bluuebunny/crossref_metadata_2025 huggingface dataset:
Transforming a poem
Authors: Cloete T.T.
Published: November 2012

N.P. van Wyk Louw wrote a short poem consisting of only two short verses. Syntactically both verses are incomplete, leaving open spaces at the beginning of verse 1 and at the end of verse 2. This allows the reader to fill in both open spaces in such a way that this single poem can be transformed into two, twenty and even more poems.
Clinical Significance of Alk-1 Gene Abnormalities in Diffuse Large Cell Lymphoma
Authors: Korashy L. , El-Zawahry H. , Abdou S. , Shahin D. , Sherif F. , Farrag W. , Abdel-Khalik O. , Salem H. , El-Sebaaie A.
Published: November 2012

Objectives

To detect relative frequency of anaplastic lymphoma kinase (ALK-1) gene abnormality in diffuse large cell lymphoma (DLCL) using fluorescence in situ hybridization (FISH), and correlate its presence with clinicopathological features which may be useful for choice of therapy and predict survival in newly diagnosed cases.

Patients and Methods

A prospective study was done between March 2004 and October 2009. Fifty patients newly diagnosed with DLCL were enrolled into the study. Immunophenotyping was done and detection of ALK-1 gene abnormalities were carried out by immunohistochemically (IHC) and FISH. Patients that proved to be ALK-1 positive were treated with standard cyclophosphamide –hydroxydaunorubicin-oncovin-prednisone (CHOP) protocol.

Results

All ALK +ve patients achieved complete remission (CR) vs. 93.5% CR and 6.5% partial remission (PR) for ALK –ve patients respectively. Disease free survival (DFS) at 24 months was 81.8% in the CHOP-14 group (ALK-1−) vs. 100% for the CHOP-21 group (ALK-1+). Overall survival (OS) at 30 months was 80.4% in the CHOP-14 group vs. 100% for the CHOP-21 group.
Antioxidant-Enriched Diet Affects Early Microglia Accumulation and Promotes Regeneration of the Striatal Dopamine System after a 6-Hydroxidopamine-Induced Lesion in a Rat
Authors: Rehnmark Anna , Strömberg Ingrid
Published: November 2012

Neuroinflammation is found both in the brain of humans suffering from Parkinson's disease and in animal models of disease. It is suggested to be involved in the pathogenesis of the disease. In the present study, in order to study the effects of antioxidants on neuroinflammation, microglial phenotypes were evaluated in rats fed with diets containing bilberries, blueberries, or crowberries at 1 and 4 weeks following striatal injection of 6-hydroxydopamine. The dopamine innervation was visualized using antibodies raised against tyrosine hydroxlase (TH) in the striatum and in the globus pallidus. One week post-lesion, the expression of Iba1-positive cells, a general microglial marker, was significantly increased in the striatum of all animals fed with antioxidant-enriched diets compared to control-diet fed animals, while the diameter of the TH-negative zone was similar in all animals. At four weeks post-lesion, the Iba1-positive microglia was significantly reduced in animals fed with antioxidant-enriched diets. The diameter of the TH-negative zone was significantly reduced in animals fed bilberry and crowberry. The expression and distribution of ED1-positive cells was similar to that of Iba1-positive cells found in the lesioned areas. A cell division marker Ki67 revealed that few microglia were proliferating in crowberry-treated animals. Otherwise dividing cells were associated with blood capillary cells. Although the antioxidant level should be equal in the entire brain, no regeneration was found in globus pallidus, suggesting the mechanism promoting regeneration in the striatum is not effective in the globus pallidus. In conclusion, diets rich in bilberries and crowberries and with high contents of antioxidants stimulate an early phase of accumulation of reactive migroglia that fades at longer time points i.e. promotes regeneration of the striatal dopamine system.
Observational constraints on entrainment and the entrainment interface layer in stratocumulus
Authors: Carman J. K. , Rossiter D. L. , Khelif D. , Jonsson H. H. , Faloona I. C. , Chuang P. Y.
Published: November 2012

Abstract. Aircraft sampling of the stratocumulus-topped boundary layer (STBL) during the Physics of Stratocumulus Top (POST) experiment was primarily achieved using sawtooth flight patterns, during which the atmospheric layer 100 m above and below cloud top was sampled at a frequency of once every 2 min. The large data set that resulted from each of the 16 flights document the complex structure and variability of this interfacial region in a variety of conditions. In this study, we first describe some properties of the entrainment interface layer (EIL), where strong gradients in turbulent kinetic energy (TKE), potential temperature and moisture can be found. We find that defining the EIL by the first two properties tends to yield similar results, but that moisture can be a misleading tracer of the EIL. These results are consistent with studies using large-eddy simulations. We next utilize the POST data to shed light on and constrain processes relevant to entrainment, a key process in the evolution of the STBL that to-date is not well-represented even by high resolution models. We define "entrainment efficiency" as the ratio of the TKE consumed by entrainment to that generated within the STBL (primarily by cloud-top cooling). We find values for the entrainment efficiency that vary by 1.5 orders of magnitude, which is even greater than the one order magnitude that previous modeling results have suggested. Our analysis also demonstrates that the entrainment efficiency depends on the strength of the stratification of the EIL, but not on the TKE in the cloud top region. The relationships between entrainment efficiency and other STBL parameters serve as novel observational contraints for simulations of entrainment in such systems.
Chemical composition of modern and fossil hippopotamid teeth and implications for paleoenvironmental reconstructions and enamel formation – Part 2: Alkaline earth elements as tracers of watershed hydrochemistry and provenance
Authors: Brügmann G. , Krause J. , Brachert T. C. , Stoll B. , Weis U. , Kullmer O. , Ssemmanda I. , Mertz D. F.
Published: November 2012

Abstract. This study demonstrates that alkaline earth elements in enamel of hippopotamids, in particular Ba and Sr, are tracers for water provenance and hydrochemistry in terrestrial settings. The studied specimens are permanent premolar and molar teeth found in modern and fossil lacustrine sediments of the Western Branch of the East African Rift system (Lake Kikorongo, Lake Albert, and Lake Malawi) and from modern fluvial environments of the Nile River. Concentrations in enamel vary by two orders of magnitude for Ba (120–9336 μg g−1) as well as for Sr (9–2150 μg g−1). The variations are partially induced during post-mortem alteration and during amelogenesis, but the major contribution originates ultimately from the variable water chemistry in the habitats of the hippopotamids which is controlled by the lithologies and weathering processes in the watershed areas. Amelogenesis causes a distinct distribution of MgO, Ba and Sr in modern and fossil enamel, in that element concentrations increase along profiles from the outer rim towards the enamel–dentin junction by a factor of 1.3–1.9. These elements are well correlated in single specimens, thus suggesting that their distribution is determined by a common, single process, which can be described by closed system Rayleigh crystallization of bioapatite in vivo. Enamel from most hippopotamid specimens has Sr/Ca and Ba/Ca which are typical for herbivores. However, Ba/Sr ranges from 0.1 to 3 and varies on spatial and temporal scales. Thus, Sr concentrations and Ba/Sr in enamel differentiate between habitats having basaltic mantle rocks or Archean crustal rocks as the ultimate sources of Sr and Ba. This provenance signal is modulated by climate change. In Miocene to Pleistocene enamel from the Lake Albert region, Ba/Sr decreases systematically with time from 2 to 0.5. This trend can be correlated with changes in climate from humid to arid, in vegetation from C3 to C4 biomass as well as with increasing evaporation of the lake water. The most plausible explanation is that Ba mobility decreased with increasing aridification due to preferential deposition with clay and Fe-oxide-hydroxide or barite on the watershed of Lake Albert.
Changes in column inventories of carbon and oxygen in the Atlantic Ocean
Authors: Tanhua T. , Keeling R. F.
Published: November 2012

Abstract. Increasing concentrations of dissolved inorganic carbon (DIC) in the interior ocean are expected as a direct consequence of increasing concentrations of CO2 in the atmosphere. This extra DIC is often referred to as anthropogenic carbon (Cant), and its inventory, or increase rate, in the interior ocean has previously been estimated by a multitude of observational approaches. Each of these methods is associated with hard to test assumptions since Cant cannot be directly observed. Results from a simpler concept with fewer assumptions applied to the Atlantic Ocean are reported on here using two large data collections of carbon relevant bottle data. The change in column inventory on decadal time scales, i.e. the storage rate, of DIC, respiration compensated DIC and oxygen is calculated for the Atlantic Ocean. We report storage rates and the confidence intervals of the mean trend at the 95% level (CI), reflecting the mean trend but not considering potential biasing effects of the spatial and temporal sampling. For the whole Atlantic Ocean the mean trends for DIC and oxygen are non-zero at the 95% confidence level: DIC: 0.86 (CI: 0.72–1.00) and oxygen: −0.24 (CI: −0.41–(−0.07)) mol m−2 yr−1. For oxygen, the whole Atlantic trend is dominated by the subpolar North Atlantic, whereas for other regions the O2 trends are not significant. The storage rates are similar to changes found by other studies, although with large uncertainty. For the subpolar North Atlantic the storage rates show significant temporal and regional variation of all variables. This seems to be due to variations in the prevalence of subsurface water masses with different DIC and oxygen concentrations leading to sometimes different signs of storage rates for DIC compared to published Cant estimates. This study suggest that accurate assessment of the uptake of CO2 by the oceans will require accounting not only for processes that influence Cant but also additional processes that modify CO2 storage.
Phytoplankton distribution in unusually low sea ice cover over the Pacific Arctic
Authors: Coupel P. , Jin H. Y. , Joo M. , Horner R. , Bouvet H. A. , Sicre M.-A. , Gascard J.-C. , Chen J. F. , Garçon V. , Ruiz-Pino D.
Published: November 2012

Abstract. A large part of the Pacific Arctic basin experiences ice-free conditions in summer as a result of sea ice cover steadily decreasing over the last decades. To evaluate the impact of sea ice retreat on the marine ecosystem, phytoplankton in situ observations were acquired over the Chukchi shelf and the Canadian basin in 2008, a year of high melting. Pigment analyses and taxonomy enumerations were used to characterise the distribution of main phytoplanktonic groups. Marked spatial variability of the phytoplankton distribution was observed in summer 2008. Comparison of eight phytoplankton functional groups and 3 size-classes (pico-, nano- and micro-phytoplankton) also showed significant differences in abundance, biomass and distribution between summer of low ice cover (2008) and heavy ice summer (1994). Environmental parameters such as freshening, stratification, light and nutrient availability are discussed as possible causes to explain the observed differences in phytoplankton community structure between 1994 and 2008.
Quantifying the role of fire in the Earth system – Part 1: Improved global fire modeling in the Community Earth System Model (CESM1)
Authors: Li F. , Levis S. , Ward D. S.
Published: November 2012

Abstract. Modeling fire as an integral part of an Earth system model (ESM) is vital for quantifying and understanding fire-climate-vegetation interactions on a global scale and from an Earth system perspective. In this study, we introduce to the Community Earth System Model (CESM) the new global fire parameterization proposed by Li et al. (2012), now with a more realistic representation of the anthropogenic impacts on fires, with a parameterization of peat fires, and with other minor modifications. The improved representation of the anthropogenic dimension includes the first attempt to parameterize agricultural fires, the economic influence on fire occurrence, and the socioeconomic influence on fire spread in a global fire model; also an alternative scheme for deforestation fires. The global fire parameterization has been tested in CESM1's land component model CLM4 in a 1850–2004 transient simulation, and evaluated against the satellite-based Global Fire Emission Database version 3 (GFED3) for 1997–2004. The simulated 1997–2004 average global totals for the burned area and fire carbon emissions in the new fire scheme are 338 Mha yr−1 and 2.1 Pg C yr−1. Its simulations on multi-year average burned area, fire seasonality, fire interannual variability, and fire carbon emissions are reasonable, and show better agreement with GFED3 than the current fire scheme in CESM1 and modified CTEM-FIRE. Moreover, the new fire scheme also estimates the contributions of global fire carbon emissions from different sources. During 1997–2004, the contributions are 8% from agricultural biomass burning, 27% from tropical deforestation and degradation fires, 5% from global peat fires (3.7% from tropical peat fires), and 60% from other fires, which are close to previous assessments based on satellite data, government statistics, or other information sources. In addition, we investigate the importance of direct anthropogenic influence (anthropogenic ignitions and fire suppression) on global fire regimes during 1850–2004, using CESM1 with the new fire scheme. Results show that the direct anthropogenic impact is the main factor driving the trends of global burned area in the whole period and fire carbon emissions only before ~ 1870.
MAREDAT: towards a World Ocean Atlas of MARine Ecosystem DATa
Authors: Buitenhuis E. T. , Vogt M. , Moriarty R. , Bednaršek N. , Doney S. C. , Leblanc K. , Le Quéré C. , Luo Y.-W. , O'Brien C. , O'Brien T. , Peloquin J. , Schiebel R. , Swan C.
Published: November 2012

Abstract. We present a summary of biomass data for 11 Plankton Functional Types (PFTs) plus phytoplankton pigment data, compiled as part of the MARine Ecosystem biomass DATa (MAREDAT) initiative. The goal of the MAREDAT initiative is to provide global gridded data products with coverage of all biological components of the global ocean ecosystem. This special issue is the first step towards achieving this. The PFTs presented here include picophytoplankton, diazotrophs, coccolithophores, Phaeocystis, diatoms, picoheterotrophs, microzooplankton, foraminifers, mesozooplankton, pteropods and macrozooplankton. All variables have been gridded onto a World Ocean Atlas (WOA) grid (1° × 1° × 33 vertical levels × monthly climatologies). The data show that (1) the global total heterotrophic biomass (2.0–6.4 Pg C) is at least as high as the total autotrophic biomass (0.5–2.6 Pg C excluding nanophytoplankton and autotrophic dinoflagellates), (2) the biomass of zooplankton calcifiers (0.9–2.3 Pg C) is substantially higher than that of coccolithophores (0.01–0.14 Pg C), (3) patchiness of biomass distribution increases with organism size, and (4) although zooplankton biomass measurements below 200 m are rare, the limited measurements available suggest that Bacteria and Archaea are not the only heterotrophs in the deep sea. More data will be needed to characterize ocean ecosystem functioning and associated biogeochemistry in the Southern Hemisphere and below 200 m. Microzooplankton database: doi:10.1594/PANGAEA.779970.
On the contribution of groundwater storage to interannual streamflow anomalies in the Colorado River basin
Authors: Rosenberg E. A. , Clark E. A. , Steinemann A. C. , Lettenmaier D. P.
Published: November 2012

Abstract. We assess the significance of groundwater storage for seasonal streamflow forecasts by evaluating its contribution to interannual streamflow anomalies in the 29 tributary sub-basins of the Colorado River. Monthly and annual changes in total basin storage are simulated by two implementations of the Variable Infiltration Capacity (VIC) macroscale hydrology model – the standard release of the model, and an alternate version that has been modified to include the SIMple Groundwater Model (SIMGM), which represents an unconfined aquifer underlying the soil column. These estimates are compared to those resulting from basin-scale water balances derived exclusively from observational data and changes in terrestrial water storage from the Gravity Recovery and Climate Experiment (GRACE) satellites. Changes in simulated groundwater storage are then compared to those derived via baseflow recession analysis for 72 reference-quality watersheds. Finally, estimates are statistically analyzed for relationships to interannual streamflow anomalies, and predictive capacities are compared across storage terms. We find that both model simulations result in similar estimates of total basin storage change, that these estimates compare favorably with those obtained from basin-scale water balances and GRACE data, and that baseflow recession analyses are consistent with simulated changes in groundwater storage. Statistical analyses reveal essentially no relationship between groundwater storage and interannual streamflow anomalies, suggesting that operational seasonal streamflow forecasts, which do not account for groundwater conditions implicitly or explicitly, are likely not detrimentally affected by this omission in the Colorado River basin.
Treatment of Macular Serous Neuroretinal Detachment in Tilted Disk Syndrome: Report of 3 Cases
Authors: Donati Maria Carla , Miele Alba , Abbruzzese Giacomo , Giuntoli Matteo , Giansanti Fabrizio , Menchini Ugo
Published: November 2012

Purpose.

To describe functional and anatomic results obtained by treatment with photodynamic therapy (PDT) or intravitreal bevacizumab (Avastin, Roche) in macular serous retinal detachment associated with tilted disk syndrome.

Methods.

Three eyes of 3 patients with symptomatic macular serous detachment associated with tilted disc syndrome (optic disc with an oblique axis, inferonasal crescent, and inferior staphyloma) were treated. In all patients, best-corrected visual acuity (BCVA) was tested and fluorescein angiography (FA) and optical coherence tomography (OCT) were performed before and about 45 days after treatment. All patients underwent a complete ophthalmologic examination including OCT at least 6 months after treatment. The first patient was treated with one low fluence (300 mW/cm2 for 83 seconds) PDT (6 months follow-up). The second patient was treated with 3 intravitreal injections of bevacizumab 1.25 mg (33 months follow-up) and the third patient was treated with 2 low fluence PDTs at 4 months and, after 1 year, 3 intravitreal injections of bevacizumab 1.25 mg (37 months follow-up).

Results.

Before treatment, all patients complained of visual loss and metamorphopsia. The OCT showed in the macular area a focal neurosensory detachment with foveal involvement. The FA showed in the macular area multiple focal areas of hyperfluorescence due to pigment epithelium atrophy and in the second and third patient also a hyperfluorescent pinpoint with minimal leakage. After treatment in all eyes, symptoms did not change, BCVA remained stable, and in OCT the foveal neuroretinal detachment was changeless. In FA, no noticeable variation of the hyperfluorescence areas was appreciated. In the second patient, the hyperfluorescent point remained unvaried, and the same occurred in the third patient after the first PDT, while after the second PDT a new leaking dot disappeared.

Conclusions.

Macular serous retinal detachment was first described in 1998 as an uncommon complication of tilted disc syndrome showing angiographic and OCT features similar to a chronic central serous chorioretinopathy. In contrast to this pathology, in our patients treatment with PDT or intravitreal bevacizumab did not succeed, probably because of a different pathogenesis of macular serous detachment. Further investigations are needed to clarify the proper therapy of this disease.
Safety and efficacy of fixed‐dose combination rilpivirine‐tenofovir‐emtricitabine (RPV/TDF/FTC) in treatment‐experienced patients infected with HIV‐1
Authors: Cevik M , Sonecha S , Nelson M
Published: November 2012

Purpose of the study

Rilpivirine (RPV) is a new non‐nucleoside reverse transcriptase inhibitor (NNRTI) which has shown non‐inferiority to efavirenz (EFV) in terms of efficacy and safety profiles. The vast majority of clinical data has been performed in the treatment naïve population and has not been studied in depth in treatment‐experienced patients. We sought to explore the safety and efficacy of RPV/TDF/FTC in treatment‐experienced patients attending our clinics.

Methods

HIV‐infected individuals commenced on RPV/TDF/FTC from December 2011 to June 2012 were retrospectively identified from a patient database. Patient demographics were extracted. Biochemical, virological and immunological parameters were collated. At baseline, 1 month and 3 month time points the following laboratory results were compared using the Kruskal‐Wallis test: CD4 count, HIV viral load, amino transferase (ALT), cholesterol, triglyceride and HDL/cholesterol ratio.

Summary of results

Sixty‐five patients (4 female) were identified. Median age was 38 years (range: 25–73). Fifty‐six patients were treatment experienced (2 re‐start); 39 on NNRTI‐based (33 on EFV), 10 on PI‐based and 4 on other regimens. 9 patients were naïve to treatment. The reasons for switch are illustrated in Fig. 1.

 Fifty‐four patients had HIV‐RNA‐1<40 copies/mL at the time of switch and all remained undetectable at 3 months. At baseline, the median CD4 count was 555 cells/mm3 (range: 209–1586) in the switch group, which increased significantly to 638 cells/mm3 (p<0.005) 3 months after switch. Switch to RPV/TDF/FTC had a favorable effect on lipid profile. At baseline the median cholesterol, triglyceride and HDL/cholesterol ratio levels were 4.8 mmol/L, 1.78 mmol/L and 4.37 respectively. At 1 month post‐switch this decreased to 4.5 mmol/L, 1.65 mmol/L and 4.24 and at 3 months post‐switch decreased to 4.1 mmol/L, 1.44 mmol/L and 4.04. Median HIV‐RNA‐1 in treatment‐naïve patients (n=9) at baseline was 50298 copies/mL, at 1 month four patients had HIV‐RNA‐1<40 copies/mL and at 3 months eight patients had HIV‐RNA‐1<40 copies/mL. RPV/TDF/FTC had no favourable effect on lipid profile in treatment‐naïve group and had no effect on ALT levels in either the switch or the treatment‐naïve group.

Conclusion

In this cohort, RPV/TDF/FTC has been shown to have a safe virological efficacy and safety profile as a switch therapy for patients suppressed on their current standard of care and are experiencing adverse events.

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Durability of lopinavir/r monotherapy in people with viral load ≤50 copies/Ml
Authors: d'Arminio Monforte A , Cozzi‐Lepri A , Andreoni M , di Perri G , Galli M , Poli A , Costantini A , Maggiolo F , Viscoli C , Sighinolfi L , Rizzardini G , Bonfanti P , Gianotti N , Perno C , Antinori A
Published: November 2012

There is debate about whether lopinavir/r mono‐therapy (LPV/r‐MT) is a valid treatment option for HIV‐infected patients who have shown perfect adherence to therapy. The objective was to evaluate the durability of LPV/r‐MT in terms of time to virological rebound (VR), time to discontinuation/intensification or a composite endpoint considering both (=treatment failure). We also identified factors associated with faster progression to treatment failure and estimated the median CD4 count over time while people were still on LPV/r‐MT. Patients enrolled in 10 clinical sites in Italy who ever started LPV/r‐MT with a viral load ≤50 copies/mL (baseline) are included. Patients’ follow‐up accrued from baseline to the date of the event of interest (VR, defined using the thresholds of 50 and 200 copies/mL, or discontinuation/intensification) or at the date of last available visit/VL measurement. Standard survival analysis employing Kaplan‐Meier curves was used. We studied 139 patients starting LPV/r‐MT on average in 2010 (IQR: 2009–2011) with a VL≤50 copies/mL already for a median of 1 month (range: 1–17). Median age 45 years (IQR: 39–50), 35% females, 32% IDU. Median time from first initiation of ART was 33 months (16–58) with no history of virological failure. Median (IQR) marker values at baseline were 611 (432–741) CD4 count cells/mm3, 937 (655–1254) CD8 count and 28 (19–47) IU/L of ALT. Median CD4 count were 519 cells/mm3 at 3 months, 660 at 6 months, 603 at 9 months and 467 at 12 months. The table shows the Kaplan‐Meier estimates by 1 year and 2 years for a number of endpoints examined. There was a wide range of estimates depending on the endpoint used. Of those stopping/intensifying, 6 people (4%) added Truvada (n=4), Kivexa (n=1) and darunavir (n=1), the remaining 8 restarted cART.

1 year
2 years

End point
No. events
Point estimate
95% CI
Point estimate
95% CI

Stop/ intensification
14
4.6%
0.7–8.5
14.0%
6.2–21.8

Single VL>50
32
19.3%
11.1–26.8
29.7%
19.2–38.8

Confirmed VL>50
8
5.7%
1.8–9.6
7.4%
1.5–13.3

Single VL>200
10
7.5%
1.6–13.4
11.1%
3.2–18.8

Single VL>200 or stop / intensification
18
10.5%
4.6–16.4
19.1%
9.2–28.8

In our ‘real‐life’ setting, by 2 years of starting LPV/r‐MT, 70% of patients remained persistently suppressed ≤50 copies/mL. This percentage was >80% when considering only confirmed virological failures while people still remaining on the drug. Our results, though lacking precision because of the small number of events, are consistent with those of recent clinical trials.
Lamivudine plus a boosted‐protease inhibitor as simplification strategy in HIV‐infected patients with toxicity to nucleoside analogues
Authors: Casado J , De la Calle C , Del Palacio M , Bañon S , Pérez Elías M , Moreno A , Moreno S
Published: November 2012

Purpose of the study

Dual therapy with lamivudine plus a PI boosted with ritonavir (PI/r) could be an alternative to standard triple therapy or PI/r monotherapy as a simplification strategy in patients with toxicity to nucleoside analogues (NA).

Methods

Retrospective cohort study of 44 HIV‐infected patients on suppressive HAART, with no chronic HBV, who simplified to this dual therapy since 2008. Virological and immunological outcome, lipids and renal changes were evaluated.

Summary of results

Mean age was 50 years (38‐70), 66% were male, and the median time of HIV infection was 18.6 years. The median nadir CD4+ count was 150 cells/ml (2–407). At inclusion, patients were receiving therapy with lamivudine plus atazanavir/r in 5 cases, lopinavir/r in 12, and darunavir/r in 27, and they had an HIV RNA level<50 copies/ml for a median time of 794 days (129–2344, 90% >6 months). The NA discontinued was tenofovir (27), didanosine (12), AZT (3), and d4T (2). The reasons for changing were toxicity in 76% of cases, especially renal impairment. They had received a mean of 8 regimens before (2–20), and 55% were in CDC‐stage C. In 11 cases, history of resistance was available (to NA in 7 cases, including the 210W mutation in four). The mutations 184V was not observed, but four patients (9%) had a previous failure to therapy including 3tC. Mutations in the protease gene were observed in 8 patients (2 to 7 mutations, the most frequent 77I and 93L), without resistance to the current PI/r. During 62.8 patient‐years of follow‐up (median, 802 days), only 2 patients failed (4.5%), due to incomplete adherence, at 27 and 141 days. Of note, these two patients had no previous failed with 3tC or PI. Overall, CD4+ count increased for 55 cells/ml. No new adverse events were observed, but total cholesterol (from 180 to 246 mg/dl, p=0.007) and triglycerides (from 166 to 195, p=0.01) increased during the first 24 weeks with improvement at 48 weeks. On the other hand, estimated glomerular filtration rate improved during follow up (from 74.2 ml/min to 83.08 ml/min after 48 weeks, p=0.1).

Conclusions

Dual therapy with lamivudine plus a boosted PI is safe and effective as simplification strategy in patients with toxicity to NA. This combination could be an alternative to mono or triple therapy in hard to treat patients, although an initial increase in lipid parameters could be observed.
Effectiveness and safety of a single‐tablet regimen of emtricitabine/efavirenz/tenofovir in HIV‐1‐infected patients in infectious diseases department
Authors: Xerinda S , Neves N , Santos S , Piñeiro C , Poínhos R , Soares J , Serrão R , Sarmento A
Published: November 2012

Objective

Evaluate the effectiveness and safety of simplification of tenofovir/emtricitabine/efavirenz (TDF/FTC/EFV) in selected treatment‐experienced HIV‐1‐infected patients who have been virologically suppressed for>3 months on their current regimen.

Methods

We selected patients who started the simplified regimen between December 1st 2008 and March 31st 2012. Exclusion criteria: prior therapeutic failure, presence of resistance mutations to any component of TDF/FTC/EFV and patients previously observed in other centers. Efficacy and safety assessments were performed at baseline, 4 weeks after switch and then every 12–24 weeks. Statistical analysis was performed with SPSS version 20.0.

Results

384 patients were evaluated; 302 (79%) male; mean age 47 (SD=10) years; median CD4 cells count was 504 cells/mm3 (367–710). Baseline median glomerular filtration rate (eGFR; Cockcroft‐Gault equation) was 100 mL/min (86–116) and median ALT was 33 U/L (21–47). Median total cholesterol (TC) was 205 mg/dL (176‐236), high‐density lipoproteins (HDL) 45 mg/dL (38–54); low‐density lipoproteins (LDL) 130 mg/dL (108–151); triglycerides (TG) 125 mg/dL (84–176). Prior NNRTI‐based regimen in 327 (85%) patients (TDF/FTC and EFV in 76%); protease inhibitor in 52 (14%) and integrase inhibitor in 5 (1%). Discontinuation of treatment occurred in 49 patients (13%) after a mean time of 1.1 years (SD=1.1) of follow‐up: nervous system symptoms (n=11), decreased eGFR (n=5), virological failure (n=5), pregnancy (n=5), gastrointestinal symptoms (n=3), rash (n=1), other reasons (n=2); 12 patients dropped out the treatment and 5 died. Occurrence of blips (transient increase in VL ≤200 copies/mL) was documented in 98 (26%) patients; in 70, VL decreased to <20 copies/mL after the blips and in 28 VL is not yet available. 317 patients (83%) achieved≥48 weeks of follow‐up after simplification. Compared with baseline, significantly higher levels of CD4 cells count, HDL and eGFR were found and lower levels of TC, LDL and TG.

CD4
AST
ALT
TC
HDL
LDL
TG
eGFR

Baseline

Median
501
27
32
203
46
130
123
100

Percentiles 25
358
22
22
174
39
108
84
85

Percentiles 75
712
36
45
236
54
151
179
113

Follow‐up

Median
541
28
32
196
49
123
115
111

Percentiles 25
397
22
22
174
41
101
80
96

Percentiles 75
734
36
46
223
57
141
155
133

p‐value
<0.001
0.395
0.513
<0.001
<0.001
<0.001
<0.001
<0.001

Conclusion

Simplification to TDF/FTC/EFV was shown to be an efficient and safe option in virologically suppressed patients and without a previous virological failure.
Intensification with maraviroc in HIV‐infected individuals (with or without liver cirrhosis) with a discordant CD4 response to cART
Authors: Blanco J , Guardo A , González‐Cordón A , Pérez I , Mallolas J , Martinez E , Arberas H , Laguno M , Martinez‐Rebollart M , Lonca M , Gatell J , Plana M
Published: November 2012

Background

Patients with a discordant response to cART, defined as persistent CD4 + T‐cell counts <200 cells/mm3 and lack CD4 increase despite virologic suppression on HAART, have an increased risk of morbidity and mortality. Several studies have suggested a potential benefit of intensification with maraviroc (MVC) on CD4+T‐cell recovery.

Methods

A 24‐week prospective, open‐label, randomized, controlled study. Subjects on cART, plasma HIV RNA <37 copies/mL for at least 12 months, and CD4 < 200 cells/L, with CD4‐gain in the previous 12 months <50 cells/µL, were randomized to add MVC (A) or continuing same cART (B). Randomisation was stratified by the presence of liver cirrhosis (CH) (n = 10) and non‐CH (n = 28). We measured by flow cytometry changes in the following parameters of CD4 + and CD8 + T‐cell subsets: activation (CD38, HLA‐DR), senescence (CD28, CD57, CD45RA and RO), coreceptors (CCR5 and CXCR4) and apoptosis (Annexin‐V).

Results

Thirty‐eight subjects were included at the final analysis. Median values were: age 51 years (IQR, 44–57), time with VL < 37 copies/mL before entry 43 months (IQR 24–62 months), baseline CD4 + T‐cell count 144 cells/µL (IQR 106–181). Four subjects were lost of follow‐up (3 in A, 1 in B). One subject from group B experienced confirmed virologic failure at week 24. Adverse events were similar in both arms. Median increase in CD4 + T‐cell count from baseline to weeks 2,4 and 24 in both groups were +15.5 vs ‐1 (p = 0.025); +16.5 vs ‐2.5 (p = 0.158); +46.5 vs + 6.50 (p = 0.190). Similar trend towards a higher CD4 increase were seen in both CH and non‐CH individuals. At W24, 8 subjects from arm A vs 1 subject from arm B achieved a CD4 + T‐cell count above 200 cells/µL (p < 0.05). Markers of immune activation (CD38 and HLA‐DR) decreased during MVC intensification, especially in CD8+ T cells (p < 0.01) whereas apoptosis did not. Additionally CCR5 expression tended to increase (p = 0.051) in CD8 T cells from arm A subjects. No significant differences were found in the immunological assay between cirrhotic and non cirrhotic individuals.

Conclusions

MVC intensification was safe and was associated with a significant a trend towards increasing CD4 + T‐cell counts both in cirrhotic as well as non‐cirrhotic patients with discordant response. The addition of MVC was associated with a decrease in markers of immune activation in both groups.
An improved finite frequency approach to robust filter design for LTI systems with polytopic uncertainties
Authors: Lee Dong Hwan
Published: November 2012

In this paper, the finite frequency robust filtering problem (‐FFRFP), design of a robust filter minimizing the norm from the disturbance input to the estimation error evaluated over a prescribed finite frequency domain, is considered for continuous‐time and discrete‐time linear time‐invariant (LTI) systems with polytopic parameter uncertainties. By means of the generalized Kalman–Yakubovich–Popov (KYP) lemma in combination with a result known as Finsler's lemma, the ‐FFRFP is cast as a linear matrix inequality (LMI) optimization. Examples are given to demonstrate that the proposed condition can achieve improvement over the previous ones in the literature. Copyright © 2012 John Wiley & Sons, Ltd.
Effects of Confinement on Microstructure and Charge Transport in High Performance Semicrystalline Polymer Semiconductors
Authors: Himmelberger Scott , Dacuña Javier , Rivnay Jonathan , Jimison Leslie H. , McCarthy‐Ward Thomas , Heeney Martin , McCulloch Iain , Toney Michael F. , Salleo Alberto
Published: November 2012

The film thickness of one of the most crystalline and highest performing polymer semiconductors, poly(2,5‐bis(3‐tetradecylthiophen‐2‐yl)thieno[3,2‐b]thiophene) (PBTTT), is varied in order to determine the effects of interfaces and confinement on the microstructure and performance in organic field effect transistors (OFETs). Crystalline texture and overall film crystallinity are found to depend strongly on film thickness and thermal processing. The angular distribution of crystallites narrows upon both a decrease in film thickness and thermal annealing. These changes in the film microstructure are paired with thin‐film transistor characterization and shown to be directly correlated with variations in charge carrier mobility. Charge transport is shown to be governed by film crystallinity in films below 20 nm and by crystalline orientation for thicker films. An optimal thickness is found for PBTTT at which the mobility is maximized in unannealed films and where mobility reaches a plateau at its highest value for annealed films.
On being a neurologist in industry
Authors: Leppert David , Glanzman Robert
Published: November 2012

Neurologists in the pharmaceutical industry have an attractive and rewarding career path that offers the chance to participate in large projects, contribute directly to clinical breakthroughs in drug development, and translate biomarker research into applied practice. This article describes the different and common features of corporate compared to academic environments, and highlights the key factors necessary for success in the business world. Integrity, communication skills, an open‐minded attitude, and an ability to handle stress and manage complex organizational structures are prerequisites that enable physician–neuroscientists to pursue successful and exciting careers in the corporate environment. ANN NEUROL 2013;73:319–326
Reduced microglial CX3CR1 expression delays neurofibromatosis‐1 glioma formation
Authors: Pong Winnie W. , Higer Samantha B. , Gianino Scott M. , Emnett Ryan J. , Gutmann David H.
Published: November 2012

Although traditional models of carcinogenesis have largely focused on neoplastic cells, converging data have revealed the importance of non‐neoplastic stromal cells in influencing tumor growth and progression. Leveraging a genetically engineered mouse model of neurofibromatosis type 1 (NF1)‐associated optic glioma, we now demonstrate that stromal microglia express the CX3CR1 chemokine receptor, such that reduced CX3CR1 expression decreases optic nerve microglia. Moreover, genetic reduction of Cx3cr1 expression in Nf1 optic glioma mice delays optic glioma formation. Coupled with previous findings demonstrating that microglia maintain optic glioma growth, these new findings provide a strong preclinical rationale for the development of future stroma‐directed glioma therapies in children. ANN NEUROL 2013;73:303–308
Tröpfchen‐Mikrofluidik für die Einzelzellanalyse
Authors: Joensson Haakan N. , Andersson Svahn Helene
Published: November 2012

Die tröpfchenbasierte Mikrofluidik dient der Isolierung und Manipulation von einzelnen Zellen und Reagentien innerhalb von monodispersen, pikolitergroßen Flüssigkapseln bei einem Umsatz von tausenden Tröpfchen pro Sekunde. Diese Qualitäten machen die Tröpfchen‐Mikrofluidik geeignet für viele Anforderungen der Einzelzellanalyse. Durch die Monodispersität lässt sich die Konzentration in den Tröpfchen quantitativ einstellen. Die Tröpfchen bieten der Zelle und ihrer unmittelbaren Umgebung ein isoliertes Kompartiment, und bei einem Durchsatz von tausenden Tröpfchen pro Sekunde ist es möglich, zehntausende bis millionen verkapselte Zellen zu prozessieren. Heterogene Zellpopulationen lassen sich somit exakt beschreiben oder seltene Zellarten identifizieren. Das kleine Volumen der Tröpfchen macht auch sehr große Screenings ökonomisch machbar. Dieser Aufsatz gibt einen Überblick über den aktuellen Stand der Einzelzellanalyse durch die Tröpfchen‐Mikrofluidik und nennt Beispiele, bei denen sie biologische Vorgänge besser verstehen hilft.
Droplet Microfluidics—A Tool for Single‐Cell Analysis
Authors: Joensson Haakan N. , Andersson Svahn Helene
Published: November 2012

Droplet microfluidics allows the isolation of single cells and reagents in monodisperse picoliter liquid capsules and manipulations at a throughput of thousands of droplets per second. These qualities allow many of the challenges in single‐cell analysis to be overcome. Monodispersity enables quantitative control of solute concentrations, while encapsulation in droplets provides an isolated compartment for the single cell and its immediate environment. The high throughput allows the processing and analysis of the tens of thousands to millions of cells that must be analyzed to accurately describe a heterogeneous cell population so as to find rare cell types or access sufficient biological space to find hits in a directed evolution experiment. The low volumes of the droplets make very large screens economically viable. This Review gives an overview of the current state of single‐cell analysis involving droplet microfluidics and offers examples where droplet microfluidics can further biological understanding.
Flow‐injection chemiluminescence determination of diazepam by oxidation with N‐bromosuccinimide
Authors: Han Suqin , Jia Shize , Guo Liang
Published: November 2012

A rapid and sensitive flow‐injection chemiluminescence (FI–CL) method is described for the determination of diazepam based on its reaction with N‐bromosuccinimide (NBS) in alkaline medium in the presence of dichlorofluorescein (DCF) as an effective energy‐transfer agent. Under optimum conditions, the proposed method allowed the measurement of diazepam over the range of 2.0 × 10−6 to 2.0 × 10−4 mol/L with a detection limit of 5.0 × 10−7 mol/L. The relative standard deviation for 11 parallel measurements of 2.0 × 10−5 mol/L diazepam was 2.1%. The method was applied satisfactorily for the determination of diazepam in pharmaceutical preparations, and the results agree well with those obtained by spectrophotometry. The use of the proposed system for the determination of diazepam in urine and plasma samples was also tested. The possible mechanism of the chemiluminescence reaction is discussed briefly. Copyright © 2012 John Wiley & Sons, Ltd.
Randomized clinical trial of trigger point infiltration with lidocaine to diagnose anterior cutaneous nerve entrapment syndrome
Authors: Boelens O B A , Scheltinga M R , Houterman S , Roumen R M
Published: November 2012

Background

Anterior cutaneous nerve entrapment syndrome (ACNES) is hardly considered in the differential diagnosis of chronic abdominal pain. Some even doubt the existence of such a syndrome and attribute reported successful treatment results to a placebo effect. The objective was to clarify the role of local anaesthetic injection in diagnosing ACNES. The hypothesis was that pain attenuation following lidocaine injection would be greater than that after saline injection.

Methods

Patients aged over 18 years with suspected ACNES were randomized to receive an injection of 10 ml 1 per cent lidocaine or saline into the point of maximal abdominal wall pain just beneath the anterior fascia of the rectus abdominis muscle. Pain was recorded using a visual analogue scale (VAS; 1–100 mm) and a verbal rating scale (VRS; 0, no pain; 4, severe pain) during physical examination just before and 15–20 min after injection. A reduction of at least 50 per cent on the VAS and/or 2 points on the VRS was considered a successful response.

Results

Between August 2008 and December 2010, 48 patients were randomized equally (7 men and 41 women, median age 47 years). Four patients in the saline group reported a successful response compared with 13 in the lidocaine group (P = 0·007).

Conclusion

Entrapped branches of intercostal nerves may contribute to the clinical picture in some patients with chronic abdominal pain. Pain reduction following local infiltration in these patients was based on an anaesthetic mechanism and not on a placebo or a mechanical (volume) effect. Registration number: NTR2016 (Nederlands Trial Register; http://www.trialregister.nl).
Recurrence pattern in patients with a pathologically complete response after neoadjuvant chemoradiotherapy and surgery for oesophageal cancer
Authors: van Hagen P , Wijnhoven B P L , Nafteux P , Moons J , Haustermans K , De Hertogh G , van Lanschot J J B , Lerut T
Published: November 2012

Background

Little is known about recurrence patterns in patients with a pathologically complete response (pCR) or an incomplete response after neoadjuvant chemoradiotherapy (CRT) followed by resection for oesophageal cancer. This study was performed to determine the pattern of recurrence in patients with a pCR after neoadjuvant CRT followed by surgery.

Methods

All patients who received neoadjuvant CRT followed by oesophagectomy between 1993 and 2009 were identified from a database, and categorized according to pathological tumour response. Recurrences were classified as locoregional or distant.

Results

One hundred and eighty-eight patients were included. Median potential follow-up was 71·6 months. A pCR was achieved in 62 (33·0 per cent) of 188 patients. Recurrence developed in 24 (39 per cent) of 62 patients with a pCR and 70 (55·6 per cent) of 126 without a pCR (P = 0·044). Locoregional recurrence with or without synchronous distant metastases occurred in eight patients (13 per cent) in the pCR group and 31 (24·6 per cent) in the non-pCR group (P = 0·095). Locoregional recurrences without synchronous distant metastases occurred four (6 per cent) and ten (7·9 per cent) patients respectively (P = 0·945). The overall 5-year survival rate was significantly higher in the pCR group than in the non-pCR group (52 versus 33·9 per cent respectively; P = 0·019).

Conclusion

Of patients with a pCR, 13 per cent still developed a locoregional recurrence. Although pCR is more favourable for survival, it is not synonymous with cure or complete locoregional disease control.
Long-term results of a randomized clinical trial comparing Roux-en-Y gastric bypass with vertical banded gastroplasty
Authors: Werling M , Fändriks L , Björklund P , Maleckas A , Brandberg J , Lönroth H , le Roux C W , Olbers T
Published: November 2012

Background

The long-term results of Roux-en-Y gastric bypass (gastric bypass) and vertical banded gastroplasty (VBG) from randomized studies have not been described in detail.

Methods

Patients were randomized to gastric bypass or VBG. Body mass index (BMI), body composition, eating habits and gastrointestinal hormones were reviewed after 6 years. The frequency of reoperation was assessed up to 10 years after surgery.

Results

Sixty-six (80 per cent) of the 82 subjects randomized were assessed for weight and BMI 6 years after surgery, 30 (81 per cent) in the gastric bypass group and 36 (80 per cent) in the VBG group. Intention-to-treat analysis demonstrated greater weight loss after gastric bypass compared with VBG, 6 years after surgery: BMI reduced from 41·8 (95 per cent confidence interval 41·3 to 42·3) to 30·3 (28·6 to 32·0) kg/m2 for gastric bypass and from 42·3 (42·8 to 44·8) to 32·9 (31·3 to 34·5) kg/m2 for VBG (P = 0·036). Gastric bypass caused a larger loss of fat mass (P = 0·026) and better preservation of lean tissue (P = 0·009). Patients having a gastric bypass had greater postprandial responses to the satiety hormones glucagon-like peptide 1 and peptide YY (P = 0·003 and P = 0·004 respectively). Ghrelin levels did not differ between the groups. Patients with a gastric bypass maintained a lower intake of fat compared with those having VBG (P = 0·013). Some 89 per cent of patients who initially had VBG had undergone, or were scheduled for, conversion to gastric bypass at latest follow-up.

Conclusion

Gastric bypass was superior to VBG regarding weight loss, body composition, dietary composition and postprandial satiety hormone responses.