absent from class bears full responsibility for all material covered in class. Quizzes will be given at the beginning of class, so please be on time. If you anticipate having to leave class early, please let your instructor know before the beginning of class. Regular attendance is crucial for success in this course.
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