bluuebunny/crossref_metadata_2025 huggingface dataset:
PMIP4-CMIP6: the contribution of the Paleoclimate Modelling Intercomparison Project to CMIP6
Authors: Kageyama Masa , Braconnot Pascale , Harrison Sandy P. , Haywood Alan M. , Jungclaus Johann , Otto-Bliesner Bette L. , Peterschmitt Jean-Yves , Abe-Ouchi Ayako , Albani Samuel , Bartlein Patrick J. , Brierley Chris , Crucifix Michel , Dolan Aisling , Fernandez-Donado Laura , Fischer Hubertus , Hopcroft Peter O. , Ivanovic Ruza F. , Lambert Fabrice , Lunt Dan J. , Mahowald Natalie M. , Peltier W. Richard , Phipps Steven J. , Roche Didier M. , Schmidt Gavin A. , Tarasov Lev , Valdes Paul J. , Zhang Qiong , Zhou Tianjun
Published: May 2016

Abstract. The goal of the Palaeoclimate Modelling Intercomparison Project (PMIP) is to understand the response of the climate system to changes in different climate forcings and to feedbacks. Through comparison with observations of the environmental impacts of these climate changes, or with climate reconstructions based on physical, chemical or biological records, PMIP also addresses the issue of how well state-of-the-art models simulate climate changes. Palaeoclimate states are radically different from those of the recent past documented by the instrumental record and thus provide an out-of-sample test of the models used for future climate projections and a way to assess whether they have the correct sensitivity to forcings and feedbacks. Five distinctly different periods have been selected as focus for the core palaeoclimate experiments that are designed to contribute to the objectives of the sixth phase of the Coupled Model Intercomparison Project (CMIP6). This manuscript describes the motivation for the choice of these periods and the design of the numerical experiments, with a focus upon their novel features compared to the experiments performed in previous phases of PMIP and CMIP as well as the benefits of common analyses of the models across multiple climate states. It also describes the information needed to document each experiment and the model outputs required for analysis and benchmarking.
Can canopy interception and biomass be inferred from cosmic-ray neutron intensity? Results from neutron transport modeling
Authors: Andreasen Mie , Jensen Karsten H. , Desilets Darin , Zreda Marek , Bogena Heye , Looms Majken C.
Published: May 2016

Abstract. Cosmic-ray neutron intensity is inversely correlated to all hydrogen present in the upper decimeters of the subsurface and the first few hectometers of the atmosphere above the ground surface. This method has been used for measuring soil moisture and snow water equivalent, but it may also be used to identify and quantify canopy interception and biomass. We use a neutron transport model with various representations of the forest and different parameters describing the subsurface to match measured profiles and time series of thermal and epithermal neutron intensities at a field site in Denmark. A sensitivity analysis is performed to quantify the effect of forest canopy representation, soil moisture, complexity of soil matrix chemistry, forest litter, soil bulk density, canopy interception and forest biomass on neutron intensity. The results show that forest biomass has a significant influence on the neutron intensity profiles at the examined field site, altering both the shape of the profiles and the ground level thermal-to-epithermal neutron ratio. The ground level thermal-to-epithermal neutron ratio increases significantly with increasing amounts of biomass and minor with canopy interception. Satisfactory agreement is found between measurements and model results at the forest site as well as two nearby sites representing agricultural and heathland ecosystems. The measured ground level thermal-to-epithermal neutron ratios of the three site range from around 0.56 to 0.82. The significantly smaller effect of canopy interception on the ground level thermal-to-epithermal neutron ratio was modeled to range from 0.804 to 0.836 for a forest with a dry and a very wet canopy (4 mm of canopy interception), respectively. At the examined field site the signal of the canopy interception is lower than the measurement uncertainty.
Reconstructing the mass balance of Brewster Glacier, New Zealand, using MODIS-derived glacier-wide albedo
Authors: Sirguey Pascal , Still Holly , Cullen Nicolas J. , Dumont Marie , Arnaud Yves , Conway Jonathan P.
Published: May 2016

Abstract. In New Zealand, direct measurements of mass balance are sparse due to the inaccessibility of glaciers in the Southern Alps and the logistical difficulties associated with maintaining a mass balance record. In order to explore the benefit of remotely sensed imaging to monitor mass balance in the Southern Alps, this research assesses the relationship between measurements of glacier surface albedo derived from MODerate resolution Imaging Spectroradiometer (MODIS) and mass balance observations using the glaciological method on Brewster Glacier over the 2005–2013 period. We confirm that minimum glacier-wide albedo is a reliable predictor for annual mass balance in this maritime environment (R2 = 0.93). Furthermore, we show that regular monitoring of glacier-wide albedo enables a new metric of winter accumulation to be derived, namely the cumulative winter albedo, that is found to correlate strongly with winter mass balance (R2 = 0.88), thus enabling the reconstruction of separate winter and summer mass balance records. This allows the mass balance record for Brewster Glacier to be extended back to the start of MODIS observations in 2000 and to confirm that the annual balance of Brewster Glacier is largely controlled by summer balance (R2 = 92 %). An application of the extended record is proposed whereby the relationship between mass balance and the photographic record of the end-of-summer snowline altitude is assessed. This allowed the annual balance record of Brewster Glacier to be reconstructed over the period 1977–2013, thus providing the longest record of mass balance for a glacier in New Zealand. Over the 37-year period, our results show that Brewster Glacier gained significant mass of up to 14.5 ± 2.7 m w.e. by 2007. This gain was offset by a marked shift toward negative balances after 2008, yielding a loss of 5.1 ± 1.2 m w.e., or 35 % of the gain accumulated over the previous 30 years. The good correspondence between mass balance of Brewster Glacier and the phase of the Pacific (Inter-)Decadal Oscillation (PDO/IPO) associated with the fast terminus retreat observed between 1978 and 1998 strongly suggests that observed mass gain of Brewster Glacier since 1977 is only offsetting a longer sequence of dominantly negative balances.
Evaluating the Palestinian Woman's Image in the Local Media from the University Female Students' Perspective in Gaza
Authors: Alloolo Fatheya S. , Kmeil Roba A. Abu
Published: May 2016

Descriptive approach via a questionnaire to evaluate the Palestinian woman's image in media at different levels in Gaza strip, Palestine. 530 female university students were drawn from three universities in Gaza strip involving the Islamic university, Al-Azhar university, and university of Palestine. The outcomes of this study show that women have two prominent traits in that media that is self-made and patient, and sacrificing. The other traits include weak and needy. In addition, at the political level, the media has demonstrated interests in the Palestinian media ladies, and shown their roles in covering the Palestinian political news. At the social level, the outcomes have proved that social media networks have contributed in shaping the mainstream supporting the Palestinian woman's social issues. Besides, at the cultural level, they have stated that customs and traditions hinder media from adopting courageous issues treating the Palestinian woman's political and social status quo. Furthermore, at the economic level, media has given an image about the working Palestinian woman's materialistic abuse. In conclusion, the media should not exaggerate in portraying the woman's image in the issues of violence. It is necessary to present a positive image about her and defend her freedom and rights. Moreover, it recommended to support her to be designated in governmental, ministerial and leadership positions, as well as, to cast light on exemplars for successful women in the field of reasoning and knowledge, and set a media plan based on justice and equality.
Assessing the impact of nicotine dependence genes on the risk of facial clefts: An example of the use of national registry and biobank data
Authors: Jugessur Astanand , Gjessing Håkon K. , Wilcox Allen J. , Nguyen Truc Trung , Nilsen Roy M. , Murray Jeffrey C. , Lie Rolv T.
Published: May 2016

Background: Maternal smoking during pregnancy has consistently been associated with risk of facial clefts in offspring, although these studies cannot establish causation. The association between maternal smoking and clefting risk may be caused by genes that influence nicotine dependence and other risk behaviors. Gamma-aminobutyric acid B receptor 2 (GABBR2), dopa decarboxylase (DDC), and cholinergic receptor nicotinic alpha 4 (CHRNA4) are three examples of genes that have previously shown strong associations with nicotine dependence. Methods: We used a population-based sample of 377 case-parent triads of cleft lip with or without cleft palate (CL/P) and 762 control-parent triads from Norway (1996-2001) to investigate whether variants in GABBR2, DDC and CHRNA4 are associated with maternal first-trimester smoking and with clefting risk. We used HAPLIN (Gjessing et al. 2006), a statistical software tailored for family-based association tests, to perform haplotype-based analyses of 12 SNPs in these genes (rs10985765, rs1435252, rs3780422, rs2779562, and rs3750344 in GABBR2; rs2060762, rs3757472, rs1451371, rs3735273, and rs921451 in DDC; rs4522666 and rs1044393 in CHRNA4). Results: When analyzed one at a time, there was little evidence of association between any of the 12 SNPs and maternal first-trimester smoking. In haplotype analyses, however, one copy of the maternal G-G-c-G-c haplotype in DDC (SNP order as above) was linked with smoking prevalence (odds ratio=1.5; 5% confidence interval: 1.0-2.1). This same haplotype also increased the risk of isolated CL/P in offspring by 1.5-fold with one copy and 2.4-fold with two copies (Ptrend=0.06). No statistically significant associations were detected with GABBR2 and CHRNA4. Conclusions: Despite strong associations previously reported between nicotine dependence and variants in GABBR2, DDC and CHRNA4, these genes were poor predictors of maternal first-trimester smoking in our data. The direct association of the DDC haplotype with CL/P suggests that this haplotype may either have direct effects on clefts or it may influence clefting risks through other yet unexplored risk behavior(s).
Using offspring-parent triads to study complex traits: A tutorial based on orofacial clefts
Authors: Jugessur Astanand , Skare Øivind , Harris Jennifer Ruth , Lie Rolv Terje , Gjessing Håkon Kristian
Published: May 2016

Health investigators routinely collect DNA and environmental data from study participants in order to assess the impact of genetic and environmental risk factors on an outcome of interest. When planning a study, alternate study designs are evaluated to minimize bias and achieve a large enough sample size from available resources. With the enormous volumes of high-quality biomedical data housed within its numerous biobanks, Norway is particularly well-suited to spearhead the investigation of a wide array of exposures and outcomes in a systematic manner. The rich array of longitudinal phenotypic data also permits an assessment of geneenvironment- timing interactions. Maximizing the research potential inherent in Norwegian biobanks is the overarching aim of Biobank Norway, an infrastructure project recently funded by the Norwegian Research Council. The development of advanced statistical tools for the analysis of high-throughput genomic data is critical to fulfill this aim and biostatistics platforms have been key elements of major biobank harmonization initiatives. However, many of these approaches have focused on traditional case-control designs. To exploit the particular advantages inherent in the Norwegian Mother and Child Cohort Study (MoBa), we describe here models to analyze the special data configurations available with offspring-parent designs. These models and the statistical tools outlined in this review were developed through the support of Biohealth Norway, a biobank platform funded by the Norwegian Functional Genomics Research Program (FUGE).
Miscellaneous / Diverse
Authors: Thelle Dag , Søgnen Randi , Nordlund Sturla , Holst Dorthe , Rossow Ingeborg , Magnus Per
Published: May 2016

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University Students’ Attitudes towards E-Learning: University of Business & Technology (UBT)-Saudi Arabia-Jeddah: A Case Study
Authors: Zabadi Abdelrahim M. , Al-Alawi Amr Hussein
Published: May 2016

Through the World Wide Web, education has become a ubiquitous service delivered anytime anywhere. Campus-based and without distance learners, higher education institutions attempt to fulfill the requirements of e-learning in conventional course transmission, to prepare students, staff, and educational institutions for the future involvements in educational processes. The study was conducted to examine attitudes of UBT students’ in Dahban and Sari campuses towards e-learning by taking (371) students from four colleges and English language center.
In sampling techniques, we used the stratified random sampling in choosing the study sample. To gather the primary data from respondents, a well-structured questionnaire, developed by the researchers. The findings indicated that UBT participants’ owns a high standard on attitude towards e-learning and their attitude results are significantly vary with their gender, technology usage and skills.
Performance of Public Mutual Funds (PMFs) in Emerging Economies: A Case of Bangladesh
Authors: Dewri Leo Vashkor , Islam Md. Rashidul
Published: May 2016

Public Mutual fund (PMF) is an instrument for pooling the funds by issuing units to the investors and investing funds in the capital market to achieve their objectives. To invest in mutual funds is a complicated trade for investors as individual assets are belongs to verity of risks and they are dubious on return on investment. There are only 43 Mutual Funds are available to choose from where the investors can invest. To take the investment decision, the investors need to know which funds are performing better than others, gives more return, which fund is more risky etc. In this study the performance evaluation of public mutual funds carried out by considering fund age, fund size, fund return, fund dividend payout, fund price earnings ratio and fund net asset value (NAV). There are only eight PMFs are available in Bangladesh. For analysis purposes the study investigates 1999 to 2015 operations of PMF. Therefore, this study analyzes 128 a firm years, for measuring PMFs performance. The study reveals that fund size, fund return, fund dividend payout and P/E ratio has significant relation on fund performance. Whereas, fund age and fund NAV has insignificant relation on fund performance.
The Relationship between Simultaneous Interpreters’ Speed of Speaking in Persian and the Quality of their Interpreting: A Gender Perspective
Authors: Hasanshahi Poorandokht , Shahrokhi Mohsen
Published: May 2016

This research sought to investigate the relationship between two complex ways of communicating, i.e., speaking and simultaneous interpreting which manifest complex linguistic and neurological processes undertaken with an incredible speed in the brain. The current study aimed at testing whether there was any significant difference between male and female interpreters’ quality of simultaneous interpretation in relation to their speed of speaking in their native language. To this end, a number of thirty participants were chosen based on their proficiency level out of fifty simultaneous interpreters. To test the research hypotheses both descriptive and inferential statistics were used. The results revealed that there was not any significant difference between male and female interpreters with regard to their quality of simultaneous interpretation. Moreover, with regard to the speed of speaking there was a difference between genders; finally, there was no association between interpreters’ speed of speaking and their quality of interpretation.
Factors Underlying Low Achievement of Saudi EFL Learners
Authors: Alrabai Fakieh
Published: May 2016

This paper is devoted to examining the factors responsible for the low achievement in English as a foreign language (EFL) among Saudi students. While some of these factors are demographic variables that pertain specifically to the learners themselves, such as gender, age, motivation, attitudes, aptitude, anxiety, autonomy, learning strategies, and learning style, most are external and outside the learners’ control. These external factors are particularly represented by sociocultural factors, such as the influence of Arabic as the first language (L1); religion, culture, and society; instructional variables, such as teacher behavior and teaching styles, the curriculum, and the teaching methods; and finally, problems with the educational system in Saudi Arabia, such as overcrowded classes, lack of teacher training, and a lack of technology. This paper begins by emphasizing the importance of English language learning for Saudis, followed by an analysis and a discussion of the factors that might explain their lack of achievement. The paper concludes by presenting some implications and offering recommendations for EFL practitioners and policymakers in the Kingdom of Saudi Arabia (KSA) to address the factors contributing to low EFL achievement among Saudi learners.
Identifying, Evaluating and Prioritizing the Factors Affecting the Effectiveness of In-Service Training Courses (Case Study: English Language Teachers of the Secondary Schools in Tehran Selected Districts)
Authors: Alinejad Zahra
Published: May 2016

The current study seeks to identify, extract, evaluate, and prioritize the factors affecting the effectiveness of in-service training course for English language teachers of the secondary schools in Tehran selected districts. The research is applied, and its data collection methodology is descriptive-survey. The statistical population is composed of all of the English language teachers (n=230) practicing in Tehran districts 2 and 4 who participated at least once in one of in-service training courses. Out of all participants, 102 were selected as the sample for data collection using stratified random sampling method. The required data were collected through one standard questionnaire. Data analysis was performed using descriptive and inferential statistical methods. The prioritization of the indices was performed using multi-criteria decision-making techniques. The results from data analysis indicated that out of three factors including individual, training, and organizational, only the organizational factor had a significant positive impact on the effectiveness of in-service training of English language teachers. Hence, using TOPSIS method, the indices relevant to the organizational dimension were ranked based on the respondents’ views. The results from this prioritization showed that, from the teachers’ perspective, the factors with the highest priority include “employment law tailored to attend educational courses”, “organizational support of educational courses”, “score tailored to the course participants in terms of promotion and upgrade”, and “existing a supportive organizational climate for education”.
The Arab Spring: A New Era of Humor Consumption and Production
Authors: Abu Hatab Wafa
Published: May 2016

The 26-year-old Tunisian street vendor, Mohammad Bouazizi set himself ablaze, sparking demonstrations and revolutions in more than one country in the Arab world. Protestors utilized all possible forms of expression to give an outlet for the long suppressed feelings, attitudes and thoughts. A new social discourse emerged where freedom of expression was imposed. Tunisia led the move and was followed by Egypt, Libya, Yemen and Syria. Though these revolting countries have many things in common, each has its own touch to the mosaic portrait of the new social discourse. Political satire has its place in this discourse where political humor has witnessed a tremendous boom. The present study was based on data obtained from cartoons, slogans, digital discourse and jokes. It investigated the use of humor by protesters in the Arab Spring countries, the linguistic devices employed and the role of intertextuality. The study revealed that humor was used in the Arab Spring countries to denigrate the presidents. Sources for intertextuality included proverbs, songs, poetry and commercials. Humor made use of some linguistic devices such as puns, synonyms, antonyms, lexical ambiguity and rhyme.
Effects of Short-term Tillage of a Long-term No-Till Land on Crop Yield and Nutrient Uptake in Two Contrasting Soil Types
Authors: Dyck Miles , Malhi Sukhdev S. , Nyborg Marvin , Puurveen Dyck
Published: May 2016

Pre-seeding tillage of long-term no-till (NT) land may alter crop production by changing the availability of some nutrients in soil. Effects of short-term (4 years) tillage (hereafter called reverse tillage [RT]) of land previously under long-term (29 or 30 years) NT, with straw management (straw removed [SRem] and straw retained [SRet]) and N fertilizer rate (0, 50 and 100 kg N ha-1 in SRet, and 0 kg N ha-1 in SRem plots), were determined on plant yield (seed + straw, or harvested as forage/silage at soft dough stage), and N and P uptake in growing seasons from 2010 to 2013 at Breton (Gray Luvisol [Typic Cryoboralf] loam) and from 2009 to 2012 at Ellerslie (Black Chernozem [Albic Argicryoll] loam), Alberta, Canada. Plant yield, N uptake and P uptake tended to be greater with RT compared to NT in most cases at both sites, although significant in a few cases only at Ellerslie. On average over both sites, RT produced greater plant yield by 560 kg ha-1 yr-1, N uptake by 5.8 kg N ha-1 yr-1, and P uptake by 1.8 kg P ha-1 yr-1 than NT. There was no consistent beneficial effect of straw retention on plant yield, N uptake and P uptake in different years. Plant yield, N uptake and P uptake increased with N fertilization at both sites, with up to the maximum rate of applied N at 100 kg N ha-1 in 3 of 4 years at Breton and in 2 of 4 years at Ellerslie. In conclusion, our findings suggested some beneficial impact of occasional tillage of long-term NT soil on crop yield and nutrient uptake.
New leaf- and litter-dwelling species of the genus Pholcus from Southeast Asia (Araneae, Pholcidae)
Authors: Huber Bernhard , Koh Joseph K.H. , Ghazali Amir-Ridhwan M. , Braima Kamil A. , Nuñeza Olga M. , Leh Moi Ung Charles , Petcharad Booppa
Published: May 2016

We describe eight new species of the genus Pholcus, and document their microhabitats. Four species are assigned to the previously described Pholcus ethagala group: P. tanahrata Huber sp. nov., P. uludong Huber sp. nov., and P. bukittimah Huber sp. nov. from the Malay Peninsula, and P. barisan Huber sp. nov. from Sumatra. These species are all litter-dwellers that build domed sheet webs on the undersides of large dead leaves on the ground. The other four species are assigned to newly created species groups: the P. tambunan group with two species from northern Borneo: P. tambunan Huber sp. nov. and P. bario Huber sp. nov.; and the P. domingo group with two species from the Philippines, Mindanao: P. domingo Huber sp. nov. and P. matutum Huber sp. nov. These latter four species are leaf-dwellers that build barely visible silk platforms tightly attached to the undersides of live leaves. The main rationale for this paper is to provide part of the taxonomic and natural history background for upcoming phylogenetic and evolutionary (microhabitat shifts) analyses.
[The difficult management of patients with type 2 diabetes and renal disease: from diagnosis to treatment]
Authors: Pontremoli Roberto , Cappadona Francesca , Solini Anna
Published: May 2016

The prevalence of type 2 diabetes mellitus and arterial hypertension is on the rise in western countries and chronic kidney disease is certainly one of their most harmful complications. This condition greatly complicates patient management. The clinician needs to wisely identify the best diagnostic algorithm and carefully balance potential risks and benefits of each therapeutic decision.Even when recommended therapeutic targets can be achieved, often a challenging task in clinical practice, residual cardiovascular and renal risk remains unacceptably high for these patients.Here we present the case of a 72-year old woman, with arterial hypertension and diabetes mellitus type 2. Despite the long clinical history of the patient, being treated for over 20 years,blood pressure and metabolic control were not satisfactory. The authors trace the patient’s treatment pathway, following the different clinical questions that led them to the modification of the patient’s therapy. The new therapy is based on chlorthalidone, sitagliptin, a combinationtherapy of ezetimibe / simvastatin, and metformin. [Article in Italian]
Successful treatment with belimumab of severe systemic lupus erythematosus not responding to standard therapy: a case report
Authors: Magnani Ottavia , Penza Elena , Murdaca Giuseppe , Puppo Francesco
Published: May 2016

Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by complex pathophysiology and heterogeneous clinical picture. Belimumab is the first biological therapy licensed for SLE. We report the case of a 24 years old woman affected by a severe form of systemic lupus erythematosus with arthritis, muscle weakness, cervical lymphadenopathy, cutaneous involvement, fever, leukopenia, low complement levels and positivity for anti-dsDNA antibodies. Treatment with high dose steroids, hydroxychloroquine, and mycophenolate mofetil did not induce remission and several disease flares were observed. Therapy with anti-BLys monoclonal antibody belimumab leads to a fast clinical and laboratory response and to stable remission lasting for 30 months allowing steroid tapering to very low maintenance dose.
From generic to biosimilar drugs: why take an innovative pace?
Authors: Barei Fereshteh , Le Pen Claude , Simoens Steven
Published: May 2016

BACKGROUND: The transition of the generic/biotechnology industry to innovation by investing in innovative R&D will enhance business expertise in biopharmaceutical development and manufacturing. The major impact of this evolution is on patient access to treatment and savings for the health care systems. OBJECTIVES: The aim of this paper is to investigate the innovative aspect of biosimilar and biobetter products, manufactured by some big generic companies. We will also try to explore the innovative business strategy, implementing this high risk product differentiation policy. METHODS: This qualitative research is conducted by a series of interviews with CEOs, physicians, and academics in different countries. The qualitative data obtained were analyzed by Nvivo9.2 software. A literature review has also contributed to our key findings. RESULTS: The results show that switching into biosimilars/biobetters is an innovative strategic choice, approved by some big generic pharmaceutical companies. The biosimilar/biobetter products can be considered innovative because of their value added quality. CONCLUSION: Expanding the product portfolio to biosimilars/biobetter can be considered as a long run strategy in the innovative business plans aiming to ensure the market access. Patients and their access to better treatments are major components of these innovative business models.
Generic and biosimilar medicines: quid?
Authors: Simoens Steven
Published: May 2016

Once intellectual property protection, data and marketing exclusivity of reference medicines have expired, generic medicines and biosimilar medicines can enter the off-patent market. This market entry is conditional on the approval of marketing authorization, pricing and reimbursement. Given that there tends to be confusion surrounding generic and biosimilar medicines, this Editorial introduces basic concepts related to generic and biosimilar medicines and presents the different studies and articles included in this supplement dedicated to generic and biosimilar medicines.
Role of antileukotrienes in acute asthma exacerbations
Authors: Urso Domenico Lorenzo , Vincenzo Daniele , Formaro Lorenzo , Federico Ada , Urso Giuseppe
Published: May 2016

Acute asthma exacerbations are one of the most frequent reasons to visit the emergency department or general practitioner. Although current standard treatments for acute asthma – including supplemental oxygen, short-acting β2-agonists, systemic corticosteroids and anticholinergics – are quite effective in most patients, they are inadequate for rapid and sustained improvement in a significant proportion. The antileukotrienes, a relatively new class of drugs, have a role in the treatment of chronic asthma. Their relatively rapid onset of action after endovenous or oral administration and their additive effect to β2-agonists led to the hypothesis that they might be of benefit in acute asthma. This review examines the efficacy of antileukotrienes in the treatment of acute asthma.
Kidney failure during HIV disease treated with tenofovir, multiple concurrent diseases and drug therapies
Authors: Manfredi Roberto , Calza Leonardo , Colangeli Vincenzo , Dentale Nicola , Verucchi Gabriella
Published: May 2016

A significant case report of a HIV infected patient in his fifties who experienced an excellent virological and immunological response to antiretroviral therapy (which has been modified just to prevent or avoid some adverse events), but developed a severe, sudden acute kidney failure while under a polypharmacy due to some underlying and overwhelming disorders (i.e. arterial hypertension, non-insulin-dependent diabetes mellitus, a recent acute heart infarction with remarkable remnants, and finally an anecdotal muscle-joint pain with self-prescription of non-steroideal anti-inflammatory drugs), represents the key point for a debate around the increasing frequency of “polypharmacy” in the field of HIV infection, even when HIV resistance to antiretroviral is not a concern. The continuing increase of mean age of HIV-infected population, plus the existing, sometimes unmodifiable risk factors for cardiovascular, dysmetabolic, and renal disorders, plus the adjunct of anecdotal illnesses prompting the resort to different drugs and medications, either prescribed for HIV infection itself, or taken for concurrent or subsequent diseases, or self-prescribed occasionally due to an intercurrent, trivial disorders per se, may prompt a complicated scenario culminating with a life-threatening acute renal failure of tubular origin. Our report gives us the opportunity to revise and discuss the expected interactions between antiretroviral therapy and the even growing exposure to multiple different drug and drug classes, which may be responsible for relevant drug interactions and direct or adjunctive end-organ impairment, up to life-threatening conditions, which may be avoided or prevented by considering carefully all comorbidites and co-treatments potentially administered to HIV infected patients, thirty years after the discovery of AIDS.
Developing novel drugs for systemic lupus erythematosus. Lessons learned from the belimumab trials
Authors: Pamfil Cristina , Fanouriakis Antonis , Boumpas Dimitrios T
Published: May 2016

Systemic lupus erythematosus is the prototypic autoimmune disease with a broad range of clinical manifestations and a complex pathogenesis. B-cells hold a central role in its pathogenesis, not only as autoantibody producing cells, but also by producing other inflammatory mediators and by presenting autoantigens to autoreactive T cells. BlyS, a soluble ligand of the TNF cytokine family, is a key factor affecting B-cell homeostasis and survival and its blockade ameliorated the disease in animal models and preclinical studies of SLE. Following an unsuccessful phase II trial of belimumab, a monoclonal antibody targeting BlyS, two large phase III studies in patients with mild-to-moderate disease, BLISS-52 and BLISS-76, met their primary endpoints showing better efficacy of the drug over standard of care alone. To this end, development of a novel more sensitive responder index and improvements in study designs were crucial. As a result, belimumab became the first drug to get approval for the treatment of SLE after more than 50 years. In this paper we discuss the rationale, development, indications, lessons learned, pitfalls and challenges for this novel therapy and point-out to additional issues that need to be addressed in the future.http://dx.doi.org/10.7175/rhc.v3i3.206
Vitamin D and inflammation in the prevention of type 2 diabetes: public health relevance
Authors: Badawi Alaa , Sadoun Eman , Al Thani Mohamed H.
Published: May 2016

The incidence of type 2 diabetes mellitus (T2DM) is increasing worldwide. To reduce the disease risk and burden at the population level, preventative strategies should be developed with minimal cost and effort and with no side-effects. Low-grade inflammation resulting from imbalances in the innate immune system has been associated with an array of chronic disorders that predispose to the later development of T2DM (e.g., obesity, metabolic syndrome, and insulin resistance). As a result, inflammation may contribute to the pathogenesis of T2DM. Therefore, attenuation of this inflammatory response via modulating the innate immune system could lead to improved insulin sensitivity and delayed disease onset. Dietary supplementation with vitamin D may represent a novel strategy toward the prevention and control of T2DM at the population level due to its anti-inflammatory and antioxidant properties. This review examines current knowledge linking T2DM to chronic low-grade inflammation and the role of vitamin D in modulating this relationship. The concept that vitamin D, via attenuating inflammation, could be employed as a novel preventive measure for T2DM is evaluated in the context of its relevance to health care and public health practices.
Exercise stress testing in clinical practice
Authors: Giallauria Francesco , Grieco Alessandra , Russo Angelo , Maresca Luigi , Mancini Maria , Vitelli Alessandra , Aurino Sara , Vigorito Carlo
Published: May 2016

Exercise stress testing is an important diagnostic tool for evaluating patient’s cardiovascular performance. The present review describes the accuracy and the value of exercise stress testing in different settings: after an acute coronary event, after percutaneous coronary intervention or coronary artery bypass graft; in patients risk assessment before non-cardiac surgery; in diabetic population; in patients with baseline electrocardiographic abnormalities. Moreover, this review provides insights relating to test accuracy in women and geriatric patients. Finally, this review explores new variables/parameters (dyspnea, chronotropic incompentence, heart rate recovery, functional capacity, integrated scores) that in the last few years added an incremental value to conventional analysis of exercise-induced angina or electrocardiographic changes.
Prophylaxis of venous thrombosis in patients with spontaneous intracerebral bleeding
Authors: Rezoagli Emanuele , Ageno Walter , Masotti Luca , Godoy Daniel , Di Napoli Mario , Paciaroni Maurizio , Rabinstein Alejandro
Published: May 2016

Spontaneous intracerebral haemorrhage (SIH) represents a severe clinical event that is associated with high rates of mortality and morbidity. Only a minority of SIH patients receive surgical treatment, whereas the majority are treated conservatively. Venous thromboembolism (VTE) is one of the most common complications in SIH patients and a potential cause of death. Because of the lack of adequate evidences from the literature, the risk to benefit ratio of pharmacologic prophylaxis of VTE, represented on the one hand by hematoma enlargement and/or rebleeding and on the other hand by an expected reduction of the risk of VTE, remains controversial. Mechanical prophylaxis is a potentially safer alternative, but the efficacy of this approach is uncertain. In the absence of specific clinical guidelines containing clear-cut recommendations, physicians have insufficient tools to assist their therapeutic decisions.
When and how is possible hemostatic therapy in non anticoagulant-associated intracerebral haemorrhage
Authors: Prisco Domenico , Grifoni Elisa , Cenci Caterina
Published: May 2016

Hematoma volume is a major determinant of outcome in spontaneous intracerebral haemorrhage (ICH) and its secondary expansion occurs frequently and early with the potential sequelae of rostrocaudal deterioration or death. Therefore, early restriction of ICH volume is of paramount importance. Although few indications appear to be available for neurosurgical measures, nonsurgical measures such as reduction of hypertension and normalisation of altered coagulation seem to be beneficial. However, the routinary use of coagulation factors outside of anticoagulant-associated spontaneous ICH cannot generally be recommended at present. Future trials on recombinant coagulation factor VIIa with stricter selection criteria of inclusion time window, ICH and intraventricular haemorrhage volume, and age of patients are needed.
The role of neuroradiology in intracerebral haemorrhage
Authors: Prosetti Daniele , Vannozzi Francesca , Scazzeri Fabio
Published: May 2016

The neuroradiologist plays a fundamental role in evaluating cerebral haemorrhage, from the clinical suspect until the final diagnosis.The neuroradiologist’s role consists not only in highlighting the presence of an haemorrhage, but also in specifying its localization and its nature, and in assessing, together with the neurosurgeon, the adequate treatment.With the aid of some case reports, this article underlines the role of neuroradiologist in the diagnostic process. For each case report discussed, computerised tomography (CT) and digital subtraction angiography (DSA) findings are given, to better highlight the diagnostic role of these techniques in the detection and characterization of intracranial haemorrhage.
Invasive fungal infections in hematology: epidemiology and risk factors
Authors: Bassetti Matteo , Caira Morena , Carvalho Agostinho
Published: May 2016

Recent Italian and International epidemiological data show that invasive fungal infections (IFI), particularly aspergillosis, are still a crucial issue for patients with acute myeloid leukemia. However, in the last years the epidemiology is changing, and in order to determine the real risk of a patient and in order to improve preventive, diagnostic and therapeutic measures, it’s important to identify all the factors (e.g. age, performance status, prophylaxis) that play a role in the development of IFI. Immunogenetics may potentially contribute to improve diagnosis providing new therapeutic tools, but results are limited by sample size and absence of thorough functional characterization moreover lack of replication limits translation of data to the clinical practice. Regarding candidemia an Italian study showed that the overall incidence remained unchanged between 2008 and 2010 but with an increase in the number of C. albicans aand C. glabrata infections.
Prophylaxis and treatment of invasive fungal infections in hematological patients
Authors: Busca Alessandro , Candoni Anna , Pagano Livio , Scaglione Francesco , Viscoli Claudio
Published: May 2016

The evidence from the literature strongly support antifungal prophylaxis in high risk haematological patients, such as patients with AML during remission induction chemotherapy and alloHSCT patients. Current antifungal prophylaxis guidelines for high risk patients recommend azoles (fluconazole, posaconazole, voriconazole) and echinocandins (micafungin) with the strongest level of evidence. In terms of treatment, the choice between empiric therapy (or fever driven) and pre-emptive therapy (or diagnostic driven) is still debated. Not a single therapeutic strategy is appropriate in every patients, in particular empirical antifungal therapy may be recommended in patients at very high risk, while a pre-emptive approach may be advised for those at standard risk. In order to exploit the synergistic and/or additive effect of two antifungal drugs it’s possible to combine two agents that work with different mechanisms of action (e.g. echinocandins + azoles or polyenes). Once the treatment has been initiated we should consider the therapeutic drug monitoring (TDM) of the drugs, especially when the pharmacokinetic variability is high and the dose-concentration effect relationships is not predictable (e.g. for itraconazole, voriconazole and posaconazole).
Invasive fungal disease in specific at-risk patients
Authors: Castagnola Elio , De Rosa Francesco Giuseppe , Nosari Anna Maria , Urbino Rosario
Published: May 2016

Hematological patients, such as patients with lymphoproliferative syndromes, pediatric patients and patients in ICU, are not conventionally classified as high risk patients for the development of IFI, however invasive fungal infections should not be underestimated. In this subset of patients, particularly patients with lymphoproliferative syndromes are classified at intermediate risk for IFI especially if treated with monoclonal antibodies, purine analogs or steroids. With regard to pediatric patients the incidence of IFD is lower than in adults and is greater in patients with acute myeloid leukemia and in allotransplant patients. Finally, in patients in ICU there is high incidence of mold and Candida. Factors associated with increased mortality is the delay in admission in intensive care units, high-dose corticosteroid therapy, and GvHD.
Epidemiology of intracerebral haemorrhage in Livorno district
Authors: Masotti Luca , Filippi Sandro , Acciai Serenella , Mechi Maria Teresa , Gori Sandra , Mannucci Annalisa , Bellizzi Anna Maria , Scotto Fabio Paolo , Cannistraro Daniela , Bini Chiara , Ubaldi Euro , Gianchecchi Daniele , Corchia Arturo , Antonelli Fabio , Pennati Paolo , Pampana Alessandro
Published: May 2016

BACKGROUND: Intracranial haemorrhage represents the most feared stroke subtype. AIM: To evaluate the burden of intracranial haemorrhage in Tuscany hospitals with special reference to Livorno district. MATERIALS AND METHODS: Data of patients discharged in 2009 from Tuscan and Livorno hospitals with codes ICD-9-CM related to any type of spontaneous intracranial haemorrhage were selected and analyzed. RESULTS: 3,472 patients were discharged from Tuscan hospitals with these diagnoses. Overall mortality was 24.3%. 50% of patients were admitted in Internal Medicine wards. Incidence of intracranial haemorrhage and intracerebral haemorrhage (ICH) in population of Livorno district was 64 and 45/100,000 inhabitants/year with related mortality of 36.5% and 39.4%respectively. Intra-hospital mortality of patients admitted in Livorno hospitals for intracranial haemorrhage were 36.7%. 40% of deaths occurred in the first 48 hours. 69.6% of intracranial haemorrhage were ICHs, 16.8% subaracnoideal. Intra-hospital mortality, admissions for intracranial haemorrhage in respect of total admissions and mortality for intracranial haemorrhage in respect to total mortality increased in the last decade. 23% of patients with intracranial haemorrhage and 16% of patients with ICH underwent to surgical procedures. ICHs related to antithrombotic treatment significantly increased in the last years. Mortality in patients on antithrombotic drugs was three times over compared to that in patients not undergone these drugs (43.7% vs 12.8%, p < 0.01). CONCLUSION: There is an increasing trend in frequency, mortality and hospital burden of intracranial haemorrhage and ICH. Efforts aimed at reducing the burden and consequences of this devasting disease are warranted.
Citation classics in epilepsy
Authors: Wilson Maryann , Nani Andrea , Cavanna Andrea Eugenio
Published: May 2016

BACKGROUND: The impact of a scientific article is proportional to the citations it has received. In this study, we set out to identify the most cited works in epileptology in order to evaluate research trends in this field. METHODS: According to the Web of Science database, articles with more than 400 citations qualify as "citation classics". We conducted a literature search on the ISI Web of Science bibliometric database for scientific articles relevant to epilepsy. RESULTS: We retrieved 67 highly cited articles (400 or more citations), which were published in 31 journals: 17 clinical studies, 42 laboratory studies, 5 reviews and 3 classification articles. Clinical studies consisted of epidemiological analyses (n=3), studies on the clinical phenomenology of epilepsy (n=5) – including behavioral and prognostic aspects – and articles focusing on pharmacological (n=6) and non-pharmacological (n=3) treatment. The laboratory studies dealt with genetics (n=6), animal models (n=27), and neurobiology (n=9) – including both neurophysiology and neuropathology studies. The majority (61%) of citation classics on epilepsy were published after 1986, possibly reflecting the expansion of research interest in laboratory studies driven by the development of new methodologies, specifically in the fields of genetics and animal models. Consequently, clinical studies were highly cited both before and after the mid 80s, whilst laboratory researches became widely cited after 1990. CONCLUSIONS: Our study indicates that the main drivers of scientific impact in the field of epileptology have increasingly become genetic and neurobiological studies, along with research on animal models of epilepsy. These articles are able to gain the highest numbers of citations in the time span of a few years and suggest potential directions for future research.