Strongly reducing magnesium(0) complexes.

A complex of a metal in its zero oxidation state can be considered a stabilized, but highly reactive, form of a single metal atom. Such complexes are common for the more noble transition metals. Although rare examples are known for electronegative late-main-group p-block metals or semimetals1-6, it is a challenge to isolate early-main-group s-block metals in their zero oxidation state7-11. This is directly related to their very low electronegativity and strong tendency to oxidize. Here we present examples of zero-oxidation-state magnesium (that is, magnesium(0)) complexes that are stabilized by superbulky, monoanionic, ß-diketiminate ligands. Whereas the reactivity of an organomagnesium compound is typically defined by the nucleophilicity of its organic groups and the electrophilicity of Mg2+ cations, the Mg0 complexes reported here feature electron-rich Mg centres that are nucleophilic and strongly reducing. The latter property is exemplified by the ability to reduce Na+ to Na0. We also present a complex with a linear Mg3 core that formally could be described as a MgI-Mg0-MgI unit. Such multinuclear mixed-valence Mgn clusters are discussed as fleeting intermediates during the early stages of Grignard reagent formation. Their remarkably strong reducing power implies a rich reactivity and application as specialized reducing agents.

Scaling confirmation of the thermodynamic dislocation theory.

The thermodynamic dislocation theory (TDT) is based on two highly unconventional assumptions: first, that driven systems containing large numbers of dislocations are subject to the second law of thermodynamics and second, that the controlling inverse timescale for these systems is the thermally activated rate at which entangled pairs of dislocations become unpinned from each other. Here, we show that these two assumptions predict a scaling relation for steady-state stress as a function of strain rate and that this relation is accurately obeyed over a wide range of experimental data for aluminum and copper. This scaling relation poses a stringent test for the validity of the TDT. The fact that the TDT passes this test means that a wide range of problems in solid mechanics, previously thought to be fundamentally intractable, can now be addressed with confidence.

[Use of the Carina active middle ear implant in otosclerosis patients]. / Einsatz des aktiven Mittelohrimplantats Carina bei Otosklerose.

Patients with otosclerosis can suffer from different grades of combined hearing loss. In addition to surgery (stapedectomy), conventional hearing aids can be used in the treatment of otosclerosis. In cases of severe conductive components in addition to sensorineural hearing loss, treatment with normal hearing aids can be difficult or impossible. In these patients, implantable hearing systems such as cochlear implants represent a possible alternative. The totally implantable Carina middle ear system can be used in patients with even high-grade sensorineural hearing loss. Based on two exemplary cases, the option of using the Carina system in otosclerosis patients and post-implantation results are reported.

Guidelines for the management of postoperative soiling in children with Hirschsprung disease.

Although most children with Hirschsprung disease ultimately achieve functional and comfortable stooling, some will experience a variety of problems after pull-through surgery. The most common problems include soiling, obstructive symptoms, enterocolitis, and failure to thrive. The purpose of this guideline is to present a rational approach to the management of postoperative soiling in children with Hirschsprung disease. The American Pediatric Surgical Association Hirschsprung Disease Interest Group engaged in a literature review and group discussions. Expert consensus was then used to summarize the current state of knowledge regarding causes, methods of diagnosis, and treatment approaches to children with soiling symptoms following pull-through for Hirschsprung disease. Causes of soiling after pull-through are broadly categorized as abnormalities in sensation, abnormalities in sphincter control, and "pseudo-incontinence." A stepwise algorithm for the diagnosis and management of soiling after a pull-through for Hirschsprung disease is presented; it is our hope that this rational approach will facilitate treatment and optimize outcomes.

[Georgia, a country of diverse aid from Germany in the ENT field]. / Georgien, ein Land vielfältiger Hilfen aus Deutschland auf dem HNO-Gebiet.

Following a long-term tradition, several teams of German ENT specialists are currently working in different Georgian clinics on a charitable basis. The current paper describes the structures of the medical and health insurance systems in this southern Caucasian country. The course of medical education for physicians in Georgia is portrayed and differences to the German situation which explain why young Georgian colleagues have difficulties when moving to Germany are highlighted. The paper describes the typical stay of a German ENT specialist in Georgia and also points out how these physicians are in turn supported in their charitable work by medical devices and equipment sent from Germany. Finally, the input that German colleagues can contribute to improving the situation in the Georgian health care system is discussed from the perspective of German ENT specialists and future goals of the cooperation between German and Georgian physicians are summarized.

Guidelines for the management of postoperative obstructive symptoms in children with Hirschsprung disease.

Although most children with Hirschsprung disease ultimately do well, many experience a variety of ongoing problems after pull-through surgery. The most common include obstructive symptoms, soiling, enterocolitis and failure to thrive. The purpose of this guideline is to present a rational approach to the management of postoperative obstructive symptoms in children with Hirschsprung disease. The American Pediatric Surgical Association Board of Governors established a Hirschsprung Disease Interest Group. Group discussions, literature review and expert consensus were then used to summarize the current state of knowledge regarding causes, methods of diagnosis, and treatment approaches to children with obstructive symptoms following pull-through for Hirschsprung disease. Causes of obstructive symptoms post-pull-through include mechanical obstruction; persistent or acquired aganglionosis, hypoganglionosis, or transition zone pull-through; internal sphincter achalasia; disordered motility in the proximal intestine that contains ganglion cells; or functional megacolon caused by stool-holding behavior. An algorithm for the diagnosis and management of obstructive symptoms after a pull-through for Hirschsprung disease is presented. A stepwise, logical approach to the diagnosis and management of patients experiencing obstructive symptoms following pull-through for Hirschsprung disease can facilitate treatment. Level of evidence V.

Insufficient Vitamin D Response to Solar Radiation in German Patients with Type 2 Diabetes or Gestational Diabetes.

Vitamin D deficiency is highly prevalent in all forms of diabetes mellitus. Recently, we reported how ultraviolet B (UVB) radiation affected vitamin D [25(OH)D3] concentrations in patients with type 1 diabetes. Our aim was to analyze whether patients with non-autoimmune diabetes, such as type 2 diabetes mellitus (T2DM) and gestational diabetes mellitus (GDM) also show the same vitamin D profile in relation to environmental factors including ambient temperature as an indirect parameter for outdoor activities. We analyzed 25(OH)D3 concentrations of T2DM (n=349) and GDM patients (n=327) at the University Hospital Frankfurt from 2005 to 2007. Additionally, daily UVB and monthly outside air temperature measurements for Frankfurt/Germany were obtained. We detected a positive correlation between UVB irradiation and 25(OH)D3 concentrations of T2DM and GDM patients (rho=0.50 and rho=0.63, p=0.003 and p<0.0001, respectively). UVB irradiation was in summer (April-October) higher than in winter (November-March) (5.6 kJ/m² vs. 0.5 kJ/m², p<0.0001). However, the prevalence of vitamin D deficiency in summer remained high with 76% in T2DM and 59% in GDM. In a stepwise regression analysis for the 25(OH)D3 concentration, significant predictors were outdoor temperature (estimate=0.02, p<0.0001), UVB radiation (estimate=-0.0015, p=0.02), year (2006 vs. 2005 estimate=-0.06, p>0.05, 2007 vs. 2005: estimate=-0.13, p<0.0001) and diabetes type (estimate=0.06, p=0.03). In conclusion, the strong correlation between UVB radiation and 25(OH)D3 concentrations in T2DM and GDM patients determines the seasonal variation. Additional determinants for the 25(OH)D3 concentrations were outdoor temperature, year, and diabetes type. Despite the effects of solar radiation both patients groups remain largely vitamin D deficient during summers.

Theories of glass formation and the glass transition.

This key-issues review is a plea for a new focus on simpler and more realistic models of glass-forming fluids. It seems to me that we have too often been led astray by sophisticated mathematical models that beautifully capture some of the most intriguing features of glassy behavior, but are too unrealistic to provide bases for predictive theories. As illustrations of what I mean, the first part of this article is devoted to brief summaries of imaginative, sensible, but disparate and often contradictory ideas for solving glass problems. Almost all of these ideas remain alive today, with their own enthusiastic advocates. I then describe numerical simulations, mostly by H Tanaka and coworkers, in which it appears that very simple, polydisperse systems of hard disks and spheres develop long range, Ising-like, bond-orientational order as they approach glass transitions. Finally, I summarize my recent proposal that topologically ordered clusters of particles, in disordered environments, tend to become aligned with each other as if they were two-state systems, and thus produce the observed Ising-like behavior. Neither Tanaka's results nor my proposed interpretation of them fit comfortably within any of the currently popular glass theories.

Improved real-world glycaemic outcomes with liraglutide versus other incretin-based therapies in type 2 diabetes.

AIM: Liraglutide (LIRA) once-daily has provided greater A1C reductions than either exenatide (EXEN) twice-daily or sitagliptin (SITA) once-daily in head-to-head trials. The objective of this analysis is to compare the real-world clinical effectiveness of these agents in the USA. METHODS: Using the IMS Health (Alexandria, VA, USA) integrated claims database, A1C outcomes in patients aged ≥ 18 years with type 2 diabetes (T2D) who initiated either LIRA, EXEN or SITA (including SITA/metformin) were retrospectively compared. Patients included in the analysis had ≥ 1 prescription for LIRA, EXEN or SITA between January and December 2010 (index period) and persisted with their index treatment regimens for 6 months post-index. Outcomes included changes in A1C from baseline (45 days pre-index through 7 days post-index) to follow-up [6 months post-index (± 45)] and the proportion of patients reaching A1C<7%. Multivariable regression models adjusted for confounding factors (e.g. age, comorbidities, baseline A1C and background antidiabetic therapy). RESULTS: The predicted change in A1C from baseline was greater for LIRA patients compared with both SITA (-1.08 vs. -0.68%; treatment difference 0.40%, p < 0.0001) and EXEN (-1.08 vs. -0.75%; treatment difference 0.32%, p < 0.001). Predicted A1C goal achievement, derived from the multivariate logistic regression model, was higher with LIRA compared with both SITA [64.4% (95% confidence interval, CI: 63.5-65.3) vs. 49.4% (95% CI: 48.5-50.4); p < 0.0001] and EXEN [64.4% (95% CI: 63.5-65.3) vs. 53.6% (95% CI: 52.6-54.6); p < 0.0001]. CONCLUSIONS: In clinical practice, LIRA was associated with significantly greater reductions in A1C and improved glycaemic goal attainment compared with either EXEN or SITA among adult patients with T2D.

Minimally invasive therapy for fetal sacrococcygeal teratoma: case series and systematic review of the literature.

OBJECTIVE: Large solid sacrococcygeal teratomas (SCT) can cause high-output cardiac failure and fetal or neonatal death. The aim of this study was to describe the outcomes of minimally invasive antenatal procedures for the treatment of fetal SCT. METHODS: A case review was performed of five fetuses with a large SCT treated antenatally using minimally invasive techniques, and a systematic literature review on fetal therapy for solid SCTs was carried out. RESULTS: Five women were referred between 17 + 5 and 26 + 4 weeks' gestation for a large fetal SCT with evidence of fetal cardiac failure. Vascular flow to the tumors was interrupted by fetoscopic laser ablation (n = 1), radiofrequency ablation (RFA; n = 2) or interstitial laser ablation ± vascular coiling (n = 2). There were two intrauterine fetal deaths. The other three cases resulted in preterm labor within 10 days of surgery. One neonate died. Two survived without procedure-related complications but had long-term morbidity related to prematurity. The systematic literature review revealed 16 SCTs treated minimally invasively for (early) hydrops. Including our cases, six of 20 hydropic fetuses survived after minimally invasive therapy (30%). Survival after RFA or interstitial laser ablation was 45% (5/11). Of 12 fetuses treated for SCT without obvious hydrops and for which perinatal survival data were available, eight (67%) survived. Mean gestational age at delivery after minimally invasive therapy was 29.7 ± 4.0 weeks. Survival after open fetal surgery in hydropic fetuses was 6/11 (55%), with a mean gestational age at delivery of 29.8 ± 2.9 weeks. CONCLUSIONS: Fetal therapy can potentially improve perinatal outcomes for hydropic fetuses with a solid SCT, but is often complicated by intrauterine death and preterm birth.

Residual antimicrobial effect of chlorhexidine digluconate and octenidine dihydrochloride on reconstructed human epidermis.

The objective of the present investigation was to examine the residual antimicrobial activity after a topical exposure of reconstructed human epidermis (RHE) to equimolar solutions of either chlorhexidine digluconate (CHG, 0.144% w/v) or octenidine dihydrochloride (OCT, 0.1% w/v) for 15 min. RHE-associated antiseptic agents were more effective on Staphylococcus aureus than on Pseudomonas aeruginosa. S. aureus was not detected after 24 h of contact, which demonstrated a microbicidal efficacy of greater than 5-log10 reduction. In contrast, P. aeruginosa was reduced by approximately 2 log10 at the same incubation time, which parallels the growth of the initial inoculum. This result could be interpreted either as a microbiostatic effect or as an adherence of P. aeruginosa to a low positively charged surface. Small amounts of CHG and OCT can penetrate the stratum corneum. Using these antiseptic agents, the viability of keratinocytes was reduced to 65-75% of that of the untreated RHE control following 24 h incubation in the presence of test microorganisms. With consideration of antimicrobial activity and cytotoxic effect, OCT corresponds better to a biocompatible antiseptic agent than CHG.

Effective temperatures in nonequilibrium statistical physics.

This paper summarizes two related effective-temperature analyses of nonequilibrium phenomena: first, dislocations in deforming crystals and, second, chaotic behaviors of defects in thermally driven Rayleigh-Bénard hydrodynamic systems. The results are encouraging for broader applications of this statistical concept.

Minimally invasive fetal therapy for hydropic lung masses: three different approaches and review of the literature.

OBJECTIVE: To report three different antenatal therapeutic approaches for fetal lung masses associated with hydrops. METHODS: Three prospectively followed cases are described, and all 30 previously published minimally invasive cases of fetal therapy for hydropic lung masses are reviewed. RESULTS: Three hydropic fetuses with large intrathoracic lung masses presented at 17, 25 and 21 weeks of gestation, respectively. An aortic feeding vessel was identified in each case and thus a bronchopulmonary sequestration (BPS) was suspected. Under ultrasound guidance, the feeding vessel was successfully occluded with interstitial laser (Case 1), radiofrequency ablation (RFA) (Case 2) and thrombogenic coil embolization (Case 3). Complete (Cases 1 and 2) or partial (Case 3) resolution of the lung mass and hydrops was observed. A healthy infant was born at term after laser therapy (Case 1), and the involved lung lobe was resected on day 2 of postnatal life. In Case 2, hydrops resolved completely following RFA, but an iatrogenic congenital diaphragmatic hernia and abdominal wall defect became apparent 4 weeks later. The neonate died from sepsis following spontaneous preterm labor at 33 weeks. In Case 3, despite technical success in complete vascular occlusion with coils, a stillbirth ensued 2 days after embolization. CONCLUSIONS: The prognosis of large microcystic or echogenic fetal chest masses associated with hydrops is dismal. This has prompted attempts at treatment by open fetal surgery, with mixed results, high risk of premature labor and consequences for future pregnancies. We have demonstrated the possibility of improved outcome following ultrasound-guided laser ablation of the systemic arterial supply. Despite technical success, RFA and coil embolization led to procedure-related complications and need further evaluation.

[Multikinase inhibitors as a new approach in neovascular age-related macular degeneration (AMD) treatment: in vitro safety evaluations of axitinib, pazopanib and sorafenib for intraocular use]. / Multikinase-inhibitoren als therapeutischer ansatz bei neovaskulärer AMD: in-vitro-evaluation der sicherheit von axitinib, pazopanib und sorafenib zur intraokularen anwendung.

BACKGROUND: Multikinase inhibitors (MKI) interfere effectively at different levels of the neovascularisation cascade. Early clinical and experimental data suggest that MKIs represent a promising novel approach for the treatment of neovascular age-related macular degeneration (AMD). However, so far little is known about the biocompatibility of MKIs regarding human ocular cells. This in vitro study investigates and compares the biocompatibility of three MKIs, axitinib, pazopanib, and sorafenib regarding ocular cells of the anterior and posterior segments, as well as organ-cultured donor corneas. METHODS: Primary human optic nerve head astrocytes (ONHA), trabecular meshwork cells (TMC), and retinal pigment epithelium (RPE), human corneal endothelial and lens epithelial cells (CEC and LEC) were treated with different concentrations of axitinib, pazopanib, or sorafenib (0.1 to 100 µg/mL). To simulate oxidative stress, the cells were additionally co-incubated with 400 µM hydrogen peroxide. Induction of cell death and cellular viability were examined by live-dead assay and tetrazolium dye reduction assay (MTT). In addition, the influence of the three substances on human corneal endothelium was evaluated in seropositive donor corneas in organ culture by phase contrast microscopy. RESULTS: Up to a concentration of 7.5 mg/mL of the substances tested in any cell type examined, no toxic effects were found. Even after 10 days of incubation of organ-cultured donor corneas with 7.5 µg/mL, axitinib, pazopanib, or sorafenib, no evidence for endothelial toxicity was found. CONCLUSION: All three MKIs tested, axitinib, pazopanib, and sorafenib showed a good biocompatibility on the investigated ocular cells. Even under conditions of oxidative stress, there were no toxic effects up to a concentration of 7.5 µg/mL. Only at higher concentrations, there was a dose-dependent decrease in cellular viability and pronounced induction of cell death. These effects on cellular viability and induction of cell death appeared to be stronger with pazopanib, followed by sorafenib, than with axitinib.

[Improvement of fixation in diabetic macular oedema patients under intravitreal ranibizumab treatment]. / Verbesserung des Fixationsverhaltens bei Patienten mit diabetischem Makulaödem unter Therapie mit Ranibizumab.

BACKGROUND: The aim of this study was to evaluate the fixation and other functional and morphological alterations in patients with diabetic macular oedema (DMO) under intravitreal ranibizumab therapy. PATIENTS AND METHODS: Thirty patients (39 eyes) with DMO with central involvement were included in this prospective study. Morphological (fluorescein angiography, OCT) as well as functional (visual acuity, microperimetry including fixation) parameters were analysed before and after three monthly intravitreal applications of ranibizumab. RESULTS: Best-corrected mean visual acuity (BCVA) increased significantly by 6.85 + 6.45 letters from 26.15 ± 13.83 to 33.03 ± 13.31 letters. Mean central retinal thickness and mean central retinal volume decreased significantly from 503.72 ± 143.78 µm, respectively (p < 0.001) before treatment to 387.05 ± 122.02 µm after the third intravitreal injection with ranibizumab. Mean retinal sensitivity obtained with microperimetry did not change significantly over the course of treatment. Mean fixation within 2° (4°) improved from 64.15 % (85.7 %) before treatment significantly to 70.15 % (91.5 %) after three intravitreal injections with ranibizumab. Mean fixation stability within 2° improved from 43.9 % before treatment significantly to 58.5 % after three intravitreal injections. CONCLUSION: DMO improved both morphologically with a significant reduction of central retinal thickness and volume and a significantly improved BCVA as well as fixation and fixation stability over the course of three monthly intravitreal injections with ranibizumab. Retinal sensitivity obtained in microperimetry did not change significantly over the course. Based on our observations we interpret and suggest fixation and fixation stability as an early functional parameter and prior to microperimetrically detectable changes of retinal sensitivity additional to BCVA during treatment of diabetic macular edema.

Fetal thoracoamniotic shunting for large macrocystic congenital cystic adenomatoid malformations of the lung.

OBJECTIVE: To evaluate fetal thoracoamniotic shunting for isolated large macrocystic congenital cystic adenomatoid malformations (CCAM) of the lung. METHODS: This was a retrospective study of 11 fetuses with macrocystic CCAM who underwent thoracoamniotic shunting. This procedure was offered if fetal hydrops or signs of evolving hydrops (such as ascites or polyhydramnios) were present, or when there were very large lesions or lesions rapidly increasing in size. If there were multiple large cysts within the lesion, a single shunt was used, aiming to traverse several cysts. RESULTS: Shunts were inserted at a mean gestational age of 24.6 (range, 17-32) weeks. Marked mediastinal shift was present in all cases. Six fetuses were hydropic and, of the remaining five, one had severe polyhydramnios, three had lesions that were rapidly increasing in size and one had a very large lesion at initial presentation. In total, four cases had polyhydramnios. Shunting one cyst always decompressed the entire lesion and hydrops and/or polyhydramnios resolved in all surviving fetuses. One hydropic fetus that underwent the procedure at 17 weeks died 1 day later. The shunt dislodged in one case and the lesion did not re-expand. No mother went into labor or had ruptured membranes before 35.6 weeks. Mean gestational age at delivery was 38.2 weeks (n = 10). All pregnancies were delivered vaginally, with no maternal complications. All newborns had uneventful lobectomies, and pathology confirmed CCAM in all cases. CONCLUSION: Fetal thoracoamniotic shunting for large macrocystic CCAM is associated with favorable outcome in most cases, and should be considered in severe cases even before hydrops develops.

Linear response theory for hard and soft glassy materials.

Despite qualitative differences in their underlying physics, both hard and soft glassy materials exhibit almost identical linear rheological behaviors. We show that these nearly universal properties emerge naturally in a shear-transformation-zone theory of amorphous plasticity, extended to include a broad distribution of internal thermal-activation barriers. The principal features of this barrier-height distribution are predicted by nonequilibrium, effective-temperature thermodynamics. Our theoretical loss modulus G''(ω) has a peak at the α relaxation rate, and a power law decay of the form ω(-ζ) for higher frequencies, in quantitative agreement with experimental data.

Tunneling magnetothermopower in magnetic tunnel junction nanopillars.

We study tunneling magnetothermopower (TMTP) in CoFeB/MgO/CoFeB magnetic tunnel junction nanopillars. Thermal gradients across the junctions are generated by an electric heater line. Thermopower voltages up to a few tens of µV between the top and bottom contact of the nanopillars are measured which scale linearly with the applied heating power and hence the thermal gradient. The thermopower signal varies by up to 10 µV upon reversal of the relative magnetic configuration of the two CoFeB layers from parallel to antiparallel. This signal change corresponds to a large spin-dependent Seebeck coefficient of the order of 100 µV/K and a large TMTP change of the tunnel junction of up to 90%.

Does gastric dilation predict adverse perinatal or surgical outcome in fetuses with gastroschisis?

OBJECTIVE: To compare perinatal and infant surgical outcomes in fetuses with gastroschisis with and without gastric dilation in a single-center cohort. METHODS: This was a retrospective study of all singleton pregnancies with a prenatal diagnosis of gastroschisis managed at University of Toronto perinatal centers between January 2001 and February 2010. Digital prenatal ultrasound images were reviewed to determine fetal gastric size within 2 weeks of delivery. Perinatal and surgical outcomes were compared in fetuses with and without gastric dilation including: gestational age at delivery, mode of delivery, indication for Cesarean section, meconium-stained amniotic fluid, birth weight percentile, Apgar scores at 1 and 5 min, umbilical artery pH, time to full enteral feeding, length of hospital stay, bowel atresia or necrosis and need for bowel resection. RESULTS: Ninety-eight fetuses with prenatally diagnosed gastroschisis managed at our center were included in the study, of which 32 (32.7%) were found to have gastric dilation. Gastric dilation predicted meconium-stained amniotic fluid at delivery (53% vs. 24%; P = 0.017), but no other adverse perinatal outcome. Surgical morbidity rates (bowel atresia, bowel necrosis, perforation diagnosed postnatally, need for bowel resection, total time to full enteral feeding and length of hospital stay) were unaffected by gastric dilation. CONCLUSIONS: In gastroschisis, fetal gastric dilation is associated with meconium-stained amniotic fluid at delivery, but is not predictive of any serious perinatal or postnatal complications. Fetal growth and well-being should be serially evaluated on ultrasound using biophysical and Doppler assessment to decide on the optimal timing and mode of delivery.

Fracture toughness of crystalline solids.

This paper describes an attempt to construct a first-principles theory of the fracture toughness of crystalline solids. It is based on the thermodynamic dislocation theory (TDT), which starts with the assertion that dislocations in solids must obey the second law of thermodynamics. A second starting assumption is that fracture is initiated when the tip of a notch is driven to undergo a dynamic shape instability. The results of this analysis are developed in comparison with measurements by Gumbsch and colleagues of the notch toughness of both predeformed and non-predeformed tungsten crystals. The theory includes a simple ad hoc conjecture regarding tip dynamics at small dislocation densities. Nevertheless, its predictions agree quantitatively with the experimental data, including both brittle and ductile fracture, over a wide range of temperatures, loading rates, and initial conditions.