bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nebenwirkungsmanagement bei Immun‐Checkpoint‐Blockade durch CTLA‐4‐ und PD1‐Antikörper beim metastasierten Melanom
Authors: Kähler Katharina C. , Hassel Jessica C. , Heinzerling Lucie , Loquai Carmen , Mössner Rotraut , Ugurel Selma , Zimmer Lisa , Gutzmer Ralf ,   für das Komitee „Kutane Nebenwirkungen“ der Arbeitsgemeinschaft Dermatologische Onkologie (ADO)
Published: July 2016

ZusammenfassungCTLA‐4 und PD‐1 sind mögliche Angriffspunkte für eine Tumor‐bedingte Herunterregulation lymphozytärer Immunantworten. Immuncheckpoint‐modulierende monoklonale Antikörper wirken gegenteilig und induzieren eine Immunantwort gegen diverse Tumoren. CTLA‐4‐ und PD1‐Antikörper modulieren die Interaktion von Tumor, Antigen‐präsentierenden Zellen und T‐Lymphozyten. Die Therapie mit dem CTLA‐4‐Antikörper Ipilimumab und den PD1‐Antikörpern Nivolumab und Pembrolizumab konnte in klinischen Studien einen Vorteil für das Gesamtüberleben der Patienten zeigen, so dass nach einer Zulassung für Ipilimumab im Jahr 2011 dann im Sommer 2015 die Zulassung der beiden PD1‐Antikörper erfolgte.Eine derartig induzierte und verstärkte Immunantwort bringt unweigerlich in analoger Wirkung Autoimmunphänomene mit sich. Die Kenntnis dieses Nebenwirkungsspektrums ist für Prophylaxe und Management durch den behandelnden Arzt unerlässlich. Als schwere Nebenwirkung ist mit einer Kolitis zu rechnen, welche sich schon früh in ausgeprägten und anhaltenden Diarrhöen bemerkbar macht. Daneben sind auch andere immunvermittelte Erkrankungen wie die Dermatitis, die Hypophysitis, die Thyreoiditis, die Hepatitis, Iridozyklitis und weitere, eher seltenere Autoimmunphänomene beschrieben worden. Durch eine frühzeitige Diagnosestellung und Therapieeinleitung können Risiken und Folgeschäden für Patienten reduziert werden.Diese Übersichtsarbeit beschreibt die Wirkung einer Immun‐Checkpoint‐Blockade beim metastasierten Melanom und stellt detailliert das Nebenwirkungsspektrum und ‐management dieser Therapeutika dar.
Challenging Gendered Inequalities in Global Health: Dilemmas for NGOs
Authors: Gideon Jasmine , Porter Fenella 
Published: July 2016

ABSTRACTThis article considers the implications of the changing funding landscape in global health for NGOs in the health sector, particularly where they have aspired to promote gender equality and justice through their health work. The article reflects on the tensions that arise as a result of the growing influence of business norms within health funding alongside what critics have termed the ‘scientization’ of global health, and it considers the gendered implications of these developments. It is argued that it is due to the under‐valuation and marginalization of community‐based work that provides spaces for women's voices in the design and delivery of health interventions that large‐scale ‘technical’ interventions receive priority. The article examines what this means in terms of NGOs’ ability to work towards producing transformative change around gender — and indeed racial — equality.
Just Global Health?
Authors: Reid‐Henry Simon 
Published: July 2016

ABSTRACTSome 40 years ago, the public health philosopher Dan Beauchamp suggested that ‘public health should be a way of doing justice’. The argument put forward in this essay is that global health should be a way of doing global justice, by ameliorating the health inequalities that exclude many millions of people globally from enjoying a healthy life and from the benefits of a fuller inclusion in modern society. The essay develops this argument in three stages. First, it sets out some points of intersection between the politics of (global) health and competing ideas of justice. It offers a very basic typology of global health policy and practice that divides it into ‘market‐justice’ and ‘social‐justice’ models, and shows why it is the market‐justice model that at present dominates. Second, the essay explores how mainstream ‘market‐justice’ approaches to global health deal with the problem of health inequality rather weakly, and it is suggested that there are both historical and geographical reasons for this. Third, three ‘social‐justice’ approaches to global health are explored that better take those historical and geographical conditions into account. In conclusion the essay offers some thoughts on the political uses of theories of justice.
Quantifying passive muscle stiffness in children with and without cerebral palsy using ultrasound shear wave elastography
Authors: Brandenburg Joline E , Eby Sarah F , Song Pengfei , Kingsley‐Berg Shirley , Bamlet William , Sieck Gary C , An Kai‐Nan 
Published: July 2016

AimThe aim of this study was to compare passive muscle stiffness in children with cerebral palsy (CP) and children with typical development using a novel ultrasound technique: ultrasound shear wave elastography (SWE).MethodWe conducted a prospective study of 13 children with CP (six females and seven males, median age 5y 1mo [interquartile range 4y 4mo–7y 8mo]) and 13 children with typical development (six females and seven males, median age 5y 3mo [interquartile range 4y 4mo–9y 4mo]). Demographic information and physical exam measurements were obtained in addition to shear modulus measurements (passive muscle stiffness) of the lateral gastrocnemius muscle at 20° plantar flexion, 10° plantar flexion, and 0° plantar flexion using SWE.ResultsChildren with CP had significantly greater shear modulus measurements at all three foot positions (p<0.050). When the shear modulus values were normalized to the baseline value for each child, there was no significant difference between the two groups.InterpretationPassive muscle stiffness, measured without the influence of spasticity, is greater in children with CP than in children with typical development when a muscle is at slack and at stretch. When shear modulus was normalized, the results indicate that muscle in children in both groups responds similarly to passive stretch. Further work includes evaluating effect of botulinum toxin on passive muscle properties.
Efficacy and safety of liraglutide compared to sulphonylurea during Ramadan in patients with type 2 diabetes (LIRA‐Ramadan): a randomized trial
Authors: Azar S. T. , Echtay A. , Wan Bebakar W. M. , Al Araj S. , Berrah A. , Omar M. , Mutha A. , Tornøe K. , Kaltoft M. S. , Shehadeh N. 
Published: July 2016

AimsCompare effects of liraglutide 1.8 mg and sulphonylurea, both combined with metformin, on glycaemic control in patients with type 2 diabetes (T2D) fasting during Ramadan.Materials and methodsIn this up to 33‐week, open‐label, active‐controlled, parallel‐group trial, adults [glycated haemoglobin (HbA1c) 7%‐10% (53‐86 mmol/mol); body mass index ≥20 kg/m2; intent to fast] were randomized (1:1) ≥10 weeks before Ramadan to either switch to once‐daily liraglutide (final dose 1.8 mg) or continue pre‐trial sulphonylurea at maximum tolerated dose, both with metformin. Primary endpoint: change in fructosamine, a validated marker of short‐term glycaemic control, during Ramadan.ResultsSimilar reductions in fructosamine levels were observed for both groups during Ramadan [liraglutide (−12.8 µmol/L); sulphonylurea (−16.4 µmol/L); estimated treatment difference (ETD) 3.51 µmol/L (95% CI: −5.26; 12.28); p = 0.43], despite lower fructosamine levels in the liraglutide group at start of Ramadan. Fewer documented symptomatic hypoglycaemic episodes were reported in liraglutide‐treated (2%, three subjects) versus sulphonylurea‐treated patients (11%, 18 subjects). No severe hypoglycaemic episodes were reported by either group. Body weight decreased more during Ramadan with liraglutide (ETD: −0.54 kg; 95% CI: −0.94;−0.14; p = 0.0091). The proportion of patients reporting adverse events was similar between groups. Liraglutide led to greater HbA1c reduction [ETD: −0.59% (−6.40 mmol/mol), 95% CI: −0.79; −0.38%; −8.63; −4.17 mmol/mol; p < 0.0001].ConclusionsDespite lower fructosamine levels and body weight at the beginning of Ramadan, use of liraglutide showed similar glycaemic improvements, fewer hypoglycaemic episodes and greater body weight reduction compared with sulphonylurea. LIRA‐Ramadan provides evidence for liraglutide being safe and efficacious for management of T2D during Ramadan fasting.
Cardiovascular safety of empagliflozin in patients with type 2 diabetes: a meta‐analysis of data from randomized placebo‐controlled trials
Authors: Salsali A. , Kim G. , Woerle H. J. , Broedl U. C. , Hantel S. 
Published: July 2016

AimTo assess the effect of empagliflozin on cardiovascular (CV) risk in patients with type 2 diabetes (T2DM) through a meta‐analysis of data from eight placebo‐controlled trials.MethodsData were analysed from eight randomized placebo‐controlled trials undertaken to investigate the efficacy and safety of empagliflozin 10 and 25 mg once daily in patients with T2DM, comprising patients at low/medium and high CV risk. Suspected CV events were prospectively adjudicated. The empagliflozin 10 and 25 mg groups were pooled for the primary analysis. The primary endpoint was a composite of CV death, non‐fatal myocardial infarction (MI), non‐fatal stroke and hospitalization for unstable angina [4‐point major adverse CV events (MACE)]. The secondary endpoint was a composite of CV death, non‐fatal MI and non‐fatal stroke (3‐point MACE). Risk estimates were calculated using Cox regression analysis.ResultsA total of 3835 patients received placebo and 7457 received empagliflozin. Total exposure was 7448.3 years for placebo and 15482.1 years for empagliflozin. Four‐point MACE occurred in 365 (9.5%) patients receiving placebo and 635 (8.5%) patients receiving empagliflozin [hazard ratio for empagliflozin vs. placebo 0.86 (95% CI 0.76, 0.98)]. Three‐point MACE occurred in 307 (8.0%) patients receiving placebo and 522 (7.0%) patients receiving empagliflozin [hazard ratio for empagliflozin vs. placebo 0.84 (95% CI 0.73, 0.96)].ConclusionsIn a meta‐analysis of data from eight randomized trials involving 11 292 patients with T2DM at low/medium or high CV risk, empagliflozin was associated with a reduced risk of 4‐point MACE and 3‐point MACE compared with placebo.
Spike‐timing dependent inhibitory plasticity to learn a selective gating of backpropagating action potentials
Authors: Wilmes Katharina Anna , Schleimer Jan‐Hendrik , Schreiber Susanne 
Published: July 2016

AbstractInhibition is known to influence the forward‐directed flow of information within neurons. However, also regulation of backward‐directed signals, such as backpropagating action potentials (bAPs), can enrich the functional repertoire of local circuits. Inhibitory control of bAP spread, for example, can provide a switch for the plasticity of excitatory synapses. Although such a mechanism is possible, it requires a precise timing of inhibition to annihilate bAPs without impairment of forward‐directed excitatory information flow. Here, we propose a specific learning rule for inhibitory synapses to automatically generate the correct timing to gate bAPs in pyramidal cells when embedded in a local circuit of feedforward inhibition. Based on computational modeling of multi‐compartmental neurons with physiological properties, we demonstrate that a learning rule with anti‐Hebbian shape can establish the required temporal precision. In contrast to classical spike‐timing dependent plasticity of excitatory synapses, the proposed inhibitory learning mechanism does not necessarily require the definition of an upper bound of synaptic weights because of its tendency to self‐terminate once annihilation of bAPs has been reached. Our study provides a functional context in which one of the many time‐dependent learning rules that have been observed experimentally – specifically, a learning rule with anti‐Hebbian shape – is assigned a relevant role for inhibitory synapses. Moreover, the described mechanism is compatible with an upregulation of excitatory plasticity by disinhibition.
Sensing of soil bulk density for more accurate carbon accounting
Authors: Lobsey C. R. , Viscarra Rossel R. A. 
Published: July 2016

SummaryMeasurements of soil bulk density can aid our understanding of soil functions and the effects of land use and climate change on soil organic carbon (C) stocks. Current methods for measuring bulk density are laborious and expensive, subject to errors and complicated by the need to measure below the soil surface. These shortcomings are emphasized when there is need to characterize the spatial (lateral and vertical) and temporal variation of soil bulk density and related properties. We developed a technique that combines gamma‐ray attenuation and visible–near infrared (vis–NIR) spectroscopy to measure ex situ the bulk density of 1‐m soil cores that are sampled freshly, wet and under field conditions. We found that the accuracy of the sensor measurements was similar to that of the conventional single‐ring method, but sensing is rapid, inexpensive, non‐destructive and practical. Sensing can be used to measure many soil cores efficiently at fine depth resolutions (e.g. every 2 cm along the core), thereby allowing effective characterization of spatial variation in both lateral and vertical directions. The measurements can be made in the field, on wet soil cores, which reduces the costs and errors associated with transport, handling, oven‐drying and laboratory measurements. We show that sensing of bulk density can be used to measure organic C stocks on either a fixed‐depth (FD) or cumulative soil mass (CSM) basis. Our sensing approach to measure bulk density meets all the requirements for inclusion in a well‐designed soil organic C accounting system; it provides accurate and verifiable data on the spatial variation of soil bulk density so that changes in C stocks might be attributed more accurately to changes in either bulk density or in C content.Highlights
Proximal soil sensors enable practical, accurate, verifiable and inexpensive measurements of bulk density for C accounting.
We describe a new sensing approach for measuring soil bulk density.
Measurements are rapid, accurate, verifiable and can be made on wet soil under field conditions and to depth.
Sensing enables measurements of C stocks using both fixed‐depth or cumulative soil mass.
The SCN8A encephalopathy mutation p.Ile1327Val displays elevated sensitivity to the anticonvulsant phenytoin
Authors: Barker Bryan S. , Ottolini Matteo , Wagnon Jacy L. , Hollander Rachel M. , Meisler Miriam H. , Patel Manoj K. 
Published: July 2016

SummaryObjectiveSCN8A encephalopathy (early infantile epileptic encephalopathy; EIEE13) is caused by gain‐of‐function mutations resulting in hyperactivity of the voltage‐gated sodium channel Nav1.6. The channel is concentrated at the axon initial segment (AIS) and is involved in establishing neuronal excitability. Clinical features of SCN8A encephalopathy include seizure onset between 0 and 18 months of age, intellectual disability, and developmental delay. Seizures are often refractory to treatment with standard antiepileptic drugs, and sudden unexpected death in epilepsy (SUDEP) has been reported in approximately 10% of patients. In a recent study, high doses of phenytoin were effective in four patients with SCN8A encephalopathy. In view of this observation, we have investigated the relationship between the functional effect of the SCN8A mutation p.Ile1327Val and its response to phenytoin.MethodsThe mutation was introduced into the Scn8a cDNA by site‐directed mutagenesis. Channel activity was characterized in transfected ND7/23 cells. The effects of phenytoin (100 μm) on mutant and wild‐type (WT) channels were compared.ResultsChannel activation parameters were shifted in a hyperpolarizing direction in the mutant channel, whereas inactivation parameters were shifted in a depolarizing direction, increasing Na channel window current. Macroscopic current decay was slowed in I1327V channels, indicating an impairment in the transition from open state to inactivated state. Channel deactivation was also delayed, allowing more channels to remain in the open state. Phenytoin (100 μm) resulted in hyperpolarized activation and inactivation curves as well as greater tonic block and use‐dependent block of I1327V mutant channels relative to WT.SignificanceSCN8A – I1327V is a gain‐of‐function mutation with altered features that are predicted to increase neuronal excitability and seizure susceptibility. Phenytoin is an effective inhibitor of the mutant channel and may be of use in treating patients with gain‐of‐function mutations of SCN8A.
Past and present dynamics of sorghum and pearl millet diversity in Mount Kenya region
Authors: Labeyrie Vanesse , Deu Monique , Dussert Yann , Rono Bernard , Lamy Françoise , Marangu Charles , Kiambi Dan , Calatayud Caroline , Coppens d'Eeckenbrugge Geo , Robert Thierry , Leclerc Christian 
Published: July 2016

AbstractCrop populations in smallholder farming systems are shaped by the interaction of biological, ecological, and social processes, occurring on different spatiotemporal scales. Understanding these dynamics is fundamental for the conservation of crop genetic resources. In this study, we investigated the processes involved in sorghum and pearl millet diversity dynamics on Mount Kenya. Surveys were conducted in ten sites distributed along two elevation transects and occupied by six ethnolinguistic groups. Varieties of both species grown in each site were inventoried and characterized using SSR markers. Genetic diversity was analyzed using both individual‐ and population‐based approaches. Surveys of seed lot sources allowed characterizing seed‐mediated gene flow. Past sorghum diffusion dynamics were explored by comparing Mount Kenya sorghum diversity with that of the African continent. The absence of structure in pearl millet genetic diversity indicated common ancestry and/or important pollen‐ and seed‐mediated gene flow. On the contrary, sorghum varietal and genetic diversity showed geographic patterns, pointing to different ancestry of varieties, limited pollen‐mediated gene flow, and geographic patterns in seed‐mediated gene flow. Social and ecological processes involved in shaping seed‐mediated gene flow are further discussed.
Eco‐immunology and bioinvasion: revisiting the evolution of increased competitive ability hypotheses
Authors: Cornet Stéphane , Brouat Carine , Diagne Christophe , Charbonnel Nathalie 
Published: July 2016

AbstractImmunity is at the core of major theories related to invasion biology. Among them, the evolution of increased competitive ability (EICA) andEICA‐refined hypotheses have been used as a reference work. They postulate that the release from pathogens often experienced during invasion should favour a reallocation of resources from (costly) immune defences to beneficial life‐history traits associated with invasive potential. We review studies documenting immune changes during animal invasions. We describe the designs and approaches that have been applied and discuss some reasons that prevent drawing generalized conclusions regardingEICAhypotheses. We detail why a better assessment of invasion history and immune costs, including immunopathologies and parasite communities, could improve our understanding of the relationships between immunity and invasion success. Finally, we propose new perspectives to revisit theEICAhypotheses. We first emphasize the neutral and adaptive mechanisms involved in immune changes, as well as timing of the later. Such investigation will help decipher whether immune changes are a consequence of pre‐adaptation, or the result of postintroduction adaptations to invasion front conditions. We next bring attention to new avenues of research that remain unexplored, namely age‐dependent immunity and gut microbiota, potential key factors underlying adaptation to invasion front environment and modulating invasion success.
Treatment of extensive erythema multiforme with topical gentian violet
Authors: Murthy Rajini K. , Van Livia , Arbiser Jack L. 
Published: July 2016

AbstractTopical and systemic therapies for erythema multiforme have been widely described in the literature. The pathogenesis of erythema multiforme involves increased expression of vascular endothelial growth factor resulting in the promotion of microvascular permeability and angiogenesis. Gentian violet has been shown to have antiangiogenic properties. Here, we present a case of erythema multiforme successfully treated with topical gentian violet. We report the case of a patient who presented with erythema multiforme. Prior pertinent history included diabetes mellitus type I, limiting the clinical use of systemic corticosteroids. Topical gentian violet was used to treat the cutaneous lesions. Our patient responded well to treatment with topical gentian violet with stabilization and resolution of the lesions without using systemic therapy that may pose serious side effects in the setting of other comorbidities such as diabetes mellitus type I. This case highlights the variable therapeutic options available for treatment of erythema multiforme, including topical gentian violet. While further studies are needed, this case demonstrates the antiangiogenic properties and clinical utility of topical gentian violet in the treatment of erythema multiforme.
Flow regulation increases food‐chain length through omnivory mechanisms in a Mediterranean river network
Authors: Ruhí Albert , Muñoz Isabel , Tornés Elisabet , Batalla Ramon J. , Vericat Damià , Ponsatí Lídia , Acuña Vicenç , von Schiller Daniel , Marcé Rafael , Bussi Gianbattista , Francés Félix , Sabater Sergi 
Published: July 2016

Summary

Dams fragment river systems worldwide, and Mediterranean‐climate rivers, characterised by highly seasonal hydrographs and adapted biotas, are particularly impacted by flow regulation. Whereas the effects of flow regulation on hydrology, sediment transport and biodiversity have long been examined, responses at the food‐web level remain understudied.

Environmental variation is a key control of food‐web structure. Thus, we predicted that flow regulation would impact food‐chain length (FCL) via changes in the flow variation regime, and we tested this prediction in a set of flow unregulated to completely regulated reaches in a Mediterranean river basin.

In each reach, we characterised flow variation, together with two other putative controls of FCL (productivity and habitat size). We combined community data with carbon and nitrogen stable isotopes to estimate food‐chain length, and Bayesian mixing models allowed estimates of dietary proportions of consumers.

Flow variation was paramount in controlling FCL in the studied river network, and this same control largely explained the degree of omnivory among top predators. Thus, omnivory mechanisms were the main proximate structural mechanism allowing shifts in food‐web structure and linking disturbance regimes to FCL.

Our results suggest that flow regulation in Mediterranean rivers may impact food‐web structure even when no significant changes in community composition are observed. If highly variable Mediterranean streams become increasingly affected by flow regulation, the resulting more stable conditions could enhance intraguild predation and thus lengthen riverine food chains.