The HLA class II allele DRB1*1501 is over-represented in patients with idiopathic pulmonary fibrosis

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive and medically refractory lung disease with a grim prognosis. Although the etiology of IPF remains perplexing, abnormal adaptive immune responses are evident in many afflicted patients. We hypothesized that perturbations of human leukocyte antigen (HLA) allele frequencies, which are often seen among patients with immunologic diseases, may also be present in IPF patients. Methods/Principal Findings: HLA alleles were determined in subpopulations of IPF and normal subjects using molecular typing methods. HLA-DRB1*15 was over-represented in a discovery cohort of 79 Caucasian IPF subjects who had lung transplantations at the University of Pittsburgh (36.7%) compared to normal reference populations. These findings were prospectively replicated in a validation cohort of 196 additional IPF subjects from four other U.S. medical centers that included both ambulatory patients and lung transplantation recipients. High-resolution typing was used to further define specific HLA-DRB1*15 alleles. DRB1*1501 prevalence in IPF subjects was similar among the 143 ambulatory patients and 132 transplant recipients (31.5% and 34.8%, respectively, p = 0.55). The aggregate prevalence of DRB1*1501 in IPF patients was significantly greater than among 285 healthy controls (33.1% vs. 20.0%, respectively, OR 2.0; 95%CI 1.3-2.9, p = 0.0004). IPF patients with DRB1*1501 (n = 91) tended to have decreased diffusing capacities for carbon monoxide (DLCO) compared to the 184 disease subjects who lacked this allele (37.8±1.7% vs. 42.8±1.4%, p = 0.036). Conclusions/Significance: DRB1*1501 is more prevalent among IPF patients than normal subjects, and may be associated with greater impairment of gas exchange. These data are novel evidence that immunogenetic processes can play a role in the susceptibility to and/or manifestations of IPF. Findings here of a disease association at the HLA-DR locus have broad pathogenic implications, illustrate a specific chromosomal area for incremental, targeted genomic study, and may identify a distinct clinical phenotype among patients with this enigmatic, morbid lung disease

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Heavy metal bioavailability in mine drainage-receiving constructed wetland plants

Mine drainages containing heavy metals pose a threat to biota because of their toxic effects, and wetlands provide a viable treatment option because of their low cost and high efficiency of metal uptake. The removal mechanisms involved in the wetland treatment process are various and plant uptake is one of these mechanisms. However, plant uptake can potentially cause metal transmission into the food chain. This study aimed to gain a better understand of the impact that is caused by interactions between plants and trace metals in wetlands receiving mine drainage --Abstract, page iii

1940-1960 eğitim reformları, toplum ve bale

Ankara : İhsan Doğramacı Bilkent Üniversitesi İktisadi, İdari ve Sosyal Bilimler Fakültesi, Tarih Bölümü, 2012.This work is a student project of the The Department of History, Faculty of Economics, Administrative and Social Sciences, İhsan Doğramacı Bilkent University.by Yasemin Başaran Doğan.Doğan, Yasemin Başaran. HIST 200-19DOĞAN HIST 200-19/1 2011-1

Cytoreductive approach to peritoneal carcinomatosis originated from colorectal cancer: Turkish experience.

Peritoneal carcinomatosis (PC) in contrast to lymph nodes and liver metastases was assumed as a terminal condition with no curative treatment options having a 5 to 9 months median survival rate until recently. Today, in properly selected patients, curative surgical treatment of PC is possible like resection of lymph nodes and liver metastases. Between 1996 and 2005, 29 patients who underwent cytoreductive surgery combined with intraperitoneal chemotherapy for PC originated from colorectal cancer (CRC) were analysed prospectively at the Department of Surgery in Dokuz Eylul University Hospital. Mean age was 54 year (range, 23-75 years). There was no peroperative mortality in 29 patients. The morbidity rate was 41% (12/29) and 6 (20%) patients required reoperation(s) for major complications. Mean and median survival time was 34 and 21 months, respectively. The overall 1-year, 3-year, and 5-year survival rates were 72%, 13%, and 7%, respectively. Mean survival time was 56 months in patients with peritoneal cancer index (PCI) 10 (P = 0.075). The mean survival time was 62 months in patients with complete cytoreduction (CC)-0 score, 21 months in patients with CC-1 score, and 7 months in patients with CC-2 and 3 scores. Patients who had CC-0 score had better survival than patients having CC-1 and CC-2 scores (P = 0.003 and P = 0.000, respectively). Patients who had CC-0 and 1 scores had better survival than patients with CC-2 score (P = 0.000). The overall 1-year, 3-year, and 5-year survival rates for patients with CC-0 score were 87%, 37%, and 25%, respectively. There was a positive correlation between the PCI and CC score (P = 0.001, correlation coefficient = 0.585 with correlation is significant at level 0.01). Cytoreductive approach combined with intraperitoneal chemotherapy and systemic chemotherapy prolongs survival in selected patients with PC of CRC with acceptable morbidity and mortality. Prognosis is better in patients with limited disease and in whom complete cytoreduction is achieved. In patients with PC of CRC, the key issue is to select the patients in whom complete cytoreduction is feasible. Better patient assessment with new diagnostic tools such as (PET)-CT or PET-magnetic resonance imaging will be used to detect more precisely the patients with low tumor burden in the new feature

originated from colorectal cancer: turkish experience

Peritoneal carcinomatosis (PC) in contrast to lymph nodes and liver metastases was assumed as a terminal condition with no curative treatment options having a 5 to 9 months median survival rate until recently. Today, in properly selected patients, curative surgical treatment of PC is possible like resection of lymph nodes and liver metastases. Between 1996 and 2005, 29 patients who underwent cytoreductive surgery combined with intraperitoneal chemotherapy for PC originated from colorectal cancer (CRC) were analysed prospectively at the Department of Surgery in Dokuz Eylul University Hospital. Mean age was 54 year (range, 23-75 years). There was no peroperative mortality in 29 patients. The morbidity rate was 41 % (12/29) and 6 (20%) patients required reoperation(s) for major complications. Mean and median survival time was 34 and 21 months, respectively. The overall 1-year, 3-year, and 5-year survival rates were 72%, 13%, and 7%, respectively. Mean survival time was 56 months in patients with peritoneal cancer index (PCI) <10, and 22 months in patients with PCI>10 (P=0.075). The mean survival time was 62 months in patients with complete cytoreduction (CC)-0 score, 21 months in patients with CC-1 score, and 7 months in patients with CC-2 and 3 scores. Patients who had CC-0 score had better survival than patients havin

Nutrient Flux, Uptake, and Transformation in a Spring-fed Stream in the Missouri Ozarks, USA

We examined nutrient flux, uptake, and transformation along a spring-fed stream in the Ozark region of Missouri, USA, over the year 2006. Water in Mill Creek originates from several springs, with a single spring contributing over 90% of the stream discharge during much of the year of study. Soluble reactive phosphate concentrations were usually low (\u3c10 μg L−1) along Mill Creek, but peaked during high discharge. Concentrations of dissolved inorganic nitrogen (DIN) were relatively high in the spring water, mainly as nitrate, but usually declined across a small pond and the 10-km length of Mill Creek. During low flows in summer and early autumn, the stream removed over 300 μg L−1 of DIN over its 10-km length, or about 80% of the initial amount. DIN retention along the stream, as a percentage of the DIN upstream, was related mainly to discharge, with higher flows having much higher DIN concentrations. The net uptake rate of DIN uptake was 0.91 μg m−2 s−1 in the stream during summer baseflow. The uptake rate declined downstream for different reaches and was closely related to DIN concentration. In experimental channels, uptake by epilithic algae was one significant sink for nitrate-N in Mill Creek. In 2006, inorganic nutrient export during a single day after a spring storm was similar to export during 40-100 days of low flow conditions in summer and early autumn. Our results suggest that significant nutrient retention can occur during baseflow periods via biological uptake, whereas substantial export occurs during high flow conditions

Effects of preoperative chemoradiotherapy on anal sphincter functions and quality of life in rectal cancer patients

Deterioration of anorectal function after long-course preoperative chemoradiotherapy combined with surgery for rectal cancer is poorly defined. We conducted a prospective study to evaluate the acute and long term effects of preoperative chemoradiotherapy on anorectal function and quality of life of the patients