Assessing the Effects of Policy Changes: Lesson from the European 1992 Experience

The paper focuses on the experience of the EMS breakdown in September 1992 as a 'crucial experiment', allowing to identify subsequent changes in policy rules and to assess the invariance of private agents' behaviour to these changes. After a brief summary of the facts, the breakdown and the aftermath, we provide estimates of the change in monetary and budget policy rules for Germany (the benchmark), two 'stayers' (France and the Netherlands) and three 'leavers' (Italy, Spain and the UK). Finally, we perform tests of super exogeneity and invariance of reduced form equations for real activity, inflation and the term structure of interest rates.

The evolution of the muscle compartment from the listing to six-month post-transplantation : a longitudinal monocentric study.

Background and aims: Body composition of the cirrhotic patient plays an important role in his prognosis. Skeletal muscle mass (sarcopenia), malnutrition, frailty (liver frailty index LFI) and myosteatosis are associated with worse outcome in cirrhotic patients. The aim of this study was to determine the best muscle-related predictor of morbidity and mortality on the waiting list and after LT and to evaluate the evolution of all muscle-related parameters up to six months post-transplant. Method: This single-center prospective observational study screened adult patients who were candidates for liver transplantation from June 2021 to September 2022. Each candidate received a functional and nutritional assessment during its pre-transplant evaluation. Muscle quantity and quality were assessed using an abdominal CT scan at the third lumbar level (L3). Sarcopenia was defined as skeletal muscle mass index (SMI) <39 cm2/m2 in females and <50 cm2/m2 in males. Myosteatosis was assessed by skeletal muscle radiodensity attenuation (SM-RA), with cut-offs of SM-RA <41 HU for patients with a BMI <24.9 kg/m2 and <33 HU for patients with a BMI ≥25 kg/ m2. Frailty was defined using the Liver Frailty Index (LFI). Time-to- event analysis was performed using Kaplan-Meier method to investigate the impact of functional variables on outcome. One-year survival was determined for patients who underwent liver transplant during this period. Univariate and multivariate Cox proportional hazard regressions were computed to identify predictors of morbid- ity and mortality on the waiting list for LT. Results: 103 patients were screened, 84 were placed on the Eurotransplant LT waiting list and 49 were transplanted during the study period. The mean age was 54 years and 67.7% were males. The primary etiology of liver disease was alcohol and 38% had a hepatocellular carcinoma. The one-year patient survival probability on the waiting list was 76.9 ± 7.2%. This probability was significantly reduced in patients with myosteatosis compared with patients with higher SM-RA values (43 ± 17% vs 95 ± 4%, p < 0.001). Compared with other muscle characteristics, myosteatosis was the strongest predict- ive factor of mortality. 28 patients had a full 6-months post-LT assessment. Of those liver transplanted patients, 57.7% were frail and 40.7% had myosteatosis before LT. At 6 months post-LT, 53.8% were frail and only 25% had myosteatosis. SMI was not different before and after LT. Compared with pre-LT data, muscle density increased with a mean delta of 4.6 HU ( p = 0.06) (Figure). The 5 chairs stand test significantly improved after LT (11.6 sec vs 9.0 sec ( p = 0.013). The other parameters (handgrip, LFI, ...) remained stable. Conclusion: Myosteatosis is significantly associated with negative pre-transplant outcomes. After LT, patients improve in muscle strength but not in muscle quantity or quality evaluated by CT-scan

Myosteatosis in the liver transplant candidate: Is it the future prognostic marker ?

INTRODUCTION: The body composition of the cirrhotic patient plays an important role in his prognosis. Several factors such as loss of skeletal muscle mass, malnutrition, and frailty (assessed by liver frailty index LFI) are closely associated with an increased risk of mortality in the liver transplant list. Myosteatosis is defined as the pathological excess of fat within the muscle expressed as a lower mean skeletal muscle radiodensity on computed tomography. Several studies have recently observed a negative impact of myosteatosis on the outcome of cirrhotic patients as well as in the postoperative outcome of patients undergoing liver transplantation (LT). There are still questions about the impact of this myosteatosis on liver function and on muscles functionality. [...

HIV-specific antibodies but not t-cell responses are associated with protection in seronegative partners of HIV-1-infected individuals in Cambodia.

International audienceTo study biological factors related to protection against HIV-1 infection in Cambodia, we recruited 48 partners of HIV-1-infected patients who remained uninfected (exposed uninfected individuals, EUs) despite unprotected sexual intercourse for more than 1 year and 49 unexposed controls (UCs). HIV-1-specific antibodies (IgA anti-gp41 and IgG anti-CD4-gp120 complex), T-cell responses, and cellular factors that may be involved in protection (peripheral blood mononuclear cell [PBMC] resistance to HIV-1 infection and beta-chemokine production) were evaluated. Anti-HIV-1 antibodies were higher in EUs than those in UCs (P = 0.01 and P = 0.04 for anti-gp41 and anti-CD4-gp120, respectively). We observed a decreased susceptibility to a primary Cambodian isolate, HIV-1KH019, in EU PBMCs as compared with UC PBMCs (P = 0.03). A weak T-cell response to one pool of HIV-1 Gag peptides was found by ELISpot in 1 of 19 EUs. Whereas T-cell specific immunity was not associated to protection, our results suggest that HIV-specific humoral immunity and reduced cell susceptibility to infection may contribute to protection against HIV-1 infection in Cambodian EUs

Molecular profiling of CD8 T cells in autochthonous melanoma identifies Maf as driver of exhaustion.

T cells infiltrating neoplasms express surface molecules typical of chronically virus-stimulated T cells, often termed "exhausted" T cells. We compared the transcriptome of "exhausted" CD8 T cells infiltrating autochthonous melanomas to those of naïve and acutely stimulated CD8 T cells. Despite strong similarities between transcriptional signatures of tumor- and virus-induced exhausted CD8 T cells, notable differences appeared. Among transcriptional regulators, Nr4a2 and Maf were highly overexpressed in tumor-exhausted T cells and significantly upregulated in CD8 T cells from human melanoma metastases. Transduction of murine tumor-specific CD8 T cells to express Maf partially reproduced the transcriptional program associated with tumor-induced exhaustion. Upon adoptive transfer, the transduced cells showed normal homeostasis but failed to accumulate in tumor-bearing hosts and developed defective anti-tumor effector responses. We further identified TGFβ and IL-6 as main inducers of Maf expression in CD8 T cells and showed that Maf-deleted tumor-specific CD8 T cells were much more potent to restrain tumor growth in vivo. Therefore, the melanoma microenvironment contributes to skewing of CD8 T cell differentiation programs, in part by TGFβ/IL-6-mediated induction of Maf