Conclusion: Conclusions: VocaSTIM ® can produce a different degree of satisfaction functional response in the majority of patients with dysphagia. As parameters to further evaluate in the future we see the best result of vocaSTIM ® is observed above muscles contractility improvements suprahyoid e infrahyoid. Key Word(s): 1. vocastim; 2. neuroestimulation; 3. rehabilitation; 4. patients- dysphagia; Presenting Author: SMOLOVICD BRIGITA Additional Authors: DJURANOVICP SRDJAN Corresponding Author: SMOLOVICD BRIGITA Affiliations: KCCG; Medical School University of Belgrade Objective: Etiology and clinical manifestation

of the peptic ulcer have changed over CDK inhibitor the past decades. The high risk of bleeding in Helicobacter pylori

(H.pylori)-negative, NSAID (non-steroidal anti-inflammatory drugs)-negative peptic ulcers highlights the clinical importance of analysis the changing trends of peptic ulcer diseases (PUD). AIM: To investigate risk factors for non-complicated and/or complicated ulcer in patients without H.pylori infection and exposure to NSAIDs. Methods: A prospective study was conducted to examine patients (pts) with endoscopically diagnosed non-complicated and/or complicated ulcer. Patients were without H.pylori infection (verified by pathohistology and serology) and without exposure to NSAIDs within 4 weeks before endoscopy. Patients were divided into 2 groups: study group of 95 pts with peptic ulcer and control group of 105 pts with dyspepsia. AZD2281 purchase The study group than were divided in two subgroups: 48 pts with bleeding ulcer and 47 pts also with ulcer but without sings of bleeding. 上海皓元医药股份有限公司 Prior to endoscopy they had completed

a questionnaire related to demographics, risk factors and habits. The platelet function, von Willebrand factor (vWf) and blood groups were determined in all patients. Histopathology analysis of antrum and corpus biopsy samples from all pts was performed according to modified Sydney system for classification of gastritis. The influence of bile reflux was analysed by calculating the Bile reflux index (BRI). Results: Male gender was at high risk for developing ulcers 55/95 (57.9%) (p = 0.001). Cigarette smoking increased the risk of ulcer disease 44/95 (46.3% vs. 34 (32.4%)) (p = 0.044). Age (p = 0.454), concomitant diseases (p = 0.530) and exposure to stress (p = 0.281) didn’t affect the ulcer rate. The same results were for different blood groups (p = 0.831) and fluctuating range of vWF (p = 0.298). Asprin used (p = 0.699) and abnormal platelet function (p = 0.108) weren’t risk factor for ulcer. Earlier treatment of duodenal ulcer increased the risk for new ulcer (p = 0.039). Intestinal metaplasia (IM) in antrum was risk factor (p = 0.003).

Conclusion: Conclusions: VocaSTIM ® can produce a different degree of satisfaction functional response in the majority of patients with dysphagia. As parameters to further evaluate in the future we see the best result of vocaSTIM ® is observed above muscles contractility improvements suprahyoid e infrahyoid. Key Word(s): 1. vocastim; 2. neuroestimulation; 3. rehabilitation; 4. patients- dysphagia; Presenting Author: SMOLOVICD BRIGITA Additional Authors: DJURANOVICP SRDJAN Corresponding Author: SMOLOVICD BRIGITA Affiliations: KCCG; Medical School University of Belgrade Objective: Etiology and clinical manifestation

of the peptic ulcer have changed over click here the past decades. The high risk of bleeding in Helicobacter pylori

(H.pylori)-negative, NSAID (non-steroidal anti-inflammatory drugs)-negative peptic ulcers highlights the clinical importance of analysis the changing trends of peptic ulcer diseases (PUD). AIM: To investigate risk factors for non-complicated and/or complicated ulcer in patients without H.pylori infection and exposure to NSAIDs. Methods: A prospective study was conducted to examine patients (pts) with endoscopically diagnosed non-complicated and/or complicated ulcer. Patients were without H.pylori infection (verified by pathohistology and serology) and without exposure to NSAIDs within 4 weeks before endoscopy. Patients were divided into 2 groups: study group of 95 pts with peptic ulcer and control group of 105 pts with dyspepsia. PD98059 The study group than were divided in two subgroups: 48 pts with bleeding ulcer and 47 pts also with ulcer but without sings of bleeding. MCE Prior to endoscopy they had completed

a questionnaire related to demographics, risk factors and habits. The platelet function, von Willebrand factor (vWf) and blood groups were determined in all patients. Histopathology analysis of antrum and corpus biopsy samples from all pts was performed according to modified Sydney system for classification of gastritis. The influence of bile reflux was analysed by calculating the Bile reflux index (BRI). Results: Male gender was at high risk for developing ulcers 55/95 (57.9%) (p = 0.001). Cigarette smoking increased the risk of ulcer disease 44/95 (46.3% vs. 34 (32.4%)) (p = 0.044). Age (p = 0.454), concomitant diseases (p = 0.530) and exposure to stress (p = 0.281) didn’t affect the ulcer rate. The same results were for different blood groups (p = 0.831) and fluctuating range of vWF (p = 0.298). Asprin used (p = 0.699) and abnormal platelet function (p = 0.108) weren’t risk factor for ulcer. Earlier treatment of duodenal ulcer increased the risk for new ulcer (p = 0.039). Intestinal metaplasia (IM) in antrum was risk factor (p = 0.003).

Conclusion: Conclusions: VocaSTIM ® can produce a different degree of satisfaction functional response in the majority of patients with dysphagia. As parameters to further evaluate in the future we see the best result of vocaSTIM ® is observed above muscles contractility improvements suprahyoid e infrahyoid. Key Word(s): 1. vocastim; 2. neuroestimulation; 3. rehabilitation; 4. patients- dysphagia; Presenting Author: SMOLOVICD BRIGITA Additional Authors: DJURANOVICP SRDJAN Corresponding Author: SMOLOVICD BRIGITA Affiliations: KCCG; Medical School University of Belgrade Objective: Etiology and clinical manifestation

of the peptic ulcer have changed over BAY 73-4506 clinical trial the past decades. The high risk of bleeding in Helicobacter pylori

(H.pylori)-negative, NSAID (non-steroidal anti-inflammatory drugs)-negative peptic ulcers highlights the clinical importance of analysis the changing trends of peptic ulcer diseases (PUD). AIM: To investigate risk factors for non-complicated and/or complicated ulcer in patients without H.pylori infection and exposure to NSAIDs. Methods: A prospective study was conducted to examine patients (pts) with endoscopically diagnosed non-complicated and/or complicated ulcer. Patients were without H.pylori infection (verified by pathohistology and serology) and without exposure to NSAIDs within 4 weeks before endoscopy. Patients were divided into 2 groups: study group of 95 pts with peptic ulcer and control group of 105 pts with dyspepsia. Erlotinib cell line The study group than were divided in two subgroups: 48 pts with bleeding ulcer and 47 pts also with ulcer but without sings of bleeding. 上海皓元 Prior to endoscopy they had completed

a questionnaire related to demographics, risk factors and habits. The platelet function, von Willebrand factor (vWf) and blood groups were determined in all patients. Histopathology analysis of antrum and corpus biopsy samples from all pts was performed according to modified Sydney system for classification of gastritis. The influence of bile reflux was analysed by calculating the Bile reflux index (BRI). Results: Male gender was at high risk for developing ulcers 55/95 (57.9%) (p = 0.001). Cigarette smoking increased the risk of ulcer disease 44/95 (46.3% vs. 34 (32.4%)) (p = 0.044). Age (p = 0.454), concomitant diseases (p = 0.530) and exposure to stress (p = 0.281) didn’t affect the ulcer rate. The same results were for different blood groups (p = 0.831) and fluctuating range of vWF (p = 0.298). Asprin used (p = 0.699) and abnormal platelet function (p = 0.108) weren’t risk factor for ulcer. Earlier treatment of duodenal ulcer increased the risk for new ulcer (p = 0.039). Intestinal metaplasia (IM) in antrum was risk factor (p = 0.003).

Results: Overall incidence of anastomotic leaks was 4.5%. Leakage rate in SMA was 2.17% versus 4.88% in HSA (p = 0.587).

Dilatation occurred in 30% of SMA and 61% of HSA (p < 0.001), 15% and 49% respectively needing ≥ 3 dilatations (p < 0.001). Both groups demonstrate an initial increase of dysphagia score, being steeper for patients with HSA (mean score 31 versus 26). Dysphagia subscales revealed at 3 months MI-503 cell line higher mean scores for solids (HSA 38 and SMA 31) than for semi-solids (HSA30 and SMA 20) and for liquids (HSA 25 and SMA 26). Dichotomized results in symptomatic/asymptomatic showed a significant higher percentage of HSA patients (33%) being symptomatic for difficulties swallowing solids compared to SMA patients (22%). HSA-patients also had a significant higher score for swallowing saliva (30 versus 20). Past 3 months no more significant differences were seen except for reflux at 1 year being 27% in HSA versus 16% for SMA. Patients in both groups gave a similar global HRQL score at all timepoints. Conclusion: Semimechanical-anastomosis results in better dysphagia scores for solids and semisolids and reduces significantly the need for dilatations, in particular repeat dilatations. The negative effect of dysphagia in the HAS group fades out over time, probably due to the treatment, i. c. dilatations. Semimechanical-anastomosis BIBW2992 can be safely used after gastric tubulisation

allowing thus resection of the lesser curvature, an important oncologic principle for distal half tumours. Key Word(s): 1. Esophageal Cancer; 2. Surgery; 3. 上海皓元 Quality of Life; Presenting Author: TONI LERUT Additional Authors: PHILIPPE NAFTEUX, JOHNNY MOONS, HANS VAN VEER, WILLY COOSEMANS, GEORGES DECKER, PAUL DELEYN Corresponding Author: PHILIPPE NAFTEUX Affiliations: University Hospital Leuven Objective: The current (7th) International Union Against Cancer (UICC) pN staging system is based on the number of positive lymph nodes but does not take into consideration characteristics of the metastatic lymph nodes itself. Although it is well known that depth of penetration of the primary carcinoma into the oesophageal wall (T)

is an important prognostic factor, little has been published about the prognostic impact of tumor penetration of the lymph node capsule in metastatic lymph nodes, which also called as extracapsular lymph node involvement. The aim of the current study was to examine the prognostic value of extracapsular (EC-LNI) and intracapsular (IC-LNI) lymph node involvement in esophageal cancer. Methods: From 2000–2010, 499 adenocarcinoma patients with primary R0-resectionwere retrieved from our prospective database. The number of resected lymph nodes, number of positive lymph nodes and number of EC-LNI/IC-LNI were determined. Extracapsular spread was defined as infiltration of cancer cells beyond the capsule of the positive lymph node. Results: Two hundred and eighteen (43%) Key Word(s): 1. Esophageal cancer; 2.

Results: Overall incidence of anastomotic leaks was 4.5%. Leakage rate in SMA was 2.17% versus 4.88% in HSA (p = 0.587).

Dilatation occurred in 30% of SMA and 61% of HSA (p < 0.001), 15% and 49% respectively needing ≥ 3 dilatations (p < 0.001). Both groups demonstrate an initial increase of dysphagia score, being steeper for patients with HSA (mean score 31 versus 26). Dysphagia subscales revealed at 3 months Apoptosis inhibitor higher mean scores for solids (HSA 38 and SMA 31) than for semi-solids (HSA30 and SMA 20) and for liquids (HSA 25 and SMA 26). Dichotomized results in symptomatic/asymptomatic showed a significant higher percentage of HSA patients (33%) being symptomatic for difficulties swallowing solids compared to SMA patients (22%). HSA-patients also had a significant higher score for swallowing saliva (30 versus 20). Past 3 months no more significant differences were seen except for reflux at 1 year being 27% in HSA versus 16% for SMA. Patients in both groups gave a similar global HRQL score at all timepoints. Conclusion: Semimechanical-anastomosis results in better dysphagia scores for solids and semisolids and reduces significantly the need for dilatations, in particular repeat dilatations. The negative effect of dysphagia in the HAS group fades out over time, probably due to the treatment, i. c. dilatations. Semimechanical-anastomosis TSA HDAC cost can be safely used after gastric tubulisation

allowing thus resection of the lesser curvature, an important oncologic principle for distal half tumours. Key Word(s): 1. Esophageal Cancer; 2. Surgery; 3. MCE公司 Quality of Life; Presenting Author: TONI LERUT Additional Authors: PHILIPPE NAFTEUX, JOHNNY MOONS, HANS VAN VEER, WILLY COOSEMANS, GEORGES DECKER, PAUL DELEYN Corresponding Author: PHILIPPE NAFTEUX Affiliations: University Hospital Leuven Objective: The current (7th) International Union Against Cancer (UICC) pN staging system is based on the number of positive lymph nodes but does not take into consideration characteristics of the metastatic lymph nodes itself. Although it is well known that depth of penetration of the primary carcinoma into the oesophageal wall (T)

is an important prognostic factor, little has been published about the prognostic impact of tumor penetration of the lymph node capsule in metastatic lymph nodes, which also called as extracapsular lymph node involvement. The aim of the current study was to examine the prognostic value of extracapsular (EC-LNI) and intracapsular (IC-LNI) lymph node involvement in esophageal cancer. Methods: From 2000–2010, 499 adenocarcinoma patients with primary R0-resectionwere retrieved from our prospective database. The number of resected lymph nodes, number of positive lymph nodes and number of EC-LNI/IC-LNI were determined. Extracapsular spread was defined as infiltration of cancer cells beyond the capsule of the positive lymph node. Results: Two hundred and eighteen (43%) Key Word(s): 1. Esophageal cancer; 2.

Twenty-five days after receiving the Armour product, the patient developed a viral syndrome and was found to be positive for HIV. Retrospective testing showed that he was HIV negative on the initial admission for his leg injury in 1985. Earlier, DHF had developed case definition criteria to assist in the identification of individuals possibly infected by heat-treated products (Table 1). Although highly suspect, the patient’s prior drug use prevented a perfect fit with the case definition

criteria [23]. Unknown to DHF and UNC investigators in early 1986, Armour, during July–December 1985, had already Staurosporine manufacturer received reports from the United Kingdom and the Netherlands of several other possible seroconversions in patients receiving Armour’s heat-treated products. While some had received other heat-treated products, the

patients had all received the Armour product heated at 60°C for 30 h. When DHF learned of the UNC patient and began to investigate in January 1986, Armour did not volunteer information concerning the European cases to DHF. However, Dr Peter Jones, director of the Newcastle Hemophilia Center in the UK, knew of the Armour-associated cases in Europe. At an AIDS conference held in Newcastle-upon-Tyne in February 1986, Dr Jones voiced concerns about the efficacy of heat treatment methods [24]. Subsequent publication of his remarks in the general circulation newspapers resulted in an uproar in the UK haemophilia community and the British government initiated enquiries directly to Armour about its product. Selleckchem ABT199 Almost simultaneously (25 February 1986), Armour met with the FDA to review the possible use the HIV ELISA test to screen donors of

source plasma used for Armour’s ‘Generation I’ clotting factor concentrate to improve safety. Armour had been testing donors of source plasma for HIV since May 1985, but considerable Armour concentrate, made from unscreened donors remained in the production sequence or public circulation [22]. At the meeting, Armour reportedly MCE公司 informed the FDA of the possible European cases, but the FDA indicated they did not consider these cases to be ‘clear cut’ seroconversions associated with Armour’s heat-treated products. Unaware of Dr Prince’s studies, the FDA reviewed the latest Meloy Laboratory data from December 1985; based on Meloy’s report, FDA assumed 5 logs of inactivation by Armour’s heat treatment process (3 logs by heating and 2 logs by lyophilization) should be sufficient viral inactivation so that Armour’s product manufactured from unscreened plasma did not need to be withdrawn from the market [22]. However, 2 days later, Armour’s internal plasma executive committee made a decision to voluntarily withhold products made from unscreened plasma unless it was the only product available to sell. No voluntary or mandatory recall was issued [22].

htm 16. Roque F. (2009). selleckchem Tamizaje del cáncer colorrectal. Extraido el dia 25 de Agosto de 2012 en: http://www.google.com.ar/#hl=es-419&tbo=d&sclient=psy 17. Aller de la Fuente R. (2004). Pólipos del colon: factores predictivos de displasia. Rev Clinica de España. pp. 204–251. 18. Normas de presentación para trabajos escritos

de la American Psichological Association APA. (2012). Extraído el día 12 de Octubre de 2012 en: http://www.capitalemocional.com/apa.htm 19. Park S. (2009). Proximal shift in the distribution of adenomatous polyps in Korea over the past ten years. Rev Heoatoaastroenterology., Vol. 56. pp. 91–92. 20. Gervaz P. (2005). Proximal location of colon cancer is a risk factor for development of metachronous colorectal cancer: a population-based

study. Rev Diseases of the Colon & Rectum, Vol. 48, Issue 2. pp. 227–232. 21. Fischer C. (2012). Prevalence of serrated adenomas of the colon and association with synchronic and metachronic neoplastic lesions. Acta Gastroenterol Latinoam, Vol. 42. 92. Presenting Author: YOON TAE JEEN Additional Authors: SEUNG-JOO NAM, JONG SOO LEE, EUN SUN KIM, BORA KEUM, HOON JAI CHUN, HONG SIK LEE, SOON HO UM, CHANG DUCK KIM, HO SANG RYU Corresponding Author: YOON TAE JEEN Affiliations: Korea University Medical Center Objective: Adequate find more bowel cleansing is essential for a high-quality, effective, and safe colonoscopy. There are rare reports that compare directly conventional polyethylene glycol (PEG) intake and picosulphate. The aim of this study is to compare the efficacy, safety, and tolerability of different regimens of oral picosulphate and PEG. Methods: This study

involved 200 adult patients undergoing elective colonoscopy and was single-blinded prospective randomized design in tertiary-care institutions of South Korea. Patients were randomized into four groups with endoscopist was blinded to the regimen. Group A: PEG 4L at 4–6 hours before procedure on the day of the colonoscopy. Group B: PEG 2L at 6:00 上海皓元 PM the day before and 4–6 hours before procedure. Group C: One of 2 sachets of sodium picosulphate at 6:00 PM the day before and 4 hours before procedure. Group D: One of 3 sachets of sodium picosulphate given at 6:00 and 09:00 PM the day before and at 4 hours before procedure. Results: PEG 4L group (both split and non-split dosage) and 3 sachets of picosulphate produced better mucosal cleansing than 2 sachets of picosulphate. Side effects were more frequent in PEG 4L than picosulphate. Patients’ preferences were most high in picosulphate than other goups. Conclusion: Picosulphate is as effective as high-volume PEG-electrolyte solution but has superior tolerance. It has fewer adverse events and is preferred by patients. Key Word(s): 1. colonoscopy; 2. picosulphate; 3.

, 2006; Clutton-Brock, 2009b). In others, it may reduce the risk of infanticide by other Everolimus manufacturer females. For example, in meerkats, pregnant females frequently kill infants born to other group members within 2–3 days of birth and breeding females often evict older subordinate females

from the group in the weeks before parturition, allowing them to return after their pups are several days old (Clutton-Brock et al., 1998b). Eviction frequently induces abortion in evicted females and evicting older subordinates (who are more likely to have conceived) may reduce the risk that the dominant female’s pups will be exposed to pregnant females. In addition, abortion increases the chances that subordinates will subsequently suckle pups born to the dominant female, so that an additional benefit of evicting subordinates to dominants Roscovitine may be that it increases contributions to rearing their pups (Young et al., 2006).

In plural breeders, rising levels of aggression between subgroups of females in large groups can eventually cause groups to split, generating two or more separate groups with distinct home ranges. For example, in macaques, increases in group size commonly lead to increased competition between females, which eventually lead to larger groups splitting and to reductions in competition for resources (Okamoto, 2004). When groups split, they typically do so along matrilineal lines so that average levels of kinship between group members tend to increase. For example, when groups of yellow baboons split, females typically remain in the same subgroup as their close maternal kin (van Horn et al., 2007). Compared with evictions,

the immediate costs of group splitting are relatively low since individuals are not forced to leave groups alone. However, it may have substantial deferred costs if one of the new groups is forced to occupy an inadequate range or is unable to compete effectively with neighbours but, as yet, few studies have been able to assess how large such effects may be. Where potential conflict or limited resources occur between individuals of contrasting fighting ability, less-powerful individuals often benefit by avoiding conflict and allowing their opponents 上海皓元医药股份有限公司 to monopolize resources without direct conflict (Bernstein, 1981; Kaufman, 1983). Subordinates commonly either avoid the proximity of dominants or adjust their behaviour to avoid conflict as soon as they are threatened and, as a result, a high proportion of potential conflicts between group members are usually resolved without fighting. Where there are consistent differences in fighting ability or power between individuals, the avoidance of conflict by weaker individuals generates hierarchies of dominance (or submission) between group members (Rowell, 1974; Silk, 1993).

The values for the reference sequences had normal distributions in all cases. The concordance between isolates was measured using two different methods (genetic distance and number of differences) to ensure that there was no unexpected bias

or skewing of the population average by one method. For the pairwise distance calculation, all positions were used, the Maximum Composite Likelihood substitution model was used, and all sites were assumed to have the same rate of variation. The cutoffs used to establish statistical significance were 1.65 SD below Paclitaxel in vivo the mean (P = 0.05) and 2.3 SD below the mean (P = 0.01) in a single-tailed analysis. A single-tailed (left side) analysis was employed because we wished to determine whether the partner sequences were significantly more related to each other than to random HCV sequences. We estimated the minimal divergence time needed to achieve the interpair nucleotide differences. These calculations are based on a nucleotide fixation rate for NS5 of 1.45 × 10−3 mutations per site per year.12, 13 When this rate was applied to both viruses from the partners, the divergence rate was 2.6 nucleotide positions

per year for the target region analyzed. This rate provided minimal time estimates and was used only to establish a plausibility window for transmission. Prior to study initiation, widths of confidence intervals (CIs) around a prevalence estimate were calculated for a range of sample Navitoclax sizes. Given a 2%-5% prevalence of HCV infection in sexual partners, the widths of CIs would be between 1% and 2% for a projected sample size of

1,000 couples and between 4% and 7% for a projected sample size of 300 couples. Demographic characteristics and risk factors for HCV infection were summarized with frequency distributions (categorical variables) and medians and ranges (continuous variables) separately for anti–HCV-positive index subjects and their partners. Data on sexual practices between partners are presented at the couple level. Duration of the sexual relationship MCE was defined as the number of years between first sexual contact with the study partner and study enrollment, minus time intervals (in years) where sexual contact was absent within the couple. For example, a couple reporting a relationship start year of 1991, study enrollment in 2001, and no sexual activity between 1998 and 1999 would be assigned 9 years for the duration of the sexual relationship. To estimate the total number of sexual contacts for each relationship, the number of sexual contacts per month for each discrete time interval in their sexual history was multiplied by the duration of the time interval and summed over all intervals in the relationship.

The values for the reference sequences had normal distributions in all cases. The concordance between isolates was measured using two different methods (genetic distance and number of differences) to ensure that there was no unexpected bias

or skewing of the population average by one method. For the pairwise distance calculation, all positions were used, the Maximum Composite Likelihood substitution model was used, and all sites were assumed to have the same rate of variation. The cutoffs used to establish statistical significance were 1.65 SD below AUY-922 the mean (P = 0.05) and 2.3 SD below the mean (P = 0.01) in a single-tailed analysis. A single-tailed (left side) analysis was employed because we wished to determine whether the partner sequences were significantly more related to each other than to random HCV sequences. We estimated the minimal divergence time needed to achieve the interpair nucleotide differences. These calculations are based on a nucleotide fixation rate for NS5 of 1.45 × 10−3 mutations per site per year.12, 13 When this rate was applied to both viruses from the partners, the divergence rate was 2.6 nucleotide positions

per year for the target region analyzed. This rate provided minimal time estimates and was used only to establish a plausibility window for transmission. Prior to study initiation, widths of confidence intervals (CIs) around a prevalence estimate were calculated for a range of sample DNA-PK inhibitor sizes. Given a 2%-5% prevalence of HCV infection in sexual partners, the widths of CIs would be between 1% and 2% for a projected sample size of

1,000 couples and between 4% and 7% for a projected sample size of 300 couples. Demographic characteristics and risk factors for HCV infection were summarized with frequency distributions (categorical variables) and medians and ranges (continuous variables) separately for anti–HCV-positive index subjects and their partners. Data on sexual practices between partners are presented at the couple level. Duration of the sexual relationship 上海皓元 was defined as the number of years between first sexual contact with the study partner and study enrollment, minus time intervals (in years) where sexual contact was absent within the couple. For example, a couple reporting a relationship start year of 1991, study enrollment in 2001, and no sexual activity between 1998 and 1999 would be assigned 9 years for the duration of the sexual relationship. To estimate the total number of sexual contacts for each relationship, the number of sexual contacts per month for each discrete time interval in their sexual history was multiplied by the duration of the time interval and summed over all intervals in the relationship.