Prognostic Value of Viremia in Patients with Long-Standing Human Immunodeficiency Virus Infection

Human immunodeficiency virus (HIV) viremia was evaluated in 73 patients with long-standing infection to investigate its relationship with clinical or biologic parameters and to assess its use as a predictor of clinical progression and death. After adjustment for other parameters, baseline HIV RNA level was significantly associated with baseline clinical stage and CD4 cell count. During follow-up (mean, 14.6 months), 16 patients died; 34 others had clinical progression of disease. In multivariate analysis, mortality was better predicted by baseline CD4 cell count (relative hazard [RH] for 100-cell decrease, 3.5; 95% confidence interval [CI], 1.5-8.2; P = .003) than by HIV RNA (P = .28) or clinical stage. HIV RNA level was the best predictor of clinical progression (RH for 1 log increase, 2.8; 95% CI, 1.6-4.9; P < .001). Monitoring of HIV RNA level may help to identify patients who might benefit from antiretroviral or prophylactic therap

Long Term Friction: from Stick-Slip to Stable Sliding

We have devised an original laboratory experiment where we investigate the frictional behaviour of a single crystal salt slider over a large number of deformation cycles. Because of its physical properties, salt, a surrogate for natural faults, allows for friction and plastic deformation and pressure solution creep to be efficient on the same timescale. During the same experiment, we observe a continuous change of the frictional behaviour of the slider under constant conditions of stiffness, temperature and loading velocity. The stick-slip regime is progressively vanishing, eventually reaching the stable sliding regime. Concomitantly, the contact interface, observed under the microscope, develops a striated morphology with contact asperities increase in length and width, arguing for an increase in the critical slip distance dc. Complementary experiments including velocity jumps show that the frictional parameters of the rate and state friction law, a and b, progressively vanish with the cumulative slip. In our experimental conditions, the ultimate stage of friction is therefore rate and state independent.Comment: 10 pages; 4 figures; 1 Tabl

Electronic structure of few-layer black phosphorus from μ\mu-ARPES

Black phosphorus (BP) stands out among two-dimensional (2D) semiconductors because of its high mobility and thickness dependent direct band gap. However, the quasiparticle band structure of ultrathin BP has remained inaccessible to experiment thus far. Here we use a recently developed laser-based micro-focus angle resolved photoemission ($\mu$-ARPES) system to establish the electronic structure of 2-9 layer BP from experiment. Our measurements unveil ladders of anisotropic, quantized subbands at energies that deviate from the scaling observed in conventional semiconductor quantum wells. We quantify the anisotropy of the effective masses and determine universal tight-binding parameters which provide an accurate description of the electronic structure for all thicknesses.Comment: Supporting Information available upon reques

Adaptation et régulation du monocyte-macrophage pour la production de l'interleukine 1 et du "tumor necrosis factor" alpha

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LignoStarch Tailored modification of starch by radiation-grafting of lignin

National audienceThermoplastic Starch (TPS) represents ca 80% of the biopolymer market, however, unlike petroleum based polymers, TPS is still manufactured by traditional methods of extrusion and injection molding. Starch is a semi-crystalline renewable biopolymer made of glucose units existing as a mixture of linear polymer chains (amylose) and branched polymer chains (amylopectin). Due to its hydrophyllic nature, starch products show retrogradation and varying mechanical properties with time. Lignin, another renewable biopolymer and a by-product of the paper industry is hydrophobic and limits water sensitivity of TPS blends. Electron Beam radiation-induced grafting of lignin models onto starch/maltodextrin is shown to result in physical stability of the blends with limited loss of mechanical properties, improved surface hydrophobicity, and to impede long-term retrogradation. Lignin, another renewable biopolymer and a by-product of the paper industry is hydrophobic and limits water sensitivity of TPS blends. Electron Beam radiation-induced grafting of lignin models onto starch/maltodextrin is shown to result in physical stability of the blends with limited loss of mechanical properties, improved surface hydrophobicity, and to impede long-term retrogradation

Response of HIV RNA to didanosine as a predictive marker of survival

OBJECTIVE: To evaluate whether early changes in viraemia in response to didanosine (ddI) predict death and occurrence of new AIDS-defining events. METHODS: Forty-three patients were followed during ddI treatment with sequential determinations of serum viraemia, mutations associated with drug resistance, CD4 counts and clinical evaluation. Patients were stratified into two groups of equal size, responders and nonresponders, using the median of individual changes in viraemia 1 month after initiation of ddI therapy. RESULTS: After 1 month of ddI, mean viraemia decreased by 0.35 log RNA copies/ml of serum (P < 0.001) in the population. A significant difference in survival (median, 14 and 35 months in nonresponders and responders, respectively; log rank, P = 0.004) and in the delay to the occurrence of new AIDS-defining events (median, 8 and 33 months in nonresponders and responders, respectively; log rank, P = 0.018) was observed. After stratification for presence of AIDS before starting ddI, viraemia response at 1 month remained predictive of both overall and AIDS-defining event-free survival (log rank, P = 0.0006 and P = 0.01). After a similar stratification for initial CD4, viraemia response still predicted overall survival (log rank, P = 0.009), but its predictive value for AIDS-defining event-free survival did not reach statistical significance (P = 0.12). High initial levels of HIV RNA, presence of mutation 215 or previous duration of zidovudine therapy were not predictive of survival. CONCLUSIONS: In patients treated with ddI, changes in viraemia at 1 month predict survival independently of initial AIDS diagnosis and initial CD4 counts

Prognostic value of viremia in patients with long-standing human immunodeficiency virus infection. Swiss HIV Cohort Study Group

Human immunodeficiency virus (HIV) viremia was evaluated in 73 patients with long-standing infection to investigate its relationship with clinical or biologic parameters and to assess its use as a predictor of clinical progression and death. After adjustment for other parameters, baseline HIV RNA level was significantly associated with baseline clinical stage and CD4 cell count. During follow-up (mean, 14.6 months), 16 patients died; 34 others had clinical progression of disease. In multivariate analysis, mortality was better predicted by baseline CD4 cell count (relative hazard [RH] for 100-cell decrease, 3.5; 95% confidence interval [CI], 1.5-8.2; P =.003) than by HIV RNA (P =.28) or clinical stage. HIV RNA level was the best predictor of clinical progression (RH for 1 log increase, 2.8; 95% CI, 1.6-4.9; P <.001). Monitoring of HIV RNA level may help to identify patients who might benefit from antiretroviral or prophylactic therapy

Nanostructured Dense Collagen-Polyester Composite Hydrogels as Amphiphilic Platforms for Drug Delivery

International audienceAssociating collagen with biodegradable hydrophobic polyesters constitutes a promising method for the design of medicated biomaterials. Current collagen‐polyester composite hydrogels consisting of pre‐formed polymeric particles encapsulated within a low concentrated collagen hydrogel suffer from poor physical properties and low drug loading. Herein, an amphiphilic composite platform associating dense collagen hydrogels and up to 50 wt% polyesters with different hydrophobicity and chain length is developed. An original method of fabrication is disclosed based on in situ nanoprecipitation of polyesters impregnated in a pre‐formed 3D dense collagen network. Composites made of poly(lactic‐co‐glycolic acid) (PLGA) and poly(lactic acid) (PLA) but not polycaprolactone (PCL) exhibit improved mechanical properties compared to those of pure collagen dense hydrogels while keeping a high degree of hydration. Release kinetics of spironolactone, a lipophilic steroid used as a drug model, can be tuned over one month. No cytotoxicity of the composites is observed on fibroblasts and keratinocytes. Unlike the incorporation of pre‐formed particles, the new process allows for both improved physical properties of collagen hydrogels and controlled drug delivery. The ease of fabrication, wide range of accessible compositions, and positive preliminary safety evaluations of these collagen‐polyesters will favor their translation into clinics in wide areas such as drug delivery and tissue engineering

Combined therapy with zidovudine and L-697,661 in primary HIV infection

OBJECTIVE: To decrease viraemia levels in primary HIV infection by using a combination of zidovudine (ZDV) and L-697,661. DESIGN: Four primary HIV-infected patients were treated for 6 months with ZDV, 250 mg twice daily, in association with the non-nucleoside reverse transcriptase inhibitor L-697,661 500 mg three times daily. Viraemia, proviral DNA, CD4 and CD8 cell counts were measured serially during 18 months. RESULTS: Viraemia decreased to undetectable levels (< 200 RNA copies/ml) in two patients. A third patient had a marked decrease followed by a rebound during therapy; viraemia levels did not vary markedly in the fourth patient. A rebound in viraemia levels was observed within 15 days of discontinuation of therapy in the three responding patients. Proviral levels evolved in parallel with viraemia but were always detectable in all patients. In the three patients with an initial decrease of viraemia, CD4 cell counts were within the normal range 2 months after initiation of therapy and did not markedly decrease after discontinuation of therapy. In the two patients with partial or no response of viraemia, mutations associated with low level of resistance to L-697,661 appeared during treatment. CONCLUSION: A marked decrease of viraemia can be achieved in some primary HIV-infected patients with combined therapy. Six months of treatment does not prevent a rebound of viraemia, which was observed within 15 days of interruption of therapy