0 ± 0.15; HFHFr, 1.6 ± 0.29; ATRA + HFHFr, 2.1 ± 0.17), albeit not to a statistically significant degree.

These results suggest that ATRA also normalizes insulin sensitivity in the diet-induced NAFLD mice, possibly by reversing leptin resistance. We examined retinoid signaling in the livers of NAFLD mice, in which ligand-dependent RAR-mediated transcriptional regulation plays a central role. Although hepatic RARα expression was not changed, expression of the RARα target gene Rarb was significantly down-regulated in HFHFr mice, whereas ATRA reversed this effect (Supporting Fig. 6A-C). This result was consistent with our previous observation that hepatic retinoid signaling is impaired in NAFLD patients22 check details and

prompted us to perform transcriptome analysis using complementary DNA microarrays. By identifying genes with elevated expression in the ATRA + HFHFr group compared with the HFHFr group, four independent probes corresponding to Lepr were ranked as the highest 10 (Table 1). This finding was consistent with the leptin-dependent effect of ATRA on insulin sensitivity. qPCR confirmed significant up-regulation of LEPRa as well as IGF binding protein 2 (IGFBP2), which is expressed in the liver in response to systemic leptin administration29 (Supporting Fig. 6D,E). This finding suggests that the leptin-signaling pathway was activated in the livers of mice fed the ATRA + HFHFr Acalabrutinib in vivo diet. We next examined the expression of leptin-signaling proteins. Consistent with

the qPCR data, Western blotting revealed that the expression of the short LEPR isoform was also significantly higher in the ATRA + HFHFr mice compared with that in the HFHFr MCE公司 group (Fig. 4E, Supporting Fig. 5C). Note that LEPRb protein expression was not detected in liver samples. Although the total JAK2 level was lower in HFHFr and ATRA + HFHFr group mice than in controls, its phosphorylation was significantly elevated in the latter group (Fig. 4E, Supporting Fig. 5D,E). Total and phosphorylated STAT3 expression were significantly up-regulated by ATRA, whereas suppressor of cytokine signaling 3 (SOCS3) was not (Fig. 4E, Supporting Fig. 5F-H). STAT3 activation in hepatocytes by ATRA was also demonstrated by immunohistochemistry, showing intense nuclear staining of STAT3 in hepatocytes throughout the liver lobule in the ATRA + HFHFr group, while STAT3 was distributed diffusely in the cytoplasm and nucleus of pericentral hepatocytes in the control and HFHFr groups (Supporting Fig. 7). No changes were observed in the levels of other leptin signaling molecules, adenosine monophosphate-activated protein kinase α, or extracellular signal-regulated kinases 1/29, 30 (data not shown).

Patients assessed as markedly improved or improved were counted as effective cases. Investigators also asked patients if they had ascites-related clinical Staurosporine datasheet symptoms at baseline and if the symptoms changed by day 7. Changes in ascites-related clinical symptoms were assessed as “resolved”, “improved”, “unchanged” or “worsened”. Patients assessed as resolved or improved were counted as effective case. Both improvement rates were calculated by dividing the number of effective case by the number of patients with symptoms at baseline. Day 1 was defined

as the period from the first administration until the second administration of trial drugs. Days 2–7 were similarly defined. Bodyweight was measured before breakfast following urination at baseline and on days 1–7, and abdominal circumference was measured before breakfast at baseline, on any day during days 2–4 and on day 7. Ascites volume was calculated at baseline and on day 7. Lower limb edema was evaluated before breakfast at baseline, on any day during days 2–4 and on day 7. Ascites-related clinical symptoms learn more were assessed at baseline and on day 7. Urine samples to determine cumulative daily urine volume were collected at baseline and on days 1 and 7, and blood samples to determine serum sodium concentration

were collected at baseline, 4–8 h and 24 h on day 1, on any day during days 2–4 and on day 7. Safety assessments, including adverse events, clinical laboratory tests, vital signs and 12-lead electrocardiogram, were conducted during the trial period. The required sample size was calculated assuming statistically significant difference for change in bodyweight from baseline on the final dosing day using one-sided paired t-test at a significance level of 0.025 and 90% power. In the previous trial, changes in bodyweight were −0.36 kg (standard deviation

[SD], 2.06) in the placebo group, −2.31 kg (SD, 2.35) in the 7.5 mg group, −1.88 kg (SD, 2.45) in the 15 mg group and −1.67 kg (SD, 1.46) in the 30 mg group.[11] In this trial, it was assumed that difference in change in bodyweight between two groups would be −1.31 kg (SD, 2.45), based on the minimum difference and the maximum SD among all treatment groups in the previous trial. Therefore, the required MCE sample size was calculated to be 75 patients per group, and we determined to enroll a minimum of 80 patients per group, considering the possibility of a number of withdrawals. Analyses were performed on the full analysis set (FAS). The FAS included all randomized patients who received the trial drugs at least once. Missing data on the final dosing day were imputed by the last data obtained after the start of treatment (the last observation carried forward method). If ascites volume calculated on day 7 was unavailable, its data was imputed by data obtained before treatment.

Consecutive comatose postcardiac arrest patients were prospectively enrolled. Routine MR brain sequences were scored by two independent blinded experts. Predefined brain regions were qualitatively scored on the fluid-attenuated inversion recovery (FLAIR) and diffusion-weighted imaging (DWI) sequences according to the severity of the abnormality on a scale from 0 to 4. The mean score of Ibrutinib mw the raters was used. Poor outcome was defined as death or vegetative state at 6 months. Sixty-eight patients with 88 brain MRI scans were included. Median time from the arrest to the initial MRI was 77 hours (IQR 58-144 hours). At 100% specificity, the “cortex

score” performed best in predicting unfavorable outcome with a sensitivity of 55%-60% (95% CI 41-74) depending on time window selection. When comparing the “cortex score” with historically used predictors for poor outcome, MRI improved the sensitivity for poor outcome over conventional predictors by 27% at 100% specificity. A qualitative MRI scoring system helps assess hypoxic-ischemic brain injury

severity following cardiac arrest and may provide useful prognostic information in comatose cardiac arrest patients. “
“Imaging techniques as confirmatory JNK inhibitor price tests may add safety to the diagnosis of brain death, but are partly not accepted either because they are too invasive, such as conventional arterial angiography, or because there is still lack of evidence of its reliability, such as magnetic resonance angiography. In this study the reliability of diffusion weighted imaging for the diagnosis of brain death was evaluated according in

terms of its sensitivity and specificity. The apparent diffusion coefficients (ADC) of 18 brain dead patients were registered from 14 distinct brain areas. The mean ADC values of the brain dead MCE patients were compared with normal controls of physiological ADC values of unaffected brain tissue. Despite a highly significant decrease of the mean ADC value in 16 patients, two patients showed mean ADC values that were within normal physiological range. An explanation may be the pseudonormalization of ADC values seen in stroke patients that depends on the time of the onset of the brain damage. We conclude, diffusion-weighted imaging may provide additional information on damage of the brain tissue but is not a practicable confirmatory test for the reliable diagnosis of brain death. “
“The objective of the current study was to evaluate the regional and voxel-wise correlation between dynamic susceptibility contrast (DSC) and arterial spin labeling (ASL) perfusion magnetic resonance imaging (MRI) measurement of cerebral blood flow (CBF) in patients with brain tumors. Thirty patients with histologically verified brain tumors were evaluated in the current study.

There was no statistically significant difference in the levels of dysfunction, discomfort, and disability associated with oral problems between moderate and high expectation group at any time point. Elderly edentulous patients had an improved overall OHRQoL after complete denture therapy, and female patients had appreciably better OHRQoL than their male counterparts. A patient’s initial expectation did not have significant influence on overall OHRQoL. “
“The application of ceramic materials for the fabrication

of dental restorations is a focus Selleck Talazoparib of interest in esthetic dentistry. The ceramic materials of choice are glass ceramics, spinel, alumina, and zirconia. Zirconia was introduced into dentistry in the 1990s because of its good mechanical and chemical properties and is currently being used as a material for frameworks, dowels, implants, abutments, and orthodontic brackets. Many in vitro studies about zirconia use have been published, but clinical long-term studies are very important. This article presents data regarding the incidence of clinical success and complications of zirconia in these dental applications. Clinical studies published to date seem to indicate that zirconia is well tolerated and sufficiently resistant. “
“Papillon-Lefèvre syndrome (PLS) is a rare autosomal

recessive disorder. The oral manifestations of the syndrome include rapidly progressive periodontal disease resulting in premature exfoliation RAD001 manufacturer of primary and permanent dentitions. Patients are often edentulous at an early age and require prosthodontic treatment. This report is the oral

rehabilitation of an edentulous 21-year-old woman with PLS. Treatment included maxillary and mandibular fixed prostheses supported by osseointegrated dental implants. At the 4-year follow-up, the patient presented significant improvements in oral function and psychosocial activities 上海皓元医药股份有限公司 and no prosthetic complications. “
“The objective of this study was to evaluate the influence of coping design modifications on maximum first principal stress (MPS) in a mathematical zirconia ceramic crown model. For a nonlinear, 3D finite element analysis, a simplified tooth model was built on the basis of the average dimensions of mandibular second molars. Virtual tooth reduction was performed to model an abutment with a flat occlusal surface and 16° convergence angle between facing walls. The cement layer was set to a thickness of 100 μm. Three different copings—one with 0.5-mm constant thickness; one with constant thickness and extended lingual and proximal collars; and a novel design with zirconia beam reinforcement—were designed to simulate zirconia ceramic restorations. The novel design had strategically positioned zirconia beams on the lingual and marginal ridges to protect veneer ceramics, and was divided into three subdesigns according to the width of the zirconia beam (0.5, 0.8, and 1 mm).

On the other hand, it has also been shown that BM-derived cells express matrix metalloproteinases and contribute to the regression of experimental liver fibrosis. These

contradictory results may arise, at least in part, from the uncertainty of various different methods that have been used in those studies. In this review article, we describe the interplay between BM and liver in the progression and regression of liver fibrosis, with an emphasis on the necessity of qualified methods with high specificity and sensitivity to evaluate the role of BM-derived cells in collagen production. “
“Recently, several studies have shown the existence of associations between lipoprotein profiles and hepatitis C virus (HCV), although only a limited amount of information Nutlin-3 chemical structure is available about the mechanisms underlying the changes in the lipoprotein profiles associated with HCV. In this study, we investigated the association between lipoprotein profile, classified according to the particle size, and lipoprotein metabolism. We used four kinds of cells for this experiment; full-length genome HCV RNA replicon cells (OR6), sub-genomic

HCV RNA replicon cells (sO), and OR6c cells and sOc cells, which were the same cell lines treated with interferon-α. The triglyceride Quizartinib supplier (TG) levels in the lipoprotein subclasses of the culture medium were measured by high-performance liquid chromatography. The mRNA expression levels of several molecules associated with lipoprotein metabolism were measured in the OR6, OR6c, sO and sOc cells. To confirm some of the results obtained using the in vitro system, liver biopsy samples obtained from the patients were also examined. The content of TG in the large low-density

lipoprotein (LDL) and medium LDL in the culture medium was increased only in the OR6 cells. The hepatic triglyceride lipase (HTGL) mRNA expression levels were lower in the OR6 cells than MCE公司 in the OR6c cells (P < 0.01). Examination of the HTGL expression levels in the patients' livers revealed a decrease in HTGL expression in the chronic hepatitis C liver as compared with that in the chronic hepatitis B or non-alcoholic steatohepatitis liver (P < 0.01). We showed that HCV inhibits HTGL production in hepatocytes, inducing a change of the lipoprotein profile. "
“Hepatocellular carcinoma (HCC) frequently arises in the context of chronic injury that promotes DNA damage and chromosomal aberrations. The cyclin-dependent kinase inhibitor p21 is an important transcriptional target of several tumor suppressors, which promotes cell cycle arrest in response to many stimuli. The aim of this study was to further delineate the role of p21 in the liver during moderate and severe injury and to specify its role in the initiation and progression of HCC.

Histocytes and phagocytes were found in one patient. But detection of bacteria, virus and other pathogens were negative. In recent years, SFTSV (severe fever with thrombocytopenia syndrome virus)

infection was selleck screening library reported in several provinces in China. It could cause multiple organ dysfunction. Change of WBC, PLT and serum enzymes were remarkably in these patients. The cases we reported here had the similar clinical features and laboratory findings with SFTS, and the clinical course of these cases consisted with virus infection. Unfortunately, neither SFTSV nor other pathogens have been detected in these cases so far. We supposed that SFTSV is not unique virus, it might be some other unknown virus or pathogens that could cause these

symptoms. More cases should be observed and further study should be done to confirm our hypothesis. Disclosures: The following people have nothing to disclose: Jie Cai, Xiling Guo, Yin Chen, Yiyue Ge, Lunbiao Cui, Yali Weng “
“The rapid emergence of nonalcoholic fatty liver disease (NAFLD) as a cause of both liver-related morbidity and mortality and cardiometabolic risk has led to the search for effective lifestyle strategies to reduce liver fat. Lifestyle intervention comprising dietary click here restriction in conjunction with increased physical activity has shown clear hepatic benefits when weight loss approximating 3%-10% of body weight is achieved. Yet, the poor sustainability of weight loss challenges the current therapeutic focus on body weight and highlights the need for alternative strategies for NAFLD management.

Epidemiologic data show an independent relationship between liver fat, physical activity, and fitness, MCE and a growing body of longitudinal research demonstrates that increased physical activity participation per se significantly reduces hepatic steatosis and serum aminotransferases in individuals with NAFLD, independent of weight loss. Mechanistic insights to explain this interaction are outlined, and recommendations for the implementation of lifestyle intervention involving physical activity are discussed. In light of the often poor sustainability of weight loss strategies, and the viability of physical activity therapy, clinicians should assess physical fitness and physical activity habits, educate patients on the benefits of fitness outside of weight loss, and focus on behavior change which promotes physical activity adoption. (HEPATOLOGY 2010) Nonalcoholic fatty liver disease (NAFLD) affects ∼30% of adults and a majority of obese individuals.1 In addition to increasing morbidity and mortality from liver disease and cancer, excess liver fat is an independent risk factor for cardiovascular disease, insulin resistance, prediabetes and type 2 diabetes.1 Thus, strategies to modulate the burden of NAFLD are likely to have benefits beyond attenuating liver disease to the broader realm of obesity-related cardiometabolic risk reduction.

Through immunohistochemistry we detect the expression of FAK and phosphorylated

FAK (p-FAK) protein in tumor tissue and make double blind IHC score. By method of microRNA extraction and Real-time PCR we detect expression of miRNA-7 in tumor tissue and adjacent tumor tissue. Through the patient clinical data combined with the characteristic of expression of FAK , p-FAK protein and miRNA-7,we compare differential levels of expression of each index and analyse the correlation of different indexes with patient clinical data in tumor and adjacent groups by the statistical Wnt inhibitor software SPSS 18. Results: 1. The expression of FAK and p-FAK (Tyr397) is significantly higher than that of the adjacent tissue. Expression of FAK and p-FAK with lymph node metastasis in colorectal cancer was significantly higher than that

of without lymph node metastasis.2. The expression of miRNA-7 in colorectal cancer tissues is significantly lower than the adjacent tissue miRNA-7 expression, and there was significant difference between the two groups by statistical analysis.3. miRNA-7 expression of cancer tissues of patients with TNM stage III/IV is significantly lower than that Selleck Opaganib of patients with stage I / II, and expression of miRNA-7 with lymph node metastasis in colorectal cancer is significantly lower than that of without lymph node metastasis. Expression level of FAK is negatively correlated with the expression of miRNA-7 level in colorectal cancer. Conclusion: Expression

of FAK and p-FAK is related with tumor growth and lymph node metastasis. High expression level of FAK i negatively correlated with the expression of miRNA-7 level in colorectal cancer, and miRNA-7 is closely related to colon cancer progression, metastasis by combining with the patient clinical date. In summary, the lower miRNA-7 expression level, the later colorectal cancer progression of patients, the poorer the prognosis. Key Word(s): 1. Colorectal cancer; 2. microRNA-7; 3. FAK; 4. Lymph metastasis; Presenting Author: XIAOHUA LI Additional Authors: YING ZHANG, YONGQUAN SHI, YONGZHAN NIE, QINGCHUAN ZHAO, JIE DING, KAICHUN WU, DAIMING FAN Corresponding Author: XIAOHUA MCE LI Affiliations: Xijing Hospital of Digestive Diseases; Xijing Hospital of Digestive Diseases, the Fourth Military Medical University; Xijing Hospital of Digestive Diseases, the Fourth Military Medical University,; Xijing Hospital of Digestive Diseases, the Fourth Military Medical University,; Xijing Hospital of Digestive Diseases, the Fourth Military Medical University,; Xijing Hospital of Digestive Diseases, the Fourth Military Medical University, Objective: Peritoneal dissemination is the overwhelming cause of mortality in patients with gastric cancer. The absence of specific markers for peritoneal metastasis in gastric cancer has made the successful surgical treatment of human gastric cancer difficult.

We found that 2 days after three pIpC injections the deletion of TRRAP was highly efficient in the liver (nearly 100%) and significantly less efficient in other organs such as brain, heart, and bone marrow as monitored by southern blotting reverse-transcription (RT)-PCR (Fig. 1B, and data not shown).14 All TRRAP-CKO mice injected with three doses of pIpC remained viable for the duration of the experiments. Thereafter, TRRAPf/ΔCre+ mice treated with pIpC were designated TRRAP-CKO mice, whereas TRRAPf/ΔCre+ injected with PBS and TRRAPf/ΔCre− injected with pIpC were designated the control group (TRRAP-Co) (Fig. 1A). To examine

the impact of TRRAP deletion on liver regeneration, we used a mouse model of toxic liver injury induced by a single injection of liver toxin CCl4.8, 19 After we induced RG7204 chemical structure CCl4 damage, mice were sacrificed at different timepoints (Fig. 1A). We observed that TRRAP-deficient mice

(TRRAP-CKO) exhibited significantly lower survival than did TRRAP containing control mice (TRRAP-Co) (Fig. 1C). Before CCl4 treatment, adult TRRAP-CKO livers were histologically normal, and liver histology was indistinguishable from that of TRRAP-containing controls (Fig. 1D; timepoint = 0 hours), suggesting that loss of TRRAP compromises mouse survival after toxic liver injury. Analysis of CCl4-induced damage revealed markedly less regeneration in livers from TRRAP-CKO compared to TRRAP-Co mice (Fig. 1D). These results show that loss of TRRAP impairs liver regeneration without altering the degree of selleck chemical initial liver injury and indicate that TRRAP may be an important factor in liver regeneration. We next assessed cell proliferation in the regenerating liver (by BrdU incorporation and PCNA immunostaining). Neither BrdU nor PCNA staining occurred in TRRAP-Co or TRRAP-CKO livers before CCl4 treatment (0 hours after CCl4 treatment), consistent with the cells being in the quiescent (G0) phase (Fig.

2A). Importantly, a sharp increase in hepatocyte proliferation in TRRAP-Co livers after CCl4 treatment (as judged BrdU and PCNA index) was markedly impaired in TRRAP-CKO livers (statistically significant, *P > 0.05) (Fig. 2A,B,D,E). Of note, DNA synthesis in nonparenchymal liver cells was also impaired in TRRAP-CKO mice compared 上海皓元 to control mice (statistical significance P > 0.05) after CCl4 injection (Fig. 2C). These results suggest that TRRAP is important for proliferation of both hepatocytes and nonparenchymal liver cells during liver regeneration. To investigate the function of TRRAP in liver regeneration, we counted mitotic figures and examined them for abnormalities and found that the number of mitotic figures was strikingly lower in livers of TRRAP-CKO mice than in TRRAP-Co mice (Fig. 3A), suggesting the possible involvement of TRRAP in mitotic progression.

3 Over past few decades, time trends of a rightward shift of CRC incidence have been reported,4–9 mainly in

Western populations, although not all reports confirm this finding.10–14 There have also been a few studies investigating the anatomic distribution of colorectal adenoma and CRC in Asian selleck chemicals llc patients, with conflicting results; some reports suggest that no distal-to-proximal shift was observed,15,16 while others suggest that a left-to-right shift of CRC was present.17–19 Because the incidence of CRC has been increasing in China, it is very important to know whether this anatomical distribution shift has been occurring because this might have major implications on the current investigation and future screening methods for CRC. Nevertheless, it is not clear whether a distal-to-proximal shift has occurred in Chinese patients. To address this issue, we examined the time trends, and patients’ sex and age in the distribution of colorectal adenoma and CRC by using a colonoscopy database of 11 025 Chinese patients in a 12-year period. This present study was not a screening study, and it was conducted in the Digestive Endoscopy Center of Changhai Hospital

(Shanghai, China), a tertiary university teaching hospital. The Digestive Endoscopy Center is an open-access endoscopic unit, and all patients were referred there by doctors at the clinics of Changhai Hospital. The patient population consisted of outpatients of Changhai Hospital. When referring patients for endoscopy, the physicians completed Gemcitabine datasheet a standard questionnaire on GI symptoms. The colonoscopy database at our center was then reviewed for reports on all patients who had lower GI symptoms and underwent colonoscopy between June 上海皓元 1998 and September 2009. All consecutive patients undergoing first diagnostic colonoscopy during the study period were included. The study of diagnostic value of alarm symptoms and age for predicting lower GI malignancy, which included the majority of the current patient population, was presented separately.20 The indication for colonoscopy, patients’ age,

sex, and colonoscopic and pathological findings were all recorded in a colonoscopy database (Endoscopy Information System; Angelwin, Beijing, China), which has been described previously.21 Written, informed consent for colonoscopy was obtained from all patients before the procedure. Ethical committee approval was obtained from Shanghai Changhai Hospital Ethics Committee for this study. According to previous studies,10,15–17 colorectal adenoma and CRC located at the cecum, ascending colon, hepatic flexure, and transverse colon were defined as right-sided lesions, while those located at the splenic flexure, descending colon, sigmoid, and rectum were defined as left-sided lesions. Patients had bowel preparation according to the center’s local guidelines.

15-0.27, 0.28-0.35, 0.36-0.64, and >0.64 μm. The ability of ISADE to resolve a mixture of standard control polystyrene beads with known sizes (0.2, 0.24, 0.3, 0.35, 0.4, and 0.5 μm) is shown in Fig. 1A. Both the size and number of beads were accurately reported with a small scatter of size around each peak, which resulted from a small variation in bead size, confirmed by scanning electron microscopy

(SEM). MP tissue factor (MP-TF) activity assay. MPs were isolated from 250 uL of PPP by centrifugation (20,000×g for 30 minutes at 4°C). The MP pellet was resuspended by sonication in 250 uL of HEPES-buffered saline containing 0.5% bovine serum albumin (BSA) (20 mM of HEPES, 120 mM of NaCl, and 1 mg/mL of BSA). A previously described25 two-stage chromogenic assay was employed with the following modifications. First, MPs were incubated for 2 hours with 2.5 mM of CaCl2, 1 nM of factor VIIa, and 150 nM of factor X (FX) in www.selleckchem.com/products/MK-1775.html the presence and absence of a TF blocking antibody (Ab). Next, absorbance measurements (to measure generated FXa) were made for every 30 seconds for 30 minutes after the addition of learn more ethylenediaminetetraacetic acid and FXa chromogenic substrate (Pefachrome 8595; Centerchem, Inc., Norwalk, CT). TF activity was calculated in relation to an Innovin TF standard. Flow cytometry was performed on a Becton

Dickinson BD LSRII (Becton Dickinson, Franklin Lakes, NJ) as per International Society on Thrombosis and Hemostasis standardization.26 Briefly, PPP (10 μL)

at 37°C was stained with Ab for 15 minutes. Secondary Ab was added for an additional 10 minutes. Samples were then diluted with 0.9 mL of Annexin V binding buffer (BD) with or without calcium. An equal volume of Beckman Coulter Flow-Count beads (Beckman Coulter, Inc., Brea, CA) were added to the samples. Ten thousand sample events were collected within the MP gate, and results were compared to isotope controls. MP concentrations in each size distribution were 上海皓元 log10-transformed for analysis. Continuous variables were analyzed for normality of distribution and expressed as mean ± standard deviation (SD) or median (range) and analyzed by analysis of variance or Wilcoxon’s/Kruskal-Wallis’ rank-sums test, as appropriate. Categorical variables were analyzed by chi-square test and correlation of continuous data by Pearson’s correlation (r value). Both uni- and multivariate logistic regression was used to model TFS using demographic and MP data. For stepwise logistic regression modeling, a P = 0.25 significance level was required for entry into the model, whereas a P = 0.05 significance was required for a covariate to remain in the model. Data were analyzed using JMP 8.0, and multivariate analyses were performed with SAS (SAS Institute Inc., Cary, NC). Significance was defined as a P value ≤0.05. Demographic, clinical, and laboratory parameters of the study population are depicted in Table 1 according to outcome, either spontaneous recovery (TFS) or LT/death.