Effects of cognitive behavioral stress management on HIV-1 RNA, CD4 cell counts and psychosocial parameters of HIV-infected persons

OBJECTIVE: To determine the effects of cognitive-behavioral stress management (CBSM) training on clinical and psychosocial markers in HIV-infected persons. METHODS: A randomized controlled trial in four HIV outpatient clinics of 104 HIV-infected persons taking combination antiretroviral therapy (cART), measuring HIV-1 surrogate markers, adherence to therapy and well-being 12 months after 12 group sessions of 2 h CBSM training. RESULTS: Intent-to-treat analyses showed no effects on HIV-1 surrogate markers in the CBSM group compared with the control group: HIV-1 RNA < 50 copies/ml in 81.1% [95% confidence interval (CI), 68.0-90.6] and 74.5% (95% CI, 60.4-85.7), respectively (P = 0.34), and mean CD4 cell change from baseline of 53.0 cells/microl (95% CI, 4.1-101.8) and 15.5 cells/microl (95% CI, -34.3 to 65.4), respectively (P = 0.29). Self-reported adherence to therapy did not differ between groups at baseline (P = 0.53) or at 12 month's post-intervention (P = 0.47). Significant benefits of CBSM over no intervention were observed in mean change of quality of life scores: physical health 2.9 (95% CI, 0.7-5.1) and -0.2 (95% CI, -2.1 to 1.8), respectively (P = 0.05); mental health 4.8 (95% CI, 1.8-7.3) and -0.5 (95% CI, -3.3 to 2.2) (P = 0.02); anxiety -2.1 (95% CI, -3.6 to -1.0) and 0.3 (95% CI, -0.7 to 1.4), respectively (P = 0.002); and depression -2.1 (95% CI, -3.2 to -0.9) and 0.02 (95% CI, -1.0 to 1.1), respectively (P = 0.001). Alleviation of depression and anxiety symptoms were most pronounced among participants with high psychological distress at baseline. CONCLUSION: CBSM training of HIV-infected persons taking on cART does not improve clinical outcome but has lasting effects on quality of life and psychological well-being.

Prognosis of Children with HIV-1 Infection Starting Antiretroviral Therapy in Southern Africa: A Collaborative Analysis of Treatment Programs

BACKGROUND: Prognostic models for children starting antiretroviral therapy (ART) in Africa are lacking. We developed models to estimate the probability of death during the first year receiving ART in Southern Africa. METHODS: We analyzed data from children ≤10 years old who started ART in Malawi, South Africa, Zambia or Zimbabwe from 2004-2010. Children lost to follow-up or transferred were excluded. The primary outcome was all-cause mortality in the first year of ART. We used Weibull survival models to construct two prognostic models: one with CD4%, age, WHO clinical stage, weight-for-age z-score (WAZ) and anemia and one without CD4%, because it is not routinely measured in many programs. We used multiple imputation to account for missing data. RESULTS: Among 12655 children, 877 (6.9%) died in the first year of ART. 1780 children were lost to follow-up/transferred and excluded from main analyses; 10875 children were included. With the CD4% model probability of death at 1 year ranged from 1.8% (95% CI: 1.5-2.3) in children 5-10 years with CD4% ≥10%, WHO stage I/II, WAZ ≥-2 and without severe anemia to 46.3% (95% CI: 38.2-55.2) in children <1 year with CD4% <5%, stage III/IV, WAZ< -3 and severe anemia. The corresponding range for the model without CD4% was 2.2% (95% CI: 1.8-2.7) to 33.4% (95% CI: 28.2-39.3). Agreement between predicted and observed mortality was good (C-statistics=0.753 and 0.745 for models with and without CD4% respectively). CONCLUSION: These models may be useful to counsel children/caregivers, for program planning and to assess program outcomes after allowing for differences in patient disease severity characteristics.

Virological outcome and management of persistent low-level viraemia in HIV-1-infected patients: 11 years of the Swiss HIV Cohort Study

BACKGROUND Management of persistent low-level viraemia (pLLV) in patients on combined antiretroviral therapy (cART) with previously undetectable HIV viral loads (VLs) is challenging. We examined virological outcome and management among patients enrolled in the Swiss HIV Cohort Study (SHCS). METHODS In this retrospective study (2000-2011), pLLV was defined as a VL of 21-400 copies/mL on ≥3 consecutive plasma samples with ≥8 weeks between first and last analyses, in patients undetectable for ≥24 weeks on cART. Control patients had ≥3 consecutive undetectable VLs over ≥32 weeks. Virological failure (VF), analysed in the pLLV patient group, was defined as a VL>400 copies/mL. RESULTS Among 9972 patients, 179 had pLLV and 5389 were controls. Compared to controls, pLLV patients were more often on unboosted PI-based (adjusted odds ratio, aOR, [95%CI] 3.2 [1.8-5.9]) and NRTI-only combinations (aOR 2.1 [1.1-4.2]) than on NNRTI and boosted PI-based regimens. At 48 weeks, 102/155 pLLV patients (66%) still had pLLV, 19/155 (12%) developed VF, and 34/155 (22%) had undetectable VLs. Predictors of VF were previous VF (aOR 35 [3.8-315]), unboosted PI-based (aOR 12.8 [1.7-96]) or NRTI-only combinations (aOR 115 [6.8-1952]), and VLs>200 during pLLV (aOR 3.7 [1.1-12]). No VF occurred in patients with persistent very LLV (pVLLV, 21-49 copies/mL; N=26). At 48 weeks, 29/39 patients (74%) who changed cART had undetectable VLs, compared to 19/74 (26%) without change (P<0.001). CONCLUSIONS Among patients with pLLV, VF was predicted by previous VF, cART regimen and VL ≥200. Most patients who changed cART had undetectable VLs 48 weeks later. These findings support cART modification for pLLV >200 copies/ml.

The Silencing of N-myc Downstream-Regulated Gene-1 in an Orthotopic Pancreatic Cancer Model Leads to More Aggressive Tumor Growth and Metastases

BACKGROUND: The understanding of molecular mechanisms leading to poor prognosis in pancreatic cancer may help develop treatment options. N-myc downstream-regulated gene-1 (NDRG1) has been correlated to better prognosis in pancreatic cancer. Therefore, we thought to analyze how the loss of NDRG1 affects progression in an orthotopic xenograft animal model of recurrence. METHODS: Capan-1 cells were silenced for NDRG1 (C(sil)) or transfected with scrambled shRNA (C(scr)) and compared for anchorage-dependent and anchorage-independent growth, invasion and tube formation in vitro. In an orthotopic xenograft model of recurrence tumors were grown in the pancreatic tail. The effect of NDRG1 silencing was evaluated on tumor size and metastasis. RESULTS: The silencing of NDRG1 in Capan-1 cells leads to more aggressive tumor growth and metastasis. We found faster cell growth, double count of invaded cells and 1.8-fold increase in tube formation in vitro. In vivo local tumors were 5.9-fold larger (p = 0.006) and the number of metastases was higher in animals with tumors silenced for NDRG1 primarily (3 vs. 1.1; p = 0.005) and at recurrence (3.3 vs. 0.9; p = 0.015). CONCLUSION: NDRG1 may be an interesting therapeutic target as its silencing in human pancreatic cancer cells leads to a phenotype with more aggressive tumor growth and metastasis.

Measurement of Higgs boson production in the diphoton decay channel in pp collisions at center-of-mass energies of 7 and 8 TeV with the ATLAS detector

A measurement of the production processes of the recently discovered Higgs boson is performed in the two-photon final state using 4.5  fb −1 of proton-proton collisions data at s √ =7  TeV and 20.3  fb −1 at s √ =8  TeV collected by the ATLAS detector at the Large Hadron Collider. The number of observed Higgs boson decays to diphotons divided by the corresponding Standard Model prediction, called the signal strength, is found to be μ=1.17±0.27 at the value of the Higgs boson mass measured by ATLAS, m H =125.4  GeV . The analysis is optimized to measure the signal strengths for individual Higgs boson production processes at this value of m H . They are found to be μ ggF =1.32±0.38 , μ VBF =0.8±0.7 , μ WH =1.0±1.6 , μ ZH =0.1 +3.7 −0.1 , and μ tt ¯ H =1.6 +2.7 −1.8 , for Higgs boson production through gluon fusion, vector-boson fusion, and in association with a W or Z boson or a top-quark pair, respectively. Compared with the previously published ATLAS analysis, the results reported here also benefit from a new energy calibration procedure for photons and the subsequent reduction of the systematic uncertainty on the diphoton mass resolution. No significant deviations from the predictions of the Standard Model are found.

From supramolecular sheets to fibers and back: establishing the critical parameters that govern the morphology of pyrene-based self-assembled materials

The precise arraying of functional entities in morphologically well-defined shapes remains one of the key challenges in the processing of organic molecules1. Among various π-conjugated species, pyrene exhibits a set of unique properties, which make it an attractive compound for the utilization in materials science2. In this contribution we report on properties of self-assembled structures prepared from amphiphilic pyrene trimers (Py3) consisting of phosphodiester-linked pyrenes. Depending on the geometry of a pyrene core substitution (1.6-, 1.8-, or 2.7- type, see Scheme), the thermally-controlled self-assembly allows the preparation of supramolecular architectures of different morphologies in a bottom-up approach: two-dimensional (2D) nanosheets3 are formed in case of 1.6- and 2.7-substitution4 whereas one-dimensional (1D) fibers are built from 1.8- substituted isomers. The morphologies of the assemblies are established by AFM and TEM, and the results are further correlated with spectroscopic and scattering data. Two-dimensional assemblies consist of an inner layer of hydrophobic pyrenes, sandwiched between a net of phosphates. Due to the repulsion of the negative charges, the 2D assemblies exist mostly as free-standing sheets. An internal alignment of pyrenes leads to strong exciton coupling with an unprecedented observation (simultaneous development of J- and H-bands from two different electronic transitions). Despite the similarity in spectroscopic properties, the structural parameters of the 2D aggregates drastically depend on the preparation procedure. Under certain conditions extra-large sheets (thickness of 2 nm, aspect ratio area/thickness ~107) in aqueous solution are formed4B. Finally, one-dimensional assemblies are formed as micrometer-long and nanometer-thick fibers. Both, planar and linear structures are intriguing objects for the creation of conductive nanowires that may find interest for applications in supramolecular electronics.

From supramolecular sheets to fibers and back: establishing the critical parameters that govern the morphology of pyrene-based self-assembled materials

The precise arraying of functional entities in morphologically well-defined shapes remains one of the key challenges in the processing of organic molecules1. Among various π-conjugated species, pyrene exhibits a set of unique properties, which make it an attractive compound for the utilization in materials science2. In this contribution we report on properties of self-assembled structures prepared from amphiphilic pyrene trimers (Py3) consisting of phosphodiester-linked pyrenes. Depending on the geometry of a pyrene core substitution (1.6-, 1.8-, or 2.7- type, see Scheme), the thermally-controlled self-assembly allows the preparation of supramolecular architectures of different morphologies in a bottom-up approach: two-dimensional (2D) nanosheets3 are formed in case of 1.6- and 2.7-substitution4 whereas one-dimensional (1D) fibers are built from 1.8- substituted isomers. The morphologies of the assemblies are established by AFM and TEM, and the results are further correlated with spectroscopic and scattering data. Two-dimensional assemblies consist of an inner layer of hydrophobic pyrenes, sandwiched between a net of phosphates. Due to the repulsion of the negative charges, the 2D assemblies exist mostly as free-standing sheets. An internal alignment of pyrenes leads to strong exciton coupling with an unprecedented observation (simultaneous development of J- and H-bands from two different electronic transitions). Despite the similarity in spectroscopic properties, the structural parameters of the 2D aggregates drastically depend on the preparation procedure. Under certain conditions extra-large sheets (thickness of 2 nm, aspect ratio area/thickness ~107) in aqueous solution are formed4B. Finally, one-dimensional assemblies are formed as micrometer-long and nanometer-thick fibers. Both, planar and linear structures are intriguing objects for the creation of conductive nanowires that may find interest for applications in supramolecular electronics.

The mobility of Nb in rutile-saturated NaCl- and NaF-bearing aqueous fluids from 1-6.5 GPa and 300-800 °C

Rutile (TiO2) is an important host phase for high field strength elements (HFSE) such as Nb in metamorphic and subduction zone environments. The observed depletion of Nb in arc rocks is often explained by the hypothesis that rutile sequesters HFSE in the subducted slab and overlying sediment, and is chemically inert with respect to aqueous fluids evolved during prograde metamorphism in the forearc to subarc environment. However, field observations of exhumed terranes, and experimental studies, indicate that HFSE may be soluble in complex aqueous fluids at high pressure (i.e., >0.5 GPa) and moderate to high temperature (i.e., >300 degrees C). In this study, we investigated experimentally the mobility of Nb in NaCl- and NaF-bearing aqueous fluids in equilibrium with Nb-bearing rutile at pressure-temperature conditions applicable to fluid evolution in arc environments. Niobium concentrations in aqueous fluid at rutile saturation were measured directly by using a hydrothermal diamond-anvil cell (HDAC) and synchrotron X-ray fluorescence (SXRF) at 2.1 to 6.5 GPa and 300-500 degrees C, and indirectly by performing mass loss experiments in a piston-cylinder (PC) apparatus at similar to 1 GPa and 700-800 degrees C. The concentration of Nb in a 10 wt% NaCl aqueous fluid increases from 6 to 11 mu g/g as temperature increases from 300 to 500 degrees C, over a pressure range from 2.1 to 2.8 GPa, consistent with a positive temperature dependence. The concentration of Nb in a 20 wt% NaCl aqueous fluid varies from 55 to 150 mu g/g at 300 to 500 degrees C, over a pressure range from 1.8 to 6.4 GPa; however, there is no discernible temperature or pressure dependence. The Nb concentration in a 4 wt% NaF-bearing aqueous fluid increases from 180 to 910 mu g/g as temperature increases from 300 to 500 degrees C over the pressure range 2.1 to 6.5 GPa. The data for the F-bearing fluid indicate that the Nb content of the fluid exhibits a dependence on temperature between 300 and 500 degrees C at >= 2 GPa, but there is no observed dependence on pressure. Together, the data demonstrate that the hydrothermal mobility of Nb is strongly controlled by the composition of the fluid, consistent with published data for Ti. At all experimental conditions, however, the concentration of Nb in the fluid is always lower than coexisting rutile, consistent with a role for rutile in moderating the Nb budget of arc rocks.

BENZENE MYELOCLASTOGENICITY AND METABOLISM IN CD-1 MICE: A CORRELATION

Benzene was studied in its target organ of effect, the bone marrow, with the micronucleus test and metaphase chromosomal analysis. Groups of 5 or 10, male and female CD-1 mice were treated with one or two p.o. or i.p. doses of benzene (440 mg/kg) or toluene (430, 860 or 1720 mg/kg) or both, and sacrificed 30 or 54h after the first dose. Benzene-treated animals were pretreated with phenobarbital (PB), 3-methylcholanthrene (3MC), (beta)-naphthoflavone ((beta)NF), SKF-525A, or Aroclor 1254. Toluene showed no clastogenic activity and reduced the clastogenic effect of co-administered benzene. None of the pretreatments protected against benzene clastogenicity. 3MC and (beta)NF greatly promoted benzene myeloclastogenicity. Dose response curves for benzene myeloclastogenicity were much steeper with 3MC induction than without. Micronuclei (MN) were 4-6 times higher by p.o. than i.p. benzene administration. This was not due to bacterial flora since no difference was found between germ-free and conventional males gavaged with benzene. A sensitive high-pressure liquid chromatographic method was developed and used to explore the relation between metabolic profiles of benzene in urine and MN after various pretreatments. Phenol (PH), trans-trans-muconic acid (MA) and hydroquinone (HQ) in the 48h male mouse urine accounted, respectively, for 12.8-22.8, 1.8-4.7 and 1.5-3.7% of the single oral dose of benzene (880, 440 and 220 mg/kg). Catechol (CT) was seen in trace amounts. MA was identified by ultraviolet and infrared spectroscopy and elemental analysis. Urinary metabolites--especially MA, HQ, and phenol glucuronide--correlated well with MN and were dependent on both the dose and the metabolism of benzene. Benzene metabolism was most inducible by cytochrome P-448 enzyme inducers, by p.o. > i.p., in males > females, and inhibited by toluene. Ph, CT or HQ administered p.o., 250, 150 and 250 mg/kg, respectively, or at 150 mg/kg x 2 after 3MC pretreatment, failed to reproduce the potent myeloclastogenicity of benzene. In fact, only HQ was mildly clastogenic. ^

(Table 1) Productivity characteristics of phytoplankton and some concomitant factors in the Kara Sea in September 1993

Primary production in water column (P_p) varied from 107 to 312 mg C/m**2/day in Yenisey Bay: from 25 to 63 mg C/m**2/day in Obskaya Guba: and from 20 to 359 mg C/m**2/day in the open sea, that is: in the western Kara Sea and Ob-Yenisey shoals. The average concentration of chlorophyll a in the photosynthesis layer (C_ph) ranged from 0.2 to 1.8 mg/m**3 in these two regions, lower than in the estuaries of Ob (1.6-21.7 mg/m**3) and Yenisey (2.0-5.2 mg/m**3) Rivers. An inverse relation between surface salinity (S) and chlorophyll concentration (C_s) and chlorophyll concentration in the photosynthesis layer was found for all of the regions. The highest values of C_s and C_ph (0.8-22 mg/m**3) were measured at S<10 ppt, and the lowest values (0.2-0.8 mg/m**3) at S>22 ppt. A similar correlation of S with values of Pp occurred only in the Yenisey Bay and offshore regions. Obtained results agree well with the "outwelling" hypothesis. It states that large part of organic matter produced in estuaries is not used in estuarine trophic chains but is transported into adjacent sea areas and increases their productivity. Low values of Pp in the study regions may be attributed to such unfavorable factors as deficiency in nutrients, low temperature and turbidity, and lack of solar radiation.