bluuebunny/crossref_metadata_2025 huggingface dataset:
Simulating the effects of phosphorus limitation in the Mississippi and Atchafalaya River plumes
Authors: Laurent A. , Fennel K. , Hu J. , Hetland R.
Published: November 2012

Abstract. The continental shelf of the northern Gulf of Mexico receives high dissolved inorganic nitrogen and phosphorus loads from the Mississippi and Atchafalaya rivers. The nutrient load results in high primary production in the river plumes and contributes to the development of hypoxia on the Louisiana shelf in summer. While phytoplankton growth is considered to be typically nitrogen-limited in marine waters, phosphorus limitation has been observed in this region during periods of peak river discharge in spring and early summer. Here we investigate the presence, spatio-temporal distribution and implications of phosphorus limitation in the plume region using a circulation model of the northern Gulf of Mexico coupled to a multi-nutrient ecosystem model. Results from a 7-yr simulation (2001–2007) compare well with several sources of observations and suggest that phosphorus limitation develops every year between the Mississippi and Atchafalaya deltas. Model simulations show that phosphorus limitation results in a delay and westward shift of a fraction of river-stimulated primary production. The consequence is a reduced flux of particulate organic matter to the sediment near the Mississippi delta, but slightly enhanced fluxes west of Atchafalaya Bay. Simulations with altered river phosphate concentrations (±50%) show that significant variation in the spatial extent of phosphorus limitation (±40% in July) results from changes in phosphate load.
Distributions of low molecular weight dicarboxylic acids, ketoacids and α-dicarbonyls in the marine aerosols collected over the Arctic Ocean during late summer
Authors: Kawamura K. , Ono K. , Tachibana E. , Charriére B. , Sempéré R.
Published: November 2012

Abstract. Oxalic and other small dicarboxylic acids have been reported as important water-soluble organic constituents of atmospheric aerosols from different environments. Their molecular distributions are generally characterized by the predominance of oxalic acid (C2) followed by malonic (C3) and/or succinic (C4) acids. In this study, we collected marine aerosols from the Arctic Ocean during late summer in 2009 when sea ice was retreating. The marine aerosols were analyzed for the molecular distributions of dicarboxylic acids as well as ketocarboxylic acids and α-dicarbonyls to better understand the source of water-soluble organics and their photochemical processes in the high Arctic marine atmosphere. We found that diacids are more abundant than ketoacids and α-dicarbonyls, but their concentrations are generally low (< 30 ng m−3), except for one sample (up to 70 ng m−3) that was collected near the mouth of Mackenzie River during clear sky condition. Although the molecular compositions of diacids are in general characterized by the predominance of oxalic acid, a depletion of C2 was found in two samples in which C4 became the most abundant. Similar depletion of oxalic acid has previously been reported in the Arctic aerosols collected at Alert after polar sunrise and in the summer aerosols from the coast of Antarctica. Because the marine aerosols that showed a depletion of C2 were collected under the overcast and/or foggy conditions, we suggest that a photochemical decomposition of oxalic acid may have occurred in aqueous phase of aerosols over the Arctic Ocean via the photo dissociation of oxalate-Fe (III) complex. We also determined stable carbon isotopic compositions (δ13C) of bulk aerosol carbon and individual diacids. The δ13C of bulk aerosols showed −26.5‰ (range: −29.7 to −24.7‰, suggesting that marine aerosol carbon is derived from both terrestrial and marine organic materials. In contrast, oxalic acid showed much larger δ13C values (average: −20.9‰, range: −24.7‰ to −17.0‰) than those of bulk aerosol carbon. Interestingly, δ13C values of oxalic acid were higher than C3 (av. −26.6‰) and C4 (−25.8‰) diacids, suggesting that oxalic acid is enriched with 13C due to its photochemical processing (aging) in the marine atmosphere.
Strengthening of the hydrological cycle in future scenarios: atmospheric energy and water balance perspective
Authors: Alessandri A. , Fogli P. G. , Vichi M. , Zeng N.
Published: November 2012

Abstract. Future climate scenarios experiencing global warming are expected to strengthen the hydrological cycle during the 21st century (21C). We analyze the strengthening of the global-scale increase in precipitation from the perspective of changes in whole atmospheric water and energy balances. By combining energy and water equations for the whole atmosphere, we obtain constraints for the changes in surface fluxes and partitioning at the surface between sensible and latent components. We investigate the differences in the strengthening of the hydrological cycle in two centennial simulations performed with an Earth system model forced with specified atmospheric concentration pathways. Alongside the Special Report on Emissions Scenario (SRES) A1B, which is a medium-high non-mitigation scenario, we consider a new aggressive-mitigation scenario (E1) with reduced fossil fuel use for energy production aimed at stabilizing global warming below 2 K. Our results show that the mitigation scenario effectively constrains the global warming with a stabilization below 2 K with respect to the 1950–2000 historical period. On the other hand, the E1 precipitation does not follow the temperature field toward a stabilization path but continues to increase over the mitigation period. Quite unexpectedly, the mitigation scenario is shown to strengthen the hydrological cycle even more than SRES A1B till around 2070. We show that this is mostly a consequence of the larger increase in the negative radiative imbalance of atmosphere in E1 compared to A1B. This appears to be primarily related to decreased sulfate aerosol concentration in E1, which considerably reduces atmospheric absorption of solar radiation compared to A1B. The last decades of the 21C show a marked increase in global precipitation in A1B compared to E1, despite the fact that the two scenarios display almost the same overall increase of radiative imbalance with respect to the 20th century. Our results show that radiative cooling is weakly effective in A1B throughout the 21C. Two distinct mechanisms characterize the diverse strengthening of the hydrological cycle in the middle and end- 21C. It is only through a very large perturbation of surface fluxes that A1B achieves a larger increase in global precipitation in the last decades of the 21C. Our energy/water budget analysis shows that this behavior is ultimately due to a bifurcation in the Bowen ratio change between the two scenarios. This work warns that mitigation policies that promote aerosol abatement, may lead to an unexpected stronger intensification of the hydrological cycle and associated changes that may last for decades after global warming is effectively mitigated. On the other hand, it is also suggested that predictable components of the radiative forcing by aerosols may have the potential to effectively contribute to the decadal-scale predictability of changes in the hydrological strength.
Do GCM's predict the climate... or macroweather?
Authors: Lovejoy S. , Schertzer D. , Varon D.
Published: November 2012

Abstract. We are used to the weather – climate dichotomy, yet the great majority of the spectral variance of atmospheric fields is in the continuous "background" and this defines instead a trichotomy with a "macroweather" regime in the intermediate range ≈10 days to 30 yr. In the weather, macroweather and climate regimes, exponents characterize the type of variability over the entire ranges and it is natural to identify them with qualitatively different synergies of nonlinear dynamical mechanisms that repeat scale after scale. Since climate models are essentially meteorological models (although with extra couplings) it is thus important to determine whether they currently model all three regimes. Using Last Millennium simulations from four GCM's, we show that control runs only reproduce macroweather and that runs with various (reconstructed) climate forcings do somewhat better but have overly weak multicentennial variabilities. A possible explanation is that the models lack – or inadequately treat – important slow "climate" processes such as land-ice or deep ocean dynamics.
Hydrochemical processes in lowland rivers: insights from in situ, high-resolution monitoring
Authors: Wade A. J. , Palmer-Felgate E. J. , Halliday S. J. , Skeffington R. A. , Loewenthal M. , Jarvie H. P. , Bowes M. J. , Greenway G. M. , Haswell S. J. , Bell I. M. , Joly E. , Fallatah A. , Neal C. , Williams R. J. , Gozzard E. , Newman J. R.
Published: November 2012

Abstract. This paper introduces new insights into the hydrochemical functioning of lowland river systems using field-based spectrophotometric and electrode technologies. The streamwater concentrations of nitrogen species and phosphorus fractions were measured at hourly intervals on a continuous basis at two contrasting sites on tributaries of the River Thames – one draining a rural catchment, the River Enborne, and one draining a more urban system, The Cut. The measurements complement those from an existing network of multi-parameter water quality sondes maintained across the Thames catchment and weekly monitoring based on grab samples. The results of the sub-daily monitoring show that streamwater phosphorus concentrations display highly complex dynamics under storm conditions dependent on the antecedent catchment wetness, and that diurnal phosphorus and nitrogen cycles occur under low flow conditions. The diurnal patterns highlight the dominance of sewage inputs in controlling the streamwater phosphorus and nitrogen concentrations at low flows, even at a distance of 7 km from the nearest sewage treatment works in the rural River Enborne. The time of sample collection is important when judging water quality against ecological thresholds or standards. An exhaustion of the supply of phosphorus from diffuse and multiple septic tank sources during storm events was evident and load estimation was not improved by sub-daily monitoring beyond that achieved by daily sampling because of the eventual reduction in the phosphorus mass entering the stream during events. The results highlight the utility of sub-daily water quality measurements and the discussion considers the practicalities and challenges of in situ, sub-daily monitoring.
Triamcinolone and Bevacizumab as Adjunctive Therapies to Panretinal Photocoagulation for Proliferative Diabetic Retinopathy
Authors: Lopez-Lopez F. , Gomez-Ulla F. , Rodriguez-Cid M. J. , Arias L.
Published: November 2012

Purpose. To evaluate efficacy of intravitreal triamcinolone (IVT) and bevacizumab (IVB) as adjunctive treatments to panretinal photocoagulation (PRP) in proliferative diabetic retinopathy (PDR). Methods. In 60 eyes of 45 patients with PDR, PRP (PRP group), PRP with IVT (IVT group), or PRP with IVB (IVB group) was performed. Regression of new vessels (NV), changes in best-corrected visual acuity (BCVA), central macular thickness (CMT), and contrast sensitivity at 1,2, and 6 months were evaluated. Results. Initial mean numbers of active NV and BCVA were 3.45 and 67.35 in the PRP group, 4.35 and 76.65 in the IVT group, and 4.79 and 75.53 in the IVB group. At the 6-month follow-up, numbers of active NV were 2.5 (P=0.064), 1.11 (P=0.000), and 1.11 (P=0.002), and there was a mean loss of 2,6 (P=0.055), 3.9 (P=0.011), and 0.9 letters (P=0.628) in the PRP, IVT, and IVB groups, respectively. Changes in CMT in the PRP and IVT groups were not significant, but significantly increased in the IVB group (P=0.032). Contrast sensitivity remained stable in PRP and IVB groups and slightly decreased in IVT group. Conclusions. Adjunctive use of both triamcinolone and bevacizumab with PRP lead to a greater reduction of active NV than PRP alone in PDR, although no differences were seen between the two of them.
Molecular Mechanisms of Trastuzumab-Based Treatment in HER2-Overexpressing Breast Cancer
Authors: Nahta Rita
Published: November 2012

The past decade of research into HER2-overexpressing breast cancer has provided significant insight into the mechanisms by which HER2 signaling drives tumor progression, as well as potential mechanisms by which cancer cells escape the anticancer activity of HER2-targeted therapy. Many of these preclinical findings have been translated into clinical development, resulting in novel combinations of HER2-targeted therapies and combinations of trastuzumab plus inhibitors of resistance pathways. In this paper, we will discuss proposed mechanisms of trastuzumab resistance, including epitope masking, cross signaling from other cell surface receptors, hyperactive downstream signaling, and failure to induce antibody-dependent cellular cytotoxicity. In addition, we will discuss the molecular mechanisms of action of dual HER2 inhibition, specifically the combination of trastuzumab plus lapatinib or trastuzumab with pertuzumab. We will also discuss data supporting therapeutic combinations of trastuzumab with agents targeted against molecules implicated in trastuzumab resistance. The roles of insulin-like growth factor-I receptor and the estrogen receptor are discussed in the context of resistance to HER2-targeted therapies. Finally, we will examine the major issues that need to be addressed in order to translate these combinations from the bench to the clinic, including the need to establish relevant biomarkers to select for those patients who are most likely to benefit from a particular drug combination.
Development of Safer Gene Delivery Systems to Minimize the Risk of Insertional Mutagenesis-Related Malignancies: A Critical Issue for the Field of Gene Therapy
Authors: Romano Gaetano
Published: November 2012

Integrating gene delivery systems allow for a more stable transgene expression in mammalian cells than the episomal ones. However, the integration of the shuttle vector within the cellular chromosomal DNA is associated with the risk of insertional mutagenesis, which, in turn, may cause malignant cell transformation. The use of a retroviral-derived vector system was responsible for the development of leukemia in five children, who participated in various clinical trials for the treatment of severe combined immunodeficiency (SCID-X1) in France and in the United Kingdom. Unfortunately, the hematological malignancy claimed the life of one patient in 2004, who was enrolled in the French clinical trial. In addition, adeno-associated-viral-(AAV-) mediated gene transfer induced tumors in animal models, whereas the Sleeping Beauty (SB) DNA transposon system was associated with insertional mutagenesis events in cell culture systems. On these grounds, it is necessary to develop safer gene delivery systems for the genetic manipulation of mammalian cells. This paper discusses the latest achievements that have been reported in the field of vector design.
Wild food plants of Remote Oceania
Authors: McClatchey Will C.
Published: November 2012

Agricultural societies partly depend upon wild foods. Relationships between an agricultural society and its wild foods can be explored by examining how the society responds through colonization of new lands that have not been previously inhabited. The oldest clear example of this phenomenon took place about 5000 years ago in the tropical Western Pacific at the “boundary” interface between Near and Remote Oceania. An inventory of wild and domesticated food plants used by people living along “the remote side of ” that interface has been prepared from the literature. This was then assessed for the roles of plants at the time of original colonization of Remote Oceania. The majority of species are wild foods, and most of these are used as leafy vegetables and fruits. The wild food plants mostly serve as supplements to domesticated species, although there are a few that can be used as substitutes for traditional staples.
Opposition-Based Discrete PSO Using Natural Encoding for Classification Rule Discovery
Authors: Khan Naveed Kazim , Baig Abdul Rauf , Iqbal Muhammad Amjad
Published: November 2012

In this paper we present a new Discrete Particle Swarm Optimization approach to induce rules from discrete data. The proposed algorithm, called Opposition-based Natural Discrete PSO (ONDPSO), initializes its population by taking into account the discrete nature of the data. Particles are encoded using a Natural Encoding scheme. Each member of the population updates its position iteratively on the basis of a newly designed position update rule. Opposition-based learning is implemented in the optimization process. The encoding scheme and position update rule used by the algorithm allows individual terms corresponding to different attributes within the rule's antecedent to be a disjunction of the values of those attributes. The performance of the proposed algorithm is evaluated against seven different datasets using a tenfold testing scheme. The achieved median accuracy is compared against various evolutionary and non-evolutionary classification techniques. The algorithm produces promising results by creating highly accurate and precise rules for each dataset.
Cartesian Stiffness Matrix Mapping of a Translational Parallel Mechanism with Elastic Joints
Authors: Ruggiu Maurizio
Published: November 2012

This paper is devoted to calculating the Cartesian stiffness matrix of a translational parallel manipulator with elastic joints. The calculation takes into account the contribution of the Jacobian variation because of the change of manipulator configuration due to the elasticity and it covers the entire theoretical workspace of the manipulator. Three kineto-static adimensional indices are proposed to measure the response of the manipulator in terms of stiffness.
Modelling and Experimental Evaluation of a Static Balancing Technique for a New Horizontally Mounted 3-UPU Parallel Mechanism
Authors: Dehkordi Maryam Banitalebi , Frisoli Antonio , Sotgiu Edoardo , Bergamasco Massimo
Published: November 2012

This paper presents the modelling and experimental evaluation of the gravity compensation of a horizontal 3-UPU parallel mechanism. The conventional Newton-Euler method for static analysis and balancing of mechanisms works for serial robots; however, it can become computationally expensive when applied to the analysis of parallel manipulators. To overcome this difficulty, in this paper we propose an approach, based on a Lagrangian method, that is more efficient in terms of computation time. The derivation of the gravity compensation model is based on the analytical computation of the total potential energy of the system at each position of the end-effector. In order to satisfy the gravity compensation condition, the total potential energy of the system should remain constant for all of the manipulator's configurations. Analytical and mechanical gravity compensation is taken into account, and the set of conditions and the system of springs are defined. Finally, employing a virtual reality environment, some experiments are carried out and the reliability and feasibility of the proposed model are evaluated in the presence and absence of the elastic components.
From the editors
Authors: Value Language
Published: November 2012

In Memoriam

The journal editors and the Department of English Studies at the Universitat Jaume I wish to pay tribute to our colleague, friend and teacher, Dr. Xavier Campos Vilanova who passed away earlier this year. Xavier showed a passionate enthusiasm for the study of the history of the English language and literature, but also for everything he did. From taking photographs, researching on the meaning of the number seven, to studying the history of Castelló – his home town –, he went deep into everything that touched his heart.

Xavier kindly accepted to supervise my doctoral thesis (Campoy) on phrasal verbs many years ago even though it did not fit his plans at the moment, since he was then deeply engaged in the study of Old English. I felt this issue on phrasal verbs would be a great opportunity to thank him for his generosity and open mindfulness. It is his wide smile and his distinctive laugh that could fill the room that we will always remember.

 

From the Editors

MULTIWORD PATTERNS: CONSIDERING PHRASAL VERBS AND THEIR UNDERLYING SEMANTIC SYSTEMS (I)

This is the first of two issues dealing with multiword patterns. The main focus of these issues is that of phrasal verbs with a special emphasis on the semantic patterns from which they arise. This first issue on this topic includes five articles related to the study of English particles as part of phrasal verbs and in lexical bundles. The issue tackles different perspectives in the analysis and use of phrasal verbs. Most articles adopt a cognitive approach in their investigation of the use and analysis of these units. Two of them, Navarro and Chung et al. also follow a corpus-based approach in their analysis.
Prevalence of dyslipidemia in HIV‐infected patients on combined antiretroviral treatment in Spain: a qualitative analysis
Authors: Estrada V , Masiá M , Iribarren J , Lozano F , Miralles C , Olalla J , Santos J , Bernardino J , Dronda F , Domingo P
Published: November 2012

Purpose

Among traditional cardiovascular risk factors, dyslipidemia could be particularly prevalent since virus, treatment and host factors may be involved in its development. Our analysis aimed to describe the prevalence of different types of dyslipidemia in a population of HIV‐infected, treatment‐experienced patients in Spain.

Methods

Cross‐sectional analysis within 10 HIV units across Spain. We collected data on demographics and cardiovascular risk factors, including lipid profile as well as information on current use of lipid‐lowering drugs. This analysis describes subjects under first‐line ART as compared with others in more advanced lines of treatment.

Results

We included 860 patients (76.3% male) with no history of CVD, with median age 45.6 years. Median time since HIV diagnosis was 3 and 14 years (p=0.000) and median time on ART was 22 and 136 months (p=0.000) respectively. Lipid profile is described in the table.

n (%)
First line regimens, n=219
Subsequent regimens, n=641
p‐value

Dyslipidemia

Total cholesterol >240 mg/dL
17 (7.9)
70 (11.1)
0.180

LDL‐cholesterol >160 mg/dL
19 (9.0)
49 (7.9)
0.636

HDL‐cholesterol <40 mg/dL
85 (39.9)
188 (30.0)
0.008

Total cholesterol/HDL ratio>5
60 (28.2)
160 (25.5)
0.447

Triglycerides≥200 mg/dL
43 (20.0)
136 (21.6)
0.616

Lipid‐lowering drugs

Statin use
10 (4.6)
101 (15.8)
0.000

Statin use AND Tcol/HDL>5
3 (33.3)
36 (36.0)
1.000

Fibrate use
7 (3.2)
12 (1.9)
0.286

Fibrate use AND TG≥200 mg/dL
3 (42.9)
9 (75.0)
0.326

Conclusions

Dyslipidemia, especially low HDL and high TG, is highly prevalent in this population regardless being in their first or more advanced lines of treatment. The use of lipid‐lowering drugs in our population is low and furthermore the control of dyslipidemia is not always achieved. Additional research is needed to understand how to achieve lipid goals in this population.
Vascular dysfunction in HIV‐infected patients
Authors: Falasca K , Ucciferri C , Tatasciore A , Tommasi R , De Caterina R , Pizzigallo E , Vecchiet J
Published: November 2012

Atherosclerotic cardiovascular disease is an increasing concern for patients with human immunodeficiency virus (HIV) infection. We investigated carotid intima‐media thickness (IMT), flow‐mediated dilation (FMD), pulse wave velocity (PWV) and the augmentation index (AIx), evaluated as indices of subclinical atherosclerosis, in HIV‐infected patients compared to uninfected subjects. We enrolled 80 HIV‐infected patients, 68 of whom treated with combined antiretroviral therapy (cART) and 12 therapy‐naïve, matched with 82 healthy subjects for age, systolic and diastolic blood pressure. We investigated IMT, FMD, PWV, AIx, viro‐immunological parameters, inflammatory markers, microalbuminuria and other biochemical parameters. Compared with uninfected subjects, HIV‐infected subjects had higher IMT, PWV and AIx values (all P=0.0001); and lower FMD (P=0.001). In the HIV+ group, naïve patients had statistically lower levels of IMT (P=0.02), and AIx (P=0.042) and higher FMD (P=0.032) compared with cART‐treated patients. In the HIV+group, IMT values was significantly related to the number of CD4+ (r=−0.31, P=0.008) and CD8+ cells (r=0.261, P=0.025), interleukin‐6 (r=0.284, P=0.015) and endothelin‐1 (r=0.302, P=0.009). Vascular dysfunction evaluated as IMT, FMD and arterial stiffness is increased in HIV‐infected subjects than in healthy subjects. Furthermore, cART‐treated patients showed higher IMT and AIx and lower FMD values than naïve patients. Our data support the hypothesis that both HIV infection and cART treatment are risk factors for accelerated arteriosclerosis.
Yield of annually performed routine physical examinations of HIV patients with stable disease
Authors: van Amsterdam M , van Assen S , Sprenger H , Wilting K , Stienstra Y , Bierman W
Published: November 2012

Background

Adequate follow‐up of HIV patients is essential in the cART era. Current guidelines advise regular assessment of the patient, yet the exact content and frequency are less clear and practices vary amongst different hospitals. The objective of this study was to determine the value of performing routine physical examination of patients with normal or near normal immune function, as part of adequate follow‐up.

Methods

In a cohort of 300 HIV‐1‐infected patients monitored in a large teaching hospital we retrospectively analysed the outcome of routine physical examinations performed at annual check‐ups in 2010. Only stable patients were eligible for inclusion (CD4 count >350 cells/mm3 if not using cART, CD4 count >100 cells/mm3 if using cART). Data was collected from the medical records. It was recorded whether or not the physical examination per se was the basis for establishing a new diagnosis.

Results

Of 300 stable HIV‐1‐infected patients (81% males) with a median age of 47 years old (range 21–79) 216 patients (72%) had physical abnormalities. Lipodystrophy (30%), lymphadenopathy (16%) and hypertension (8.3%) were the most common findings. Two‐thirds of all findings were already known from the past medical history or could be related to current complaints. In 24 patients (8.0%), the physical examination was the basis for establishing a new diagnosis: 6/24 patients (25%) ‐ all men who have sex with men (MSM) ‐ had a concurrent sexually transmitted disease, 8/24 patients (33%) had hypertension. The other 10/24 (42%) patients had a large variety of diagnoses, of which a bradycardia due to a total atrioventricular block was clinically the most relevant diagnosis. Factors associated with the yield of the physical examination could not be identified.

Conclusion

Routine physical examination per se was the basis for establishing new diagnoses in only 8% of stable HIV infected patients. However, most diagnoses were of little clinical relevance, suggesting that the additional value of routine physical examination in stable HIV patients is limited. Based on our findings, the regular standard assessment could be restricted to measuring blood pressure and the performance of anogenital examination in MSM.
Impaired neurocognitive function among HIV‐infected Thais on stable antiretroviral therapy for more than 7 years
Authors: Avihingsanon A , Maek‐a‐nantawat W , Sithinamsuwan P , Ananworanich J , Suksawak S , Saysombut N , Charoenporn W , Phanuphak P , Valcour V
Published: November 2012

Background

There are limited data on HIV‐associated neurocognitive disorders (HANDs) from resource‐constraint region and few studies have firm documentation of duration of treatment and suppression of plasma virus. This study aimed to estimate the prevalence of HIV‐related cognitive deterioration among HIV‐infected patients who were on stable ART and to describe the pattern of neurocognitive impairment (NCI), daily life disturbance and associated factors.

Methods

This was a cross‐sectional evaluation of cognition in a sample of HIV adults at HIV‐NAT, the Thai Red Cross AIDS Research Centre with data captured over a 6‐month period. The Montreal Cognitive Assessment (MoCA), International HIV Dementia Scale (IHDS) and Activities of Daily Living Questionnaire (ADLQ) scale were administered. NCI was defined as a score of ≤10 on the IHDS or <26 on the MoCA. The HIV‐NAT Cohort Database was explored to retrieve sociodemographic data and clinical factors.

Results

Among the 162 patients evaluated, the mean (±SD) age was 42.8 (±7.3) years and 56.8% were male. HBV and HCV co‐infection frequencies were 11.7% and 7.4%, respectively. The mean (±SD) duration of ART was 9.03 (±3.12) years. Of all, 59.3% were concurrently on protease inhibitor (PI) based regimens. 97.5% had virologic success with HIV‐RNA load of less 200 copies/mL. The prevalence of NCI was 68.5% by MoCA and 75.8% by IHDS. Tests on visuospatial cognition, language and abstraction were most commonly poor scores (81.5%, 89.5% and 74.1%, respectively). Among these, 54.9% and 61.3%, respectively, were asymptomatic without overt daily functioning interference. Daily self‐care and household care were the most commonly endorsed daily activity defects (16.7% and 12.3%, respectively). Remaining as a couple (p=0.001), duration of education <12 years (p<0.001) and heterosexual risk (p=0.001) were associated with NCI. The MoCA and IHDS scales correlated to each other (r2=0.177, p=0.024). Logistic regression demonstrated fewer years of education and remaining as a couple were associated with impaired MoCA scale (P=0.001 and 0.008, respectively).

Conclusion

Impaired cognitive function is commonly detected among HIV‐infected Thais on stable ART for over 7 years. The frequency of NCI is higher than that reported in other settings. However the performance characteristics of our screens have not been firmly established in this setting and the cut‐off levels used may over‐estimate NCI.
Prevalence and determinants of unemployment among ageing HIV‐1‐infected and HIV‐uninfected individuals
Authors: Stolte I , Kuiper J , Schouten J , Wit F , Reiss P , Sluiter J , Prins M
Published: November 2012

Purpose of the study

People living with HIV (PLWH) appear to be at increased risk for earlier onset of age‐associated non‐communicable co‐morbidity (AANCC) and declines in physical and mental capacities, compared to the general population [1]. This earlier onset of AANCC in the setting of HIV infection is likely to negatively affect work participation and quality of life. Present study investigates prevalence and determinants of unemployment among older HIV‐1‐infected and HIV‐uninfected participants of the AGEhIV Cohort Study.

Methods

Data were collected (Oct. 2010–Jan. 2012) within the ongoing prospective AGEhIV Cohort Study, recruiting HIV‐1‐infected patients >45 years from a tertiary care HIV outpatient clinic, and HIV‐uninfected Public Health Service attendants, comparable regarding age, gender and ethnicity. Data on socio‐demographics, lifestyle, quality of life, AANCC and unemployment were collected, using a self‐administered questionnaire and through medical examination. Current analysis was restricted to participants in the working age (45–65 years). Logistic regression analysis was used to study determinants of unemployment.

Summary of results

The majority from the first enrolled 277 HIV‐1‐infected and 251 HIV‐uninfected subjects was male (88%), Dutch (76%) and homosexual (74%). About 50% was highly educated and the median age was 52 [IQR: 48–57]. Almost all (94%) HIV‐1‐infected individuals were on cART, median time since first ART was 11 years [IQR: 4–15], median time since HIV‐diagnosis was 12 years [IQR: 7–18] and they had been diagnosed with more AANCC than HIV‐uninfected individuals (p<0.01). Unemployment was higher among HIV‐1‐infected (36.5%) compared to HIV‐uninfected participants (21.9%) (p<0.01). In multivariate analysis, being HIV‐infected (ORadj 2.0 [95% CI: 1.3–3.3]), experiencing >2 AANCC (ORadj 3.1 [95% CI: 1.4–6.8]), lower physical health status (ORadj 2.0 [95% CI: 1.6–2.6]), being unmarried (ORadj 2.1 [95% CI: 1.3–3.2]) and older age (ORadj 60‐65 yrs: 9.1 [95% CI: 4.5–18]) were independently associated with higher levels of unemployment.

Conclusions

Unemployment among HIV‐1‐infected individuals is higher compared to HIV‐uninfected individuals, independent of socio‐demographic characteristics, lifestyle, quality of life or number of concomitantly diagnosed AANCC. This suggests that, apart from these factors, specific HIV‐related determinants, such as stage of HIV disease, but also experienced stigma, work related conditions, influence unemployment.
Screening for alcohol use disorders in HIV patients
Authors: Ward C , Ahmad S
Published: November 2012

Many chronic health conditions have been linked to alcohol consumption, as well as excess morbidity, mortality and an increased financial burden on the National Health Service (NHS). The British HIV Association (BHIVA) recommends that HIV patients be asked about alcohol due to its effect on adherence to antiretroviral therapy. National Institute of Health and Clinical Excellence (NICE) guidelines recommend screening for alcohol use disorders in patients attending genitourinary medicine (GUM) clinics. In this study we looked at the use of a screening tool for alcohol use disorders in HIV patients in a metropolitan city. We assessed HIV patients over a 6‐month period for alcohol use disorders using the AUDIT‐C questionnaire. Patients with a score >4 were identified as higher risk and provided with brief advice about alcohol and offered written information and support. Demographic data was collected along with hepatitis B and C status, information on sexually transmitted infection (STI) testing and diagnosis. 352 patients were reviewed with a mean age of 41. 297 (84.4%) patients were male, 235 (66.8%) were white British and 251 (71.3%) were men who have sex with men (MSM). 277 (78.7%) patients were on antiretroviral therapy with 254 (91.7%) of these having an undetectable viral load. Alcohol use disorders were assessed using the AUDIT‐C score in 332 (94.3%) patients with no patient declining assessment. 166 (50%) patients had an AUDIT‐C score >4 signifying higher risk. Alcohol advice was provided to 161 (97%) of these patients and a Drink Smart guide offering advice on alcohol self help offered to 103 (64%) patients and accepted by 45 (43.7%). An opportunistic STI screen was offered to 258 (73.3%) patients on that visit in line with best practice guidelines and was accepted by 83 (32.2%). 25 infections were found in 20 patients, of which 13 (65%) had AUDIT‐C scores >4. There were 8 active hepatitis C co‐infected patients of which 3 had an AUDIT‐C score >4 and 12 chronic hepatitis B co‐infected patients with 3 having an AUDIT‐C score >4. Our results show that screening for alcohol use disorders using the AUDIT‐C questionnaire has high acceptability among HIV patients; however the data is biased to Caucasian MSM. Alcohol use has been shown to exacerbate liver damage in patients with chronic hepatitis, increase the likelihood of STI acquisition and compromise immunity. It is therefore important to screen for and quantify alcohol use as part of routine HIV clinical practice.
Clock‐drawing test as a screening tool for HIV‐associated neurocognitive disorder (HAND)
Authors: Levy I , Goldstein A , Maor Y , Rahav G , Litachewsky V , Fischel T
Published: November 2012

Introduction

Current tests for diagnosing HIV‐associated neurocognitive dysfunction (HAND) consume time and energy and are not very practical as a screening tool in the busy clinic. The clock‐drawing test (CDT) was reported sensitive to subcortical pathology associated with periventricular and deep white matter. In addition, CDT has shown to be sensitive to executive dysfunction.

Aim

The aim of this study was to determine the value of a clock‐drawing test as a screening tool for diagnosing HAND. Methods: The CDT that we used was largely based on Rouleau et al. (1992). The patient is asked to draw a clock, first the frame, than the numbers, and than the hands showing the time 10 to 2. The interpretation is based on the following criteria: frame, numbers, hands, center, general impression. If acceptable‐2 points, non‐acceptable‐0, and acceptable but deviating‐1 point. Other validated neurocognitive tests (e.g. TMA, TMB, DSST, etc) were used as the “gold standard”.

Results

In the primary analysis 54 patients were included: 47 men and 7 women. Sensitivity was 77%, specificity 90%, positive predictive value 71.4%, negative predictive value 92.5%. In this preliminary study we found CDT to be a valid screening tool for HAND. It correlates highly with other well‐established screening tools, but demands less resources (human and technological). It is especially good for ruling out the disease.
Raltegravir‐based post‐exposure prophylaxis (PEP): a safe, well‐tolerated alternative regimen
Authors: Annandale D , Richardson C , Fisher M , Richardson D
Published: November 2012

Three‐drug regimens are routinely recommended in the UK for PEP after possible high‐risk exposure to HIV. The current Department of Health and British Association for Sexual Health and HIV first‐line regimen is lopinavir/ritonavir, tenofovir and emtricitabine (Truvada). Raltegravir‐based regimens may be used as an alternative. This is a review of the use of raltegravir‐containing PEP to identify why and when this is initiated and its tolerability and safety compared to first‐line PEP. From February 2010 to April 2012, 509 courses of PEP were prescribed; 33 (6.5%) raltegravir‐containing PEP. Pharmacy records identified eligible patients; these were compared to 33 courses of first‐line PEP in the same time period. 18/33 (54%) of raltegravir‐containing PEP were initiated due to potential drug‐drug interactions with ritonavir, 3/33 (10%) due to the resistance profile of the contact and 12/33 (36%) due to intolerance of first‐line regimen. All switches to raltegravir‐based PEP occurred by day 3 of the course with 83% identified on day 1. All switches to raltegravir‐containing PEP due to the resistance profile of the contact took place by day 3 of the course. Patients switching due to drug intolerance was largely due to gastrointestinal side effects between days 1 to 16; 2 cases were due to ALT changes. 19 courses of raltegravir‐containing PEP were commenced on day one. Reported side effects in the raltegravir‐containing PEP were lower than courses of first‐line PEP: 10/19 (53%) patients reported no side effects by day 28 treatment compared to 5/33 (15%) patients on first‐line PEP. 12/14 (79%) patients on first‐line PEP who were switched to raltegravir‐containing PEP reported improvement in their side effects. There were no significant liver or renal toxicities in the raltegravir group; 3 patients on first‐line PEP had a significant ALT rise. One patient who started first‐line PEP was found to be HIV‐positive at baseline. An MSM who received raltegravir‐containing PEP seroconverted 4.5 months after the course of PEP. He reported 3 episodes of unsafe sexual behaviour since PEP. Raltegravir‐based regimens are safe and as well tolerated when compared to first‐line regimen. Switching to raltegravir‐based regimen is associated with a decrease in reported side effects. Self‐reported adherence is better if patients are started on raltegravir. This study suggests that raltegravir‐based PEP may be a preferred first‐choice regimen.
HIV‐infection during treatment of a chronic hepatitis B virus infection: implications for PrEP?
Authors: Storim J , Jochum C , Timm J , Schadendorf D , Esser S
Published: November 2012

The protective effect of oral tenofovir disoproxil fumarate (TDF) with or without emtricitabine (FTC) as pre‐exposure prophylaxis (PrEP) against HIV differed significantly among clinical studies and poor PrEP‐adherence was closely associated with PrEP‐failure. Despite HIV‐infections during PrEP‐exposure the development of resistance mutations against PrEP was rarely observed so far. As PrEP is an emerging tool against HIV transmission, it is important to identify risk‐factors for PrEP‐failure and the induction of PrEP‐associated resistance mutations against antiretroviral drugs. We here present the case of a 25‐year old MSM who was successfully treated with TDF due to a chronic hepatitis B virus (HBV) infection (HBV‐DNA always <357 IU/ml after ten months of treatment). As HIV tests were negative when the treatment was initiated and six months later, no routine HIV tests were performed although the patient repetitively acquired sexually transmitted infections (STI). After 30 months, an HIV infection (subtype B) was diagnosed during a syphilis re‐infection. At this point, HIV was TDF‐resistant (K65R and A62V mutations within the reverse transcriptase gene). Retrospective analysis of frozen serum samples revealed HIV‐seroconversion 12 months prior to diagnosis and low HIV‐RNA levels from seroconversion to diagnosis (always <400 copies/ml). The TDF‐based therapy of the chronic HBV‐infection resembles a TDF‐HIV‐PrEP. But here poor therapy adherence is an unlikely cause for the 'PrEP‐failure' as the constantly suppressed HBV‐DNA indicates therapeutic TDF‐levels over years. Combining TDF with FTC might have augmented the prophylactic effect. However, TDF‐levels in the rectal mucosa are high and should therefore protect MSM who practice receptive anal intercourse. On the other hand, the concomitant STI of our patient may have promoted HIV transmission (via compromising the mucosal barrier function and promoting inflammatory reactions) and therefore possibly counteracted TDF‐effects. Finally, infection with a TDF‐resistant virus strain might explain the lack of protection in this case. But K65R is a rarely transmitted drug resistance mutation and low level viremia for one year suggests considerable TDF effectiveness. In fact, we here rather present a K65R mutation induced by a PrEP‐like TDF therapy. The development of the K65R mutation in a PrEP‐like situation emphasizes the urgent need of regular HIV‐tests during PrEP exposure.
HIV‐1 drug resistance among antiretroviral treatment‐naïve Ethiopian patients
Authors: Mulu A , Maier M , Liebert U
Published: November 2012

Background

In many African countries, access to antiretroviral treatment (ART) has been significantly scaled up over the last five years. Nevertheless, data on drug resistance mutation are scarce. The objective of the current study was to determine the predominant subtypes of HIV‐1 as well as to identify baseline mutations with potential drug resistance among ART‐naïve patients from Ethiopia.

Methods

Genotypic drug resistance on the entire protease and partial reverse transcriptase (codons 1–335) regions of the pol gene was determined by an in‐house protocol in 160 ART‐naïve patients. Genotypic drug resistance was defined as the presence of one or more resistance‐related mutations, as specified by the consensus of the Stanford University HIV drug resistance database (HIVDB) available at http://hivdb.stanford.edu/ and the 2011 International AIDS Society (IAS) mutation list (http://www.iasusa.org/resistance‐mutations/).

Results

A predominance of HIV‐1 subtype C (98.7%) was observed. According to the IAS mutation list, antiretroviral drug resistance mutations were detected in 20 patients (13%). However, the level of drug resistance is 5.2% (8/155) when the most conservative method, HIVDB algorithms were applied. In both algorithms, none had major PI mutation and mutation‐conferring resistance to NRTI and NNRTI were not overlapping.

Conclusions

There is strong evidence for clade homogeneity in Ethiopia and low influx of other subtypes to the country. The level of transmitted drug resistance exceeds that of WHO estimates and indicates that many HIV‐infected individuals on ART are practicing risk‐related behaviours. The results also show that HIV drug resistance testing should be installed in resource limited settings.
Transmission of primary resistance mutation K103N in a cluster of Belgian young patients from different risk groups
Authors: Ruelle J , Ingels M , Jnaoui K , Ausselet N , Sasse A , Verhofstede C , Goubau P
Published: November 2012

Background

We analysed the distribution of an HIV‐1 subtype B strain resistant to efavirenz and nevirapine among incident infections in the Belgian population.

Method

The Belgian AIDS reference laboratories searched their databases for HIV‐1 subtype B sequences harbouring the K103N mutation in the reverse transcriptase (RT) or the C67S and V77I mutations in the protease (PR). We included the earliest RT sequence available of drug‐naïve patients as well as sequences related to treatment failure. Fifty sequences were aligned omitting the codon 103 and submitted to phylogenetic analysis. Epidemiological data were collected through the Institute of Public Health national database. In addition, three sequences from the cluster were analysed by deep sequencing using the Roche GS Junior platform.

Results

Phylogenetic analysis revealed the presence of a 24 virus sequences cluster. All except one of those sequences resulted from patients who were ARV‐naïve at the time of sampling, and 21 had the K103N mutation. Two thirds of the clustered patients were infected through homosexual or bisexual contacts while the others were heterosexuals. No case was related to migrants contaminated abroad. Fifteen of the clustered patients were diagnosed between January 2011 and June 2012; 87% of them were aged between 20 and 29 at the time of diagnosis. Interestingly, 60% of them reside in the province of Namur. Deep sequencing analysis of 3 individuals sampled near seroconversion revealed no other resistance mutations at a frequency>1% than those already picked up by Sanger sequencing (RT A98S, K103N; PR V77I), except the RT V90I.

Conclusion

We identified a transmission cluster of drug resistant HIV‐1 variants mainly including homo‐ and heterosexual young adults. Most individuals are of Belgian origin and are living around the city of Namur (Belgium). The K103N mutation had no apparent impact on transmission fitness as its spread raised during the last years. These observations may impact on local prevention and ARV prophylaxis strategies.
HIV‐1 drug resistance‐associated mutations among antiretroviral‐naïve Thai patients with chronic HIV‐1 infection
Authors: Manosuthi W , Thongyen S , Nilkamhang S , Manosuthi S , Sungkanuparph S
Published: November 2012

Purpose of study

Antiretroviral therapy (ART) has been scaled up in resource‐limited settings. This study aimed to determine the prevalence of HIV‐1 drug resistance‐associated mutations (DRAMs) among patients with chronic HIV‐1 infection and to compare DRAMs between CRF01_AE and B subtypes.

Methods

ART‐naïve Thai patients who were indicated for ART initiation between 2010 and 2011 were prospectively enrolled. Genotypic assays of reverse transcriptase and protease genes were performed within 4 weeks prior to ART. DRAMs were assessed using International AIDS Society USA 2011 list.

Summary of results

A total of 330 patients were included. HIV‐1 subtypes included CRF01_AE (241, 73.0%), B (79, 23.9%), and others (10, 3.1%). Median (IQR) CD4 was 66 (23–172) cells/mm3 and median (IQR) HIV‐1 RNA was 5.2 (4.6–5.8) log copies/mL. The prevalence of patients with≥1 DRAMs to any antiretroviral agents was 17.6%; 17.0% to NNRTIs, 0.6% to NRTIs, and 0.6% to protease inhibitors (PIs). V106I (23, 7.0%), V179D (14, 4.2%), V179T (6, 1.8%), E138A (5, 1.5%), V90I (4, 1.2%), K103N (3, 0.9%), Y181C (3, 0.9%), and P225H (1, 0.3%) were DRAMs to NNRTIs. M184V (1, 0.3%) and T215S (1, 0.3%) were DRAMs to NRTIs. M46L (2, 0.6%) was the only major DRAM to PI. Minor DRAMs to PIs including I13V, M36I, H69K, and L89M were more frequently observed in CRF_01 AE but A71V/T and V77I were more common in subtype B (P < 0.05). By multivariate analysis, the factors ‘HIV‐1 subtype B’ and ‘low pretreated CD4 cell count’ were associated with higher rate of DRAMs.

Conclusion

HIV‐1 DRAMs, especially to NNRTIs, is emerging in a middle‐income country after a widespread use of NNRTI‐based ART. HIV genotypic assay prior to ART initiation in patients with chronic HIV‐1 infection should be considered.