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Recent studies emphasize that incorporating lithium metal electrodes can increase the energy density of next generation batteries. However, the production of lithium metal with high purity requires multi-stage purification steps due to its high reactivity. Furthermore, subsequent handling under inert conditions is required to prevent degradation. To circumvent handling of lithium metal and further improve energy density, researchers are exploring reservoir-free cells often referred to as “anode-free” cells. Reservoir-free cells are assembled without using lithium metal. Instead, lithium is electrodeposited at the interface between a current collector and a solid electrolyte from positive electrode materials during the first charge. Despite the potential of reservoir-free cells, there is limited understanding of the purity of electrodeposited lithium metal and how impurities might affect the electrochemical kinetics. This study examines first the purity of electrodeposited lithium at the steel|Li 6 PS 5 Cl interface. Then, it shows how impurities in lithium electrodes affect stripping capacity when using commercial lithium metal foils with both Li 6 PS 5 Cl and Li 6.25 Al 0.25 La 3 Zr 2 O 12 as solid electrolytes. By using time-of-flight secondary mass spectrometry and X-ray photoelectron spectrometry, we reveal that a lithium layer with high purity is electrodeposited at the negative electrode in reservoir-free cells and that common impurities in lithium metal (reservoir-type) electrodes like e.g. sodium negatively influence the accessible lithium capacity during discharge. Lithium metal is considered the next-generation material for electrodes in solid-state batteries. But is all lithium metal equal? Here, the authors analyze the influence of lithium purity and show how different lithium metal samples can be, especially when electrodeposited in “anode-free” cells.

Objective To explore the acceptance of uncoated drug-free mini-tablets 2 mm in diameter in children aged 0.5–6 years and their ability to swallow the mini-tablets. Methods 60 children aged 0.5–6 years (10 subjects per year of life) were enrolled in our prospective, open random, two-way cross-over exploratory pilot study. The children were administered either an uncoated drug-free mini-tablet 2 mm in diameter with a beverage of their choice or 3 ml of glucose syrup 15% followed by the other formulation. Deglutition was visually assessed for the two different dosage forms using a predefined criteria list. Results The study hypothesis was that children would accept the liquid formulation better than the solid mini-tablets. Surprisingly, the authors found that the acceptance of the mini-tablets, defined as immediate swallowing or chewing first with subsequent swallowing, was higher or at least equal to that of the syrup. Very young children (6–12 months) were fully capable of swallowing the mini-tablets and may even accept them better than the sweet liquid formulation. Some children aged between 2 and 4 years chewed the tablets before swallowing, but still accepted them quite well. The acceptance rate of the mini-tablets in the different age groups was much higher than expected. Conclusions Uncoated mini-tablets seem to be a very promising alternative to liquid formulations and could be used at an earlier age in paediatric drug therapy than previously anticipated.

Background Up to now, only limited data on long-term medical treatment in congenital hyperinsulinism (CHI) is available. Moreover, most of the drugs used in CHI are therefore not approved. We aimed to assemble more objective information on medical treatment in CHI with regard to type and duration, dosage as well as side effects. Methods We searched MEDLINE (from 1947) and EMBASE (from 1988) using the OVID interface for relevant data to evaluate medical treatment in a large cohort of patients with CHI from different clinical centers. Randomized, controlled trials were not available. We evaluated case reports and case series. No language restrictions were made. Results A total number of 619 patients were medically treated and information regarding conservative treatment was available. Drugs used were diazoxide (in 84 % of patients), somatostatin analogues (16 %), calcium channel antagonists (4 %) and glucagon (1 %). Mean dose of diazoxide was 12.5 (±4.3) mg/kg ⋅ d (range 2–60 mg/kg ⋅ d), mean duration of diazoxide treatment until remission was 57 months. Side effects of diazoxide were usually not severe. The causal relation between diazoxide and severe side effects, e.g. heart failure (3.7 %) remains doubtful. Mean dose of octreotide was 14.9 (±7.5) μg/kg ⋅ d (range 2.3–50 μg/kg ⋅ d), of lanreotide 67.3 (±39.8) mg ⋅ month (range 10–120 mg ⋅ month). Mean duration of treatment with somatostatin analogues until remission was 49 months. Frequent side effects included tachyphylaxis and mild gastrointestinal symptoms. The risk of persistent growth deceleration was low (<5 %). Conclusions Severe side effects are rare and a causal relation remains disputable. We conclude that long-term conservative treatment of CHI is feasible.

The merging trends of digitalization and servitization harbor extensive and largely unexplored potential for manufacturing firms. Digital systems can be linked with product-service bundles to build novel digitalized product-service systems (PSS), which use digital architectures to provide services independently and proactively. This paper gives an overview of service digitalization in industrial firms and describes three types of digitalized PSS, differentiated by purpose and by technical and organizational architecture. Each of the three types addresses a different stage of the product life cycle and improves performance or efficiency; in the long run, digitalized PSS can help improve a firm's overall innovation activity.

In type 2 diabetes mellitus (T2DM) there is a progressive loss of beta-cell function. One new approach yielding promising results is the use of the orally active dipeptidyl peptidase-4 (DPP-4) inhibitors. However, every new compound for T2DM has to prove long-term safety especially on cardiovascular outcomes. Systematic review and meta-analysis of the effects of sitagliptin and vildagliptin therapy on main efficacy parameters and safety. SELECTION CRITERIA, DATA COLLECTION, AND ANALYSIS: Randomized controlled clinical studies of at least 12 weeks' duration in T2DM. DPP-4 inhibitors versus placebo showed glycosylated hemoglobin A1c (A1c) improvements of 0.7% versus placebo but not compared to monotherapy with other hypoglycemic agents (0.3% in favor of controls). The overall risk profile of DPP-4 inhibitors was low, however a 34% relative risk increase (95% confidence interval 10% to 64%, P = 0.004) was noted for all-cause infection associated with sitagliptin use. No data on immune function, health-related quality of life and diabetic complications could be extracted. DPP-4 inhibitors have some theoretical advantages over existing therapies with oral antidiabetic compounds but should currently be restricted to individual patients. Long-term data on cardiovascular outcomes and safety are needed before widespread use of these new agents.

Background Chronic antibody-mediated rejection (cAMR) is the leading cause of late kidney graft loss, but current therapies are often ineffective. Rabbit anti-human thymocyte immunoglobulin (rATG) may be helpful, but its use is virtually undocumented. Methods Data were analyzed retrospectively from nine pediatric kidney transplant patients with cAMR were treated with rATG (1.5 mg/kg × 5 days) at our center after non-response to pulsed prednisolone, intravenous immunoglobulin, rituximab, and increased immunosuppressive intensity (including switching to belatacept in some cases), with or without bortezomib. Results The median time from diagnosis to cAMR was 179 days. rATG was started 5–741 days after diagnosis. Median estimated glomerular filtration rate (eGFR) increased from 40 mL/min/1.73 m 2 when rATG was started to 62 mL/min/1.73 m 2 9 months later ( p  = 0.039). Four patients showed substantially higher eGFR after 9 months and 2 patients showed a small improvement; eGFR continued to decline in 3 patients after starting rATG. No grafts were lost during follow-up. At last follow-up, donor-specific antibodies (DSAs) were no longer detectable in 4 out of 8 patients for whom data were available, median fluorescence intensity had decreased substantially in 1 out of 8 patients; anti-HLA DQ DSAs persisted in 2 out of 8 patients. No adverse events with a suspected relation to rATG, including allergic reactions, leukocytopenia or infections, were observed in any of the patients. Conclusions In this small series of patients, rATG appears a promising treatment for unresponsive cAMR. Further evaluation, including earlier introduction of rATG, is warranted.

The merging trends of digitalization and servitization harbor extensive and largely unexplored potential for manufacturing firms. Digital systems can be linked with product-service bundles to build novel digitalized product-service systems (PSS), which use digital architectures to provide services independently and proactively. This paper gives an overview of service digitalization in industrial firms and describes three types of digitalized PSS, differentiated by purpose and by technical and organizational architecture. Each of the three types addresses a different stage of the product life cycle and improves performance or efficiency; in the long run, digitalized PSS can help improve a firm's overall innovation activity.

OVERVIEW: The merging trends of digitalization and servitization harbor extensive and largely unexplored potential for manufacturing firms. Digital systems can be linked with product-service bundles to build novel digitalized product- service systems (PSS), which use digital architectures to provide services independently and proactively. This paper gives an overview of service digitalization in industrial firms and describes three types of digitalized PSS, differentiated by purpose and by technical and organizational architecture. Each of the three types addresses a different stage of the product life cycle and improves performance or efficiency; in the long run, digitalized PSS can help improve a firm's overall innovation activity.

Poor prognosis of anaplastic thyroid cancer and advanced disease in differentiated and medullary thyroid cancer, together with absence of effective therapeutic measures, has induced recent intensified basic and clinical research in this area. The aim of this article is to assess the effects of new drug treatment for advanced thyroid cancer. We searched MEDLINE and EMBASE until the end of September 2011 for relevant data. Further sources were reference lists of original publications and review articles. We included prospective studies that investigated drug interventions for advanced thyroid cancer published in any language. We did not include trials solely communicated as abstracts. For inclusion, studies had to report overall survival, progression-free survival or similar, or response outcomes. Data were extracted by one author and checked by the other. All tables are part of this publication. Because only non-comparative studies were included, we had to focus on descriptive analysis. Twenty-four studies with 715 patients were included; 18 studies investigated kinase inhibitors, the remainder various drugs. All studies reported response (only one complete response was observed; proportions of partial response were up to 49%). Median progression-free survival was about 12 months, ranging from 3.7 to 27.9 months. Adverse events (at least grade 3) of kinase inhibitors included hypertension, hand foot syndrome and diarrhoea (10%, 16% and 9%, respectively). Due to bias-prone data, any interpretation of newer pharmacotherapy options for advanced thyroid cancer is limited because only non-comparative studies could be included. Therefore, we strongly argue the need for adequate randomized controlled trials that should provide a better basis for therapeutic decision making in thyroid cancer.

Poor prognosis of anaplastic thyroid cancer and advanced disease in differentiated and medullary thyroid cancer, together with absence of effective therapeutic measures, has induced recent intensified basic and clinical research in this area. The aim of this article is to assess the effects of new drug treatment for advanced thyroid cancer. We searched MEDLINE and EMBASE until the end of September 2011 for relevant data. Further sources were reference lists of original publications and review articles. We included prospective studies that investigated drug interventions for advanced thyroid cancer published in any language. We did not include trials solely communicated as abstracts. For inclusion, studies had to report overall survival, progression-free survival or similar, or response outcomes. Data were extracted by one author and checked by the other. All tables are part of this publication. Because only non-comparative studies were included, we had to focus on descriptive analysis. Twenty-four studies with 715 patients were included; 18 studies investigated kinase inhibitors, the remainder various drugs. All studies reported response (only one complete response was observed; proportions of partial response were up to 49%). Median progression-free survival was about 12 months, ranging from 3.7 to 27.9 months. Adverse events (at least grade 3) of kinase inhibitors included hypertension, hand foot syndrome and diarrhoea (10%, 16% and 9%, respectively). Due to bias-prone data, any interpretation of newer pharmacotherapy options for advanced thyroid cancer is limited because only non-comparative studies could be included. Therefore, we strongly argue the need for adequate randomized controlled trials that should provide a better basis for therapeutic decision making in thyroid cancer. [PUBLICATION ABSTRACT]