Showing papers by "University of Münster published in 2015"

A classification of chronic pain for ICD-11.

Abstract: Chronic pain has been recognized as pain that persists past normal healing time5 and hence lacks the acute warning function of physiological nociception.35 Usually pain is regarded as chronic when it lasts or recurs for more than 3 to 6 months.29 Chronic pain is a frequent condition, affecting an estimated 20% of people worldwide6,13,14,18 and accounting for 15% to 20% of physician visits.25,28 Chronic pain should receive greater attention as a global health priority because adequate pain treatment is a human right, and it is the duty of any health care system to provide it.4,13 The current version of the International Classification of Diseases (ICD) of the World Health Organization (WHO) includes some diagnostic codes for chronic pain conditions, but these diagnoses do not reflect the actual epidemiology of chronic pain, nor are they categorized in a systematic manner. The ICD is the preeminent tool for coding diagnoses and documenting investigations or therapeutic measures within the health care systems of many countries. In addition, ICD codes are commonly used to report target diseases and comorbidities of participants in clinical research. Consequently, the current lack of adequate coding in the ICD makes the acquisition of accurate epidemiological data related to chronic pain difficult, prevents adequate billing for health care expenses related to pain treatment, and hinders the development and implementation of new therapies.10,11,16,23,27,31,37 Responding to these shortcomings, the International Association for the Study of Pain (IASP) contacted the WHO and established a Task Force for the Classification of Chronic Pain. The IASP Task Force, which comprises pain experts from across the globe,19 has developed a new and pragmatic classification of chronic pain for the upcoming 11th revision of the ICD. The goal is to create a classification system that is applicable in primary care and in clinical settings for specialized pain management. A major challenge in this process was finding a rational principle of classification that suits the different types of chronic pain and fits into the general ICD-11 framework. Pain categories are variably defined based on the perceived location (headache), etiology (cancer pain), or the primarily affected anatomical system (neuropathic pain). Some diagnoses of pain defy these classification principles (fibromyalgia). This problem is not unique to the classification of pain, but exists throughout the ICD. The IASP Task Force decided to give first priority to pain etiology, followed by underlying pathophysiological mechanisms, and finally the body site. Developing this multilayered classification was greatly facilitated by a novel principle of assigning diagnostic codes in ICD-11, termed “multiple parenting.” Multiple parenting allows the same diagnosis to be subsumed under more than 1 category (for a glossary of ICD terms refer to Table ​Table1).1). Each diagnosis retains 1 category as primary parent, but is cross-referenced to other categories that function as secondary parents. Table 1 Glossary of ICD-11 terms. The new ICD category for “Chronic Pain” comprises the most common clinically relevant disorders. These disorders were divided into 7 groups (Fig. ​(Fig.1):1): (1) chronic primary pain, (2) chronic cancer pain, (3) chronic posttraumatic and postsurgical pain, (4) chronic neuropathic pain, (5) chronic headache and orofacial pain, (6) chronic visceral pain, and (7) chronic musculoskeletal pain. Experts assigned to each group are responsible for the definition of diagnostic criteria and the selection of the diagnoses to be included under these subcategories of chronic pain. Thanks to Bedirhan Ustun and Robert Jakob of the WHO, these pain diagnoses are now integrated in the beta version of ICD-11 (http://id.who.int/icd/entity/1581976053). The Task Force is generating content models for single entities to describe their clinical characteristics. After peer review overseen by the WHO Steering Committee,39 the classification of chronic pain will be voted into action by the World Health Assembly in 2017. Figure 1 Organizational chart of Task Force, IASP, and WHO interactions. The IASP Task Force was created by the IASP council and its scope defined in direct consultation of the chairs (R.D.T. and W.R.) with WHO representatives in 2012. The Task Force reports to ... 2. Classification of chronic pain Chronic pain was defined as persistent or recurrent pain lasting longer than 3 months. This definition according to pain duration has the advantage that it is clear and operationalized. Optional specifiers for each diagnosis record evidence of psychosocial factors and the severity of the pain. Pain severity can be graded based on pain intensity, pain-related distress, and functional impairment. 2.1. Chronic primary pain Chronic primary pain is pain in 1 or more anatomic regions that persists or recurs for longer than 3 months and is associated with significant emotional distress or significant functional disability (interference with activities of daily life and participation in social roles) and that cannot be better explained by another chronic pain condition. This is a new phenomenological definition, created because the etiology is unknown for many forms of chronic pain. Common conditions such as, eg, back pain that is neither identified as musculoskeletal or neuropathic pain, chronic widespread pain, fibromyalgia, and irritable bowel syndrome will be found in this section and biological findings contributing to the pain problem may or may not be present. The term “primary pain” was chosen in close liaison with the ICD-11 revision committee, who felt this was the most widely acceptable term, in particular, from a nonspecialist perspective.

Frustrated Lewis pair chemistry: development and perspectives.

Abstract: Frustrated Lewis pairs (FLPs) are combinations of Lewis acids and Lewis bases in solution that are deterred from strong adduct formation by steric and/or electronic factors. This opens pathways to novel cooperative reactions with added substrates. Small-molecule binding and activation by FLPs has led to the discovery of a variety of new reactions through unprecedented pathways. Hydrogen activation and subsequent manipulation in metal-free catalytic hydrogenations is a frequently observed feature of many FLPs. The current state of this young but rapidly expanding field is outlined in this Review and the future directions for its broadening sphere of impact are considered.

Updated European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist anticoagulants in patients with non-valvular atrial fibrillation.

Abstract: The current manuscript is an update of the original Practical Guide, published in June 2013[Heidbuchel H, Verhamme P, Alings M, Antz M, Hacke W, Oldgren J, et al. European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace 2013;15:625-51; Heidbuchel H, Verhamme P, Alings M, Antz M, Hacke W, Oldgren J, et al. EHRA practical guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation: executive summary. Eur Heart J 2013;34:2094-106]. Non-vitamin K antagonist oral anticoagulants (NOACs) are an alternative for vitamin K antagonists (VKAs) to prevent stroke in patients with non-valvular atrial fibrillation (AF). Both physicians and patients have to learn how to use these drugs effectively and safely in clinical practice. Many unresolved questions on how to optimally use these drugs in specific clinical situations remain. The European Heart Rhythm Association set out to coordinate a unified way of informing physicians on the use of the different NOACs. A writing group defined what needs to be considered as 'non-valvular AF' and listed 15 topics of concrete clinical scenarios for which practical answers were formulated, based on available evidence. The 15 topics are (i) practical start-up and follow-up scheme for patients on NOACs; (ii) how to measure the anticoagulant effect of NOACs; (iii) drug-drug interactions and pharmacokinetics of NOACs; (iv) switching between anticoagulant regimens; (v) ensuring adherence of NOAC intake; (vi) how to deal with dosing errors; (vii) patients with chronic kidney disease; (viii) what to do if there is a (suspected) overdose without bleeding, or a clotting test is indicating a risk of bleeding?; (xi) management of bleeding complications; (x) patients undergoing a planned surgical intervention or ablation; (xi) patients undergoing an urgent surgical intervention; (xii) patients with AF and coronary artery disease; (xiii) cardioversion in a NOAC-treated patient; (xiv) patients presenting with acute stroke while on NOACs; and (xv) NOACs vs. VKAs in AF patients with a malignancy. Additional information and downloads of the text and anticoagulation cards in >16 languages can be found on an European Heart Rhythm Association web site (www.NOACforAF.eu).

Integrated all-photonic non-volatile multi-level memory

Abstract: Researchers use phase-change materials to demonstrate an integrated optical memory with 13.4 pJ switching energy.

Small-bowel capsule endoscopy and device-assisted enteroscopy for diagnosis and treatment of small-bowel disorders: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline.

Abstract: Small-bowel capsule endoscopy (SBCE) 1 ESGE recommends that prior to SBCE patients ingest a purgative (2 L of polyethylene glycol [PEG]) for better visualization. Strong recommendation, high quality evidence. However, the optimal timing for taking purgatives is yet to be established. 2 ESGE recommends that SBCE should be performed as an outpatient procedure if possible, since completion rates are higher in outpatients than in inpatients. Strong recommendation, moderate quality evidence. 3 ESGE recommends that patients with pacemakers can safely undergo SBCE without special precautions. Strong recommendation, low quality evidence. 4 ESGE suggests that SBCE can also be safely performed in patients with implantable cardioverter defibrillators and left ventricular assist devices. Weak recommendation, low quality evidence. 5 ESGE recommends the acceptance of qualified nurses and trained technicians as prereaders of capsule endoscopy studies as their competency in identifying pathology is similar to that of medically qualified readers. The responsibility of establishing a diagnosis must however remain with the attending physician. Strong recommendation, moderate quality evidence. 6 ESGE recommends observation in cases of asymptomatic capsule retention. Strong recommendation, moderate quality evidence. In cases where capsule retrieval is indicated, ESGE recommends the use of device-assisted enteroscopy as the method of choice. Strong recommendation, moderate quality evidence. Device-assisted enteroscopy (DAE) 1 ESGE recommends performing diagnostic DAE as a day-case procedure in patients without significant underlying co-morbidities; in patients with co-morbidities and/or those undergoing a therapeutic procedure, an inpatient stay is recommended. Strong recommendation, low quality evidence The choice between different settings also depends on sedation protocols. Strong recommendation, low quality evidence. 2 ESGE suggests that conscious sedation, deep sedation, and general anesthesia are all acceptable alternatives: the choice between them should be governed by procedure complexity, clinical factors, and local organizational protocols. Weak recommendation, low quality evidence. 3 ESGE recommends that the findings of previous diagnostic investigations should guide the choice of insertion route. Strong recommendation, moderate quality evidence. If the location of the small-bowel lesion is unknown or uncertain, ESGE recommends that the antegrade route should be generally preferred. Strong recommendation, low quality evidence. In the setting of massive overt bleeding, ESGE recommends an initial antegrade approach. Strong recommendation, low quality evidence. 4 ESGE recommends that, for balloon-assisted enteroscopy (i. e., single-balloon enteroscopy [SBE] and double-balloon enteroscopy [DBE]), small-bowel insertion depth should be estimated by counting net advancement of the enteroscope during the insertion phase, with confirmation of this estimate during withdrawal. Strong recommendation, low quality evidence. ESGE recommends that, for spiral enteroscopy, insertion depth should be estimated during withdrawal. Strong recommendation, moderate quality evidence. Since the calculated insertion depth is only a rough estimate, ESGE recommends placing a tattoo to mark the identified lesion and/or the deepest point of insertion. Strong recommendation, low quality evidence. 5 ESGE recommends that all endoscopic therapeutic procedures can be undertaken at the time of DAE. Strong recommendation, moderate quality evidence. Moreover, when therapeutic interventions are performed, additional specific safety measures are needed to prevent complications. Strong recommendation, high quality evidence.

Safer Electrolytes for Lithium-Ion Batteries: State of the Art and Perspectives

Abstract: Lithium-ion batteries are becoming increasingly important for electrifying the modern transportation system and, thus, hold the promise to enable sustainable mobility in the future. However, their large-scale application is hindered by severe safety concerns when the cells are exposed to mechanical, thermal, or electrical abuse conditions. These safety issues are intrinsically related to their superior energy density, combined with the (present) utilization of highly volatile and flammable organic-solvent-based electrolytes. Herein, state-of-the-art electrolyte systems and potential alternatives are briefly surveyed, with a particular focus on their (inherent) safety characteristics. The challenges, which so far prevent the widespread replacement of organic carbonate-based electrolytes with LiPF6 as the conducting salt, are also reviewed herein. Starting from rather "facile" electrolyte modifications by (partially) replacing the organic solvent or lithium salt and/or the addition of functional electrolyte additives, conceptually new electrolyte systems, including ionic liquids, solvent-free, and/or gelled polymer-based electrolytes, as well as solid-state electrolytes, are also considered. Indeed, the opportunities for designing new electrolytes appear to be almost infinite, which certainly complicates strict classification of such systems and a fundamental understanding of their properties. Nevertheless, these innumerable opportunities also provide a great chance of developing highly functionalized, new electrolyte systems, which may overcome the afore-mentioned safety concerns, while also offering enhanced mechanical, thermal, physicochemical, and electrochemical performance.

Electrochemical in situ investigations of SEI and dendrite formation on the lithium metal anode

Abstract: This comparative work studies the self-enforcing heterogeneity of lithium deposition and dissolution as the cause for dendrite formation on the lithium metal anode in various liquid organic solvent based electrolytes. In addition, the ongoing lithium corrosion, its rate and thus the passivating quality of the SEI are investigated in self-discharge measurements. The behavior of the lithium anode is characterized in two carbonate-based standard electrolytes, 1 M LiPF6 in EC/DEC (3 : 7) and 1 M LiPF6 in EC/DMC (1 : 1), and in two alternative electrolytes 1 M LiPF6 in TEGDME and 1 M LiTFSI in DMSO, which have been proposed in the literature as promising electrolytes for lithium metal batteries, more specifically for lithium/air batteries. As a result, electrolyte decomposition, SEI and dendrite formation at the lithium electrode as well as their mutual influences are understood in the development of overpotentials, surface resistances and lithium electrode surface morphologies in subsequent lithium deposition and dissolution processes. A general model of different stages of these processes could be elaborated.

Land use intensification alters ecosystem multifunctionality via loss of biodiversity and changes to functional composition

Abstract: Global change, especially land-use intensification, affects human well-being by impacting the delivery of multiple ecosystem services (multifunctionality). However, whether biodiversity loss is a major component of global change effects on multifunctionality in real-world ecosystems, as in experimental ones, remains unclear. Therefore, we assessed biodiversity, functional composition and 14 ecosystem services on 150 agricultural grasslands differing in land-use intensity. We also introduce five multifunctionality measures in which ecosystem services were weighted according to realistic land-use objectives. We found that indirect land-use effects, i.e. those mediated by biodiversity loss and by changes to functional composition, were as strong as direct effects on average. Their strength varied with land-use objectives and regional context. Biodiversity loss explained indirect effects in a region of intermediate productivity and was most damaging when land-use objectives favoured supporting and cultural services. In contrast, functional composition shifts, towards fast-growing plant species, strongly increased provisioning services in more inherently unproductive grasslands.

Single-photon emission from localized excitons in an atomically thin semiconductor

Abstract: Single-photon sources are basic building blocks for quantum communications, processing, and metrology. Solid-state quantum emitters in semiconductors have the potential for robust and reliable generation of photons, and atomically thin transition metal dichalcogenides, such as MoS2, MoSe2, WS2, and WSe2, are a promising new class of two-dimensional semiconductors with a direct optical bandgap in the visible or near-IR. Here, we observe bright and stable single-photon emission from localized excitons in a monolayer of tungsten diselenide (WSe2). The emitters appear at the edges of the flakes and are linearly polarized. The spectral width of their emission is below 120 μeV in a freestanding WSe2 monolayer. Photoluminescence excitation spectroscopy reveals the excitonic nature of the emitters and provides evidence that these single excitons originate from free excitons trapped in local potential wells at the edges of the atomically thin flakes. We find that the emitters can also be deterministically created by scratching the WSe2 monolayer. Their excellent spectral stability implies that these localized single-photon emitters could find application in optoelectronics. Our results light the way to single exciton physics and quantum optics with atomically thin semiconductors.

Ewing Sarcoma: Current Management and Future Approaches Through Collaboration

Abstract: Ewing sarcoma (ES) is an aggressive sarcoma of bone and soft tissue occurring at any age with a peak incidence in adolescents and young adults. The treatment of ES relies on a multidisciplinary approach, coupling risk-adapted intensive neoadjuvant and adjuvant chemotherapies with surgery and/or radiotherapy for control of the primary site and possible metastatic disease. The optimization of ES multimodality therapeutic strategies has resulted from the efforts of several national and international groups in Europe and North America and from cooperation between pediatric and medical oncologists. Successive first-line trials addressed the efficacy of various cyclic combinations of drugs incorporating doxorubicin, vincristine, cyclophosphamide, ifosfamide, etoposide, and dactinomycin and identified prognostic factors now used to tailor therapies. The role of high-dose chemotherapy is still debated. Current 5-year overall survival for patients with localized disease is 65% to 75%. Patients with metastases have a 5-year overall survival < 30%, except for those with isolated pulmonary metastasis (approximately 50%). Patients with recurrence have a dismal prognosis. The many insights into the biology of the EWS-FLI1 protein in the initiation and progression of ES remain to be translated into novel therapeutic strategies. Current options and future approaches will be discussed.

Telomerase activation by genomic rearrangements in high-risk neuroblastoma

Abstract: Neuroblastoma is a malignant paediatric tumour of the sympathetic nervous system. Roughly half of these tumours regress spontaneously or are cured by limited therapy. By contrast, high-risk neuroblastomas have an unfavourable clinical course despite intensive multimodal treatment, and their molecular basis has remained largely elusive. Here we have performed whole-genome sequencing of 56 neuroblastomas (high-risk, n = 39; low-risk, n = 17) and discovered recurrent genomic rearrangements affecting a chromosomal region at 5p15.33 proximal of the telomerase reverse transcriptase gene (TERT). These rearrangements occurred only in high-risk neuroblastomas (12/39, 31%) in a mutually exclusive fashion with MYCN amplifications and ATRX mutations, which are known genetic events in this tumour type. In an extended case series (n = 217), TERT rearrangements defined a subgroup of high-risk tumours with particularly poor outcome. Despite a large structural diversity of these rearrangements, they all induced massive transcriptional upregulation of TERT. In the remaining high-risk tumours, TERT expression was also elevated in MYCN-amplified tumours, whereas alternative lengthening of telomeres was present in neuroblastomas without TERT or MYCN alterations, suggesting that telomere lengthening represents a central mechanism defining this subtype. The 5p15.33 rearrangements juxtapose the TERT coding sequence to strong enhancer elements, resulting in massive chromatin remodelling and DNA methylation of the affected region. Supporting a functional role of TERT, neuroblastoma cell lines bearing rearrangements or amplified MYCN exhibited both upregulated TERT expression and enzymatic telomerase activity. In summary, our findings show that remodelling of the genomic context abrogates transcriptional silencing of TERT in high-risk neuroblastoma and places telomerase activation in the centre of transformation in a large fraction of these tumours.

Resistance to cancer chemotherapy: failure in drug response from ADME to P-gp.

Abstract: Cancer chemotherapy resistance (MDR) is the innate and/or acquired ability of cancer cells to evade the effects of chemotherapeutics and is one of the most pressing major dilemmas in cancer therapy. Chemotherapy resistance can arise due to several host or tumor-related factors. However, most current research is focused on tumor-specific factors and specifically genes that handle expression of pumps that efflux accumulated drugs inside malignantly transformed types of cells. In this work, we suggest a wider and alternative perspective that sets the stage for a future platform in modifying drug resistance with respect to the treatment of cancer.

Chemie frustrierter Lewis‐Paare: Entwicklung und Perspektiven

Abstract: Der Begriff “frustrierte Lewis-Paare” (FLPs) bezeichnet Kombinationen von Lewis-Sauren und Lewis-Basen in Losung, die aufgrund sterischer oder elektronischer Faktoren an der Bildung eines stabilen Addukts gehindert werden. Die verbleibende Lewis-Aziditat und -Basizitat ermoglicht den Zugang zu neuen kooperativen Reaktionen mit zugesetzten Substraten. Die Fixierung und Aktivierung von kleinen Molekulen durch FLPs fuhrte zur Entdeckung einer Vielzahl von neuen Reaktionen und ungewohnlichen Reaktionswegen. Die Aktivierung von Diwasserstoff und die anschliesende Umsetzung in metallfreien katalytischen Hydrierungsreaktionen ist ein haufig beobachtetes Merkmal von FLPs. In diesem Aufsatz wird der aktuelle Stand dieses jungen Forschungsgebietes der Chemie beschrieben und die zukunftige Ausrichtung des sich rasch weiterentwickelnden Konzepts der frustrierten Lewis-Paare betrachtet.

European Consensus on the Diagnosis and Management of Iron Deficiency and Anaemia in Inflammatory Bowel Diseases

Abstract: European Consensus on the Diagnosis and Management of Iron Deficiency and Anaemia in Inflammatory Bowel Diseases

Mechanical Surface Modification of Lithium Metal: Towards Improved Li Metal Anode Performance by Directed Li Plating

Abstract: The effect of mechanical surface modification on the performance of lithium (Li) metal foil electrodes is systematically investigated. The applied micro-needle surface treatment technique for Li metal has various advantages. 1) This economical and efficient technique is able to cover a wide range of surface area with a simple rolling process, which can be easily conducted. 2) This technique achieves improved rate capability and cycling stability, as well as a reduced interfacial resistance. The micro-needle treatment improves the rate capability by 20% (0.750 mAh at a rate of 7C) and increases the cycling stability by 200% (85% of the initial discharge capacity after 150 cycles) compared to untreated bare Li metal (0.626 mAh at a rate of 7C, 85% of the initial discharge capacity after only 70 cycles). 3) This technique efficiently suppresses Li formation of high surface area Li during the Li deposition process, as preferred sites for controlled Li plating are generated.

Effects and safety of rituximab in systemic sclerosis: an analysis from the European Scleroderma Trial and Research (EUSTAR) group

Abstract: OBJECTIVES To assess the effects of Rituximab (RTX) on skin and lung fibrosis in patients with systemic sclerosis (SSc) belonging to the European Scleroderma Trial and Research (EUSTAR) cohort and using a nested case-control design. METHODS Inclusion criteria were fulfilment of American College of Rheumatology classification criteria for SSc, treatment with RTX and availability of follow-up data. RTX-treated patients were matched with control patients from the EUSTAR database not treated with RTX. Matching parameters for skin/lung fibrosis were the modified Rodnan Skin Score (mRSS), forced vital capacity (FVC), follow-up duration, scleroderma subtype, disease duration and immunosuppressive co-treatment. The primary analysis was mRSS change from baseline to follow-up in the RTX group compared with the control group. Secondary analyses included change of FVC and safety measures. RESULTS 63 patients treated with RTX were included in the analysis. The case-control analysis in patients with severe diffuse SSc showed that mRSS changes were larger in the RTX group versus matched controls (N=25; -24.0±5.2% vs -7.7±4.3%; p=0.03). Moreover, in RTX-treated patients, the mean mRSS was significantly reduced at follow-up compared with baseline (26.6±1.4 vs 20.3±1.8; p=0.0001). In addition, in patients with interstitial lung disease, RTX prevented significantly the further decline of FVC compared with matched controls (N=9; 0.4±4.4% vs -7.7±3.6%; p=0.02). Safety measures showed a good profile consistent with previous studies in autoimmune rheumatic diseases. CONCLUSIONS The comparison of RTX treated versus untreated matched-control SSc patients from the EUSTAR cohort demonstrated improvement of skin fibrosis and prevention of worsening lung fibrosis, supporting the therapeutic concept of B cell inhibition in SSc.

Effect of remote ischemic preconditioning on kidney injury among high-risk patients undergoing cardiac surgery: a randomized clinical trial.

Abstract: Importance No interventions have yet been identified to reduce the risk of acute kidney injury in the setting of cardiac surgery. Objective To determine whether remote ischemic preconditioning reduces the rate and severity of acute kidney injury in patients undergoing cardiac surgery. Design, Setting, and Participants In this multicenter trial, we enrolled 240 patients at high risk for acute kidney injury, as identified by a Cleveland Clinic Foundation score of 6 or higher, between August 2013 and June 2014 at 4 hospitals in Germany. We randomized them to receive remote ischemic preconditioning or sham remote ischemic preconditioning (control). All patients completed follow-up 30 days after surgery and were analyzed according to the intention-to-treat principle. Interventions Patients received either remote ischemic preconditioning (3 cycles of 5-minute ischemia and 5-minute reperfusion in one upper arm after induction of anesthesia) or sham remote ischemic preconditioning (control), both via blood pressure cuff inflation. Main Outcomes and Measures The primary end point was the rate of acute kidney injury defined by Kidney Disease: Improving Global Outcomes criteria within the first 72 hours after cardiac surgery. Secondary end points included use of renal replacement therapy, duration of intensive care unit stay, occurrence of myocardial infarction and stroke, in-hospital and 30-day mortality, and change in acute kidney injury biomarkers. Results Acute kidney injury was significantly reduced with remote ischemic preconditioning (45 of 120 patients [37.5%]) compared with control (63 of 120 patients [52.5%]; absolute risk reduction, 15%; 95% CI, 2.56%-27.44%; P = .02). Fewer patients receiving remote ischemic preconditioning received renal replacement therapy (7 [5.8%] vs 19 [15.8%]; absolute risk reduction, 10%; 95% CI, 2.25%-17.75%; P = .01), and remote ischemic preconditioning reduced intensive care unit stay (3 days [interquartile range, 2-5]) vs 4 days (interquartile range, 2-7) ( P = .04). There was no significant effect of remote ischemic preconditioning on myocardial infarction, stroke, or mortality. Remote ischemic preconditioning significantly attenuated the release of urinary insulinlike growth factor–binding protein 7 and tissue inhibitor of metalloproteinases 2 after surgery (remote ischemic preconditioning, 0.36 vs control, 0.97 ng/mL 2 /1000; difference, 0.61; 95% CI, 0.27-0.86; P Conclusions and Relevance Among high-risk patients undergoing cardiac surgery, remote ischemic preconditioning compared with no ischemic preconditioning significantly reduced the rate of acute kidney injury and use of renal replacement therapy. The observed reduction in the rate of acute kidney injury and the need for renal replacement warrants further investigation. Trial Registration German Clinical Trials Register Identifier:DRKS00005333

The genomes of two key bumblebee species with primitive eusocial organization

Abstract: The shift from solitary to social behavior is one of the major evolutionary transitions Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation

Peripheral arterial disease and critical limb ischaemia: still poor outcomes and lack of guideline adherence

Abstract: Aims Only few and historic studies reported a bad prognosis of peripheral arterial disease (PAD) and critical limb ischaemia (CLI). The contemporary state of treatment and outcomes should be assessed. Methods and results From the largest public health insurance in Germany, all in- and outpatient diagnosis and procedural data were retrospectively obtained from a cohort of 41 882 patients hospitalized due to PAD during 2009–2011, including a follow-up until 2013. Patients were classified in Rutherford categories 1–3 ( n = 21 197), 4 ( n = 5353), 5 ( n = 6916), and 6 ( n = 8416). The proportions of patients with classical risk factors such as hypertension, dyslipidaemia, and smoking declined with higher Rutherford categories (each P < 0.001) while diabetes, chronic kidney disease, and chronic heart failure increased (each P < 0.001). Angiographies and revascularizations were performed less often in advanced PAD (each P < 0.001). In-hospital amputations increased continuously from 0.5% in Rutherford 1–3 to 42% in Rutherford 6, as also myocardial infarctions, strokes, and deaths (each P < 0.001). Among 4298 amputated patients with CLI, 37% had not received any angiography or revascularization neither during index hospitalization nor the 24 months before. During follow-up (mean 1144 days), 7825 patients were amputated and 10 880 died. Kaplan–Meier models projected 4-year mortality risks of 18.9, 37.7, 52.2, and 63.5% in Rutherford 1–3, 4, 5, and 6, and for amputation of 4.6, 12.1, 35.3, and 67.3%, respectively. In multivariable Cox regression models, PAD categories were significant predictors of death, amputation, myocardial infarction, and stroke (each P < 0.001). Length of in-hospital stay (5.8 ± 6.7 days, 10.7 ± 11.1days, 15.2 ± 13.8 days and 22.1 ± 20.3 days; P < 0.001) and mean case costs (3662 ± 3186 €, 5316 ± 6139 €, 6021 ± 4892 €, and 8461 ± 8515 €; P < 0.001) increased continuously in Rutherford 1–3, 4, 5, and 6. While only 49% of the patients suffered from CLI, these produced 65% of in-hospital costs (141 million €), and 56% during follow-up (336 million €). Conclusion Regardless of recent advances in PAD treatment, current outcomes remain poor especially in CLI. Despite overwhelming evidence for reduction of limb loss by revascularization, CLI patients still received significantly less angiographies and revascularizations.

Resonant internal Quantum transitions and femtosecond radiative decay of excitons in monolayer WSe2

Abstract: Atomically thin two-dimensional crystals have revolutionized materials science. In particular, monolayer transition metal dichalcogenides promise novel optoelectronic applications, owing to their direct energy gaps in the optical range. Their electronic and optical properties are dominated by Coulomb-bound electron-hole pairs called excitons, whose unusual internal structure, symmetry, many-body effects and dynamics have been vividly discussed. Here we report the first direct experimental access to all 1s A excitons, regardless of momentum--inside and outside the radiative cone--in single-layer WSe2. Phase-locked mid-infrared pulses reveal the internal orbital 1s-2p resonance, which is highly sensitive to the shape of the excitonic envelope functions and provides accurate transition energies, oscillator strengths, densities and linewidths. Remarkably, the observed decay dynamics indicates an ultrafast radiative annihilation of small-momentum excitons within 150 fs, whereas Auger recombination prevails for optically dark states. The results provide a comprehensive view of excitons and introduce a new degree of freedom for quantum control, optoelectronics and valleytronics of dichalcogenide monolayers.

Adherence to diabetes medication: a systematic review.

Abstract: Aims To investigate the extent of and factors associated with adherence to Type 2 diabetes medication. Methods The CINAHL, Embase, International Pharmaceutical Abstracts, Medline, PubMed and PsychINFO databases were searched for the period January 2004 to July 2013. Papers were included in the present review if they reported the prevalence of adherence (the percentage of the study population that is classified as adherent) to Type 2 diabetes medication and used validated adherence measures with a defined cut-off point to indicate adherence. Reported factors were classified as potential predictors if the studies that examined that particular variable reported consistent findings. Results Of the 27 studies included in the present review, the prevalence of adherence ranged from 38.5 to 93.1%. Only six out of 27 studies (22.2%) reported prevalence of adherence of ≥ 80% among their study population. Depression and medication cost were found to be consistent and potentially modifiable predictors for diabetes medication-taking behaviour. The associations between adherence and other factors were inconsistent among the reviewed studies. Conclusions Adherence to diabetes medication remains an ongoing problem. This review has highlighted the urgent need to develop consensus about what constitutes good adherence in diabetes. Further research is needed to clarify modifiable factors, in addition to depression and medication cost, that influence adherence and may provide a focus for targeted interventions to promote adherence, optimize diabetes control and limit the progression of diabetes.

Methotrexate, Doxorubicin, and Cisplatin (MAP) Plus Maintenance Pegylated Interferon Alfa-2b Versus MAP Alone in Patients With Resectable High-Grade Osteosarcoma and Good Histologic Response to Preoperative MAP: First Results of the EURAMOS-1 Good Response Randomized Controlled Trial

Abstract: PurposeEURAMOS-1, an international randomized controlled trial, investigated maintenance therapy with pegylated interferon alfa-2b (IFN-α-2b) in patients whose osteosarcoma showed good histologic response (good response) to induction chemotherapy.Patients and MethodsAt diagnosis, patients age ≤ 40 years with resectable high-grade osteosarcoma were registered. Eligibility after surgery for good response random assignment included ≥ two cycles of preoperative MAP (methotrexate, doxorubicin, and cisplatin), macroscopically complete surgery of primary tumor, < 10% viable tumor, and no disease progression. These patients were randomly assigned to four additional cycles MAP with or without IFN-α-2b (0.5 to 1.0 μg/kg per week subcutaneously, after chemotherapy until 2 years postregistration). Outcome measures were event-free survival (EFS; primary) and overall survival and toxicity (secondary).ResultsGood response was reported in 1,041 of 2,260 registered patients; 716 consented to random assignment (MAP, n = 35...

Unfolding the Mechanism of Sodium Insertion in Anatase TiO2 Nanoparticles

Abstract: It is frequently assumed that sodium-ion battery chemistry exhibits a behavior that is similar to the more frequently investigated lithium-ion chemistry. However, in this work it is shown that there are great, and rather surprising, differences, at least in the case of anatase TiO2. While the generally more reducing lithium ion is reversibly inserted in the anatase TiO2 lattice, sodium ions appear to partially reduce the rather stable oxide and form metallic titanium, sodium oxide, and amorphous sodium titanate, as revealed by means of in situ X-ray diffraction, ex situ X-ray photoelectron spectroscopy, scanning electron microscopy, and Raman spectroscopy. Nevertheless, once the electrochemical transformation of anatase TiO2 is completed, the newly formed material presents a very stable long-term cycling performance, excellent high rate capability, and superior coulombic efficiency, highlighting it as a very promising anode material for sodium-ion battery applications.

Cobalt(III)-Catalyzed Directed C ? H Coupling with Diazo Compounds: Straightforward Access towards Extended π-Systems

Abstract: The first highly efficient and scalable cobalt-catalyzed directed C-H functionalization with carbene precursors is presented. This methodology provides a modular route towards a new class of conjugated polycyclic hydrocarbons with tunable emission wavelengths both in solution and in the solid state.

Batf3 maintains autoactivation of Irf8 for commitment of a CD8α(+) conventional DC clonogenic progenitor

Abstract: The transcription factors Batf3 and IRF8 are required for the development of CD8α+ conventional dendritic cells (cDCs). Murphy and colleagues characterize the Batf3-IRF8 interactions that allow differentiation toward CD8α+ cDCs.

Prospective multicenter international surveillance of azole resistance in Aspergillus fumigatus.

Abstract: To investigate azole resistance in clinical Aspergillus isolates, we conducted prospective multicenter international surveillance. A total of 3,788 Aspergillus isolates were screened in 22 centers from 19 countries. Azole-resistant A. fumigatus was more frequently found (3.2% prevalence) than previously acknowledged, causing resistant invasive and noninvasive aspergillosis and severely compromising clinical use of azoles.