bluuebunny/crossref_metadata_2025 huggingface dataset:
Simplification to atazanavir/ritonavir+lamivudine in virologically suppressed HIV‐infected patients: 24‐weeks interim analysis from ATLAS‐M trial
Authors: Fabbiani Massimiliano , Di Giambenedetto Simona , Quiros‐Roldan Eugenia , Latini Alessandra , Vullo Vincenzo , Antinori Andrea , Castagna Antonella , Orofino Giancarlo , Francisci Daniela , Grilli Elisabetta , Madeddu Giordanu , Grima Pierfrancesco , Rusconi Stefano , Del Pin Barbara , Mondi Annalisa , Borghetti Alberto , Focà Emanuele , Colafigli Manuela , De Luca Andrea , Cauda Roberto
Published: November 2014

Introduction

We report interim 24‐weeks efficacy data of ATLAS‐M trial, a phase IV, multicentre, open‐label, randomized study designed to show 48‐weeks, non‐inferior efficacy (margin of −12%) of treatment simplification to atazanavir/ritonavir (ATV/r)+lamivudine (3TC) versus maintaining 3‐drugs ATV/r‐based cART.

Methods

Subjects on ATV/r+2 NRTIs, without previous treatment failure (TF), with HIV‐RNA <50copies/mL for >3 months and CD4>200 cells/mm3 for >6 months were eligible. At baseline, patients were randomized to switch to ATV/r+3TC (arm one) or to maintain the original 3‐drug regimen (arm two). Primary endpoint: proportion of patients free of TF at week 48. TF was defined as treatment modification for any reason, including virological failure (VF=two consecutive HIV‐RNA>50 copies/mL or a single value >1000 copies/mL). Enrollment of 266 patients was planned.

Results

A total of 266 patients (78% males, median age 44 years, median CD4 603 cells/µL, 79% treated with a tenofovir‐containing backbone) were enrolled. At the time of analysis, 24 weeks data were available for 84 and 87 patients in arm one and two, respectively. At baseline, subjects in the two arms did not differ for the main characteristics. At 24 weeks, at the intention to treat analysis the proportion of patients free of TF was 91.7% (95% CI 85.8–97.6) and 85.1% (95% CI 77.6–92.6) in arm one and two, respectively (difference +6.6%, 95% CI −2.9/+16.1). VF was observed in two patients randomized to arm one (one at baseline, before treatment simplification) and one to arm two without resistance mutations. Clinical and laboratory adverse events occurred at similar rates in the two arms. At week 24, patients in arm one showed a greater increase in CD4 (mean change +90 vs +10 cells/µL, p=0.007). A greater increase in total cholesterol (+18 vs −2 mg/dL, p<0.001), HDL (+4 vs +0 mg/dL, p=0.001) and LDL (+12 vs +0 mg/dL, p=0.001) was also observed in arm one without differences in other lipid parameters. Renal function showed a significant improvement in arm one (mean change in eGFR +5 vs −2 mL/min/1.73m2 in arm two, p=0.001). No significant differences in bilirubin levels or other laboratory parameters were observed between the two arms.

Conclusions

This interim analysis suggests a 24‐weeks non‐inferior efficacy of treatment simplification to ATV/rit+3TC as compared to continuation of ATV/rit +2 NRTI in virologically suppressed patients. Follow‐up until 48‐weeks is scheduled to confirm these data.
Monotherapy with darunavir/ritonavir is effective and safe in clinical practice
Authors: Pasquau Juan , López‐Cortés Luis , Isabel Mayorga Maria , Viciana Pompeyo , del Mar Arenas María , José Ríos Maria , Hernández‐Quero José , Castaño Manuel , Dolores Merino María , Márquez Manuel , Vergara Antonio , Terrón Alberto , Téllez Francisco , Hidalgo‐Tenorio Carmen
Published: November 2014

Introduction

Monotherapy against HIV has undoubted theoretical advantages and has good scientific fundaments. However, it is still controversial and here we will analyze the efficacy and safety of MT with darunavir with ritonavir (DRV/r) on patients who have received this treatment in our hospitals.

Materials and Methods

Observational retrospective study that includes patients from 10 Andalusian hospitals that have received DRV/r in MT and that have been followed over a minimum of 12 months. We carried out a statistical descriptive analysis based on the profile of patients who had been prescribed MT and the efficacy and safety that were observed, paying special attention to treatment failure and virological evolution.

Results

DRV/r was prescribed to 604 patients, of which 41.1% had a CD4 nadir <200/mmc. 33.1% had chronic hepatitis caused by HCV, had received an average of five lines of previous treatment and had a history of treatment failure to analogues in 33%, to non‐analogues 22 and protease inhibitors (PI) in 19.5%. 76.6% proceeded from a previous treatment with PI. The simplification was the main criteria for the instauration of MT in the 81.5% and the adverse effects in the 18.5%. We managed to maintain MT in 84% of cases, with only 4.8% of virological failure (VF) with viral load (VL) >200 c/mL and 3.6% additional losses due to VF with VL between 50 and 200 copies/mL. Thirty three genotypes were performed after failure without findings of resistance mutations to DRV/r or other IPs. Only 23.7% of patients presented some blips during the period of exposition to MT. Eighty seven percent of all determinations of VL had <50 copies/mL, and only 4.99% had >200 copies/mL. Although up to 14.9% registered at some point an AE, only 2.6% abandoned MT because of AE and 1.2% because of voluntary decision. Although the average of total and LDL cholesterol increases 10 mg/dL after 2 years of follow‐up, so did HDL cholesterol in 3mg/dL and the values of triglycerides (−14 mg/dL) and GPT (−6 UI/mL) decreased. The average count of CD4 lymphocytes increased from 642 to 714/mm3 at 24 weeks.

Conclusions

In a very broad series of patients obtained from clinical practice, data from clinical trials was confirmed: MT with DRV as a de‐escalation strategy is very safe, it's associated to a negligible rate of adverse effects and maintains a good suppression of HIV replication. VF (with >50 or >200 copies/mL) is always under 10% and in any case without consequences.
ACTG‐HIV symptoms changes in patients switched to RPV/FTC/TDF due to previous intolerance to CART. Interim analysis of the PRO‐STR study
Authors: Podzamczer Daniel , Rozas Nerea , Domingo Pere , Ocampo Antonio , Van den Eynde Eva , Deig Elisabeth , Vergara Antonio , Knobel Hernando , Pasquau Juan , Antela Antonio , Crespo Manuel , Clotet Bonaventure , Muñoz Jessica , Fernandez Pedro , Geijo Paloma , Rodríguez de Castro Eduardo , Diz Julio , Casado Araceli , Torres Covadonga
Published: November 2014

Introduction

Tolerability and convenience are crucial aspects for the long‐term success of combined antiretroviral therapy (cART). The aim of this study was to investigate the impact in routine clinical practice of switching to the single tablet regimen (STR) RPV/FTC/TDF in patients with intolerance to previous cART, in terms of patients’ well‐being, assessed by several validated measures.

Methods

Prospective, multicenter study. Adult HIV‐infected patients with viral load under 1.000 copies/mL while receiving a stable ART for at least the last three months and switched to RPV/FTC/TDF due to intolerance of previous regimen, were included. Analyses were performed by ITT. Presence/magnitude of symptoms (ACTG‐HIV Symptom Index), quality of life (EQ‐5D, EUROQoL & MOS‐HIV), adherence (SMAQ), preference of treatment and perceived ease of medication (ESTAR) through 48 weeks were performed.

Results

Interim analysis of 125 patients with 16 weeks of follow up was performed. 100 (80%) were male, mean age 46 years. Mean CD4 at baseline was 629.5±307.29 and 123 (98.4%) had viral load <50 copies/mL; 15% were HCV co‐infected. Ninety two (73.6%) patients switched from a NNRTI (84.8% from EFV/FTC/TDF) and 33 (26.4%) from a PI/r. The most frequent reasons for switching were psychiatric disorders (51.2%), CNS adverse events (40.8%), gastrointestinal (19.2%) and metabolic disorders (19.2%). At the time of this analysis (week 16), four patients (3.2%) discontinued treatment: one due to adverse events, two virologic failures and one with no data. A total of 104 patients (83.2%) were virologically suppressed (<50 copies/mL). The average degree of discomfort in the ACTG‐HIV Symptom Index significantly decreased from baseline (21±15.55) to week 4 (10.89±12.36) & week 16 (10.81±12.62), p<0.001. In all the patients, quality of life tools showed a significant benefit in well‐being of the patients (Table 1). Adherence to therapy significantly and progressively increased (SMAQ) from baseline (54.4%) to week 4 (68%), p<0.001 and to week 16 (72.0%), p<0.001.

Conclusions

Switching to RPV/FTC/TDF from another ARV regimen due to toxicity, significantly improved the quality of life of HIV‐infected patients, both in mental and physical components, and improved adherence to therapy while maintaining a good immune and virological response.
Switching to lamivudine plus darunavir/r dual therapy in a cohort of treatment‐experienced HIV‐positive patients: the experience of an Italian centre
Authors: Borghetti Alberto , Mondi Annalisa , Piccoli Benedetta , Gagliardini Roberta , Lamonica Silvia , Ciccarelli Nicoletta , D'Avino Alessandro , Pallavicini Federico , Cauda Roberto , De Luca Andrea , Fabbiani Massimiliano , Di Giambenedetto Simona
Published: November 2014

Introduction

According to recent evidence about boosted protease inhibitors (PIs/r)‐simplified regimens, the combination of 3TC and DRV/r 800/100 mg could represent a feasible option for optimizing antiretroviral therapy (ART) in treatment‐experienced HIV+ patients.

Patients and Methods

We retrospectively evaluated patients switching to 3TC+DRV/r, with at least six months of viral suppression, no resistance mutation to DRV or 3TC and not HBV‐coinfected: incidence of ART discontinuation and of virological failure (VF: 2 consecutive HIV‐RNA determinations>49 cps/mL or a single one≥1000 cps/mL) and the probability of remaining discontinuation‐free during one‐year follow‐up (FU), as well as changes in laboratory parameters at 1, 3, 6 and 12 months were estimated.

Results

We included 94 patients: 74 males, mostly MSM (39.4%), with 49 years old, 9 years of HIV disease, 8 years of ART (median values). Median nadir CD4 count and zenith viral load (log10) were 194 cells/µL and 4.90, respectively. Ten patients were HCV‐coinfected and 38 had at least a previous VF. Seventy‐four patients were on an NRTIs‐based triple regimen (mainly TDF/FTC or 3TC/ABC) whereas 14 on another PI‐based dual therapy (mainly LPV/r). Incidence of treatment discontinuation was 12.4 per 100 patients‐year follow‐up (PYFU), but only 2 patients experienced a VF (3.5 per 100 PYFU). Mean time free from discontinuation was 5 years (95% CI 4–6), with a cumulative one‐year estimated probability of staying on 3TC+DRV/r of 85.9%. At three months, a trend of increased CD4 cells count (+42 cells/µL, p 0.059) was observed, but not confirmed at later time point; an increase of total cholesterol (TC, +17mg/dL, p 0.008) and LDL (+19 mg/dL, p 0.002), and a decreased level of AST and ALT (−2 UI/L, p 0.045; −5 UI/L, p 0.009, respectively) were also detected. Total bilirubin was reduced (−0.71 mg/dL, p 0.038). At 6 and 12 months, alteration of lipid profile was similar, with also an increased TC/HDL ratio (+0.48, p=0.030, at six months) and HDL/LDL ratio (−0.04, p=0.035, at 12 months). A significant decrease in ALT levels (−6 UI/L, 0.013) and a diminishing trend for AST and total bilirubin, as well as a significant increase in renal function (GFR +4mL/min, p 0.048) were observed at 12 months.

Conclusions

These observations on 3TC+DRV/r‐based dual therapy simplification in virologically suppressed patients show a good profile of efficacy and safety. An extended FU time is needed in order to establish the real impact of this promising therapeutic choice.
Safety and therapeutic efficacy of the switch to maraviroc+darunavir/ritonavir in HIV/HCV coinfected patients: initial results from GUSTA study
Authors: Gagliardini Roberta , Rossetti Barbara , Bianco Claudia , Rusconi Stefano , Colafigli Manuela , Prinapori Roberta , Francisci Daniela , Fantauzzi Alessandra , Orofino Giancarlo , Vignale Francesca , Di Giambenedetto Simona , De Luca Andrea
Published: November 2014

Introduction

HIV/HCV coinfection is a risk factor for hepatic injury in patients receiving HAART and previous studies support a favourable effect of antiretroviral regimens including maraviroc (MVC) on the course of coinfection compared with other antiretroviral drugs. There are few observations about MVC use in simplified treatment of coinfected patients.Objective: To evaluate the efficacy and the safety of simplification to darunavir (DRV)/ritonavir (r)/maraviroc (MVC) in virologically HIV‐suppressed patients and to explore the effect of simplified treatment on coinfected patients.

Material and Methods

GUSTA study is a randomized two arms trial that compares the switch to DRV/r/MVC with standard HAART with three drugs. The study enrols patients with HIV‐1 RNA<50cp/mL>6 months, R5 tropism, CD4>200 cells/mm. Survival analysis was used to analyze factors associated to time‐to a single viral load (VL) over 50cp/mL and FIB‐4>1.45.

Results

We included 62 patients with at least the 24 week follow‐up for FIB‐4 analysis: males 75.8%, heterosexuals 48.4%, HCV+12.9% median age 48.3 years (IQR41.1;53.5), time from HIV diagnosis 11.0 years (IQR7.3;16.7), CD4 cells 659/mm (IQR478;882), nadir CD4 203/mm (IQR115;286), FPR 46 (IQR30;70), baseline (BL) FIB‐4 1.11 (IQR0.75;1.35). At BL no differences were observed in the two arms, except for platelets (−34.96 109/L, in the study arm, p=0.028) and CD4 at nadir (−70cell/µL, p0.051). After 24 weeks a significant reduction in total bilirubin (TB) (−0.55 mg/dL, p=0.025) and alkaline phosphatase(AP) (−12.96 UI/L, p=0.002) was observed in the study group. A statistically significant difference in mean change of TB (0.61 mg/dL, p=0.016) and AP (13.23 UI/L, p=0.04) at 24 week between control and study group was observed. No grade 3/4 transaminase elevation was observed for any patient even if HIV/HCV coinfected and receiving MVC. A single HCV negative patient in the control arm had grade 3 bilirubin increase. Including all patients with at least one follow‐up HCV status was not associated with an increased risk of detectable VL (n=114, 4072 person‐week‐follow‐up [IQR12;51.6]), nor with FIB‐4>1.45 (n=98, 3513 person‐week‐follow‐up [IQR11.4;50.9]).

Conclusions

The initial results from GUSTA study show that ART‐regimen including MVC did not increase the incidence of adverse events or severe laboratory liver abnormalities in HIV‐1‐infected patients with or without HCV coinfection. Coinfected patients did not show an increased risk of failure on simplification treatment with MVC/DRV/r.
DRV concentrations and viral load in CSF in patients on DRV/r 600/100 or 800/100mg once daily plus two NRTI
Authors: Di Yacovo Silvana , Molto Jose , Ferrer Elena , Curran Adrian , Jayne Else Laura , Clotet Bonaventura , Tiraboschi Juan , Niubo Jordi , Vila Antonia , Podzamczer Daniel
Published: November 2014

Introduction

Darunavir/r (DRV/r) is currently used at a dose of 800/100 mg once daily (OD) in a high proportion of patients. Pharmacokinetic data suggest that 600/100 OD may be effective, reducing toxicity and cost. However, drug concentrations in reservoirs such as cerebrospinal fluid (CSF) might not be adequate to inhibit viral replication. We aimed to evaluate concentrations of DRV and HIV‐1 viral load (VL) in CSF patients receiving DRV 600/100 mg OD.

Methods

DRV600 is an ongoing randomized open study comparing DRV/r 800/100 mg (DRV800) vs 600/100 mg (DRV600) OD plus TDF/FTC or ABC/3TC in 100 virologically suppressed patients (eudraCT 2011‐006272‐39). Here we present the results of a CSF sub‐study. A lumbar puncture (LP) was performed in participating patients after at least six months of inclusion in the study, 20–28 hours after a dose of DRV/r. VL (PCR, LOD 40 copies/mL) was determined in CSF and in plasma. DRV concentrations were quantified in CSF by liquid chromatography mass spectrometry (LC/MS/MS) and in plasma using high‐performance liquid chromatography (HPLC).

Results

Sixteen patients were included (eight in each arm). All DRV600 patients and four out of eight DRV800 patients received TDF/FTC, and the other four ABC/3TC. 75% were males, median (range) age was 48 (17–71) years, CD4 cell count 532 cells/mL (190–1,394). Median total time on DRV/r was 30 (11–57) months, and since the beginning of the study 8 (6–12) months in DRV800 and 10 (7–12) months in DRV600 patients. LP was performed a median of 26 (24–28) hours after the last DRV/r+TVD or KVX dose. In DRV600 patients the median DRV plasma levels were 1,674 (326–3,742) ng/mL, CSF levels 17.08 (5.79–30.19) ng/mL and DRV CSF:plasma ratio 0.0084 (0.0028–0.0388), while in the DRV800 arm, median DRV plasma levels were 1,707 (958–3,910) ng/mL, CSF levels 13.23 (3.47–32.98) ng/mL and DRV CSF:plasma ratio 0.0104 (0.0018–0.0262). All patients had VL<40 copies/mL in plasma and 14 patients VL<40 copies/mL in CSF. Two patients (1 in each arm, and taking TDF/FTC) had detectable VL in CSF (280 and 159 c/mL). These patients had the lowest CSF DRV concentrations (5.47 and 3.47 ng/mL), with plasma DRV concentrations of 802 and 958 ng/mL respectively.

Conclusions

CSF DRV concentrations and CSF VL were similar between patients receiving DRV/r 800/100 mg or 600/100 mg OD. Low CSF DRV concentrations might be associated with viral escape in CNS. This may be taken into account in patients receiving OD DRV/r. Larger studies should confirm these findings.
Low level HIV viremia is more frequent under protease‐inhibitor containing firstline therapy than under NNRTI‐regimens
Authors: Wiesmann Frank , Braun Patrick , Knickmann Mechthild , Knechten Heribert
Published: November 2014

Introduction

An association of persistent low level viremia (LLV) below 500 copies/mL and a higher risk of therapy failure is still point of controversial discussion. Furthermore, it seems that LLV occurs more frequently in patients with protease‐inhibitor regimens than in NNRTI‐ / or integrase‐inhibitor containing therapies. The focus of this work was to assess the prevalence of LLV (50–200 copies/mL) and weak viremia (201–500 copies/mL) in firstline‐treated patients according to their therapy regimen.

Methods

A total of 832 and 944 patients from 23 German centres were under firstline therapy in 2012 and 2013, respectively. All patients received their therapy for more than 24 weeks. VL data was related to clinical data retrospectively including ART‐composition, subdivided into NNRTIs (Efavirenz, Nevirapine), PIs (Atazanavir, Darunavir, Lopinavir) and INIs (Raltegravir). Low viremic patients were classified into two arms of 50–200 copies/mL (group A) and 201–500 copies/mL (group B).

Results

Success of therapy was defined as <50 copies/mL and was observed in 90.0% and 91.1% (2012/2013), respectively. An additional 2.0% and 2.3% had LLV. The amount of viremic patients with VLs <500 copies/mL differed significantly between NNRTI‐based firstline regimens 1.7% and 2.5% and PI‐based regimens 4.8% and 5.7% (2012/2013), respectively. LLV was clearly less often observed in EFV‐based‐ (1.6% and 1.1% [group A] / 0.4% and 0.4% [group B]) or NVP‐based firstline therapies (1.0% and 3.6% [group A] + 0% and 0% [group B]) than in ATV‐based‐ (7.5% and 3.8% [group A] + 1.5% and 2.5% [group B]), DRV‐based‐ (2.9% and 3.0% [group A] + 2.2% and 0% [group B]) or LPV‐based firstline therapies (1.6% and 3.3% [group A] + 0.8% and 2.5% [group B]) and also in parts for RAL‐based regimens (0% and 3.7% [group A] + 0% and 1.9% [group B]).

Conclusions

LLV is more often observed under PI‐based firstline than under NNRTI‐regimens. Only one NNRTI‐patient of group B remained on therapy. A possible explanation for this discrepancy might be the fact that physicians seem to tolerate LLV more often in PI‐regimens than in NNRTI‐regimens due to a higher genetic barrier against resistance and it remains a point of discussion if constant LLV does affect immune recovery and risk of therapy failure.
Clinical and laboratorial impact of antiretroviral therapy in a cohort of Portuguese patients chronically infected with HIV‐2
Authors: Miranda Ana , Peres Susana , Moneti Virginia , Azevedo Telma , Aldir Isabel , Mansinho Kamal
Published: November 2014

Introduction

HIV‐2 infection is endemic in West Africa and some European countries, namely Portugal. HIV‐2 antiretroviral (ARV) treatment presents some restrains related to intrinsic resistance to non‐nucleoside reverse transcriptase inhibitors (NNRTI) and fusion inhibitors, and poorer response to protease inhibitors (PI).

Material and Methods

Retrospective observational study of a cohort of 135 infected HIV‐2 patients, diagnosed between 1989 and 2008.

Objectives

Evaluation of epidemiologic, clinical, immunologic and virologic progression, comparing to groups of patients (naïve vs ARV experienced); characterization of therapeutic, immunologic and virologic response. SPSS version 20.0 was used for statistical analysis.

Results

The study included 135 patients: 41% (n=55) naïve and 59% (n=80) with ARV experience. The comparison between groups (naïve vs ARV) revealed: male prevalence 76% vs 50%; mean age 54.5 years vs 54.8 (p=0.90); main geographic origin Guiné Bissau (47% vs 44%) and Portugal (22% vs 33%); and transmission mainly acquired by heterosexual contact (87% vs 80%). Mean time since diagnosis was 14 vs 13 years (p=0.31); 2% vs 50% presented AIDS criteria at diagnosis (p<0.001) and 93% vs 38% registered TCD4>350 cell/mm3 at diagnosis (p<0.001). Immunological evolution showed no significant decline in naïve population (Δ=−67 cell/mm3 – p=0.18) and a significant recovery in ARV experienced (Δ=+207 cell/mm3 – p<0.001). Global mortality rate found was 18% (6% vs 13% – p=0.122). Eighty patients initiated ARV: 84% presented a time interval of ARV exposure between 0–5 years (42%) and 5–10 years (42%). Fifty percent experienced ≤2 ARV regimens and the remaining >2 regimes. Considering the first ARV therapy: 56% initiated PI, 30% NTRI and 5% integrase inhibitor (II)‐based regimens. Currently, 54 patients maintain regular follow‐up and ARV therapy: 60% NTRI+PI; 37% NRTI+PI+II and 3% NRTI+II. TDF/FTC is the backbone in 56%. Most frequent PIs are LPV/r (54%), DRV/r (19%) and ATV/r (12%). Mean time of exposure to NRTI=3 years, PI=7 years and II=2 years. Immunologic recovery was sustained for each of the ARV class considered (NRTI Δ=+144 cell/mm3; PI=Δ+92 cell/mm3; II=Δ=+116 cell/mm3).

Conclusions

This is a cohort accompanied for a long period and the majority of patients present extensive ARV experience. The ARV‐experienced patients registered a favourable response to treatment, with sustained immune recovery (Δ=+207 cell/mm3) and virologic control in 74%. Immunologic behaviour evidenced a sustained gain for each of the ARV class considered.
NOAA's winter outlook favors weak El Niño, lower‐than‐average precipitation
Authors: Wendel JoAnna
Published: October 2014

Water shortages due to severe drought will continue to persist in California even if the state receives an average amount of precipitation this winter, said Kevin Werner, western regional climate services director at the National Atmospheric and Oceanic Association (NOAA). This prediction came during NOAA's winter 2014–2015 outlook for U.S. precipitation and temperature, released on 16 October.
Land Surface Model Development Needs for Weather Prediction
Authors: Hunt Eric , Wegiel Jerry , Chen Fei
Published: October 2014

Scientists from the land surface modeling (LSM) community met in Boulder, Colo., in late June to discuss ways to better meet the modeling needs of weather prediction agencies. This was the eighth meeting of the Weather Research and Forecasting LSM working group known as WG14 since its inception in 2000. The workshop was organized and hosted by the Air Force Weather Agency and the National Center for Atmospheric Research.
History of storm surge in Florida strongly underestimated
Authors: Schultz Colin
Published: October 2014

The observational hurricane record for northwestern Florida is just 160 years long, yet hurricane activity is known to vary strongly over thousands of years. Digging back into the prehistoric hurricane record, Lin et al. found that scientists' reliance on such a narrow slice of observations has led them to severely underestimate the frequency with which large hurricanes have slammed into Florida's Gulf Coast.
A simple model to calculate when drought causes plants to die
Authors: Schultz Colin
Published: October 2014

To build a realistic ecosystem model requires, among other things, designing a way to calculate when plants will persevere through hostile conditions and when they will wither and die. Using a simplified model of trees' internal hydrological systems, Manzoni et al. have built a model meant to calculate when changes in environmental conditions will cause a tree stress and when they will push it toward critical failure.
Thermal properties of methane hydrate‐bearing sediments and surrounding mud recovered from Nankai Trough wells
Authors: Muraoka M. , Ohtake M. , Susuki N. , Yamamoto Y. , Suzuki K. , Tsuji T.
Published: October 2014

This paper presents the measurement of the thermal constants of natural methane hydrate‐bearing sediments and mud layer samples recovered from wells. Core samples were recovered from the Tokai‐oki test wells (Nankai Trough, Japan) in 2004. The thermal conductivity, thermal diffusivity, and specific heat of the samples were simultaneously determined using the hot‐disk transient method. The thermal conductivity of natural hydrate‐bearing sediments decreased slightly with increasing porosity. In addition, the thermal diffusivity of hydrate‐bearing sediments decreased as the porosity increased. Moreover, we also used simple models to calculate the thermal conductivity and diffusivity. Estimations of the distribution model (geometric mean model) were relatively consistent with the measured results, suggesting that sand grains and hydrates should be independently distributed for hydrate‐bearing sediments, which exhibit a pore‐filling pattern. The measurement results were also consistent with the thermal diffusivity, which was estimated by dividing the thermal conductivity obtained from the distribution model by the specific heat taken from the arithmetic mean. Finally, our estimate of the thermal conductivity of silt soil was much lower than that for sand soil in hydrate‐bearing sediment, which suggests that the small grains influence thermal conductivity.
Insights into mantle structure and flow beneath Alaska based on a decade of observations of shear wave splitting
Authors: Perttu Anna , Christensen Douglas , Abers Geoffrey , Song Xiaodong
Published: October 2014

SKS shear wave splitting measurements from three Program for Array Seismic Studies of the Continental Lithosphere experiments (Broadband Experiment Across the Alaska Range, Alaska Receiving Cross Transect of the Inner Core, and Multidisciplinary Observations Of Subduction), which form a north/south transect across Alaska, show a remarkably simple pattern of two large anisotropy domains. In the northern domain, extending from the 70 km contour of the subducting Pacific plate north to the Arctic Ocean, fast directions are consistently in the NE‐SW direction. These directions are essentially parallel to the absolute plate motion direction in northern Alaska and parallel to the strike of the subducting plate above the mantle wedge, suggesting that they represent some combination of plate‐scale asthenospheric flow in the upper mantle and flow along the subducting plate in the mantle wedge. A strong wedge component beneath the Alaska Range is required to explain systematics of splitting delay times. In the southern domain, which extends south from the 70 km depth contour to the subducting plate, fast directions are in the NW‐SE direction, a 90° rotation from the northern domain. These fast directions are parallel to the dip of the subducting plate in the direction of convergence and represent entrained flow beneath the subducting slab; the Pacific Plate absolute motion approximately parallels local convergence. Two major factors seem to control flow in these regions, absolute plate motion in the north and the subduction of the Pacific plate in the south, although both subduction‐driven wedge flow and absolute plate motion contribute to the southern part of the northern regime.
Centrifugation
Authors: Gallagher Sean R.
Published: October 2014

Centrifugation is a ubiquitous technique in the life science laboratory that uses specialized equipment (centrifuges) to spin, or centrifuge, samples in rotors, generating centrifugal force for a range of applications that include pelleting of precipitates, isolating organelles, and protein and DNA purification. The unit describes basic applications, definitions, and references, and provides up‐to‐date tables for rotor specifications from major suppliers. © 2014 by John Wiley & Sons, Inc.
Digital Image Processing and Analysis with ImageJ
Authors: Gallagher Sean R.
Published: October 2014

ImageJ is a freely available, cross‐platform (e.g., Windows, Mac, Linux) image processing and analysis program developed by the NIH. In addition to being readily available for no cost, ImageJ is supported by a wide range of constantly evolving user‐created functionalities to address a remarkable range of applications, complementing commercial software that typically comes with imaging instruments such as digital gel‐imaging systems or microscopy workstations. New processing/analysis macros and plug‐ins are routinely added to the support site, and are frequently validated via refereed publications. With the continued improvements and growth of fluorescence‐based applications, ImageJ continues to be a mainstay in the laboratory. ImageJ has extensive support materials available online, its base code is regularly updated, and a survey of Medline references indicates that it is one of the most widely used image‐analysis packages available today. © 2014 by John Wiley & Sons, Inc.
Characterization of cleaning and disinfecting tasks and product use among hospital occupations
Authors: Saito Rena , Virji M. Abbas , Henneberger Paul K. , Humann Michael J. , LeBouf Ryan F. , Stanton Marcia L. , Liang Xiaoming , Stefaniak Aleksandr B.
Published: October 2014

Background

Healthcare workers have an elevated prevalence of asthma and related symptoms associated with the use of cleaning/disinfecting products. The objective of this study was to identify and characterize cleaning/disinfecting tasks and products used among hospital occupations.

Methods

Workers from 14 occupations at five hospitals were monitored for 216 shifts, and work tasks and products used were recorded at five‐minute intervals. The major chemical constituents of each product were identified from safety data sheets.

Results

Cleaning and disinfecting tasks were performed with a high frequency at least once per shift in many occupations. Medical equipment preparers, housekeepers, floor strippers/waxers, and endoscopy technicians spent on average 108–177 min/shift performing cleaning/disinfecting tasks. Many occupations used products containing amines and quaternary ammonium compounds for >100 min/shift.

Conclusions

This analysis demonstrates that many occupations besides housekeeping incur exposures to cleaning/disinfecting products, albeit for different durations and using products containing different chemicals. Am. J. Ind. Med. 58:101–111, 2015. © 2014 Wiley Periodicals, Inc.
Inducing Axial Chirality in a “Geländer” Oligomer by Length Mismatch of the Oligomer Strands
Authors: Rickhaus Michel , Bannwart Linda Maria , Neuburger Markus , Gsellinger Heiko , Zimmermann Kaspar , Häussinger Daniel , Mayor Marcel
Published: November 2014

Helical molecules are not only esthetically appealing due to their structural beauty, they also display unique physical properties as a result of their chirality. We describe herein a new approach to “Geländer” oligomers by interlinking two oligomer strands of different length. To compensate for the dimensional mismatch, the longer oligo(benzyl ether) oligomer wraps around the oligophenyl backbone. The new “Geländer” oligomer 1 was assembled in a sequence of functional‐group transformations and cross‐coupling steps followed by final cyclizations based on nucleophilic substitution reactions, and was fully characterized, including X‐ray diffraction analysis. The isolation of pure enantiomers enabled the racemization process to be studied by circular dichroism spectroscopy.
Hyperbranched polyester polyol modified with polylactic acid
Authors: Mesias Ricardo , Murillo Edwin A.
Published: October 2014

In this study the modification of a hyperbranched polyester polyol of second generation (HBP2G) with polylactic acid (PLA) was carried out. The proportions employed of PLA were: 10 (HBP2G90), 25 (HBP2G75), 40 (HBP2G60), and 55 wt % (HBP2G45). The materials obtained were characterized by acid value, hydroxyl value, infrared, nuclear magnetic resonance (NMR), chromatography exclusion size (SEC), dynamic light scattering, thermogravimetric, differential scanning calorimetry, and rheology analyses. The analyses of the acid values and hydroxyl values showed that the reaction between HBP2G and PLA occurred. The greater modification degree was 92.00%. The NMR spectrum shows that evidently the PLA was grafted onto the HBP2G. The SEC analysis revealed that all samples presented values ​​of average molecular weight (Mn) and weight average molecular weight (Mw) higher than the HBP2G. The thermal stability of the materials increased with respect to HBP2G and it was independent of the modification degree. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41589.
Multiscale approach to the morphology, structure, and segmental dynamics of complex degradable aliphatic polyurethanes
Authors: Špírková Milena , Machová Luďka , Kobera Libor , Brus Jiří , Poręba Rafał , Serkis Magdalena , Zhigunov Alexander
Published: October 2014

A multiscale approach spanning from the segmental (subnanometer) up to micrometer level was applied for detailed study of the self‐assembly of aliphatic block polyurethane (PU) elastomers. To understand the principles of the self‐organization of hard and soft segments in the complex multi‐component systems, several two‐component model PU samples, that is, the products of 1,6‐diisocyanatohexane (HDI) with three diols differing in the length and constitution were also prepared, characterized, and investigated: (i) polycarbonate‐based macrodiol (MD), (ii) biodegradable oligomeric diol (DL‐L; product of butane‐1,4‐diol and D,L‐lactide), and (iii) butane‐1,4‐diol (BD). The study (particularly 13C‐1H PILGRIM NMR spectra) reveals complex internal organization and interesting (application appealing) behavior of multi‐component PUs. Hard segments (HDI+BD products) feature self‐assembled and significantly folded chain conformations with interdomain spacing 15–22 nm (small‐angle X‐ray scattering analysis). The small domains are hierarchically assembled in various structural formations of µm size (spherulites) depending on PU composition, as detected by transmission electron microscopy and atomic force microscopy. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41590.
Flow characteristics of three enhanced oil recovery polymers in porous media
Authors: Wei Bing
Published: October 2014

This article presents an experimental study aiming to explore the relationship among rheological properties, flow characteristics in porous media, and enhanced oil recovery (EOR) performance of three typical EOR polymers. The results suggest that xanthan gum exhibits a very pronounced shear‐thinning behavior, which is probably also the reason explaining its moderate adsorption extent within porous media (thickness of adsorbed layer, e = 3.1 μm). The advanced viscoelastic properties coupled with the less adsorption extent compared to the hydrophobically modified copolymer (HMSPAM) allow xanthan gum to establish a “piston‐like” displacement pattern and lead up to 49.4% original oil in place (OOIP) of the cumulative oil recovery during polymer flooding. Regarding HMSPAM, the significant permeability reduction of the porous media induced by multilayer adsorption (e = 5.6 μm) results in much higher drive forces (ΔP) in the extended waterflooding stage, which further raises the cumulative oil recovery by 18.5% OOIP. In general, xanthan gum and HMSPAM totally produced 84% OOIP which is 15% higher than the extensively used EOR polymer, hydrolyzed polyacrylamide (HPAM), under the same experimental conditions. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41598.
Performance of the marginal structural models under various scenarios of incomplete marker's values: A simulation study
Authors: Vourli Georgia , Touloumi Giota
Published: October 2014

Marginal structural models (MSMs) have been proposed for estimating a treatment's effect, in the presence of time‐dependent confounding. We aimed to evaluate the performance of the Cox MSM in the presence of missing data and to explore methods to adjust for missingness. We simulated data with a continuous time‐dependent confounder and a binary treatment. We explored two classes of missing data: (i) missed visits, which resemble clinical cohort studies; (ii) missing confounder's values, which correspond to interval cohort studies. Missing data were generated under various mechanisms. In the first class, the source of the bias was the extreme treatment weights. Truncation or normalization improved estimation. Therefore, particular attention must be paid to the distribution of weights, and truncation or normalization should be applied if extreme weights are noticed. In the second case, bias was due to the misspecification of the treatment model. Last observation carried forward (LOCF), multiple imputation (MI), and inverse probability of missingness weighting (IPMW) were used to correct for the missingness. We found that alternatives, especially the IPMW method, perform better than the classic LOCF method. Nevertheless, in situations with high marker's variance and rarely recorded measurements none of the examined method adequately corrected the bias.
Luminescent properties and energy transfer in the green phosphors LaBSiO5:Tb3+,Ce3+
Authors: Wang Zhengliang , Cheng Ping , He Pei , Liu Yong , Zhou Yayun , Zhou Qiang
Published: October 2014

LaBSiO5 phosphors doped with Ce3+ and Tb3+ were synthesized using the conventional solid‐state method at 1100 °C. The phase purity and luminescent properties of these phosphors are investigated. LaBSiO5:Tb3+ phosphors show intense green emission, and LaBSiO5 phosphors doped with Ce3+ show blue–violet emission under UV light excitation. LaBSiO5 phosphors co‐doped with Ce3+ and Tb3+ exhibit blue–violet and green emission under excitation by UV light. The blue–violet emission is due to the 5d–4f transition of Ce3+ and the green emission is ascribed to the 5D4 → 7 F5 transition of Tb3+. The spectral overlap between the excitation band of Tb3+ and the emission band of Ce3+ supports the occurrence of energy transfer from Ce3+ to Tb3+, and the energy transfer process was investigated. Copyright © 2014 John Wiley & Sons, Ltd.
Universal probe amplification: Multiplex screening technologies for genetic variations
Authors: Park Jung Hun , Park Ki Soo , Lee Kyungmee , Jang Hyowon , Park Hyun Gyu
Published: October 2014

In order to achieve multiplex screening of genetic variations, multiplex amplification of target genomic DNA is necessary. Universal amplification technology meets this requirement by simultaneously amplifying a number of different regions within the target genomic DNA using a single pair of universal primers and thus eliminating the limitations associated with the use of multiple pairs of primers. We comprehensively review universal probe amplification and its use with multiplex technologies for the identification of the most representative genetic variation, i. e. single nucleotide polymorphisms. The progress and key issues relating to universal probe amplification are discussed and the representative technologies are summarized with an emphasis on their application for the identification of susceptibility to human diseases.
Randomized clinical trial of the impact of surgical ward-care checklists on postoperative care in a simulated environment
Authors: Pucher P H , Aggarwal R , Qurashi M , Singh P , Darzi A
Published: October 2014

Background

Complications are a common and accepted risk of surgery. Failure to optimize the management of patients who suffer postoperative morbidity may result in poorer surgical outcomes. This study aimed to evaluate a checklist-based tool to improve and standardize care of postoperative complications.

Methods

Surgical trainees conducted baseline ward rounds of three patients with common postoperative complications in a high-fidelity simulated ward environment. Subjects were randomized to intervention or control groups, and final ward rounds were conducted with or without the aid of checklists for management of postoperative complications. Adherence to critical care processes was assessed, in addition to technical (Surgical Ward-care Assessment Tool, SWAT) and non-technical (Ward NOn-TECHnical Skills (W-NOTECHS) scale) performance. Subjects completed a feedback questionnaire regarding their perception of the checklists.

Results

Twenty trainees completed 120 patient assessments. All intervention group subjects opted to use the checklists, resulting in significantly fewer critical errors compared with controls (median (i.q.r.) 0 (0–0) versus 60 (40–73) per cent; P < 0·001). The intervention group demonstrated improved patient management (SWAT-M) (P < 0·001) and non-technical skills (P = 0·043) between baseline and final ward rounds, whereas controls did not (P = 0·571 and P = 0·809 respectively). A small learning effect was seen with improvement in patient assessment (SWAT-A) in both groups (P < 0·001). Intervention group subjects found checklists easy and effective to use, and would want them used for their own care if they were to experience postoperative complications.

Conclusion

Checklist use resulted in significantly improved standardization, evidence-based management of postoperative complications, and quality of ward rounds. Simulation-based piloting aided appropriate use of checklists and staff engagement. Checklists represent a low-cost intervention to reduce rates of failure to rescue and to improve patient care.
Control of Cellular Function by Reversible Photoregulation of Translation
Authors: Ogasawara Shinzi
Published: October 2014

The use of light as an external stimulus offers the potential for spatiotemporal control and is thus ideal for controlling gene expression in living cells. In commonly used caging systems, once the caging compound is removed, protein expression cannot be stopped, due to the irreversibility of the uncaging reaction. We have developed a reversible method for regulating protein expression with the aid of a photoresponsive cap that can control the translation of mRNA in a reversible manner through triggering of cis–trans photoisomerization of the cap. In its trans form, the photoresponsive cap completely inhibited translation, whereas the cis form yielded protein (12.7 times more translated protein than in the trans form). Moreover, we succeeded in controlling the levels, timing and duration of protein expression in living mammalian cells. Additionally, neuronal differentiation of PC12 cells was photoinduced by controlling constitutively active H‐Ras 61L protein expression.
Insights into the Active Species of Nanoparticle‐Functionalized Hierarchical Zeolites in Alkylation Reactions
Authors: Grau‐Atienza Aida , Campos Rafael , Serrano Elena , Ojeda Manuel , Romero Antonio A. , Garcia‐Martinez Javier , Luque Rafael
Published: November 2014

Supported iron oxide nanoparticles have been incorporated onto hierarchical zeolites by microwave‐assisted impregnation and mechanochemical grinding. Nanoparticle‐functionalised porous zeolites were characterised by a number of analytical techniques such as XRD, N2 physisorption, TEM, and surface acidity measurements. The catalytic activities of the synthesised nanomaterials were investigated in an alkylation reaction. The results pointed to different species with varying acidity and accessibility in the materials, which provided essentially different catalytic activities in the alkylation of toluene with benzyl chloride under microwave irradiation, selected as the test reaction.
Application of Cationic Poly(lactic‐co‐glycolic acid) Iron Oxide/Chitosan‐Based Nanocomposite for the Determination of Paraoxon
Authors: Tiwari Ida , Gupta Mandakini , Pandey Chandra Mouli
Published: October 2014

The preparation of stable oleic‐acid‐capped iron‐oxide nanoparticles is reported, which were further coated with cationic poly (d,l‐lactic‐co‐glycolic acid) and chitosan in aqueous media by using a nano‐emulsion technique. The prepared composite was used to modify a glassy carbon electrode and the electrochemical behavior and stability of modified electrode were investigated by using cyclic voltammetry. This platform was then utilized to prepare an electrochemical pesticide biosensor based on the inhibition study of the enzyme acetylcholinesterase. Furthermore, the response characteristics show that this fabricated electrode has a shelf life of about 3–4 months and has good adhesion properties along with homogeneous dispersion at the electrode surface. The linear range and detection limit for paraoxon pesticide detection was found to be 9.55–37.1 nM and 8.91 nM, respectively.
Synergistic Catalysis: Enantioselective Addition of Alkylbenzoxazoles to Enals
Authors: Meazza Marta , Ceban Victor , Pitak Mateusz B. , Coles Simon J. , Rios Ramon
Published: October 2014

A novel catalytic enantioselective methodology based on synergistic catalysis is reported. The strategy involves: 1) the metal‐Lewis‐acid activation of alkylazaarenes, and 2) the secondary‐amine activation of enals. Consequently, highly functionalized chiral alkylazaarenes were obtained in good yields and with reasonable stereoselectivity.
ortho‐Fluoroazobenzenes: Visible Light Switches with Very Long‐Lived Z Isomers
Authors: Knie Christopher , Utecht Manuel , Zhao Fangli , Kulla Hannes , Kovalenko Sergey , Brouwer Albert M. , Saalfrank Peter , Hecht Stefan , Bléger David
Published: October 2014

Improving the photochemical properties of molecular photoswitches is crucial for the development of light‐responsive systems in materials and life sciences. ortho‐Fluoroazobenzenes are a new class of rationally designed photochromic azo compounds with optimized properties, such as the ability to isomerize with visible light only, high photoconversions, and unprecedented robust bistable character. Introducing σ‐electron‐withdrawing F atoms ortho to the NN unit leads to both an effective separation of the n→π* bands of the E and Z isomers, thus offering the possibility of using these two transitions for selectively inducing E/Z isomerizations, and greatly enhanced thermal stability of the Z isomers. Additional para‐electron‐withdrawing groups (EWGs) work in concert with ortho‐F atoms, giving rise to enhanced separation of the n→π* transitions. A comprehensive study of the effect of substitution on the key photochemical properties of ortho‐fluoroazobenzenes is reported herein. In particular, the position, number, and nature of the EWGs have been varied, and the visible light photoconversions, quantum yields of isomerization, and thermal stabilities have been measured and rationalized by DFT calculations.