bluuebunny/crossref_metadata_2025 huggingface dataset:
Very Late Hazard with Stenting versus Balloon Angioplasty for ST‐Elevation Myocardial Infarction: A 16‐Year Single‐Center Experience
Authors: BRODIE BRUCE R. , POKHAREL YASHASHWI , GARG ANKIT , KISSLING GRACE , HANSEN CHARLES , MILKS SALLY , COOPER MICHAEL , MCALHANY CHRISTOPHER , STUCKEY THOMAS D.
Published: December 2013

Objectives

This study compares very late outcomes following primary percutaneous coronary intervention for ST‐elevation myocardial infarction (STEMI) with stenting versus balloon angioplasty (BA).

Background

Stenting compared with BA for STEMI improves outcomes at 6–12 months, but comparisons beyond 6–12 months have not been studied. Recent studies have shown that stent thrombosis (ST) continues to increase beyond 3–5 years and may be higher with drug‐eluting stents (DES) than bare metal stents (BMS). We hypothesized that there may be a very late hazard with stenting versus BA due to very late ST.

Methods

From 1994 to 2010 consecutive patients with STEMI treated with BA (n = 601) or stenting (n = 1,594) were prospectively enrolled in our registry and followed for 1–16 years.

Results

Patients treated with BA were older, were more often female, had more three‐vessel disease, and had smaller vessels. Stented patients had trends for less stent/lesion thrombosis (ST/LT) and target vessel (TV) reinfarction at 1 year. In landmark analyses >1 year, stented patients had more very late ST/LT (6.1% vs. 2.9%, P = 0.002) and more TV reinfarction (7.9% vs. 3.1%, P < 0.001) which remained significant after adjusting for baseline risk. The greatest differences in very late outcomes were between DES and BA, but there were also significant differences between BMS and BA.

Conclusions

There appears to be a very late hazard with stenting versus BA for STEMI. These data should encourage new strategies for prevention of very late ST with both BMS and DES including the development of bio‐absorbable polymers and stent platforms. (J Interven Cardiol 2014;27:21–28)
Impact of lipoprotein(a) levels and apolipoprotein(a) isoform size on risk of coronary heart disease
Authors: Hopewell J. C. , Seedorf U. , Farrall M. , Parish S. , Kyriakou T. , Goel A. , Hamsten A. , Collins R. , Watkins H. , Clarke R. ,   the PROCARDIS Consortium
Published: December 2013

Objectives

Observational and genetic studies have shown that lipoprotein(a) [Lp(a)] levels and apolipoprotein(a) [apo(a)] isoform size are both associated with coronary heart disease (CHD) risk, but the relative independence of these risk factors remains unclear. Clarification of this uncertainty is relevant to the potential of future Lp(a)‐lowering therapies for the prevention of CHD.

Methods

Plasma Lp(a) levels and apo(a) isoform size, estimated by the number of kringle IV (KIV) repeats, were measured in 995 patients with CHD and 998 control subjects. The associations between CHD risk and fifths of Lp(a) levels were assessed before and after adjustment for KIV repeats and, conversely, the associations between CHD risk and fifths of KIV repeats were assessed before and after adjustment for Lp(a) levels.

Results

Individuals in the top fifth of Lp(a) levels had more than a twofold higher risk of CHD compared with those in the bottom fifth, and this association was materially unaltered after adjustment for KIV repeats [odds ratio (OR) 2.05, 95% confidence interval (CI) 1.38–3.04, P < 0.001]. Furthermore, almost all of the excess risk was restricted to the two‐fifths of the population with the highest Lp(a) levels. Individuals in the bottom fifth of KIV repeats had about a twofold higher risk of CHD compared with those in the top fifth, but this association was no longer significant after adjustment for Lp(a) levels (OR 1.13, 95% CI 0.77–1.66, P = 0.94).

Conclusions

The effect of KIV repeats on CHD risk is mediated through their impact on Lp(a) levels, suggesting that absolute levels of Lp(a), rather than apo(a) isoform size, are the main determinant of CHD risk.
Occlusal tooth wear in Chinese adults with shortened dental arches
Authors: Zhang Q. , Witter D. J. , Bronkhorst E. M. , Bartlett D. W. , Creugers N. H. J.
Published: December 2013

To assess associations between occlusal tooth wear and shortened dental arches (SDA) in Chinese 40 years and older subjects. From a sample of 1462 urban and rural adults, those presenting with SDA (n = 150) were compared with a control group of 65 randomly selected subjects with complete dentitions (CDA). Occlusal wear was assessed using a modified Smith and Knight index – the occlusal tooth wear index (OWTI) – and analysed using multivariate (logistic) regression. There was no significant effect from SDA on severe occlusal wear (OTWI score 3 or 4: OR = 2·016; 95% CI = 0·960–4·231; P = 0·064). Higher age was associated with severe occlusal wear (P values ≤0·007) and with higher mean OTWI scores; urban had less often severe occlusal wear than rural residents (OR = 0·519; P = 0·008). Higher mean OTWI scores were associated with rural residents, except for anterior teeth. Females had lower mean OTWI score for anterior teeth (effect = −0·153; P = 0·030). Premolars in SDA had higher mean OTWI scores compared with those in CDA (effect = +0·213; P = 0·006). In SDA, more posterior occluding pairs (POPs) were associated with lower mean OTWI sores for anterior teeth (effect: −0·158; P = 0·008) and higher scores for molars (effect: +0·249, P = 0·003). Subjects with SDA or CDA presented comparable occlusal wear, but premolars in SDA tend to have higher probability for having occlusal wear. Fewer numbers of POPs were associated with more wear in anterior teeth.
INDUSTRIAL AGGLOMERATION AND EMPLOYER COMPLIANCE WITH SOCIAL SECURITY CONTRIBUTION: EVIDENCE FROM CHINA
Authors: Chen Bin R. , Wu Mingqin
Published: December 2013

This paper, by using annual surveys of Chinese manufacturing firms from 2001 to 2007, investigates the relationship between industrial agglomeration and employer compliance with required pension contributions. The result of panel fixed‐effect estimation shows that in the more agglomerated industrial areas, firms comply with pension mandates at a higher level. Our finding is robust to various specifications and estimations employing instrumental variables.
Fetoscopic endoluminal tracheal occlusion (FETO) for congenital diaphragmatic hernia in Australia and New Zealand: Are we willing, able, both or neither?
Authors: Cundy Thomas P , Gardener Glenn J , Andersen Chad C , Kirby Christopher P , McBride Craig A , Teague Warwick J
Published: December 2013

Aim

An estimated 140 pregnancies are diagnosed with congenital diaphragmatic hernia (CDH) in Australia and New Zealand each year, with these fetuses having a less than even chance of 1‐year survival. Fetoscopic endoluminal tracheal occlusion (FETO) is a relatively new technique that offers a prenatal interventional strategy for selective cases of CDH. This is not routinely offered in Australia or New Zealand. The aim of this systematic review is to critically appraise controlled clinical trials investigating the role of FETO in moderate and severe isolated CDH and explore whether this treatment is justified within our region.

Methods

A systematic literature search of multiple electronic databases was undertaken, with restrictions to human subjects and controlled clinical trials.

Results

Nine relevant studies were identified. No current evidence was found in favour of FETO for moderate severity CDH. For severe CDH, the most recent evidence demonstrates significantly improved survival following FETO performed using contemporary percutaneous minimally invasive techniques. Optimum timing for balloon insertion, removal and occlusion duration remains conjectural. Substantial variation in survival rates observed among control groups highlights the impact of post‐natal care in prenatally diagnosed CDH.

Conclusion

Until recently, evidence to support a role for FETO in prenatal CDH management was weak. Recently reported and ongoing controlled trials give cause for optimism, with improved FETO safety and increased survival reported for severe CDH cases. Should Australasia embrace FETO for selected CDH cases, a co‐ordinated, evidence‐informed service should be established under the guidance of experienced international partnerships.
North–South divide: Distribution and outcome of respiratory viral infections in paediatric intensive care units in Cape Town (South Africa) and Nottingham (United Kingdom)
Authors: Lonngren Camilla , Morrow Brenda M , Haynes Sarah , Yusri Taha , Vyas Harish , Argent Andrew C
Published: December 2013

Aim

This study aims to describe and compare the spectrum, course, seasonality and outcome of children with virus‐associated respiratory symptoms (VARS) admitted to two paediatric intensive care units (PICUs) in the United Kingdom (UK) and South Africa (SA).

Methods

Cross‐sectional study of routinely collected data on subjects admitted to PICU with respiratory symptoms and positive respiratory viral polymerase chain reaction between July 2009 and July 2011.

Results

Six hundred forty‐six samples yielding 765 viral isolates (74% from SA) from 599 patients (53% male; median (interquartile range) age 6.0 (2.3–16.5) months) were included. Rhinovirus, respiratory syncytial virus and adenovirus were most commonly isolated. Adenovirus was more prevalent in SA (24.3% vs. 16.8%, P = 0.03). Possible or likely nosocomial viral acquisition occurred in 78% of isolates in SA versus 48% in the UK (P < 0.0001).Total mortality was 13.5%; 17% in SA versus 4% in the UK (P < 0.0001). Mortality for community acquired VARS was 8.4% versus 16.1% in those with possible nosocomial viral acquisition (P = 0.009). Factors independently associated with mortality were: SA study site (adjusted odds ratio (OR) 3.4, 95% confidence interval (CI) 1.4–8.5; P = 0.008); age (months) (OR 1.0, 95% CI 1.0–1.02; P = 0.001); Paediatric Index of Mortality 2 score (%) (OR 1.0, 95% CI 1.01–1.03; P = 0.0002) and isolation of adenovirus (OR 3.0, 95% CI 1.8–5.0; P < 0.0001).

Conclusions

The outcome of children with VARS was worse in SA compared with the UK PICU. Nosocomial VARS was highlighted as an important concern and requires further investigation.
Non‐operative advances: What has happened in the last 50 years in paediatric surgery?
Authors: Holland Andrew JA , McBride Craig A
Published: December 2013

Paediatric surgeons remain paediatric clinicians who have the unique skill set to treat children with surgical problems that may require operative intervention. Many of the advances in paediatric surgical care have occurred outside the operating theatre and have involved significant input from medical, nursing and allied health colleagues. The establishment of neonatal intensive care units, especially those focusing on the care of surgical infants, has greatly enhanced the survival rates and long‐term outcomes of those infants with major congenital anomalies requiring surgical repair. Educational initiatives such as the advanced trauma life support and emergency management of severe burns courses have facilitated improved understanding and clinical care. Paediatric surgeons have led with the non‐operative management of solid organ injury following blunt abdominal trauma. Nano‐crystalline burn wound dressings have enabled a reduced frequency of painful dressing changes in addition to effective antimicrobial efficacy and enhanced burn wound healing. Burns care has evolved so that many children may now be treated almost exclusively in an ambulatory care setting or as day case‐only patients, with novel technologies allowing accurate prediction of burn would outcome and planning of elective operative intervention to achieve burn wound closure.
Supported playgroups as a setting for promoting physical activity of young children: Findings from a feasibility study in south‐west Sydney, Australia
Authors: Weber Danielle , Rissel Chris , Hector Debra , Wen Li Ming
Published: December 2013

Aim

This study examined the feasibility of the supported playgroups (SPGs) setting to promote physical activity among young children and increase staff and parental knowledge of the physical activity recommendations for young children.

Methods

A 10‐week Active Play@Playgroup intervention was conducted with 28 co‐ordinators and 174 parents attending SPGs located in south‐west Sydney. The intervention involved training and providing support to SPG co‐ordinators to help promote active play and reduce screen time for young children. The effectiveness of the intervention was evaluated using pre‐ and post‐intervention surveys. The main outcomes included changes in parents' knowledge of physical activity recommendations for 0‐ to 5‐year‐olds, and children's physical activity and sedentary behaviours outside of playgroup.

Results

The mean time children spent playing actively outdoors during the week increased (pre: 1.48 h/day vs. post: 1.95 h/day, P = 0.02), and the time parents spent playing actively with their children increased both during weekdays (pre: 1.57 h/day vs. post: 2.42 h/day, P = 0.01) and on the weekend (pre: 2.95 h/day vs. post: 3.83 h/day, P = 0.02). There was also a significant increase in the proportion of parents with correct knowledge of recommended screen time for 0‐ to <2‐year‐olds (pre: 7.9% vs. post: 23.4%, P = 0.02).

Conclusions

It is feasible and potentially effective to use the SPG setting to promote active play among young children and increase parents' knowledge of physical activity recommendations for young children.
Retrospective review of 200 children hospitalised with acute asthma. Identification of intervention points: A single centre study
Authors: Giarola Blake F , McCallum Gabrielle B , Bailey Emily J , Morris Peter S , Maclennan Carolyn , Chang Anne B
Published: December 2013

Aim

Indigenous Australians with asthma have higher morbidity and mortality compared with non‐Indigenous Australians. In children hospitalised with acute asthma, we aimed to (i) determine if acute severity, risk factors and management differed between Indigenous and non‐Indigenous children; and (ii) identify intervention points to reduce morbidity and mortality of asthma.

Methods

Retrospective review of 200 children hospitalised to Royal Darwin Hospital with asthma. We compared admission characteristics, severity indices, treatment, discharge plans and readmissions in Indigenous and non‐Indigenous children.

Results

Median age was 3.6 years (interquartile range 2.2, 6.8). A significantly higher proportion of Indigenous children (95.2%) were exposed to tobacco smoke compared with non‐Indigenous children (45.7%). The difference in proportions was −0.41 (95% confidence interval (CI) −0.60, −0.22). Other risk factors, asthma severity (moderate 83.9% vs. 83.3%; severe 16% vs. 16.1%), length of stay (1.9 vs. 1.3 days) and readmission rate (27.4% vs. 27.5%) were similar between Indigenous and non‐Indigenous children. Indigenous children were significantly more likely to be followed up in a community clinic (difference in proportions = 0.10, 95% CI 0.1, 0.17) and less likely by a paediatrician. Only 62.5% of all children had an asthma action plan on discharge.

Conclusion

Unlike other common respiratory diseases requiring hospitalisation, biological factors are unlikely major contributors to the known gap in asthma outcomes between Indigenous and non‐Indigenous children. Intervention points include better identification, documentation and management of tobacco smoke exposure, delivery of salbutamol and discharge planning (including education and utilisation of asthma action plans).
Insult to injury: Transient encephalopathy in a brain‐injured adolescent
Authors: Peters Jurriaan M , Fernández Iván Sánchez
Published: December 2013

We report on an adolescent with prior brain injury who responded to abrupt drug changes and an electrolyte imbalance with a significant alteration in the level of consciousness. In children with prior brain injury, paediatricians should consider the concept of a ‘fragile brain’ with limited ‘cognitive reserve’ and increased susceptibility to relatively minor toxic‐metabolic insults. Psychoactive and central nervous system drugs should be managed with prudence in these patients.
Epidermal nevus syndrome with hypophosphatemic rickets in a young girl
Authors: Sukkhojaiwaratkul Dabuswinee , Mahachoklertwattana Pat , Poomthavorn Preamrudee
Published: December 2013

Epidermal nevus syndrome (ENS) is a rare congenital disorder. It is characterised by epidermal nevi and abnormalities of multiple organs, including central nervous system, skeleton, cardiovascular and genitourinary systems and eyes. Hypophosphatemic rickets‐associated ENS has rarely been reported. We report a 46‐month‐old girl who presented with a classical feature of hypophosphatemic rickets. Examination of skin revealed multiple melanocytic nevi at her trunk, face and both arms with verrucous plaques at both axillae and neck, and yellow plaques at the back along Blaschko's lines. Histopathology of the skin lesions was compatible with epidermal nevi and nevus sebaceous. Therefore, the diagnosis of ENS was made. Apart from typical rickets, the skeletal X‐rays interestingly displayed fibrous dysplasia‐like lesions along right femur, tibia and fibula. Hypophosphatemic rickets was treated with alfacalcidol and phosphate solution. After 3 months of treatment, clinical improvement of hypophosphatemic rickets was clearly demonstrated. Her blood chemistries were normalised at 5 months following the treatment. In conclusion, hypophosphatemic rickets is a rare presentation of ENS. Our patient also demonstrated an additional abnormal bone finding, fibrous dysplasia‐like lesions, associated with rachitic changes. This highlights heterogeneity of this condition and importance of thorough evaluation of patients with ENS.
Implementation of written consent for newborn screening in Victoria, Australia
Authors: Charles Taryn , Pitt James , Halliday Jane , Amor David J
Published: December 2013

Aims

There has been increasing evidence of a lack of public awareness of newborn screening and concern about inadequate consent being obtained from parents. Apprehension also exists in relation to storage and secondary use of screening samples. Our objective was to introduce a written consent process across Victoria as a means of strengthening programme transparency, quality and supporting parental choice. In addition, more comprehensive information covering all aspects of the programme was developed.

Methods

A ‘two‐stage’ written consent protocol allowed parents to give separate consent for (i) their baby to be screened and (ii) secondary use of the sample in de‐identified health research. At the time of sample collection, parents were asked to complete the consent form, included as part of the screening card. The protocol was piloted in four public hospitals and subsequently implemented statewide.

Results

Twelve months of laboratory data showed that although refusals for screening increased, overall participation remained above 99%. The percentage of parents opting out of research use was 6.5%. Provider compliance with the new protocol was high, with only 1.4% of cards received without a completed consent form.

Conclusion

This quality improvement project has demonstrated that parents can participate more fully in newborn screening without jeopardising high uptake. As a secondary benefit, the public health resource of stored cards can be maintained with parental support. Future work needs to examine the quality of consent being given by parents and investigation of the reasons why some choose to decline.
Standardising paediatric resuscitation training in New South Wales, Australia: RESUS4KIDS
Authors: O'Leary Fenton , Allwood Margaret , McGarvey Kathryn , Howse Julie , Fahy Karyn
Published: December 2013

Aim

A key competency for all health‐care workers (HCWs) who care for children is the ability to respond to a child in respiratory or cardiorespiratory arrest. However, evidence suggests that medical and nursing staff may not have the knowledge and clinical skills to respond to these emergencies. The aim of this project was to create a standardised, evidence‐based, paediatric life support course that would be available free to all HCWs in New South Wales (NSW), including NSW Ambulance.

Methods

A paediatric life support course was designed along current education principles. It used e‐learning as pre‐learning and a face‐to‐face short practical course, combining team work and communication with practical paediatric resuscitation skills training. The programme was designed to empower local trainers to deliver a standardised course to local participants.

Results

A total of 14 000 participants have completed the mandatory e‐learning component, and over 8600 participants have completed the short practical course, across all NSW Local Health Districts, including NSW Ambulance. RESUS4KIDS has also been adopted by the universities of Sydney and Newcastle undergraduate medical and nursing programmes. Outside of NSW and ACT, over 400 participants have completed the course in facilities in Queensland, South Australia, Victoria and the Northern Territory.

Conclusion

We have developed a course that is available, at no cost to individuals or facilities, to all HCWs in NSW, including students, paramedics and general practitioners. We would encourage all other jurisdictions to consider adopting the programme.
Reasons for the overly optimistic beliefs of parents of children with diabetes
Authors: Freckleton Evril , Sharpe Louise , Mullan Barbara
Published: December 2013

Aims

The purposes of this study are to investigate parents' beliefs about the likelihood of diabetes outcomes for their child, the reasons that they give for these beliefs and the relationship between the beliefs and parental psychopathology.

Methods

Seventy‐one mothers of children with diabetes completed a questionnaire about the likelihood of certain diabetes outcomes and measures of psychopathology. Both qualitative and quantitative data were collected at a single time point.

Results

Mothers generally held very optimistic views about their children's future, and this was associated with less maternal depressive symptoms. Mothers typically used their previous experiences and belief that diabetes is controllable to justify optimistic beliefs about short‐term consequences. In contrast, formation of mothers' views on long‐term consequences generally relied on information from a variety of sources.

Conclusion

The results suggest that it is usual and helpful for mothers of children with diabetes to hold overly optimistic views about their children's futures. Medical evidence appears to have little influence on mothers' beliefs about likely outcomes for their children.
Natural polymer-stabilized multiple water-in-oil-in-water emulsions: a novel dermal drug delivery system for 5-fluorouracil
Authors: Hoppel Magdalena , Mahrhauser Denise , Stallinger Christina , Wagner Florian , Wirth Michael , Valenta Claudia
Published: December 2013

Objectives

The aim of this study was to create multiple water-in-oil-in-water (W/O/W) emulsions with an increased long-term stability as skin delivery systems for the hydrophilic model drug 5-fluorouracil.

Methods

Multiple W/O/W emulsions were prepared in a one-step emulsification process, and were characterized regarding particle size, microstructure and viscosity. In-vitro studies on porcine skin with Franz-type diffusion cells, tape stripping experiments and attenuated total reflectance-fourier transform infrared spectroscopy (ATR-FTIR) were performed.

Key findings

The addition of Solagum AX, a natural polymer mixture of acacia and xanthan gum, led to multiple W/O/W emulsions with a remarkably increased long-term stability in comparison to formulations without a thickener. The higher skin diffusion of 5-fluorouracil from the multiple emulsions compared with an O/W-macroemulsion could be explained by ATR-FTIR. Shifts to higher wave numbers and increase of peak areas of the asymmetric and symmetric CH2 stretching vibrations confirmed a transition of parts of the skin lipids from an ordered to a disordered state after impregnation of porcine skin with the multiple emulsions.

Conclusions

Solagum AX is highly suitable for stabilization of the created multiple emulsions. Moreover, these formulations showed superiority over a simple O/W-macroemulsion regarding skin permeation and penetration of 5-fluorouracil.
Ascorbic acid 6-palmitate: a potent inhibitor of human and soybean lipoxygenase-dependent lipid peroxidation
Authors: Mohamed Riyaz , Tarannum Shaista , Yariswamy Manjunath , Vivek Hamse K , Siddesha Jalahalli M , Angaswamy Nataraju , Vishwanath Bannikuppe S
Published: December 2013

Objectives

Lipoxygenases (LOX) are the key enzymes involved in the biosynthesis of leukotrienes and reactive oxygen species, which are implicated in pathophysiology of inflammatory disorders. This study was conducted to evaluate the inhibitory effect of water-soluble antioxidant ascorbic acid and its lipophilic derivative, ascorbic acid 6-palmitate (Vcpal) on polymorphonuclear lymphocyte 5-LOX and soybean 15-LOX (sLOX) in vitro.

Methods

LOX activity was determined by measuring the end products, 5-hydroperoxy eicosatetraenoic acid (5-HETE) and lipid hydroperoxides, by spectrophotometric and high performance liquid chromatography methods. The substrate-dependent enzyme kinetics and docking studies were carried out to understand the nature of inhibition.

Key findings

Vcpal potently inhibited 5-LOX when compared with its inhibitory effect on sLOX (IC50; 2.5 and 10.3 μm respectively, P = 0.003). Further, Vcpal inhibited 5-LOX more strongly than the known synthetic drugs: phenidone and nordihydroguaiaretic acid (P = 0.0007). Enzyme kinetic studies demonstrated Vcpal as a non-competitive reversible inhibitor of 5-LOX. In-silico molecular docking revealed high MolDock and Rerank score for Vcpal than ascorbic acid, complementing in-vitro results.

Conclusion

Both in-vitro and docking studies demonstrated Vcpal but not ascorbic acid as a non-competitive inhibitor of 5-LOX- and sLOX-induced lipid peroxidation, suggesting a key role for lipophilic nature in bringing about inhibition.
Do Antarctic lichens modify microclimate and facilitate vascular plants in the maritime Antarctic? A comment to Molina‐Montenegro et al. ()
Authors: Casanova‐Katny Angélica , Palfner Götz , Torres‐Mellado Gustavo A. , Cavieres Lohengrin A.
Published: December 2013

A recent article published by Molina‐Montenegro et al. (Journal of Vegetation Science24: 463) examines the association of Antarctic native plant and lichen species to the lichen Usnea antarctica on Fildes Peninsula, King George Island, maritime Antarctica. The authors report that on two sites, five out of 13 and four out of 11 species of lichens and mosses were spatially associated with U. antarctica, suggesting positive interactions between them. Although Deschampsia antarctica does not grow naturally associated with U. antarctica, Molina‐Montenegro et al. carried out a transplantation experiment to demonstrate that the macrolichen acts as a nurse plant, improving the survival of the grass. Serious conceptual and methodological discrepancies emerge from a critical evaluation of this study, challenging their conclusions. First, we suspect that the author confused some lichen taxa, and we also disagree with macrolichens being treated as cushion plants, because rootless, poikilohydric and poikilothermic thallophytes such as lichens are unable to create a stable, enclave‐like microhabitat as vascular cushion plants do. Indeed, a critical evaluation of some of the micro‐environmental parameters measured indicates that there are no biologically meaningful differences between the U. antarctica thalli and surrounding open areas. Second, the lack of consideration of the life history of the species under study leads to confusion when (a) referring to the succession sequence of species that colonize the studied area and (b) interpreting the putative distribution patterns promoted by Usnea versus the substrate preferences of associated species. Third, the authors intend to demonstrate experimentally that Usnea can facilitate the survival of D. antarctica plants, transplanting adult plants and not seedlings between the lichen thalli, and it is not clear how the grass was planted – between or within the lichens – as at both experimental sites the lichens grow on stones or rocks. Facilitative interactions are present in the Antarctic and may play a pivotal role in the structure and functioning of the fragile Antarctic ecosystems. However, more rigorous and well‐planned research is needed to assess its presence, importance and involved mechanisms.
How to optimize current therapy of HCV genotype 1 infection with boceprevir
Authors: Bourlière Marc , Adhoute Xavier , Wendt Astrid , Ansaldi Christelle , Oules Valérie , Castellani Paul
Published: December 2013

Treatment with first generation protease inhibitors (PIs) is a milestone in the history of HCV therapy. Triple therapy with boceprevir (BOC) improves sustained virological response (SVR) by 30% in treatment naïve genotype 1 patients and by 50–60% in relapsers, 40–45% in partial responders and 25% in null responders compared with the Pegylated Interferon (PEG‐IFN) and ribavirin regimen. To optimize BOC treatment, screening and access to treatment must be improved in genotype 1 patients. To select the ideal candidate for immediate treatment with triple therapy, an individual risk/benefit ratio must be assessed. Recent data have shown that patients with compensated cirrhosis and more advanced disease may also benefit from this regimen. Moreover, in HCV patients with extrahepatic manifestations, patients with HCV recurrence after liver transplantation and HIV‐HCV co‐infected patients, immediate treatment with triple therapy should be discussed. There is growing evidence that triple therapy with BOC is cost‐effective in genotype 1 patients. Finally, the treatment design of BOC must be optimized in relation to baseline characteristics, so that optimal stopping rules can be followed, Drug‐drug interactions (DDIs) can be prevented and AEs can be accurately prevented and managed.
Impact of HBV therapy on the incidence of hepatocellular carcinoma
Authors: Triolo Michela , Corte Cristina Della , Colombo Massimo
Published: December 2013

Hepatocellular carcinoma (HCC) is a frequent, long term complication of chronic infection with hepatitis B virus (HBV) with an annual incidence ranging from 2 to 5%, often independent from the histological stage of underlying liver disease and serological status. Nevertheless, HCC is more often seen in older patients in whom HBV has been asserting its pro‐oncogenic properties through both indirect and direct mechanisms. In Europe, HBV‐related HCC is associated with cirrhosis in most patients, whereas this is not true in Asia and Africa where the tumour is also common among carriers with mild hepatic fibrosis, probably because of the coexistence of environmental co‐carcinogens (aflatoxin) and long standing infection that is often acquired perinatally. Since hepatitis B‐related carcinogenesis develops independently of the onset of cirrhosis, antiviral treatments such as nucleo(t)side analogues (NAs) that may result in the regression of fibrosis, prevent clinical decompensation and variceal bleeding, often fail to prevent HCC.

Studies enrolling patients treated with lamivudine or rescued with adefovir, i.e. regimens characterized by limited potency and a low to moderate genetic barrier, have clearly been shown to help prevent HCC in patients with chronic hepatitis but not in those with cirrhosis, and in general not in patients that cannot achieve a sustained virological response.

More potent anti‐HBV drugs, such as entecavir and tenofovir, have been shown to improve the prevention of HCC in responders with cirrhosis, although HCC may still occur even in low risk patients. To attenuate HCC related outcomes, HBV replication must permanently be suppressed and HCC surveillance by abdominal ultrasound should be maintained even in responder patients.
Regression of fibrosis after HBV antiviral therapy. Is cirrhosis reversible?
Authors: Calvaruso Vincenza , Craxì Antonio
Published: December 2013

Long‐lasting HBV‐DNA suppression is considered to be the best surrogate end‐point of antiviral therapy in patients with hepatitis B virus (HBV) related chronic hepatitis or cirrhosis, and it is a prerequisite to prevent liver‐related complications and improve survival. Treatment with oral antiviral drugs in patients with HBV cirrhosis is effective in restoring liver function and improving survival even in those with decompensated cirrhosis. These agents are generally well‐tolerated for long‐term treatment, and several evidences have demonstrated that they are able to reverse liver fibrosis and prevent the occurrence of HCC.
Optimizing treatment for HCV genotype 4: PEG‐IFN alfa 2a vs. PEG‐IFN alfa 2b; the debate continues
Authors: Esmat Gamal , El Kassas Mohamed , Hassany Mohamed , Gamil Mohamed , El Raziky Maissa
Published: December 2013

Hepatitis C virus (HCV) remains one of the leading causes of morbidity and mortality worldwide. Combined therapy with pegylated interferon (PEG‐IFN) and ribavirin is the current standard of care treatment for HCV genotype 4. Two types of PEG‐IFN are commercially available. The limited number of trials that were conducted for HCV genotype 4 and the few head to head comparisons make it impossible to know which is the best option? In this article we review all available PEG‐IFN trials performed worldwide for HCV genotype 4 since 2004. Unless another molecule is developed as a standalone for the treatment of HCV, PEG‐IFN will continue to be a source of debate.
HBeAg‐positive chronic hepatitis B: why do I treat my patients with pegylated interferon?
Authors: Kao Jia‐Horng
Published: December 2013

Although chronic hepatitis B (CHB) is a global health threat, it is now a preventable and treatable disease. Seven agents have been approved for the treatment of CHB. Although many patients prefer potent long‐term nucleos(t)ide analogues (NAs) as the first‐line therapy because they are convenient to use and well‐tolerated, a finite duration of pegylated interferon (PEG‐IFN) is still an attractive strategy because it provides higher rates of off‐therapy host immune control over hepatitis B virus (HBV) compared with NAs. In addition, the rates of HBeAg/HBsAg loss or seroconversion increase over time in patients who respond to PEG‐IFN therapy. Nevertheless, these benefits are limited to 30% of all patients, and significant adverse effects are still a concern. Therefore, patients who can benefit most from PEG‐IFN therapy should be more carefully selected according to baseline host and viral predictors, such as age, ALT level, viral load, HBV genotype and HBV mutants. In addition, on‐treatment predictors including HBV DNA, HBeAg and HBsAg kinetics, can help decide who should continue or discontinue PEG‐IFN and shift to NA. Understanding these factors can help determine personalized PEG‐IFN therapy for CHB patients. In the near future, the treatment paradigm of CHB should be tailored on the basis of viral (HBV DNA level, HBV genotype and HBV mutants) and host (age, gender, ALT level and host genetic polymorphisms) factors, disease status (stage of fibrosis and comorbidities) and the selection of antiviral agents (immunomodulatory effect, antiviral potency, adverse effects and rate of drug resistance).
Treatment of hepatitis C virus genotype 3‐infection
Authors: Pol Stanislas , Vallet‐Pichard Anaïs , Corouge Marion
Published: December 2013

The treatment of hepatitis C virus (HCV) infection with pegylated interferon (PEG‐IFN) alfa and ribavirin (800 mg daily) (RBV) is the standard of care (SOC) for hepatitis C virus genotype 3‐infection leading to a sustained virological response (SVR) in around 65% of patients.

A better understanding of the HCV life‐cycle has recently resulted in the development of several potential direct‐acting antiviral drugs (DAAs) targeting viral proteins (NS3/4A protease, NS5B nucleos(t)idic and non‐nucleos(t)idic polymerase, NS5A viral replication complex). First generation protease inhibitors in combination with PEG‐IFN/RBV are not efficient in genotype 3‐infected patients. The combination of PEG‐IFN/RBV with Daclatasvir, a NS5A inhibitor for 12–24 weeks results in a SVR in around 75% while the triple combination of PEG‐IFN/RBV with the oral nucleotidic polymerase inhibitor Sofosbuvir (GS‐7977) for 12 weeks in naïve patients results in a SVR in more than 95%. The results of the first oral combination of Sofosbuvir and RBV for 12 weeks in genotype 3‐infected patients have been rather disappointing with a slightly lower SVR than after 24 weeks of PEG‐IFN: around 60%, and only 30% in patients with cirrhosis. Extending treatment from 12 to 16 weeks in treatment experienced patients doubled the SVR rate and an 80% SVR rate is expected by extending treatment to 24 weeks. The best oral combination of new DAAs is probably the combination of Sofosbuvir and a NS5A inhibitor (Daclatasvir, Ledipasvir…) for 24 weeks, which resulted in a 100% SVR rate in a limited series. The use of cyclophilin inhibitors, a host‐targeted antiviral, in association with DAAs and/or RBV may also be of interest.

The oral combination of new DAAs (dual or triple combination of different antivirals) or of DAAs and host targets such as cyclophilin will probably become the SOC for genotype 3‐infected treatment‐naïve or ‐experienced patients.
Is there still a role for PEG IFN+RBV therapy in patients with HCV genotype 1?
Authors: Serfaty Lawrence
Published: December 2013

Boceprevir and telaprevir‐based triple therapy is now the standard of care for the treatment of genotype 1 patients. However, dual therapy with pegylated interferon and ribavirin should be discussed in treatment‐naïve patients with good predictors of response. A recent published trial has shown in non‐cirrhotic patients with low viral load at baseline, similar efficacy of a 24‐week course of dual therapy vs a 24‐week course of boceprevir‐based triple therapy in case of rapid virological response. Accordingly, addition of protease inhibitor should be discussed after 4 weeks of dual therapy in this easy‐to‐treat population.
A brief history of hepatitis milestones
Authors: Trepo Christian
Published: December 2013

Hepatitis has been a major plague of mankind. The history of the discovery of causative viruses is one of the most fascinating scientific adventures of this half century. Individualization of several types of hepatitis only emerged after world war two. Their identification has been associated with milestones which revolutionized medicine and public health. The discovery of HBV brought the first ever vaccine not prepared by tissue culture but initially directly from plasma and soon the first vaccine produced by genetic engineering. HBV vaccine proved to be the first “anti‐cancer” vaccine by preventing hepatocellular carcinoma and practically eradicating it from childhood in Taiwan. Successful vaccines became also available for HAV and more recently HEV. The discovery of HCV in 1989 opened a new era since it was the first virus was identified by a direct molecular approach. Two billion people are infected with HBV and 350 million are chronic carriers of the virus. The extraordinary effectiveness of HBV vaccination was best illustrated in Taiwan and Singapore where in less than 2 decades HBs Ag carriers dropped from 9,1% to 2,7% and HCC from 27% to 17%. Successful development of nucleos(t)ides analogs make it now possible to fully control disease progression with a daily pill long term therapy. The progress in HCV therapy has been even more spectacular and successful treatment jumped from 6 % with interferon alone in 1986 to more than 80% in 2013 with triple combination therapies. Remarkably chronic hepatitis C is the only chronic disease which is curable. It will be soon possible to eradicate HCV infection with, an all oral, daily single pill (containing several molecules) for 3 to 6 months which will cure over 90% of patients. This unprecedented therapeutic victory benefiting hundred millions of people matches the triumphs over small pox, polio and tuberculosis. The next 10 years should undoubtedly witness cure or full control over all forms of acute and chronic hepatitis.
HCV direct‐acting antiviral agents: the best interferon‐free combinations
Authors: Schinazi Raymond , Halfon Philippe , Marcellin Patrick , Asselah Tarik
Published: December 2013

For HCV infection, there have been major advancements during last several years with large numbers of ongoing trials with various direct‐acting antivirals (DAA) showing high potency, favourable tolerability profile, higher barrier to resistance, shortened treatment duration, all oral regimen, pan‐genotypic, fewer drug interactions and reduced pill burden. By 2014, several DAAs are anticipated to complete successful phase III trials and will be commercially available. Initially, a wave of IFN‐based regimen (sofosbuvir, faldaprevir and simeprevir) will be available for treatment of HCV genotype 1. In the near future, combination of antiviral agents with additive potency that lack cross‐resistance with good safety profile will likely be the new recommended regimens, making HCV, the first chronic viral infection to be eradicated worldwide with a finite duration of combination DAA therapy without IFN or ribavirin. The aim of this review was to summarize the results obtained from recent DAA combination studies without IFN.
K2O‐rich trapped melt in olivine in the Nakhla meteorite: Implications for petrogenesis of nakhlites and evolution of the Martian mantle
Authors: Goodrich Cyrena Anne , Treiman Allan H. , Filiberto Justin , Gross Juliane , Jercinovic Michael
Published: December 2013

We used new analytical and theoretical methods to determine the major and minor element compositions of the primary trapped liquid (PTLs) represented by melt inclusions in olivine and augite in the Martian clinopyroxenite, Nakhla, for comparison with previously proposed compositions for the Nakhla (or nakhlite) parent magma. We particularly focused on obtaining accurate K2O contents, and on testing whether high K2O contents and K2O/Na2O ratios obtained in previous studies of melt inclusions in olivine in Nakhla could have been due to unrepresentative sampling, systematic errors arising from electron microprobe techniques, late alteration of the inclusions, and/or boundary layer effects. Based on analyses of 35 melt inclusions in olivine cores, the PTL in olivine, PTLoliv, contained (by wt) approximately 47% SiO2, 6.3% Al2O3, 9.6% CaO, 1.8% K2O, and 0.9% Na2O, with K2O/Na2O = 2.0. We infer that the high K2O content of PTLoliv is not due to boundary layer effects and represents a real property of the melt from which the host olivine crystallized. This melt was cosaturated with olivine and augite. Its mg# is model‐dependent and is constrained only to be ≥19 (equilibrium Fo = 40). Based on analyses of 91 melt inclusions in augite cores, the PTL in augite, PTLaug, contained (by wt) 53–54% SiO2, 7–8% Al2O3, 0.8–1.1% K2O, and 1.1–1.4% Na2O, with K2O/Na2O = 0.7–0.8. This K2O content and K2O/Na2O ratio are significantly higher than inferred in studies of melt inclusions in augite in Nakhla by experimental rehomogenization. PTLaug was saturated only with augite, and in equilibrium with augite cores of mg# 62. PTLaug represents the Nakhla parent magma, and does not evolve to PTLoliv by fractional crystallization. We therefore conclude that olivine cores in Nakhla (and, by extension, other nakhlites) are xenocrystic. We propose that PTLoliv and PTLaug were generated from the same source region. PTLoliv was generated first and emplaced to form olivine‐rich cumulate rocks. Shortly thereafter, PTLaug was generated and ascended through these olivine‐rich cumulates, incorporating fragments of wallrock that became the xenocrystic olivine cores in Nakhla. The Nakhla (nakhlite) mantle source region was pyroxenitic with some olivine, and could have become enriched in K relative to Na via metasomatism. A high degree of melting of this source produced the silica‐poor, alkali‐rich magma PTLoliv. Further ascension and decompression of the source led to generation of the silica‐rich, relatively alkali‐poor magma PTLaug. Potassium‐rich magmas like those involved in the formation of the nakhlites represent an important part of the diversity of Martian igneous rocks.
Zinc isotopic composition of iron meteorites: Absence of isotopic anomalies and origin of the volatile element depletion
Authors: Chen Heng , Nguyen Bach Mai , Moynier Frédéric
Published: December 2013

High‐precision Zn isotopic compositions measured by MC‐ICP‐MS are documented for 32 iron meteorites from various fractionally crystallized and silicate‐bearing groups. The δ66Zn values range from −0.59‰ up to +5.61‰ with most samples being slightly enriched in the heavier isotopes compared with carbonaceous chondrites (0 < δ66Zn < 0.5). The δ66Zn versus δ68Zn plot of all samples defines a common linear fractionation line, which supports the hypothesis that Zn was derived from a single reservoir or from multiple reservoirs linked by mass‐dependent fractionation processes. Our data for Redfields fall on a mass fractionation line and therefore refute a previous claim of it having an anomalous isotopic composition due to nonmixing of nucleosynthetic products. The negative correlation between δ66Zn and the Zn concentration of IAB and IIE is consistent with mass‐dependent isotopic fractionation due to evaporation with preferential loss of lighter isotopes in the vapor phase. Data for the Zn concentrations and isotopic compositions of two IVA samples demonstrate that volatile depletion in the IVA parent body is not likely the result of evaporation. This is important evidence that favors the incomplete condensation origin for the volatile depletion of the IVA parent body.
Multicentre surveillance study on feasibility, safety and efficacy of antifungal combination therapy for proven or probable invasive fungal diseases in haematological patients: the SEIFEM real‐life combo study
Authors: Candoni A. , Caira M. , Cesaro S. , Busca A. , Giacchino M. , Fanci R. , Delia M. , Nosari A. , Bonini A. , Cattaneo C. , Melillo L. , Caramatti C. , Milone G. , Scime’ R. , Picardi M. , Fanin R. , Pagano L.
Published: December 2013

This multicentre observational study evaluated the feasibility, efficacy and toxicity of antifungal combination therapy (combo) as treatment of proven or probable invasive fungal diseases (IFDs) in patients with haematological malignancies. Between January 2005 and January 2010, 84 cases of IFDs (39 proven and 45 probable) treated with combo were collected in 20 Hematological Italian Centres, in patients who underwent chemotherapy or allogeneic haematopoietic stem cell transplantation for haematological diseases. Median age of patients was 34 years (range 1–73) and 37% had less than 18 years. Acute leukaemia was the most common underlying haematological disease (68/84; 81%). The phase of treatment was as follows: first induction in 21/84 (25%), consolidation phase in 18/84 (21%) and reinduction/salvage in 45/84 (54%). The main site of infection was lung with or without other sites. The principal fungal pathogens were as follows: Aspergillus sp. 68 cases (81%), Candida sp. six cases (8%), Zygomycetes four cases (5%) and Fusarium sp. four cases (5%). The most used combo was caspofungin+voriconazole 35/84 (42%), caspofungin + liposomal amphotericin B (L‐AmB) 20/84 (24%) and L‐AmB+voriconazole 15/84 (18%). The median duration of combo was 19 days (range 3–180). The overall response rate (ORR) was 73% (61/84 responders) without significant differences between the combo regimens. The most important factor that significantly influenced the response was granulocyte (PMN) recovery (P 0.009). Only one patient discontinued therapy (voriconazole‐related neurotoxicity) and 22% experienced mild and reversible adverse events (hypokalaemia, ALT/AST increase and creatinine increase). The IFDs‐attributable mortality was 17%. This study indicates that combo was both well tolerated and effective in haematological patients. The most used combo regimens were caspofungin + voriconazole (ORR 80%) and caspofungin + L‐AmB (ORR 70%). The ORR was 73% and the mortality IFD related was 17%. PMN recovery during combo predicts a favourable outcome. Clinical Trials Registration: NCT00906633.