Although

not discussed in this paper, there are other significant research challenges to be addressed if we are to optimize and advance Treatment for All particularly for those living with inhibitors or a rarer factor deficiency. Notably these include:  Improving treatment options for patients with rarer factor deficiencies, such as factor II, factor V, factor VII, factor V+VIII, factor X, factor XI and factor XIII. Health outcomes research – analysis, surveillance and data collection.  Over the past 50 years we have witnessed major improvements to the safety and efficacy of treatment for inherited bleeding disorders, and a greater understanding of their management. The challenge of answering government and payer demands for evidence-based medicine and cost Selleckchem Barasertib justification for the advances, or for the introduction and further enhancement of treatment are ever-present and growing. As a global CAL-101 purchase community we must recognize the challenge and build capacity to produce the necessary outcomes-based data to defend and support continued treatment advances. The need to have a surveillance system becomes more and more important as ministries of health want to know the expected outcomes of investing resources into haemophilia [30]. Even with the improvements of recent decades, further enhancement of the therapeutic options

are needed to improve access to treatments, enhance convenience, elevate quality of life and mitigate treatment complications such as inhibitor development. In order to achieve these goals, detailed and objective clinical outcomes data must be available from

large patient populations to serve as the critical comparator for evaluating the influence of new interventions. Beginning in 2013, the WFH Development 上海皓元 Model will be expanded to include a sixth element – the ability to track and report patient health outcomes through surveillance, enhanced data collection and outcomes analysis. In doing so, the WFH will build on its current data collection and analysis expertise from the WFH Global Survey [7]. Today, the WFH Global Survey, begun in 1998, reports national, regional, global and longitudinal trend data from over 100 countries collected through an annual survey of patient registries for a set of targeted demographic and treatment metrics. Quantifiable data contained in national registries and the WFH Global Survey facilitates the measurement of the effectiveness of healthcare programs. The WFH will continue to promote the establishment of national registries through collaboration between national patient organizations, healthcare professionals, HTCs and ministries of health [29,49]. This new WFH Development Model element will also support a new WFH research initiative to provide access and support of clinical outcomes collation and analysis infrastructures.

35 This is in line with recent findings showing down-regulation of TNFR1-dependent oxidative stress in cultured human tracheal smooth muscle cells upon HO-1 overexpression.30 In consequence, downstream signaling of TNF was affected by HO-1 induction, because we found significantly reduced levels of activated p38, Erk42/44, and activated Erk42 in CoPP-treated

mice—all involved in TNF-dependent gene transcription. Recent studies in a PSC and fibrosis model http://www.selleckchem.com/screening/gpcr-library.html in OPN- or TNFR1-knockout mice showed that both factors are crucial for the establishment of 3,5-diethoxycarbonyl-1,4-dihydrocollidine–induced toxic fibrosis.36 Both OPN and TNFR1 were found to be down-regulated in our mouse model. We could show that HO-1 induction prevents the progression of selleck products fibrosis, indicated by, for example, lower levels of hydroxyproline, as well as decreased expression levels of collagens I and III, which both are highly present in fibrotic livers.37 Likewise, expressions of collagens I and III were found to be significantly reduced in CoPP-treated mice, even when fibrosis was already established. Antifibrotic activity of HO-1 could either be a consequence of reduced inflammation or mediated by a specific antifibrotic mechanism. Our findings are in line with reports showing

that specific overexpression of HO-1 in HSCs attenuates CCl4-induced liver fibrosis in rats.38 We also found evidence that HO-1 induction might even resolve established fibrosis. The ratio between MMP and TIMP expression seems to be crucial for the switch from fibrosis progression to fibrolysis.39 We found that HO-1 induction directly interfered with HSC activation, whereas it induced the expression of MMP-9 and -13 more dramatically than the expression of TIMP1. The ratio of MMP-13/TIMP-1 has been linked to fibrolysis,40

and, in fact, we found fibrolytic activity caused by HO-1 induction. These findings suggest that HO-1 bears anti-inflammatory, antifibrotic, and fibrolytic capacity. Fibrosis progression frequently 上海皓元医药股份有限公司 results in the development of HCC.41 This process is accompanied by increased proliferation and growth-factor activity. TGF-β1, which is one of the most potent profibrogenic cytokines,42 has been linked to wound healing and carcinoma progression.43 Beside proliferation, TGF-β has been shown to be involved in differentiation of fibroblasts into myofibroblasts as well as in ECM production and deposition.43 TGF-β2 has been shown to be specifically expressed in epithelial cells of proliferating bile ducts in fibrotic livers of rats and humans44 and could, therefore, support PSC formation. We could show that TGF-β2 was significantly down-regulated in Mdr2ko mice upon HO-1 induction, independently of the time point of treatment onset, indicating that HO-1 induction would reduce bile duct proliferation and liver inflammation.

Furthermore, because the pathogenesis and severity of NASH has been linked to TLR4 and TLR9 activation of KCs,[23, 24] we tested whether ablation of DC populations results in up-regulation of KC expression of TLRs. We found that KCs from NASH(-DC) liver exhibited selleck chemicals markedly elevated TLR9 expression (Fig. 6D). IHC staining confirmed increased TLR9 expression in NASH(-DC) liver (Fig. 6E). TLR4 was similarly up-regulated on KCs and liver tissues

in NASH(-DC) mice (Fig. 6F). Taken together, these data imply that DC depletion results in activation of innate immune cells in NASH. Because DCs have recently been implicated in the clearance of dead cells in other contexts,[11, 22] and a pathogenic role for sterile inflammation is emerging in NASH,[23] we postulated that—in the absence of DCs—delayed the clearance of apoptotic cells and necrotic debris results in augmentation of sterile inflammation within the liver, precipitating effector cell proliferation

and activation. Augmented sterile inflammation in the hepatic microenvironment is supported by our observation of increased apoptotic bodies and mediators of apoptosis in NASH(-DC) liver (Fig. 4A-D). Additionally, levels of high-mobility group box 1 (HMGB1), a marker of sterile inflammation, were elevated in NASH(-DC) liver, compared to controls (Supporting Fig. 10A). Selleckchem PLX 4720 We also found that—compared with other hepatic APCs—liver DCs express high levels of C-type lectin domain family 9 member A (CLEC9A) (Supporting Fig. 10B), 上海皓元医药股份有限公司 a type II membrane protein with an extracellular C-type

lectin domain, which is essential for DC recognition and clearance of necrotic cells.[26, 27] To directly test whether hepatic DCs are vital to the clearance of necrotic debris in NASH liver, we compared in vivo uptake of exogenously administered 7-amino-actinomycin-positive necrotic cells by CD11c+MHCII+ liver DCs, compared with other MHCII+ APC subsets. We found that DCs achieved greater capture of necrotic elements in vivo (Supporting Fig. 10C). Consistent with these observations, DCs from NASH liver also captured necrotic debris in vitro at a higher rate than other APC subsets (Supporting Fig. 10D). Furthermore, in NASH, DCs acquired greater capacity for necrotic cellular clearance, compared to DCs from control liver (Supporting Fig. 10E). We also tested DC capacity to clear apoptotic bodies in NASH. We found that NASH DCs captured Annexin V+ apoptotic cells in vivo at higher rates, compared with other MHCII+ APC subsets (Supporting Fig. 10F). Furthermore, NASH DCs captured apoptotic bodies at modestly higher rates than DCs from control liver (Supporting Fig. 10F). Taken together, these data suggest that DCs may limit sterile inflammation in NASH by their clearance of necrotic cellular debris and apoptotic bodies, whereas absence of DCs leaves the diseased liver with APCs less equipped for this task.

This difference was driven largely by the increased incidence of hepatic flares in the placebo group. Serious adverse events that were considered by the investigator to be related to study medication occurred in four patients, one in the tenofovir DF group (hepatitis) and three in the placebo group (two with

increased ALT and one with abdominal pain). No deaths occurred during the study. All adverse events occurring in ≥5% of patients are listed in Table 3. The most common adverse events were pharyngitis, nasopharyngitis, increased ALT, acne, and upper respiratory tract infection. The only adverse events for which there was a statistically significant between-group difference (all higher in the placebo group) were increased ALT (tenofovir DF, 6%; placebo, 22%; P = 0.024), acne (tenofovir DF, 4%; placebo, 19%; P = 0.029), and lymphadenopathy (tenofovir DF, 0%; placebo, 11%; P = 0.027). One patient in the tenofovir DF group discontinued the study ABT-263 concentration due to syncope. This patient had a history of syncope, and this adverse event was not considered to be related to study medication. Two patients in the placebo group were discontinued due to sustained grade 4 ALT elevation for ≥16 weeks and were enrolled in the open-label phase of the study at week 40 (Fig. 1). No patients in either group experienced Belinostat chemical structure a ≥6% decrease in lumbar spine BMD at any time

during the study. Five patients, three in the tenofovir DF group and two in the placebo group, had a decrease

of >4% in lumbar spine BMD. None of these patients experienced a bone fracture or other bone-related adverse event. The mean change in lumbar spine BMD z score from baseline to week 72 was −0.05 in the tenofovir DF group and 0.07 in the placebo group. Corresponding mean change in whole-body BMD z scores from baseline to week 72 were −0.15 and 0.06, respectively. Both treatment groups experienced an overall increase in mean lumbar spine BMD. There was a greater increase in mean BMD in the placebo group than the tenofovir DF group at all visits at which BMD was measured: weeks 24 (tenofovir DF, 2%; placebo, 3%; P = 0.005), 48 MCE公司 (tenofovir DF, 4%; placebo, 6%; P = 0.046), and 72 (tenofovir DF, 5%; placebo, 8%; P = 0.053). There were no observed grade 3 or 4 increases in serum creatinine or decrease in serum phosphorus, and no patient had a confirmed increase from baseline creatinine of ≥0.5 mg/dL. Eight patients, six in the tenofovir DF group and two in the placebo group, had a confirmed increase in serum creatinine of 0.3 mg/dL. All of these elevations were transient or within the normal range. The mean change in creatinine from baseline to week 72 was 0.1 mg/dL in both treatment groups. Hepatobiliary adverse events were reported in three patients in the tenofovir DF group (all cases of hepatitis) and 10 patients in the placebo group (eight cases of hypertransaminasemia and two cases of hepatomegaly).

4). To test whether continuous NF-κB activation is needed for the observed changes, we compared gene expression in 4-week-old mice with sustained NF-κB activation with animals MI-503 where CAIKK2 expression was inhibited for 3 days by DOX readministration. DOX readministration for 3 days inhibited CAIKK2 expression

(Fig. 5A). Histological analyses revealed that the livers from DOX-readministered mice exhibited less inflammation (Desmet score: control 0, CAIKK2LAP 0.8 ± 0.5) compared to those from mice without DOX readministration (Desmet score: control 0, CAIKK2LAP 2.5 ± 0.8, P = 6 × 10−3) (Fig. 5B,C). Expression of stress response genes and chemokines was reversed in DOX-treated animals, suggesting that these processes require

continuous NF-κB activation (Fig. 5D). Furthermore, 12-week-old animals were readministered DOX for 3 weeks. Histological analyses, as well as hydroxyproline assay, revealed that despite the NF-κB system being switched off, hepatic fibrosis did not regress within this time frame (Supporting Fig. S5). Although 3 weeks might have been too short to significantly reduce the extent of liver fibrosis, HSC activation markers were all down-regulated after readministration of DOX (Fig. 5E), suggesting that activation of HSCs is dependent on signaling pathway sustained activation of the hepatic NF-κB system. Given the increased presence of macrophage surface markers as well as genes involved in macrophage activation in our microarray analysis (Fig. 4D), we hypothesized that activation of hepatocellular NF-κB signaling leads to liver fibrosis development by way of macrophage recruitment. To test whether hepatocyte-mediated recruitment of macrophages contributes to liver fibrogenesis, we injected clodronate liposomes, an established macrophage-depleting agent. Injection of clodronate liposomes from age 3 to 12 weeks resulted in a marked decrease in macrophage surface marker F4/80, as well as attenuated lysozyme

M and Cxcl10 expression, whereas CAIKK2 expression was intact (Fig. 6A,B; Supporting Fig. S6B). Unaltered levels of F4/80 expression were observed in animals injected with control liposomes (Fig. MCE 6B). Clodronate administration did not reduce the extent of hepatic damage (Supporting Fig. S6A), or the extent of overall inflammation as suggested by unaltered levels of several inflammation-related genes (Supporting Fig. S6B). On the other hand, we observed attenuated fibrogenesis as evidenced by Sirius-red staining (Fig. 6C) and by Desmet scoring (Fig. 6D). A reduction of collagen deposition was also confirmed by hydroxyproline assay and morphometrical analysis of Sirius-red-stained sections (Fig. 6C,E). Thus, our data indicate that sustained hepatocellular NF-κB activation leads to liver fibrosis development by way of recruitment and activation of macrophages.

Five major categories of CLD were considered: alcohol-related liver disease (ALD), chronic hepatitis B (CH-B), chronic hepatitis C (CH-C), NAFLD, and iron overload (defined at the transferrin saturation level of 50% or higher). Alcohol-related liver disease was presumed in subjects who reported excessive

alcohol consumption and had elevated serum aminotransferases (both defined in Table 1). CH-B was defined as being positive for HBsAg, regardless of the anti-HBc or anti-HBs status. It is important to note that the length time for HBsAg-positivity was not available in the NHANES data collection, so we could not reliably distinguish between those with recent and chronic HepB infection. Furthermore, individuals with positive serology for anti-HCV were defined as hepatitis C antibody positive (HCV+). Of the HCV+ patients with available BMN673 data, approximately 75% were selleck chemical HCV RNA positive and were considered to have CH-C. Finally, subjects were presumed to have NAFLD if they had elevated serum aminotransferases in the absence of any other evidence of CLD, such as alcohol use, iron overload, or a positive hepatitis B or hepatitis C serologic

test. Together, individuals with ALD, CH-B, HCV, iron overload, and NAFLD were included in the cohort of CLD. Subjects without evidence of CLD, according to the inclusion criteria described here, were considered to have no CLD and were used as controls. Given the lack of additional iron studies needed to establish the diagnosis of hemochromatosis, we elected not to study iron overload separately. Because NHANES does not collect information on the date of diagnosis for diabetes, we were unable to distinguish between type I and II diabetes. However, because we have limited our assessment of diabetes to adults only, we believe that these patients with diabetes mostly have type II diabetes. A self-reported history of receiving hepatitis A and B vaccinations was collected from the NHANES Immunization questionnaires. Vaccination against hepatitis A (or hepatitis B) was defined as receiving at least one dose

of the vaccine. If fewer than two doses of HepA vaccine (fewer than three for HepB vaccine) were reported, the series MCE公司 was presumed incomplete. Effective vaccination was defined as any number of doses of HepA (or HepB) vaccine and positive anti-HAV (positive anti-HBs without anti-HBc). The quality measure (QM) for HepA vaccination (or HepB vaccination) was defined for all study participants using the Medicare definition for QM for patients with hepatitis C: “percentage of individuals aged 18 years and older with a diagnosis of hepatitis C who received at least one injection of hepatitis A (or B) vaccine, or who had documented immunity to hepatitis A (or B)”.39, 40 When defining QM, in addition to anti-HBs immunity, natural immunity for hepatitis B was defined as positive anti-HBc (regardless of anti-HBs) in the absence of HBsAg.

A fiberglass dowel was cemented in a condemned maxillary lateral incisor prior to its extraction. A microCT scan was performed of the extracted tooth creating a large volume of data in DICOM format. This set of images was imported to image-processing software to inspect the internal architecture of structures. The outer surface and the spatial relationship

of dentin, FRC dowel, cement layer, and voids were reconstructed. Three-dimensional spatial architecture of structures and volumetric analysis revealed see more that 9.89% of the resin cement was composed of voids and that the bonded area between root dentin and cement was 60.63% larger than that between cement and FRC dowel. SEM imaging demonstrated the presence of voids similarly observed using microCT technology (aim 1). MicroCT technology was able www.selleckchem.com/products/dabrafenib-gsk2118436.html to nondestructively measure the volume of voids within the cement layer and the bonded surface area at the root/cement/FRC interfaces (aim 2). Clinical significance: The interfaces

at the root dentin/cement/dowel represent a timely and relevant topic where several efforts have been conducted in the past few years to understand their inherent features. MicroCT technology combined with 3D reconstruction allows for not only inspecting the internal arrangement rendered by fiberglass adhesively bonded to root dentin, but also estimating the volume of voids and contacted bond area between the dentin and cement layer. “
“The purpose of

this study was to evaluate the effect of simulated disinfections (2% glutaraldehyde, 1% sodium hypochlorite, MCE and microwave energy) on the surface hardness of Trilux, Biocler, Biotone, New Ace, and Magister commercial artificial teeth. Specimens (n = 10) were made with the teeth included individually in circular blocks of acrylic resin, leaving the labial surface exposed. Cycles of simulated chemical disinfection were accomplished with the specimens immersed in the solutions at room temperature for 10 minutes, followed by tap water washing for 30 seconds and storage in distilled water at room temperature for 7 days until the next disinfection. Simulated disinfection by microwave energy was carried out in a domestic oven with 1300 W at a potency of 50% for 3 minutes with the specimens individually immersed in 150 ml of distilled water. Control (no disinfection) and the experimental groups (first and third disinfection cycles) were submitted to Knoop hardness measurements with indentations at the center of the labial tooth surface. Data were submitted to repeated measure two-way ANOVA and Tukey’s test (α = 0.05). Biocler, Magister, and Trilux showed lower surface microhardness when submitted to microwave.

We studied the predictive value of donor MBL genotyping for bacterial infections in our own center. The MBL genotypes of 290 donor livers used for orthotopic transplantation between 1987 and 2010 were determined. Notably, this cohort represents the largest single-center cohort of LT patients in which associations between the donor MBL2 genotype

and bacterial infections have been analyzed. In three different ways, we categorized donor livers as MBL-sufficient or MBL-insufficient Maraviroc according to the stratification systems used in the cited studies, and we analyzed associations with clinically significant and laboratory-confirmed bacterial infections occurring during the first 3 months after LT by chi-square analysis with Fisher’s exact test (Table 1). Thirty-eight percent of LT recipients experienced one or more infectious episodes, and this is comparable to the numbers reported by the previous studies.1, 4, 5 Importantly, none of the three stratifications resulted in a statistically significant association between the donor MBL genotype and clinically significant infections. In addition, HIF-1 activation when we analyzed associations with site-specific infections, independently of MBL genotype stratification, we observed no significant increases in the risk of intra-abdominal infections

or bacteremia in patients who underwent transplantation with MBL-insufficient livers. However, in two of the three types of MBL genotype stratification, significantly more pneumonia was diagnosed in patients who underwent transplantation with MBL-deficient livers. In conclusion, this retrospective study indicates that in 上海皓元 our center, the donor MBL2 genotype is not helpful in predicting the risk of bacterial infection after LT. Lilian A. Curvelo M.D., Ph.D.*,

Emmeloes de Mare-Bredemeijer M.D.*, Ilse de Canck M.Sc.‡, Martine van Thielen M.Sc.‡, Geert Kazemier M.D., Ph.D.†, Herold Metselaar M.D., Ph.D.*, Jaap Kwekkeboom Ph.D.*, * Departments of Gastroenterology and Hepatology, Rotterdam, the Netherlands, † Surgery, Erasmus MC: University Medical Center Rotterdam, Rotterdam, the Netherlands, ‡ R&D Discovery, Innogenetics NV, Zwijnaarde, Belgium. “
“See article in J. Gastroenterol. Hepatol. 2010; 25: 259–263 Clearance of hepatitis B surface antigen (HBsAg) from serum, normalization of transaminase values, and appearance of antibodies against HBsAg (anti-HBs) are associated with disease resolution in acute or chronic hepatitis B virus (HBV) infections. However, transmission of HBV infection by blood containing antibodies against hepatitis B core antigen (anti-HBc) has been reported, indicating that serum from HBsAg-negative patients with markers of a past HBV infection may still contain infectious HBV particles.

Methods: Plasmaid Beclinl – SiRNA were constructed and transfected into MiaPaCa2 cells. The expression of Slug was detected by RT – PCR and Western blotting. The cell cycle arrest and apoptotic rates of the cells were detected by flow cytometry. Results: There was a significant change in the cell cycle arrest of Miapaca2 cells after Beclinl check details – SiRNA transduction. But the apoptosis rate was not significantly change. Furthermore, the cell cycle arrest and apoptosis was significantly affected after

treating with Gemcitabine. Conclusion: Beclin1 inhibition showed a greater suppressive effect on Gemcitabine-induced apoptosis and cell cycle arrest of Miapaca2 cells Key Word(s): 1. Beclinl; 2. SiRNA; 3. cell cycle; 4. Gemcitabine; Presenting Author: MENGYAO JI Additional Authors: WEIGUO DONG Corresponding Author: MENGYAO JI Affiliations: Wuhan university Objective: Pancreatic cancer (PC) is one of most common gastrointestinal cancers with poor prognosis. This study aimed to explain the roles and mechanisms of EBP50 involved

in pancreatic cancer. Methods: The quantum dots assay was used to detect EBP50 expression in 40 samples with normal pancreatic tissues, 80 samples with pancreatic cancer tissues, 40 find more samples with L-PanIN tissues and 40 samples with H-PanIN tissues. The EBP50 plasmid was transfected into PC cell line PANC-1, and CCK-8, colony-forming, flow cytomtry and nude mice assays were performed to investigate the influence of EBP50 over-expression on the growth of PANC-1 in vivo and in vitro. Finally, the protein levels of β-catenin, pRb, P27 and cyclin E were measured by western blot. Results: The relative values

for NP, L-PanIN, H-PanIN and PC were 67.34 ± 2.69, 65.51 ± 1.92, 70.13 ± 2.61, and 36.81 ± 1.22 respectively. The H-PanIN tissues showed the highest EBP50 expression (P < 0.05), while pancreatic cancer presented the lowest EBP50 expression (P < 0.05). EBP50 expression in PC tissues was significantly associated with TMN staging, differentiation level and lymph node metastasis (P < 0.05). MCE公司 Up-regulating EBP50 significantly inhibited the growth, the colony-forming ability of cells and arrested the G1-to-S progression. Additionally, over-expression of EBP50 attenuated β-catenin activity, and decreased cyclin E and p-Rb expression compared with controls. The volumes and mass of tumors induced by EBP50-PANC-1 cells were significantly less than PANC-1(P < 0.05). Conclusion: EBP50 inhibits the proliferation through attenuating β-catenin activity and decreasing cyclin E and phosphorylated Rb expression in PC cells. Key Word(s): 1. EBP50; 2. PC.; 3. Progression; 4.

Group B had the highest favorable failure mode. Within the limitations

of this study, the use of a smaller FRC dowel and RRC is recommended rather than enlargement of dowel spaces to accurately fit larger FRC dowels, as the enlargement of dowel space may increase the risk of unfavorable failure. “
“Since the introduction of the endosseous concept to North America in 1982, there have been new permutations of the original ad modum Branemark design to meet the unique GSI-IX solubility dmso demands of treating the edentulous maxilla with an implant restoration. While there is a growing body of clinical evidence to assist the student, faculty, and private practitioner in the algorithms for design selection, confusion persists because of difficulty in assessing the external and internal validity of the relevant studies. The purpose of this article is to review clinician- and patient-mediated factors for implant restoration of the edentulous maxilla in light of the hierarchical level of available evidence, with the aim of elucidating the benefit/risk calculus of various treatment

modalities. “
“To investigate the influence of rehabilitation characteristics in the incidence of peri-implant pathology (P-iP). A total of 1350 patients selleck screening library (270 with P-iP matched for age, gender, and time of follow-up with 1080 controls without P-iP) rehabilitated with dental implants were included. The effect of the independent variables [Implant length in millimeters (IL); implant diameter in millimeters; implant surface (IS); presence of cantilevers; implant:crown ratio (ICR), type of abutment (TA); abutment height; fracture of prosthetic components (FPCs); type of prosthetic reconstruction (TPR); type of material used in the prosthesis (TMUP); loosening of prosthetic components (LPCs); and passive misfit (PM) diagnosed within the previous year] was evaluated

through bivariate analysis (chi-square), with level of significance of 5%. Crude odds ratios (OR) with 95% confidence intervals and the attributable fraction (AF) were calculated for the independent variables individually identified as factors associated with the incidence of peri-implant 上海皓元 pathology. The following variables were identified as risk factors: machined IS (p = 0.015; OR = 1.46), 17° TA (p = 0.000; OR = 3.06), completely edentulous TPR (p = 0.000; OR = 2.49), TMUP (p = 0.000; metal-acrylic OR = 2.29; acrylic OR = 4.90; metal-ceramic OR = 8.43), 1:1 ICR (p = 0.002; OR = 1.54), FPC (p = 0.000; OR = 3.01), LPC (p = 0.000; OR = 4.15), and PM (p = 0.002; OR = 20.36). The attributable fraction rendered the following theoretical potential reductions in the cases if the exposure to the variables was removed: IS (31.5%), TA (67.3%), TMUP (5.4% to 73.3%), ICR (35%), FPC (66.8%), LPC (73.8%), and PM (95.1%).