julilili42/papers huggingface dataset:
Perinatal regionalisation in the UK: an international perspective
2014-04-10

Extremely low gestational age neonates (ELGANs) are probably the most vulnerable of all patient groups. Caring for these infants requires specialised services with a good infrastructure, dedication of the entire team and experience. Numerous studies have shown that perinatal outcomes are better in large centres providing the highest level of care compared to smaller ones or those working in a less experienced or lower level setting.1 Nonetheless, drawing practical conclusions from these data, namely to rigorously centralise perinatal care, meets resistance, in the UK and abroad. Or how else can the recent findings by Marlow et al , reported in this issue, be explained? They found that only 56% of ELGANs were born in hospitals providing the highest level of perinatal care.2 This low rate cannot be due to biology or distance: in Finland, for example, a country with an area 1.5 times that of the UK, provision of the highest level neonatal care is concentrated to only 5 centres, with many patients having long distances to ...
Human dignity and war
2014-04-10

War as sustained combat between political communities is a moral evil (Walzer 2006; Levy and Thompson 2010). War signals the breakdown of law and order and develops a deadly dynamic of its own. Conflicts are no longer settled by moral reasoning, legal adjudication or political negotiation, but by well-organized armed forces. War always goes along with death and destruction. Troops are moved strategically to overcome violent resistance and to defeat an enemy. As a rule, not only fighters are victimized on the battlefield, but entire societies suffer. The number of non-combatants dying from the direct and indirect consequences of sustained combat such as economic shortages, famines, displacement or disrupted healthcare and social security systems by far exceeds military casualties. Additionally, warfare goes along with the categorization, and, in most cases, dehumanization of opponents. Adversaries are no longer considered individual human beings but enemies who may be killed without further justification. Given the recent increase in ethnic conflicts, the traditional distinction between combatants and non-combatants blurs even further. War was never restricted to the battlefield, but today's wars more than ever target civilian populations. Depending on the severity of the fighting and the number of atrocities committed, it takes a generation or more to overcome the social disruptions of war and to re-establish a robust peace among former combatants and their successors.
Martin Luther's conception of human dignity
2014-04-10

Martin Luther's notion of human dignity is, in line with the entire Christian tradition, identical to the notion of humankind as the image of God (Gen. 1.26f). This at once determines the horizon within which Luther – critically – engages the corresponding notions of humankind as the image of God in scholasticism and mysticism, Renaissance philosophy and humanism (cf. Trinkaus 1970; Ebeling 1975: 320–4). With respect to his understanding of the idea of humankind as the image of God, Luther's most prominent document is the Disputatio de homine (1536), which discusses this understanding in light of the dispute between philosophy and theology (WA 39 I: 175–7). As becomes clear from a glance at thesis 20, the very first thesis announces how fundamentally controversial the basic anthropological notion is: ‘Philosophy, human wisdom, defines human beings as endowed with the gift of reason, with senses and with corporeality’ (WA 39 I: 175.3f). Following this classical determination of the human being as ‘rational animal’ or ‘zoon logon echon’, which stems from the Aristotelian tradition, theses 2–19 contain a critical engagement with philosophical anthropology. According to Luther, theology, on the ground of its universal claim to truth, cannot restrict itself to moving within a religious domain nor can it simply integrate and subject itself to philosophical standards. As such, then, it is the nature of theology as an academic discipline – as critical reference to other universal claims to truth – to engage in conflict and dispute.
Empagliflozin as Add-On to Metformin in Patients With Type 2 Diabetes: A 24-Week, Randomized, Double-Blind, Placebo-Controlled Trial
2014-04-11

OBJECTIVE To investigate the efficacy and tolerability of empagliflozin as an add-on to metformin therapy in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS Patients with HbA1c levels of ≥7% to ≤ 10% (≥53 to ≤86 mmol/mol) while receiving metformin (≥1,500 mg/day) were randomized and treated with once-daily treatment with empagliflozin 10 mg (n = 217), empagliflozin 25 mg (n = 213), or placebo (n = 207) for 24 weeks. The primary end point was the change in HbA1c level from baseline at week 24. Key secondary end points were changes from baseline in weight and mean daily glucose (MDG) at week 24. RESULTS At week 24, adjusted mean (SE) changes from baseline in HbA1c were −0.13% (0.05)% (−1.4 [0.5] mmol/mol) with placebo, −0.70% (0.05)% (−7.7 [0.5] mmol/mol) with empagliflozin 10 mg, and −0.77% (0.05)% (−8.4 [0.5] mmol/mol) with empagliflozin 25 mg (both P &amp;lt; 0.001). Empagliflozin significantly reduced MDG level and systolic and diastolic blood pressure (BP) versus placebo. Adjusted mean (SE) changes from baseline in weight were −0.45 kg (0.17 kg) with placebo, −2.08 kg (0.17 kg) with empagliflozin 10 mg, and −2.46 kg (0.17 kg) with empagliflozin 25 mg (both P &amp;lt; 0.001). Adverse events (AEs) were similar across groups (placebo 58.7%; empagliflozin 49.5–57.1%). Confirmed hypoglycemic AEs were reported in 0.5%, 1.8%, and 1.4% of patients receiving placebo, empagliflozin 10 mg, and empagliflozin 25 mg, respectively. Events consistent with urinary tract infections were reported in 4.9%, 5.1%, and 5.6% of patients, and events consistent with genital infections were reported in 0%, 3.7%, and 4.7% of patients, respectively. CONCLUSIONS Empagliflozin 10 and 25 mg for 24 weeks as add-on to metformin therapy significantly improved glycemic control, weight, and BP, and were well-tolerated.
ERGO: A pilot study of ketogenic diet in recurrent glioblastoma
2014-04-11

Limiting dietary carbohydrates inhibits glioma growth in preclinical models. Therefore, the ERGO trial (NCT00575146) examined feasibility of a ketogenic diet in 20 patients with recurrent glioblastoma. Patients were put on a low-carbohydrate, ketogenic diet containing plant oils. Feasibility was the primary endpoint, secondary endpoints included the percentage of patients reaching urinary ketosis, progression-free survival (PFS) and overall survival. The effects of a ketogenic diet alone or in combination with bevacizumab was also explored in an orthotopic U87MG glioblastoma model in nude mice. Three patients (15%) discontinued the diet for poor tolerability. No serious adverse events attributed to the diet were observed. Urine ketosis was achieved at least once in 12 of 13 (92%) evaluable patients. One patient achieved a minor response and two patients had stable disease after 6 weeks. Median PFS of all patients was 5 (range, 3-13) weeks, median survival from enrollment was 32 weeks. The trial allowed to continue the diet beyond progression. Six of 7 (86%) patients treated with bevacizumab and diet experienced an objective response, and median PFS on bevacizumab was 20.1 (range, 12-124) weeks, for a PFS at 6 months of 43%. In the mouse glioma model, ketogenic diet alone had no effect on median survival, but increased that of bevacizumab-treated mice from 52 to 58 days (p<0.05). In conclusion, a ketogenic diet is feasible and safe but probably has no significant clinical activity when used as single agent in recurrent glioma. Further clinical trials are necessary to clarify whether calorie restriction or the combination with other therapeutic modalities, such as radiotherapy or anti-angiogenic treatments, could enhance the efficacy of the ketogenic diet.
Pediatric posttransplant relapsed/refractory B-precursor acute lymphoblastic leukemia shows durable remission by therapy with the T-cell engaging bispecific antibody blinatumomab
2014-04-11

We report on posttransplant relapsed pediatric patients with B-precursor acute lymphoblastic leukemia with no further standard of care therapy who were treated with the T-cell engaging CD19/CD3-bispecific single-chain antibody construct blinatumomab on a compassionate use basis. Blast load was assessed prior to, during and after blinatumomab cycle using flow cytometry to detect minimal residual disease, quantitative polymerase chain reaction for rearrangements of the immunoglobulin or T-cell receptor genes, and bcr/abl mutation detection in one patient with Philadelphia chromosome-positive acute lymphoblastic leukemia. Blinatumomab was administered as a 4-week continuous intravenous infusion at a dosage of 5 or 15 μg/m(2)/day. Nine patients received a total of 18 cycles. Four patients achieved complete remission after the first cycle of treatment; 2 patients showed a complete remission from the second cycle after previous reduction of blast load by chemotherapy. Three patients did not respond, of whom one patient proceeded to a second cycle without additional chemotherapy and again did not respond. Four patients were successfully retransplanted in molecular remission from haploidentical donors. After a median follow up of 398 days, the probability of hematologic event-free survival is 30%. Major toxicities were grade 3 seizures in one patient and grade 3 cytokine release syndrome in 2 patients. Blinatumomab can induce molecular remission in pediatric patients with posttransplant relapsed B-precursor acute lymphoblastic leukemia and facilitate subsequent allogeneic hematopoietic stem cell transplantation from haploidentical donor with subsequent long-term leukemia-free survival.
Orbitofrontal response to drug-related stimuli after heroin administration
2014-04-11

The compulsion to seek and use heroin is frequently driven by stress and craving during drug-cue exposure. Although previous neuroimaging studies have indicated that craving is mediated by increased prefrontal cortex activity, it remains unknown how heroin administration modulates the prefrontal cortex response. This study examines the acute effects of heroin on brain function in heroin-maintained patients. Using a crossover, double-blind, placebo-controlled design, 27 heroin-maintained patients performed functional magnetic resonance imaging 20 minutes after the administration of heroin or placebo (saline) while drug-related and neutral stimuli were presented. Images were processed and analysed with statistical parametric mapping. Plasma concentrations of heroin and its main metabolites were assessed using high-performance liquid chromatography. Region of interest analyses showed a drug-related cue-associated blood-oxygen-level-dependent activation in the orbitofrontal cortex (OFC) in heroin-dependent patients during both treatment conditions (heroin and placebo). This activation of the OFC was significantly higher after heroin than after placebo administration. These findings may indicate the importance of OFC activity for impulse control and decision-making after regular heroin administration and may emphasize the benefit of the heroin-assisted treatment in heroin dependence.
Gold(I)‐, Palladium(II)‐, Platinum(II)‐, and Mercury(II)‐Catalysed Spirocyclization of 1,3‐Enynediols: Reaction Scope
2014-04-11

Abstract The spirocyclization of different 1,3‐enynediols was investigated. The reaction was only efficient for the synthesis of [5,6]‐spiroacetals. In this case, the reaction was characterized by almost quantitative yields, short reaction times, and low catalyst loadings (0.5–1 %). When the synthesis of [6,6]‐spiroacetals was attempted, the reaction suffered from poor regioselectivity and a higher propensity of the intermediate dienol ethers to decompose under the acidic conditions, and it became no longer viable. But it is possible to generate the dienol ethers cleanly under milder conditions as a mixture of regioisomers. This striking difference in reaction efficiency was explained by the unstable dienol ethers cyclizing more quickly to give [5,6]‐spiroacetals than to give [6,6]‐spiroacetals. In this study, the successful application of a new cationic palladium pincer complex for electrophilic alkyne activation at room temperature has been demonstrated for the first time.
Organization of the Escherichia coli aerobic enzyme complexes of oxidative phosphorylation in dynamic domains within the cytoplasmic membrane
2014-04-12

Abstract The E scherichia coli cytoplasmic membrane contains the enzyme complexes of oxidative phosphorylation ( OXPHOS ). Not much is known about their supramolecular organization and their dynamics within the membrane in this model organism. In mitochondria and other bacteria, it was demonstrated by nondenaturing electrophoretic methods and electron microscopy that the OXPHOS complexes are organized in so‐called supercomplexes, stable assemblies with a defined number of the individual enzyme complexes. To investigate the organization of the E . coli enzyme complexes of aerobic OXPHOS in vivo, we established fluorescent protein fusions of the NADH :ubiquinone oxidoreductase, the succinate:ubiquinone oxidoreductase, the cytochrome bd ‐I, and the cytochrome bo 3 terminal oxidases, and the F o F 1 ATP ‐synthase. The fusions were integrated in the chromosome to prevent artifacts caused by protein overproduction. Biochemical analysis revealed that all modified complexes were fully assembled, active, and stable. The distribution of the OXPHOS complexes in living cells was determined using total internal reflection fluorescence microscopy. The dynamics within the membrane were detected by fluorescence recovery after photobleaching. All aerobic OXPHOS complexes showed an uneven distribution in large mobile patches within the E . coli cytoplasmic membrane. It is discussed whether the individual OXPHOS complexes are organized as clustered individual complexes, here called “segrazones.”
Combinatorial inhibition of Plk1 and PKCβ in cancer cells with different p53 status
2014-04-12

PKCβ and Plk1 are fascinating targets in cancer therapy. Therefore, we combined Enzastaurin targeting PKCβ and SBE13 targeting Plk1 to test synergistic effects in cells with different p53 status. We analyzed cell proliferation and apoptosis induction, and did Western blot and FACScan analyses to examine the combined PKCβ and Plk1 inhibition. p53-wild-type cells are more resistant to the combinatorial treatment than p53-deficient cells, which displayed a synergistic reduction of cell proliferation after the combination. HeLa, MCF-7 and HCT116(p53wt) and HCT116(p53-/-) cells differed in their cell cycle distribution after combinatorial treatment in dependence on a functional p53-dependent G1/S checkpoint (p53-deficient cells showed an enrichment in S and G2/M, p53-wild-type cells in G0/G1 phase). hTERT-RPE1 cells did not show the synergistic effects of cancer cells. Thus, we demonstrate for the first time that Plk1 inhibition using SBE13 enhances the effects of Enzastaurin in cancer cells. HCT116(p53wt) and HCT116(p53-/-) cells confirmed the p53-dependence of different effects after Plk1 and PKCβ inhibition observed in HeLa and MCF-7 cells. Obviously, p53 protects cells from the cytotoxicity of Enzastaurin in combination with SBE13. For that reason this combination can be useful to treat p53-deficient cancers, without displaying toxicity to normal cells, which all have functional p53.
Can minimal running shoes imitate barefoot heel-toe running patterns? A comparison of lower leg kinematics
2014-04-13

Background: Numerous studies about the interaction between footwear (and barefoot) and kinematic and kinetic outcomes have been published over the last few years. Recent studies however lead to the conclusion that the assumed interactions depend mainly on the subjects' experience of barefoot (BF) walking/running, the preferred running strike pattern, the speed, the hardness of the surface, the thickness of the midsole material, and the runners' level of ability. The aim of the present study was to investigate lower leg kinematics of BF running and running in minimal running shoes (MRS) to assess comparability of BF kinematics in both conditions. To systematically compare both conditions we monitored the influencing variables described above in our measurement setup. We hypothesized that running in MRS does not alter lower leg kinematics compared to BF running. Methods: Thirty-seven subjects, injury-free and active in sports, ran BF on an EVA foam runway, and also ran shod wearing Nike Free 3.0 on a tartan indoor track. Lower-leg 3D kinematics was measured to quantify rearfoot and ankle movements. Skin markers were used in both shod and BF running. Results: All runners revealed rearfoot strike pattern when running barefoot. Differences between BF and MRS running occurred particularly during the initial stance phase of running, both in the sagittal and the frontal planes. BF running revealed a flatter foot placement, a more plantar flexed ankle joint and less inverted rearfoot at touchdown compared to MRS running. Conclusion: BF running does not change the landing automatically to forefoot running, especially after a systematic exclusion of surface and other influencing factors. The Nike Free 3.0 mimics some BF features. Nevertheless, changes in design of the Nike Free should be considered in order to mimic BF movement even more closely.
Why privacy is not enough privacy in the context of “ubiquitous computing” and “big data”
2014-04-15

Purpose – Ubiquitous computing and “big data” have been widely recognized as requiring new concepts of privacy and new mechanisms to protect it. While improved concepts of privacy have been suggested, the paper aims to argue that people acting in full conformity to those privacy norms still can infringe the privacy of others in the context of ubiquitous computing and “big data”. Design/methodology/approach – New threats to privacy are described. Helen Nissenbaum's concept of “privacy as contextual integrity” is reviewed concerning its capability to grasp these problems. The argument is based on the assumption that the technologies work, persons are fully informed and capable of deciding according to advanced privacy considerations. Findings – Big data and ubiquitous computing enable privacy threats for persons whose data are only indirectly involved and even for persons about whom no data have been collected and processed. Those new problems are intrinsic to the functionality of these new technologies and need to be addressed on a social and political level. Furthermore, a concept of data minimization in terms of the quality of the data is proposed. Originality/value – The use of personal data as a threat to the privacy of others is established. This new perspective is used to reassess and recontextualize Helen Nissenbaum's concept of privacy. Data minimization in terms of quality of data is proposed as a new concept.
Positions and Numbers of FKS Mutations in Candida albicans Selectively Influence In Vitro and In Vivo Susceptibilities to Echinocandin Treatment
2014-04-15

ABSTRACT Candidemia is the fourth most common kind of microbial bloodstream infection, with Candida albicans being the most common causative species. Echinocandins are employed as the first-line treatment for invasive candidiasis until the fungal species is determined and confirmed by clinical diagnosis. Echinocandins block the FKS glucan synthases responsible for embedding β-(1,3)- d -glucan in the cell wall. The increasing use of these drugs has led to the emergence of antifungal resistance, and elevated MICs have been associated with single-residue substitutions in specific hot spot regions of FKS1 and FKS2 . Here, we show for the first time the caspofungin-mediated in vivo selection of a double mutation within one allele of the FKS1 hot spot 1 in a clinical isolate. We created a set of isogenic mutants and used a hematogenous murine model to evaluate the in vivo outcomes of echinocandin treatment. Heterozygous and homozygous double mutations significantly enhance the in vivo resistance of C. albicans compared with the resistance seen with heterozygous single mutations. The various FKS1 hot spot mutations differ in the degree of their MIC increase, substance-dependent in vivo response, and impact on virulence. Our results demonstrate that echinocandin EUCAST breakpoint definitions correlate with the in vivo response when a standard dosing regimen is used but cannot predict the in vivo response after a dose escalation. Moreover, patients colonized by a C. albicans strain with multiple mutations in FKS1 have a higher risk for therapeutic failure.
Multiatom entanglement in cold Rydberg mixtures
2014-04-15

We present an efficient method for generating maximum entanglement in one-dimensional atomic lattices. The proposed method relies on adiabatic rapid transfer into two Rydberg states with strongly asymmetric interactions. The method is suitable for Rydberg states in the absence of applied electrostatic fields. We show numerical simulations of entanglement generation in rubidium atoms using calculated van der Waals potentials under realistic experimental conditions. We study the effect of the chosen Rydberg states on the final entanglement.
How to Pay Envious Managers – a Theoretical Analysis
2014-04-15

Abstract This paper analyses how envy affects the decisions of competing managers and their optimal stock‐based compensation from the perspective of shareholder value. We consider a typical framework in which managers can induce effort to reduce production costs and make decisions regarding production volume. At first glance, envy between managers from competing firms appears to be an unfavorable characteristic because it does not align the interests of managers with those of shareholders. However, our model finds that envy is a powerful incentive mechanism. The model yields three key findings: (i) envious managers outperform self‐interested managers, (ii) firms optimally hire envious managers, and (iii) shareholders do not grant any stock‐based compensation to envious managers.
Between Oxoborate and Nitridoborate: The Oxonitridoborate Oxide La3(OBN2)O2
2014-04-15

Abstract The new compound La 3 (OBN 2 )O 2 was prepared by a solid state reaction of LaOCl and Li 3 (BN 2 ) at 1200 °C in a fused niobium ampoule. A single crystal structure refinement [ Pnma , Z = 4, a = 1269.8(2) pm, b = 368.94(5) pm, c = 1101.1(2) pm] indicates the presence of a planar (OBN 2 ) 5– ion, which is structurally related to the (BN 3 ) 6– ion. The arrangement of atoms in the structure corresponds to a slightly modified structure of Ca 3 (CBN)Cl 2 [ Pnma , Z = 4, a = 1386.7(9) pm, b = 384.7(3) pm, c = 1124.7(6) pm].
Local minimizers of the Willmore functional
2014-04-15

Abstract Since the Willmore functional is invariant with respect to conformal transformations and reparametrizations, the kernel of the second derivative of the functional at a critical point will always contain a subspace generated by these transformations. We prove that the second derivative being positive definite outside this space is a sufficient condition for a critical point to be a local minimizer.