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$H_2$ Receptor Antagonists and Gastric Cancer in the Elderly: A Nested Case-Control Study (노인 인구에서 $H_2$ Receptor Antagonist와 위암과의 관련성: 코호트 내 환자-대조군 연구)

  • Kim, Yoon-I;Heo, Dae-Seog;Lee, Seung-Mi;Youn, Kyoung-Eun;Koo, Hye-Won;Bae, Jong-Myon;Park, Byoung-Joo
    • Journal of Preventive Medicine and Public Health
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    • v.35 no.3
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    • pp.245-254
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    • 2002
  • Objective : To test if the intake of $H_2$ receptor antagonists ($H_2$-RAs) increases the risk of gastric cancer in the elderly. Methods : The source population for this study was drawn from the responders to a questionnaire survey administered to the Korea Elderly Pharmacoepidemiological Cohort (KEPEC), who were beneficiaries of the Korean Medical Insurance Corporation, were at least 65 years old, and residing in Busan in 1999. The information on $H_2$-RAs exposure was obtained from a drug prescription database compiled between inn. 1993 and Dec. 1994. The cases consisted of 76 gastric cancer patients, as confirmed from the KMIC claims data, the National Cancer Registry and the Busan Cancer Registry. The follow-up period was from Jan. 1993 to Dec. 1998. Cancer free controls were randomly selected by 1:4 individual matching, which took in to consideration the year of birth and gender. Information on confounders was collected by a mail questionnaire survey. The odds ratios, and their 95% confidence intervals, were calculated using a conditional logistic regression model. Results : After adjusting for a history of gastric ulcer symptoms, medication history, and body mass index, the adjusted OR (aOR) was 4.6 (95% CI=1.72-12.49). The odds ratio of long term use (more than 7 days) was 2.3 (95% CI=1.07-4.82). The odds ratio of short term use was 4.6 (95% CI=1.26-16.50). The odds ratio of parenteral use was 4.4 195% CI=1.16-17.05) and combination use between the oral and parenteral routes (aOR, 16.8; 95% CI=1.21-233.24) had the high risk of gastric cancer. The aOR of cimetidine was 1.7 (95% CI=1.04-2.95). The aOR of ranitidine was 2.0 (95% CI=1.21-3.40). The aOR of famotidine was 1.7 (95% CI=0.98-2.80). Conclusion : The intake of $H_2$-RAs might increase the risk of gastric cancer through achlorhydria in the elderly.

Clinical Study after Video-Assisted Thoracic Surgery and Mid-Axillary Thoracotomy for Recurrent Spontaneous Pneumothorax (재발성 자연 기흉에 대한 정중액과 개흉술과 비디오 흉강경수술의 비교연구)

  • 이정상
    • Journal of Chest Surgery
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    • v.32 no.1
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    • pp.43-48
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    • 1999
  • Background: Although treatment of spontaneous pneumothorax by video-assisted thoracic surgery(VATS) has generally shown better clinical results than conventional thoracotomy, treatment of spontaneous pneumothorax by midaxillary thoracotomy(MAXT) has also shown good clinical results. The author studied to compare the clinical results of MAXT group I and VATS group II. Material and Method : Group I included 30 midaxillary thoracotomy among 83 operative cases of spontaneous pneumothorax from Jan. 1992 to Dec. 1993. Group II included 30 VATS among 101 operative cases of pneumothorax from Jan. 1994 to Aug. 1995. The author selected the 30 patients, age 18 to 25 years, with recurrent spontaneous pneumothorax in each group. The author analyzed the operative indication, gender, operating time, amounts of the used staplers, tube drainage, total amounts of analgesics used during postoperative 24hr, tube stay time, postoperative complications and mortality. Result: The follow-up periods of both procedures were from 6 to 43 months. The operating time from start of skin incision to end of skin closure was 84.79${\pm}$21.70(from 40 to 150) minutes in MAXT group I and 108.8${\pm}$42.02(from 58 to 120) minutes in VATS group II(P<0.001). The numbers of the used staples useo was 1.31${\pm}$0.6(from 0 to 3) in group I and 3.41${\pm}$2.37(from 0 to 11) in group II. The amounts of postoperative 24hour tube drainage were 220.76${\pm}$106.73(from 65 to 400) ml in group I and 260.63${\pm}$233.18(from 70 to 320) in group II(P>0.05). The amounts of postoperative 24 hourly used analgesics(Tarasyn ) was 1.38${\pm}$1.32(from 0 to 5) amples in group I and 0.72${\pm}$1.02(from 0 to 4) amples in group II (P<0.05). The postoperative tube stay is 5.45${\pm}$30.9 (from 3 to 7) days in group I and 4.75${\pm}$3.1(9 from 2 to 14) days in group II(P>0.05). The number of complications after operations was 2 cases of prolonged air leakage in group I, and in group II. (P is not significant). The number of recurrence after the operation was one in group I and also one in group II(P is not significant). In conclusion, there were no statistical differences in the postoperative 24 hour chest tube drainage, days of postoperative tube stay, postoperative complications and recurrence in the analysis between group I and group II. Conclusion: The author found that group II of VATS between 18 years and 25 years of age in recurrent spontaneous pneumothorax, statistically, requires longer operative time, more number of autosuture staples and less postoperative analgesic dosage than the midaxillary thoracotomy group I.

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Report on the Effects Lipemic Specimen in Anti-ds DNA Antibody Test (Anti-ds DNA 항체 검사 시 Lipemic 검체의 영향에 관한 보고)

  • Cheon, Jun Hong;Kim, Whe Jung;Kim, Sung Ho;Moon, Hyoung Ho;Yoo, Seon Hee
    • The Korean Journal of Nuclear Medicine Technology
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    • v.18 no.1
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    • pp.153-157
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    • 2014
  • Purpose: SLE (systemic lupus erythematosus) is an inflammatory autoimmune disease, characterized by various autoantibody. The detection of Anti double-stranded DNA (Anti-ds DNA) is important in the diagnostics of SLE, and include the American College of Rheumatology (ACR) diagnostic criteria for SLE. Also SLE disease activity and correlativity with the level Anti-ds DNA antibody have been reported and Anti-ds DNA antibody quantitative test is very useful for tracing before and after SLE treatment. When These Anti-ds DNA antibody test (Farr assay: $^{125}I$ labeled ds-DNA and bound Anti-ds DNA antibodies complex in serum is precipitated by ammonium sulfate and used to centrifugation, measured it) inhaled supernatant after centrifugation, a lipemic specimen does not facilitate the formation of precipitate and also occurs situation was inhaled with precipitate. To solve these problems, The Influence of the degree of lipemic specimen was evaluated. Materials and Methods: September 2012 to February 2013, We selected lipemic samples (n=81) of specimen commissioned by Anti-ds DNA antibody test. Lipemic samples were done pre-treatment (high-speed centrifugation: 14,000 rpm 5 mins) used a micro-centrifuge (Eppendorf Model 5415D). At the same time lipemic specimen and pre-treatment samples were performed Anti-ds DNA antibody test (Anti-ds DNA kit, Trinity Biotech, Ireland). Statistical analysis were analyzed Pearson's correlation coefficients and regression and paired t-test, and Difference (%). Results: Experimental group 1 (Lipemic Specimen Anti-ds DNA Ab concentration ${\leq}7IU/mL$) at y=0.368X+4.732, $R^2=0.023$, Pearson's correlation coefficient was 0.154, paired t-test (P=0.003), Difference (%) mean 65.7 and showed a statistically significant difference. Experimental group 2 (Lipemic Specimen Anti-ds DNA Ab concentration ${\geq}8IU/mL$) at y=0.983X+0.298, $R^2=0.994$, Pearson's correlation coefficient showed 0.997, paired t-test (P=0.181), Difference (%) mean -5.53 made no statistically significant difference. Conclusion: Lipemic sample of low Anti-ds DNA Ab concentration (2.5-7 IU/mL) and the result is obtained pre-treatment (high-speed centrifugation: 14,000 rpm 5 mins) were made a significant difference statistically. Anti-ds DNA is one of the primary auto-antibodies present in patients with SLE, and remain an important diagnostic test for SLE. Therefore, we recommend preprocessing (high-speed centrifugation: 14,000 rpm 5 mins) in order to exclude the influence of lipemic specimen.

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Effect of MRI Media Contrast on PET/MRI (PET/MRI에 있어 MRI 조영제가 PET에 미치는 영향)

  • Kim, Jae Il;Kim, In Soo;Lee, Hong Jae;Kim, Jin Eui
    • The Korean Journal of Nuclear Medicine Technology
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    • v.18 no.1
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    • pp.19-25
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    • 2014
  • Purpose: Integrated PET/MRI has been developed recently has become a lot of help to the point oncologic, neological, cardiological nuclear medicine. By using this PET/MRI, a ${\mu}-map$ is created some special MRI sequence which may be divided parts of the body for attenuation correction. However, because an MRI contrast agent is necessary in order to obtain an more MRI information, we will evaluate to see an effect of SUV on PET image that corrected attenuation by MRI with contrast agent. Materials and Methods: As PET/MRI machine, Biograph mMR (Siemens, Germany) was used. For phantom test, 1mCi $^{18}F-FDG$ was injected in cylinderical uniformity phantom, and then acquire PET data about 10 minutes with VIBE-DIXON, UTE MRI sequence image for attenuation correction. T1 weighted contrast media, 4 cc DOTAREM (GUERBET, FRANCE) was injected in a same phatnom, and then PET data, MRI data were acquired by same methodes. Using this PET, non-contrast MRI and contrast MRI, it was reconstructed attenuation correction PET image, in which we evanuated the difference of SUVs. Additionally, for let a high desity of contrast media, 500 cc 2 plastic bottles were used. We injected $^{18}F-FDG$ with 5 cc DOTAREM in first bottle. At second bottle, only $^{18}F-FDG$ was injected. and then we evaluated a SUVs reconstructed by same methods. For clinical patient study, rectal caner-pancreas cancer patients were selected. we evaluated SUVs of PET image corrected attenuastion by contrast weighted MRI and non-contrast MRI. Results: For a phantom study, although VIBE DIXON MRI signal with contrast media is 433% higher than non-contrast media MRI, the signals intensity of ${\mu}-map$, attenuation corrected PET are same together. In case of high contrast media density, image distortion is appeared on ${\mu}-map$ and PET images. For clinical a patient study, VIBE DIXON MRI signal on lesion portion is increased in 495% by using DOTAREM. But there are no significant differences at ${\mu}-map$, non AC PET, AC-PET image whether using contrast media or not. In case of whole body PET/MRI study, %diff between contras and non contrast MRAC at lung, liver, renal cortex, femoral head, myocardium, bladder, muscle are -4.32%, -2.48%, -8.05%, -3.14%, 2.30%, 1.53%, 6.49% at each other. Conclusion: In integrated PET/MRI, a segmentation ${\mu}-map$ method is used for correcting attenuation of PET signal. although MRI signal for attenuation correciton change by using contrast media, ${\mu}-map$ will not change, and then MRAC PET signal will not change too. Therefore, MRI contrast media dose not affect for attenuation correction PET. As well, not only When we make a flow of PET/MRI protocol, order of PET and MRI sequence dose not matter, but It's possible to compare PET images before and after contrast agent injection.

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Longitudinal Study of the Subgingival Microbial Change after Tetracycline Topical Application (Tetracycline 국소도포가 치은연하 세균분포에 미치는 영향)

  • Choi, Kwang-Choon;Lee, Young-Hee;Lee, Jin-Yong;Chung, Chong-Pyoung;Son, Seong-Heui
    • The Journal of the Korean Society for Microbiology
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    • v.21 no.4
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    • pp.503-513
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    • 1986
  • Previous studies have developed the technique of topical application of tetracycline(TC) into the periodontal pockets and examined the change of clinical parameters and subgingival microbial morphotypes. The purpose of this study was to longitudinally examine the clinical and microbiological effects of topically applied TC in a double-blind and split-mouth design. Thirteen patients with moderate periodontitis, who were treated with or without TC application and scaling treatment, were examined. TC gel(3%) was used to apply into the selected periodontal pockets twice a week for 2 weeks. During the experiment, clinical parameters and subgingival microbial morphotypes were examined, and for isolation of black-pigmented Bacteroides(BPB) and streptococci, an anaerobic sample culturing was done at week 0, 2, and 7. In clinical observation the TC-scaled group exhibited a significant decrease of Gingival Inflammatory Index, Plaque Index, Sulcus Bleeding Index, pocket depth, and gingival crevicular fluid when compared to the TC-unsealed, placebo-scaled, and placebo-unsealed groups. The result of microbial morphotype observation showed a significant increase of coccal form and a decrease of spirochetes in the TC-scaled, TC-unscaled, and placebo-scaled groups. The culture study of streptococci revealed that TC with scaling treatment resulted in a significant increase of S. sanguis I at week 2, but its proportion had returned to the base line level. The anaerobic culture study showed that BPB was significantly reduced in the TC-scaled and TC-unsealed groups at week 7. Among BPB species, B. intermedius declined significantly with time treatment(week 2 and 7) in the TC-scaled and TC-unsealed groups. These results suggest that the settled pathogenic microflora can be succeeded by nonpathogenic microflora in periodontal pockets after TC treatment.

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A study on improvement of misdiagnosis rate in aortic regurgitation disease by physically correcting EF in 2D echo cardiography (대동맥판 역류질환 진단시 이면성심초음파 박출계수의 보정을 통한 오진율 개선에 관한 연구)

  • Choi, Kwan-Woo;Son, Soon-Yong
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.13 no.5
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    • pp.2142-2147
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    • 2012
  • This study is aimed at decreasing wrong diagnosis with corrected EF(Ejection Fraction) of 2D echo cardiography by analysing the physical time-resolution difference between Cine MRI and 2D echo cardiography and applying the corrected EF in 2D echocardiography. From February 2010 to December 2011, among the 110 patients who had undergone both 2D echo cardiography and cine MRI only 37 patient were selected suffering aortic valve regurgitation. ED, ES and SV were measured and EF was calculated in each system while normal ranges of Cine MRI and 2D echocardiography were compared to evauate misdiagnosis rate. The correlation of physical time resolution between 2D echocardiography and MRI was evaluated and the differences were corrected with linear regression coefficient which is derived from linear regression analysis. Blandt-Altman plot was used to evaluate the reliability of corrected 2D echo cardiography EF and compare the error among measured values. The values were compared with MRI normal range and misdiagnosis rate was measured again. As a result, misdiagnosis rates of physical time resolution were measured to be 32.4%(12people) before the correction of EF and 18.9%(7people) after the correction. Also, EF confirmed in Blandt-Altman plot were almost the same with MRI EF. In conclusion, when diagnosing aortic regurgitation disease, simply using 2D echocardiography can easily raise the misdiagnosis rates, therefore considering the MRI machine's physical merits, correcting the time resolution difference is important by calculating time resolution wrong diagnosis would decrease and it is considered to be useful in clinical circumstances.

Intakes of Energy and Nutrients and Risk of Breast Cancer - Case-Control Study in Daegu.Gyeongbuk Area, Korea - (영양소 섭취 수준과 유방암 위험 - 대구.경북지역 환자-대조군 연구 -)

  • Lee, Eun-Ju;Lee, Won-Kee;Suh, Su-Won;Suh, Bo-Hyun;Lee, Hye-Sung
    • Journal of Nutrition and Health
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    • v.41 no.8
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    • pp.754-766
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    • 2008
  • This study was performed to evaluate the effect of nutrient intake levels on the relative risk of breast cancer in the Daegu and Gyeongbuk area. The case subjects were 103 patients newly diagnosed as breast cancer at Kyungpook National University Hospital. The control subjects were 159 healthy women without breast cancer-related disease in the same community selected by frequency matching of age and menopausal status. The survey was administered by individual interviews by trained dietitians using semiquantitative food frequency questionnaires. The odds ratios were determined by using unconditional logistic regression after adjusting for the confounding factors found in the analysis of general characteristics of the subjects. In overall, it has been found that high consumptions of energy and carbohydrates significantly raised the relative risk of breast cancer, and that high intakes of total fat, plant fat, dietary fiber, all kinds of fatty acids, vitamin E and calcium significantly lowered the risk of breast cancer. The results of the study suggest that the possible protective factors to the breast cancer risk include a higher intakes of total fat, especially plant fat, dietary fiber, and micronutrients such as vitamin E, folic acid, calcium, phosphorus and potassium. On the other hand, high intakes of energy and carbohydrate appeared to be the risk factors.

Studies on the phrases of Yellow Emperor's internal classic(黃帝內經) for the physiology on the spleen and stomach (비위생리(脾胃生理)에 수용(授用)되는 황제내경(黃帝內經) 어구(語句)에 관(關)한 연구(硏究))

  • Won, Jin-Hui
    • The Journal of Korean Medicine
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    • v.16 no.2 s.30
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    • pp.453-489
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    • 1995
  • The research of the phrases related with physiology of stomach and spleen in the contents of Huang Di Nei Jing(黃帝內經) known as the Bible of oriental medicine will make a contribution to a deep understanding of disease of stomach and spleen and a proper clinical diagnosis and treatment of them. In this research of the most appropriate glosses recorded nine kinds of representative medical books including Huang Di Nei Jing Somoon(黃帝內經素問) of Wang Bing(王氷) were picked out: The summaries of the selected contents are as follows: 1. The word 'saliva(涎)' in 'the spleen controls saliva(脾爲涎)' can be viewed as a generic term referring to oral cavity secretion gland as well as the secretion fluid of salivary gland. 2. The phases 'a large reservoir(太倉)', barn organs', 'a reserboir of food stuff', 'a stomach as the market(胃爲之市)', etc mean the function of stomach to receive food(胃主受納). 3. The phase 'generation of five tastes(五味出焉)' means both 'the function of stomach to transform food into chyme(胃主腐熟)' and 'the channelling function of spleen.(脾主運化)' 4. The flowing of the food-Qi(食氣) into stomach brings about spreading Jung(精) into liver and then percolating Jung(精) flow into channel. The channel-Qi(脈氣) flows into lung through channel. As a result, all kinds of channels gather together in lung and Jung(精) is sent into skin and hair. The assembly of Jung(精) with skins and channels moves Qi(氣) into fu-organ and so jung(精) and mental activity(神明) in fu-organ(府) come to be in four organs(四臟). Then if Qi(氣) comes back to power balance unit(權衡) being in the state of equilibrium(權衡以平), the hole of Qi(氣口) comes to determine the matter of life and death through achieving Chun-quan-chi(-寸-關-尺). The above mentioned phrases means the digestion, asorption and transmission of food. When food is taken in stomach, Jung-Qi(精氣) comes to be over flowed upward into spleen, back into lung, finally downward into bladders through water-conduit(水道) controlled by lung. When water- Jung(水精) radiates into whole body with channels of five organs(五臟), both of them fit together with and yin-yang(陰-陽). Therefore, the grasping of the rise and decline of yin-yang(陰C-陽) is necessary to consult patients. The above mentioned phrases is properly viewed to designate the asorption, transmission and excretion of food. 5. Spleen controls flesh(脾之合肉也), the state of spleen is known by human lips, and what this means is that liver plays functions of spread and expansion(肝主疏泄). 6. The phrase 'Jung Jung'((中精)) in 'gallbladder dominates Jung jung(膽主中精)', which in one of the specific expression of 'liver plays functions of spread and expansion(肝主疏泄). 7. It is right that the phase 'The eleven organs in all are determined by gallbladder'(凡十,一臟取決於膽也) is correctly paraphrased as 'only one of ten organs, spleen, is determined by gallbladder'.(凡十,一臟取決於膽也), 8. The small intestine is an organ. which receives the materials digested and sends them out. This means that the function of transforming materials(化物) factually refers to that of separating clearity and blur(泌別淸濁). And it is also thought to have the function of ascending clearity and descending blur(升淸降濁), 9. A large intestine is a transmitting organ(傳導之官) from which a change comes out(變化出焉). the phrase 'change'(變化) in this sentence means both the intake of water and nutrition and the formation procedure of stool through excretion of mucocele.

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Analysis of Molecular Epidemiological Properties of Staphylococcus aureus Isolates from Domestic Animals and Human Patients by PCR (Polymerase Chain Reaction을 활용한 국내 동물과 사람환자에서 분리한 Staphylococcus aureus 분리주의 분자역학적 특성분석)

  • Woo Yong-Ku;Kim Shin
    • Korean Journal of Microbiology
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    • v.41 no.1
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    • pp.24-37
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    • 2005
  • This study was conducted to analyze the molecular epidemiological properties and to select the most efficient and reliable PCR method on 116 of Staphylococcus aureus (S. aureus) isolates from Korean cattle, black goat, pig, dog, chicken, mouse and also human clinical cases from hospital. The distribution patterns of SSG [species specific genes; coagulase (coa), protein A (spa), nuclease (nuc) and aroA (RsaI) gene] were analyzed by PCR method. Among the SSGs, the nuc-gene was found in all strains $(100\%)$ tested and followed by coa-gene $(87.9\%)$, spa-gene $(91.4\%)$ and aroA-gene $(26.7\%)$, in order. The genetic subtyping by RFLP method was performed on the coa [AluI] and aroA-gene [RsaI] PCR products. The mecA-gene PCR and PCR-RFLP techniques were chosen to detect and verify of MRSA strains. Only the human strains $(12.1\%)$ were detected the positive mecA-gene products (533 bp), which were divided into two specific bands [201 & 332 bp] by HhaI enzyme digestion. On coa-gene and spa-gene typing, coa-gene was typed with ten kinds of genotype and coa-3 type were determined as the most predominant genotype, while spa-gene was divided into eleven kinds of genotype and also spa-7 type were selected the most prevalent genotype based on their genetic variations. On the aroA and coa-gene subtyping by PCR-RFLP, aroA-gene products were discriminated with only seven types of genotype, while coa-gene products were further divided into an eleven genotype, respectively. In comparison of SID values of five PCR based typing methods, the coa-PCR-RFLP (SID0.894) was evaluated the most efficient and reliable tools and followed by coa-PCR (SID0.883) and aroA-PCR-RFLP (SID0.462), in order. In conclusion, we could determined that the coa-PCR-RFLP method was the most suitable genetic analysis tool for S. aureus and MRSA strains from domestic animals and humans.

Analysis of the major factors of influence on the conditions of the Intensity Modulated Radiation Therapy planning optimization in Head and Neck (두경부 세기견조방사선치료계획 최적화 조건에서 주요 인자들의 영향 분석)

  • Kim, Dae Sup;Lee, Woo Seok;Yoon, In Ha;Back, Geum Mun
    • The Journal of Korean Society for Radiation Therapy
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    • v.26 no.1
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    • pp.11-19
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    • 2014
  • Purpose : To derive the most appropriate factors by considering the effects of the major factors when applied to the optimization algorithm, thereby aiding the effective designing of a ideal treatment plan. Materials and Methods : The eclipse treatment planning system(Eclipse 10.0, Varian, USA) was used in this study. The PBC (Pencil Beam Convolution) algorithm was used for dose calculation, and the DVO (Dose Volume Optimizer 10.0.28) Optimization algorithm was used for intensity modulated radiation therapy. The experimental group consists of patients receiving intensity modulated radiation therapy for the head and neck cancer and dose prescription to two planned target volume was 2.2 Gy and 2.0 Gy simultaneously. Treatment plan was done with inverse dose calculation methods utilizing 6 MV beam and 7 fields. The optimal algorithm parameter of the established plan was selected based on volume dose-priority(Constrain), dose fluence smooth value and the impact of the treatment plan was analyzed according to the variation of each factors. Volume dose-priority determines the reference conditions and the optimization process was carried out under the condition using same ratio, but different absolute values. We evaluated the surrounding normal organs of treatment volume according to the changing conditions of the absolute values of the volume dose-priority. Dose fluence smooth value was applied by simply changing the reference conditions (absolute value) and by changing the related volume dose-priority. The treatment plan was evaluated using Conformal Index, Paddick's Conformal Index, Homogeneity Index and the average dose of each organs. Results : When the volume dose-priority values were directly proportioned by changing the absolute values, the CI values were found to be different. However PCI was $1.299{\pm}0.006$ and HI was $1.095{\pm}0.004$ while D5%/D95% was $1.090{\pm}1.011$. The impact on the prescribed dose were similar. The average dose of parotid gland decreased to 67.4, 50.3, 51.2, 47.1 Gy when the absolute values of the volume dose-priority increased by 40,60,70,90. When the dose smooth strength from each treatment plan was increased, PCI value increased to $1.338{\pm}0.006$. Conclusion : The optimization algorithm was more influenced by the ratio of each condition than the absolute value of volume dose-priority. If the same ratio was maintained, similar treatment plan was established even if the absolute values were different. Volume dose-priority of the treatment volume should be more than 50% of the normal organ volume dose-priority in order to achieve a successful treatment plan. Dose fluence smooth value should increase or decrease proportional to the volume dose-priority. Volume dose-priority is not enough to satisfy the conditions when the absolute value are applied solely.