bluuebunny/crossref_metadata_2025_split huggingface dataset:
Input subsidy programs in sub‐Saharan Africa: a synthesis of recent evidence
Authors: Jayne T.S. , Rashid Shahidur 
Published: October 2013

AbstractInput subsidy programs have once again become a major plank of agricultural development strategies in Africa. Ten African governments spend roughly US$1 billion annually on input subsidy programs (ISPs), amounting to 28.6% of their public expenditures on agriculture. This article reviews the microlevel evidence on ISPs undertaken since the mid 2000s. We examine the characteristics of subsidy beneficiaries, crop response rates to fertilizer application and their influence on the performance of subsidy programs, the impacts of subsidy programs on national fertilizer use and the development of commercial input distribution systems, and finally the impact of ISPs on food price levels and poverty rates. The weight of the evidence indicates that the costs of the programs generally outweigh their benefits. Findings from other developing areas with a higher proportion of crop area under irrigation and with lower fertilizer prices—factors that should provide higher returns to fertilizer subsidies than in Africa—indicate that at least a partial reallocation of expenditures from fertilizer subsidies to R&D and infrastructure would provide higher returns to agricultural growth and poverty reduction. However, because ISPs enable governments to demonstrate tangible support to constituents, they are likely to remain on the African landscape for the foreseeable future. Hence, the study identifies ways in which benefits can be enhanced through changes in implementation modalities and complementary investments within a holistic agricultural intensification strategy. Among the most important of these are efforts to reduce the crowding out of commercial fertilizer distribution systems and programs to improve soil fertility to enable farmers to use fertilizer more efficiently. The challenges associated with achieving these gains are likely to be formidable.
Influence of multi‐lumen extensions on fluid flow through intravenous cannulae
Authors: Levine D. M. , Garden A. L. , Truong H. T. , Bergemann J. , Eames P. 
Published: October 2013

SummaryMulti‐lumen extensions used to infuse multiple fluids via a single intravenous cannula might increase resistance and so limit the flow that can be achieved. We constructed low‐pressure and high‐pressure models and compared the effect of two different multi‐lumen extensions on flow rate. Both multi‐lumen extensions reduced flows by up to 76% (p < 0.001). The effect was greatest with large cannulae and in the high‐pressure model, with the longer and narrower extension most impeding flow. Multi‐lumen extensions can therefore significantly impede fluid flow, and should be avoided or removed when rapid infusion is required. These effects are less important in paediatric anaesthesia where smaller cannulae are used. Manufacturers should include internal diameter or flow effects on the packaging of these extensions to assist clinicians in making such decisions.
Adalimumab maintains remission of Crohn's disease after up to 4 years of treatment: data from CHARM and ADHERE
Authors: Panaccione R. , Colombel J.‐F. , Sandborn W. J. , D'Haens G. , Zhou Q. , Pollack P. F. , Thakkar R. B. , Robinson A. M. 
Published: October 2013

SummaryBackgroundTherapies that maintain remission for patients with Crohn's disease are essential. Stable remission rates have been demonstrated for up to 2 years in adalimumab‐treated patients with moderately to severely active Crohn's disease enrolled in the CHARM and ADHERE clinical trials.AimTo present the long‐term efficacy and safety of adalimumab therapy through 4 years of treatment.MethodsRemission (CDAI <150), response (CR‐100) and corticosteroid‐free remission over 4 years, and maintenance of these endpoints beyond 1 year were assessed in CHARM early responders randomised to adalimumab. Corticosteroid‐free remission was also assessed in all adalimumab‐randomised patients using corticosteroids at baseline. Fistula healing was assessed in adalimumab‐randomised patients with fistula at baseline. As observed, last observation carried forward and a hybrid nonresponder imputation analysis for year 4 (hNRI) were used to report efficacy. Adverse events were reported for any patient receiving at least one dose of adalimumab.ResultsOf 329 early responders randomised to adalimumab induction therapy, at least 30% achieved remission (99/329) or CR‐100 (116/329) at year 4 of treatment (hNRI). The majority of patients (54%) with remission at year 1 maintained this endpoint at year 4 (hNRI). At year 4, 16% of patients taking corticosteroids at baseline were in corticosteroid‐free remission and 24% of patients with fistulae at baseline had healed fistulae. The incidence rates of adverse events remained stable over time.ConclusionsProlonged adalimumab therapy maintained clinical remission and response in patients with moderately to severely active Crohn's disease for up to 4 years. No increased risk of adverse events or new safety signals were identified with long‐term maintenance therapy. (clinicaltrials.gov number: NCT00077779).
Cardiac complications and diabetes in thalassaemia major: a large historical multicentre study
Authors: Pepe Alessia , Meloni Antonella , Rossi Giuseppe , Caruso Vincenzo , Cuccia Liana , Spasiano Anna , Gerardi Calogera , Zuccarelli Angelo , D'Ascola Domenico G. , Grimaldi Salvatore , Santodirocco Michele , Campisi Saveria , Lai Maria E. , Piraino Basilia , Chiodi Elisabetta , Ascioti Claudio , Gulino Letizia , Positano Vincenzo , Lombardi Massimo , Gamberini Maria R. 
Published: October 2013

SummaryThe relationship between diabetes mellitus (DM) and cardiac complications has never been systematically studied in thalassaemia major (TM). We evaluated a large retrospective historical cohort of TM to determine whether DM is associated with a higher risk of heart complications. We compared 86 TM patients affected by DM with 709 TM patients without DM consecutively included in the Myocardial Iron Overload in Thalassaemia database where clinical/instrumental data are recorded from birth to the first cardiovascular magnetic resonance (CMR) exam. All of the cardiac events considered were developed after the DM diagnosis. In DM patients versus non‐DM patients we found a significantly higher frequency of cardiac complications (46·5% vs. 16·9%, P < 0·0001), heart failure (HF) (30·2% vs. 11·7%, P < 0·0001), hyperkinetic arrhythmias (18·6% vs. 5·5%, P < 0·0001) and myocardial fibrosis assessed by late gadolinium enhancement (29·9% vs. 18·4%, P = 0·008). TM patients with DM had a significantly higher risk of cardiac complications [odds ratio (OR) 2·84, P < 0·0001], HF (OR 2·32, P = 0·003), hyperkinetic arrhythmias (OR 2·21, P = 0·023) and myocardial fibrosis (OR 1·91, P = 0·021), also adjusting for the absence of myocardial iron overload assessed by T2* CMR and for the covariates (age and/or endocrine co‐morbidity). In conclusion, DM significantly increases the risk for cardiac complications, HF, hyperkinetic arrhythmias and myocardial fibrosis in TM patients.
Myeloma stem cell concepts, heterogeneity and plasticity of multiple myeloma
Authors: Hajek Roman , Okubote Samuel A. , Svachova Hana 
Published: October 2013

SummaryMultiple myeloma (MM) is a haematological malignancy characterized by the accumulation of clonal plasma cells (PCs) in the bone marrow (BM). Although novel therapeutic strategies have prolonged survival of patients, the disease remains difficult to treat with a high risk of relapse. The failure of therapy is thought to be associated with a persistent population of the so‐calledMMstem cells or myeloma initiating cells (MIC) that exhibit tumour‐initiating potential, self‐renewal and resistance to chemotherapy. However, the population responsible for the origin and sustainability of tumour mass has not been clearly characterized so far. This review summarizes current myeloma stem cell concepts and suggests that high phenotypic and intra‐clonal heterogeneity, together with plasticity potential ofMMmight be other contributing factors explaining discrepancies among particular concepts and contributing to the treatment failure.
Assessing the extirpative quality of a radical prostatectomy technique: categorisation and mapping of technical errors
Authors: Barré Christian , Thoulouzan Matthieu , Aillet Geneviève , Nguyen Jean‐Michel 
Published: October 2013

Objective
To examine the extirpative quality of an open radical prostatectomy (RP) technique by first categorising and mapping all intraprostatic incisions into benign tissue and then determining a cumulative technical error rate given by all intraprostatic incisions into benign and malignant tissue.
Patients and Methods
We performed a retrospective review of prospectively collected data relating to 1065 men with clinically localised prostate cancer who underwent open retropubic RP (70.6% nerve‐sparing surgery [NSS]) by a single surgeon (January 2005 to December 2011).
We recorded all intraprostatic incisions: (i) iatrogenic positive surgical margins (PSMs), (ii) deep or superficial benign capsular incisions (BCIs), (iii) incisions into benign prostate glands at the prostate apex or bladder neck (benign glandular tissue incisions [BGTIs]), and determined incision location, length and nature (solitary/multiple).
We evaluated: (i) associations between benign incisions, NSS and PSMs, (ii) significant predictors for PSM risk by multivariate analysis, (iii) postoperative biochemical recurrence (BCR)‐free survival (Kaplan–Meier method).
Results
Intraprostatic incision rates were 2.3% pT2 PSMs, 6.0% BCIs and 5.4% BGTIs. There were slight variations in rate over time and with NSS technique. Benign incisions were located as follows: 46.8% right posterolateral, 37.5% left posterolateral, and 15.7% bilateral for BCIs; 58.6% bladder neck and 41.4% apical for BGTIs.
The median (range) incision length, for solitary and multiple incisions respectively, was 4 (1–13) and 9 (2–25) mm for BCIs and 1 (1–5) and 2 (2–6) mm for BGTIs.
BCI rate, but not BGTI rate, was significantly associated with NSS (P = 0.004) and PSM (P = 0.005), and increased PSM risk 3.6‐fold.
A PSM increased BCR risk two‐fold (odds ratio 2.078, 95% confidence interval 1.383–3.122).
BCR‐free survival decreased significantly even for short PSMs (<1 mm; P < 0.001).
Conclusions
Although the pT2 PSM rate was low (2.3%), the cumulative technical error rate (patients with at least one pT2 PSM, BCI or BGTI) was five‐fold higher (12.5%).
Categorising and mapping intraprostatic incisions is a tool surgeons can use in self‐audits to identify areas of potential improvement, reduce errors, and improve surgical skills.
Parthanatos: mitochondrial‐linked mechanisms and therapeutic opportunities
Authors: Fatokun Amos A , Dawson Valina L , Dawson Ted M 
Published: October 2013

Cells die by a variety of mechanisms. Terminally differentiated cells such as neurones die in a variety of disorders, in part, via parthanatos, a process dependent on the activity of poly (ADP‐ribose)‐polymerase (PARP). Parthanatos does not require the mediation of caspases for its execution, but is clearly mechanistically dependent on the nuclear translocation of the mitochondrial‐associated apoptosis‐inducing factor (AIF). The nuclear translocation of this otherwise beneficial mitochondrial protein, occasioned by poly (ADP‐ribose) (PAR) produced through PARP overactivation, causes large‐scale DNA fragmentation and chromatin condensation, leading to cell death. This review describes the multistep course of parthanatos and its dependence on PAR signalling and nuclear AIF translocation. The review also discusses potential targets in the parthanatos cascade as promising avenues for the development of novel, disease‐modifying, therapeutic agents.Linked ArticlesThis article is part of a themed issue on Mitochondrial Pharmacology: Energy, Injury & Beyond. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2014.171.issue‐8
Insulin autoimmune syndrome (Hirata Disease) in European Caucasians taking α‐lipoic acid
Authors: Gullo Damiano , Evans Joseph L. , Sortino Grazia , Goldfine Ira D. , Vigneri Riccardo 
Published: October 2013

SummaryObjectiveLipoic acid (LA) is a widely used nutritional supplement and is sometimes used as an adjuvant treatment for diabetic neuropathy and other conditions. Insulin autoimmune syndrome (IAS, Hirata disease) is a rare cause of spontaneous hypoglycaemia, extremely high serum insulin levels and high titres of autoantibodies against endogenous insulin despite no prior exposure to exogenous insulin. In Japanese individuals, IAS is associated with the human leucocyte antigen (HLA) HLA‐DRB1*04:06 allele and often occurs upon exposure to sulphhydryl‐containing compounds including LA. Only one case has been reported in Caucasians. We now report six Caucasian patients taking LA with IAS and describe a unique HLA subtype in these patients.Research Design and MethodsSix Caucasian patients (M = 3; F = 3), median age 63 years, presented with spontaneous episodes of fasting and postabsorptive hypoglycaemia associated with mainly neuroglycopenic symptoms. No patient was treated with insulin or had an insulinoma. Hypoglycaemic symptoms appeared 30 and 120 days after taking lipoic acid (LA; 600 mg/day). Case histories and standard laboratory analyses were utilized.ResultsDiscontinuation of LA resulted in a reduction in hypoglycaemic episodes. All patients were treated with oral or iv glucose and prednisone (12·5–25 mg/day). HLA analysis revealed the HLA‐DRB1*04:03 allele in five patients, while the HLA‐DRB1*04:06 allele was present in one patient.ConclusionsThis is the first report of LA‐related IAS in Caucasians who possess the HLA‐DRB1*04:03 allele, implicating this allele in the genetic susceptibility to IAS in Caucasians. The greater occurrence of the HLA‐DRB1*04:03 allele in Caucasian and other populations, combined with the growing use of LA in developed countries, may be a future predictor of additional cases of IAS.
Selection criteria for selective dorsal rhizotomy in children with spastic cerebral palsy: a systematic review of the literature
Authors: Grunt Sebastian , Fieggen A Graham , Vermeulen R Jeroen , Becher Jules G , Langerak Nelleke G 
Published: October 2013

AimInformation regarding the selection procedure for selective dorsal rhizotomy (SDR) in children with spastic cerebral palsy (CP) is scarce. Therefore, the aim of this study was to summarize the selection criteria for SDR in children with spastic CP.MethodA systematic review was carried out using the following databases: MEDLINE, CINAHL, EMBASE, PEDro, and the Cochrane Library. Additional studies were identified in the reference lists. Search terms included ‘selective dorsal rhizotomy’, ‘functional posterior rhizotomy’, ‘selective posterior rhizotomy’, and ‘cerebral palsy’. Studies were selected if they studied mainly children (<18y of age) with spastic CP, if they had an intervention of SDR, if they had a detailed description of the selection criteria, and if they were in English. The levels of evidence, conduct of studies, and selection criteria for SDR were scored.ResultsFifty‐two studies were included. Selection criteria were reported in 16 International Classification of Functioning, Disability and Health model domains including ‘body structure and function’ (details concerning spasticity [94%], other movement abnormalities [62%], and strength [54%]), ‘activity’ (gross motor function [27%]), and ‘personal and environmental factors’ (age [44%], diagnosis [50%], motivation [31%], previous surgery [21%], and follow‐up therapy [31%]). Most selection criteria were not based on standardized measurements.InterpretationSelection criteria for SDR vary considerably. Future studies should describe clearly the selection procedure. International meetings of experts should develop more uniform consensus guidelines, which could form the basis for selecting candidates for SDR.
Host selection, oviposition behaviour and leaf traits in a specialist willow sawfly on species of Salix (Salicaceae)
Authors: BRACCINI CELINA L. , VEGA ANDREA S. , CHLUDIL HUGO D. , LEICACH SILVIA R. , FERNANDEZ PATRICIA C. 
Published: October 2013

Plant genotype influences plant–herbivore interactions by affecting insect attraction, acceptance and development. Here we linked oviposition behaviour of the specialist willow sawfly Nematus oligospilus Förster (Hymenoptera: Tenthredinidae) with leaf traits on different Salix L. (Salicaceae) genotypes. This was done as a first step to find oviposition cues that guide females to their host plants.
By means of choice and no‐choice bioassays we analysed host selection according to willow genotype and leaf surface. We also studied larval performance, adult fecundity and effect of experience on host selection. Nematus oligospilus prefers to oviposit on S. nigra. The least preferred genotype, S. viminalis, showed better larval performance and highest adult fecundity. Host preference was not modified by larval feeding experience.
By means of light and scanning electron microscopy we described ovipositor and leaf micromorphology. The egg is laid inside the epidermis or between the epidermis and adjacent chlorenchyma, showing a tight association with the leaf. Leaf toughness was lowest for S. nigra and higher for S. viminalis and S. babylonica. Total nitrogen and protein content were higher on S. viminalis and S. babylonica. Total phenolics and phenolic glycosides were the highest and more diverse on S. nigra. Salicin content levels correlate with oviposition preference, suggesting the role of salicylates as oviposition stimulants.
Results suggest that oviposition preference on S. nigra may be related to lower leaf toughness and ease of injection of female saw‐like ovipositor, and motivated by the presence of phenolic glycosides. Nitrogen levels may explain better larval performance and adult fecundity in S. viminalis. Thus, a balance among the different leaf traits determines the outcomes observed in this study.
Imaging the seizure during surgery with a hyperspectral camera
Authors: Noordmans Herke Jan , Ferrier Cyrille , de Roode Rowland , Leijten Frans , van Rijen Peter , Gosselaar Peter , Klaessens John , Verdaasdonk Ruud 
Published: October 2013

SummaryAn epilepsy patient with recurring sensorimotor seizures involving the left hand every 10 min, was imaged with a hyperspectral camera during surgery. By calculating the changes in oxygenated, deoxygenated blood, and total blood volume in the cortex, a focal increase in oxygenated and total blood volume could be observed in the sensory cortex, corresponding to the seizure‐onset zone defined by intracranial electroencephalography (EEG) findings. This probably reflects very local seizure activity. After multiple subpial transections in this motor area, clinical seizures abated.
Dimethylfumarate induces apoptosis in human mast cells
Authors: Förster Anja , Preussner Liane M. , Seeger Jens M. , Rabenhorst Anja , Kashkar Hamid , Mrowietz Ulrich , Hartmann Karin 
Published: October 2013

AbstractMast cells modulate autoimmune diseases such as psoriasis and multiple sclerosis. Fumaric acid esters (FAEs) are widely used for the treatment of psoriasis, and dimethylfumarate (DMF) has recently been approved for multiple sclerosis. In this study, we analysed the cytotoxic effect of FAEs on human mast cells. Specifically, cell death was analysed in the human mast cell line HMC‐1 and in primary cord blood‐derived mast cells (CBMCs) after incubation with fumaric acid (FA), monomethylfumarate (MMF), DMF and calcium bis(monomethylfumarate) (Ca‐MF). Our data show that only DMF potently induces apoptotic cell death in HMC‐1 cells and CBMCs. DMF‐mediated apoptosis was associated with increased expression of Bax and Bak and activation of caspase‐9 and caspase‐6. Interestingly, DMF also enhanced the sensitivity of CBMCs towards TRAIL‐ and dexamethasone‐induced apoptosis. These findings demonstrate for the first time that DMF induces apoptosis of human mast cells, primarily via the mitochondrial apoptotic pathway. Our study contributes to the understanding of the beneficial effects of FAEs in autoimmune diseases and provides a rationale for exploiting FAEs for other diseases associated with mast cells.
A novel adamantyl benzylbenzamide derivative, AP736, suppresses melanogenesis through the inhibition of cAMP‐PKA‐CREB‐activated microphthalmia‐associated transcription factor and tyrosinase expression
Authors: Lee Chang Seok , Jang Won‐Hee , Park Miyoung , Jung Kyoungmi , Baek Heung Soo , Joo Yung Hyup , Park Young‐Ho , Lim Kyung‐Min 
Published: October 2013

AbstractMelanogenesis is essential for the protection of skin against UV, but excessive production of melanin causes unaesthetic hyperpigmentation. Much effort is being made to develop effective depigmenting agents. Here, we found that a tyrosinase inhibitor, AP736 (5‐adamantan‐1‐yl‐N‐(2,4‐dihydroxy‐benzyl)‐2,4‐dimethoxy‐benzamide) potently suppresses tyrosinase expression, and the mechanism underlying was elucidated. AP736 attenuated the melanin production induced by diverse melanogenic stimuli in murine and human melanocytes. It suppressed the expression of key melanogenic enzymes; tyrosinase, tyrosinase‐related protein‐1 and tyrosinase‐related protein‐2. The expression of microphthalmia‐associated transcription factor (MiTF), a major promoter of melanogenesis was also decreased. AP736 inhibited the activation of cAMP response element‐binding protein (CREB) and phosphokinase A (PKA), and cAMP elevation, reflecting that cAMP‐PKA‐CREB signalling axis was suppressed, resulting in the downregulation of MiTF and tyrosinase. Along with the previously reported tyrosinase inhibitory activity, the suppression of cAMP‐PKA‐CREB‐mediated MiTF and tyrosinase expression by AP736 may be efficient for the treatment for hyperpigmentation.
Is climate warming more consequential towards poles? The phenology of Lepidoptera in Finland
Authors: Valtonen Anu , Leinonen Reima , Pöyry Juha , Roininen Heikki , Tuomela Jukka , Ayres Matthew P. 
Published: October 2013

AbstractThe magnitude and direction of phenological shifts from climate warming could be predictably variable across the planet depending upon the nature of physiological controls on phenology, the thermal sensitivity of the developmental processes and global patterns in the climate warming. We tested this with respect to the flight phenology of adult nocturnal moths (3.33 million captures of 334 species) that were sampled at sites in southern and northern Finland during 1993–2012 (with years 2005–2012 treated as an independent model validation data set). We compared eight competing models of physiological controls on flight phenology to each species and found strong support for thermal controls of phenology in 66% of the species generations. Among species with strong thermal control of phenology in both the south and north, the average development rate was higher in northern vs. southern populations at 10 °C, but about the same at 15 and 20 °C. With a 3 °C increase in temperature (approximating A2 scenario of IPPC for 2090–2099 relative to 1980–1999) these species were predicted to advance their phenology on average by 17 (SE ± 0.3) days in the south vs. 13 (±0.4) days in the north. The higher development rates at low temperatures of poleward populations makes them less sensitive to climate warming, which opposes the tendency for stronger phenological advances in the north from greater increases in temperature.