Hyperbranched polyglycerols as building blocks for complex amphiphilic structures: synthesis, characterization and applications

Among hyperbranched polymers, polyglycerol is one of the most promising and commonly used macromolecules due to its biocompatibility and versatility. However, the synthesis of high molecular weight polyglycerols still involves many intricacies and has only been understood to a limited extent. Furthermore, only few complex structures like star or block copolymers incorporating polyglycerol have been realized so far. Particularly biocompatible block copolymers are considered promising candidates for biomedical applications.rnThe scope of this thesis was the enhancement of the synthetic process leading to polyglycerol derivatives which implies improved molecular weight control for a broad molecular weight range as well as the assembly of more complex structures like amphiphilic block copolymers. Further insight into the relation between reaction solvent, degree of deprotonation during the ring-opening multibranching polymerization of glycidol and the characteristics of the obtained polymers were achieved within the scope of this work. Based on these results, a novel concept for the preparation of hyperbranched polyglycerols with molecular weights up to 20,000 g/mol was developed, applying a two step synthesis pathway. Starting from a partially deprotonated TMP core, low molecular weight hb-PGs were prepared using the known synthetic protocol that has been established since the late 1990ies. In a subsequent reaction sequence, these well defined polymers were used as hyperbranched macroinitiator cores in order to obtain high molecular weight hb-PGs with remarkably low polydispersity (Mw/Mn < 1.8). Molecular weight control was shown to be excellent and undesired low molecular weight side products were absent. Furthermore, the technique of continuous spin fractionation has been discovered as an efficient method for polyglycerol work-up to remove quantitatively residual monomer- and oligomer traces from hb-PG compositions to result in samples with significantly reduced polydispersities. Based on these results the synthesis of amphiphilic block copolymers containing hydrophilic hyperbranched polyglycerol blocks and linear, apolar poly(propylene oxide) blocks has been significantly improved and augmented to hb-PG-b-l-PPO-b-hb-PG ABA block copolymers. The influence of different polyglycerol-based amphiphiles on the fibril formation was studied by Thioflavin T Fluorescence showing remarkable increasing lag times which is promising in order to enhance the stability of this protein. In addition the first synthesis of poly(glyceryl glycerols) (PGG), introducing a new solketyl glycidyl ether monomer (IGG) was shown. It was furthermore demonstrated that core-functional carbosilane wedges allow application in block copolymer synthesis. Bisglycidolized amine functional polymers were successfully employed as macroinitiators for glycidol polymerization. This resulted in the first example of amphiphilic hyperbranched-hyperbranched polymer structures. Finally, it has been shown that the previously reported synthetic pathway to carboxylated hyperbranched polyglycerol polyelectrolytes can also be applied for the amphiphilic linear-hyperbranched block copolymers. These novel biocompatible and highly amphiphilic polyelectrolytes offer great potential for further investigations. rnrn

Non-aqueous dispersions of particles and their applications

In the current work, three studies about non-aqueous dispersions of particles were carried out by using an amphiphilic block copolymer poly(isoprene)-block-poly(methyl methacrylate) (PI-b-PMMA) as stabilizer:rn1. Dispersions of polyurethane and polyurea porous particles for polymer compositesrn2. Dispersions of PMMA and PU particles with PDI dye for study of Single Molecule Spectroscopy Detectionrn3. Dispersions of graphene nanosheets for polymer compositesrnrnIn the first study, highly porous polyurethane and polyurea particles were prepared in a non-aqueous emulsion. The preparation of porous particles consisted of two parts: At first, a system was developed where the emulsion had high stability for the polymerization among diisocyanate, diol and water. In the second part, porous particles were prepared by using two methods fission/fusion and combination by which highly porous particles were obtained. In this study, the applications of porous particles were also investigated where polyurethane particles were tested as filling material for polymer composites and as catalyst carrier for polyethylene polymerization. rnrnIn the second study, PMMA and PU particles from one non-aqueous emulsion were investigated via single molecule fluorescence detection. At first the particles were loaded with PDI dye, which were detected by fluorescence microscopy. The distribution and orientation of the PDI molecules in the particles were successfully observed by Single Molecule Fluorescence Detection. The molecules were homogenously distributed inside of the particles. In addition they had random orientation, meaning that no aggregations of dye molecules were formed. With the results, it could be supposed that the polymer chains were also homogenously distributed in the particles, and that the conformation was relatively flexible. rnrnIn the third part of the study, graphene nanosheets with high surface area were dispersed in an organic solvent with low boiling point and low toxicity, THF, stabilized with a block copolymer PI-b-PMMA. The dispersion was used to prepare polymer composites. It was shown that the modified graphene nanosheets had good compatibility with the PS and PMMA matrices. rn

Surgical treatment of upper, middle and lower cervical injuries and non-unions by anterior procedures

The goals of any treatment of cervical spine injuries are: return to maximum functional ability, minimum of residual pain, decrease of any neurological deficit, minimum of residual deformity and prevention of further disability. The advantages of surgical treatment are the ability to reach optimal reduction, immediate stability, direct decompression of the cord and the exiting roots, the need for only minimum external fixation, the possibility for early mobilisation and clearly decreased nursing problems. There are some reasons why those goals can be reached better by anterior surgery. Usually the bony compression of the cord and roots comes from the front therefore anterior decompression is usually the procedure of choice. Also, the anterior stabilisation with a plate is usually simpler than a posterior instrumentation. It needs to be stressed that closed reduction by traction can align the fractured spine and indirectly decompress the neural structures in about 70%. The necessary weight is 2.5 kg per level of injury. In the upper cervical spine, the odontoid fracture type 2 is an indication for anterior surgery by direct screw fixation. Joint C1/C2 dislocations or fractures or certain odontoid fractures can be treated with a fusion of the C1/C2 joint by anterior transarticular screw fixation. In the lower and middle cervical spine, anterior plating combined with iliac crest or fibular strut graft is the procedure of choice, however, a solid graft can also be replaced by filled solid or expandable vertebral cages. The complication of this surgery is low, when properly executed and anterior surgery may only be contra-indicated in case of a significant lesion or locked joints.

Body Mass Index and Cancer Risk: The Evidence for Causal Association

Increased body mass index (BMI), as an approximation of body adiposity, is a risk factor for developing several adult malignancies. To quantify these risks, we reported a comprehensive systematic review (Lancet 2008; 371: 569-78) of prospective observational studies determining associations between BMI and risk of incident cancer for 20 cancer types. We demonstrated that associations are: (i) sex-specific; (ii) exist for a wider range of malignancies than previously thought; and (iii) are broadly consistent across geographic populations. In the present paper, we tested these data against the Bradford-Hill criteria of causal association, and argue that the available data support strength of association, consistency, specificity, temporality, biological gradient, plausibility, coherence and probably analogy. However, the experimental evidence supporting reversibility is currently lacking, though indirect evidence from longitudinal data in cohort studies and long-term follow-up post-bariatric surgery is emerging. We additionally assessed these data against appropriate adjustment for available confounding factors; measurement error and study design; and residual confounding; and found lack of alternative explanations. We conclude that there is considerable evidence to support a causal association between BMI and risk for many cancer types, but in order to establish the role of weight control in cancer prevention, there is a need to develop trial frameworks in which to better test reversibility.

A Novel Method for the Homogenization of Daily Temperature Series and Its Relevance for Climate Change Analysis

Instrumental daily series of temperature are often affected by inhomogeneities. Several methods are available for their correction at monthly and annual scales, whereas few exist for daily data. Here, an improved version of the higher-order moments (HOM) method, the higher-order moments for autocorrelated data (HOMAD), is proposed. HOMAD addresses the main weaknesses of HOM, namely, data autocorrelation and the subjective choice of regression parameters. Simulated series are used for the comparison of both methodologies. The results highlight and reveal that HOMAD outperforms HOM for small samples. Additionally, three daily temperature time series from stations in the eastern Mediterranean are used to show the impact of homogenization procedures on trend estimation and the assessment of extremes. HOMAD provides an improved correction of daily temperature time series and further supports the use of corrected daily temperature time series prior to climate change assessment.

Early and late urodynamic assessment of ileal orthotopic bladder substitutes combined with an afferent tubular segment

PURPOSE: Limited information is available concerning changes in the urodynamic characteristics of orthotopic bladder substitutes with time. Therefore, we compared early and late urodynamic results in patients with an ileal orthotopic bladder substitute combined with an afferent tubular segment. MATERIALS AND METHODS: Of 139 patients surviving at least 5 years after cystoprostatectomy and ileal orthotopic bladder substitution with an afferent tubular segment 119 underwent urodynamic assessment, including 66 at a median of 9 months (early) and 77 at a median of 62 months (late). Of these patients 24 were assessed at each time point. Simultaneously all patients were asked to complete a bladder diary and questionnaire regarding continence for at least 3 days in the week preceding the urodynamic study. RESULTS: Urodynamic parameters were comparable in patients who were evaluated early and late postoperatively. In addition, median values at early and late urodynamic evaluation in the 24 patients with the 2 examinations showed no statistically significant differences for volume at first desire to void (300 vs 333 ml, p = 0.85), pressure at first desire to void (12 vs 13 cm H2O, p = 0.57), maximum cystometric capacity (450 vs 453 ml, p = 0.84), end filling pressure (19 vs 20 cm H2O, p = 0.17), reservoir compliance (25 vs 28 ml/cm H2O, p = 0.58) or post-void residual urine volume (5 vs 15 ml, p = 0.27). CONCLUSIONS: Urodynamic results after 5 years of living with an ileal orthotopic bladder substitute with an afferent tubular segment show grossly unchanged urodynamic characteristics. Patients maintain a reservoir capacity and micturition pattern consistent with a normal life-style. Reservoir pressure remained low, thereby protecting and preserving upper tract function. To achieve these results patients must be regularly followed, and the causes of bacteriuria, increased post-void residual urine and bladder outlet obstruction must be recognized and dealt with accordingly.

[Old and new interventional therapies in the treatment of symptomatic benign prostate hyperplasia (BPH)]

Benign Prostatic Hyperplasia is a common entity among the aging male population. Its prevalence is increasing with age and is around 80% in the over 80-years old. The androgen-estrogen ratio changes in favor of the estrogens, which leads to a growth of prostatic tissue, presenting histologically as hyperplasia. BPH can cause irritative or obstructive symptoms or both. Nowadays we speak of bladder storage or bladder voiding symptoms, summarised as LUTS (Lower Urinary Tract Symptoms). LUTS has a structural and a functional component, the structural being caused by the size of the adenoma itself the functional depending on the muscle tone of the bladder neck and the prostatic urethra. To investigate LUTS, we use validated symptom scores, sonography for residual urine and eventually a urodynamic evaluation. There are 3 grades of BPH. The indication for an interventional therapy is relative in BPH II, and absolute in BPH III. Prior to treatment, other diseases mimicking the same symptoms, have to be ruled out and adequatly treated. Electro-resection of the prostate (TUR-P) remains the standard therapy and the benchmark any new technology has to compete with. TUR-P has good short- and longterm results, but can be associated with a considerable perioperative morbidity, and the learning curve for the operator is long. The most promising of the newer techniques is the Holmium-Laser-Enucleation of the prostate (Laser-TUR-P), showing at least identical short- and median-term results, but a lower perioperative morbidity than TUR-P For several minimally-invasive techniques, indications are limited. TUMT TUNA, WIT and laser-coagulation all produce a coagulation necrosis of the prostatic tissue by thermic damage with secondary tissue shrinking. Urodynamic results however, are not comparable to TUR-P or Laser-TUR-P, and significantly more secondary interventions within 2 to 5 years are required. Minimal-invasive techniques present a favorable alternative for younger patients without complications of BPH, and for older patients with relevant comorbidities, and can usually be performed under local anaesthesia. The morbidity is low and further therapies remain possible later, if necessary.

Regional and overall ventilation inhomogeneities in preterm and term-born infants

OBJECTIVES: We compared ventilation inhomogeneity assessed by electrical impedance tomography (EIT) and multiple breath washout (MBW) in preterm and term-born infants. We hypothesised that EIT measurements in spontaneously breathing infants are repeatable and that differences in regional ventilation distribution measured by EIT can distinguish between preterm and term-born infants. DESIGN: Cross-sectional group comparison study. SETTING: Lung function laboratory at a University Children's Hospital. PARTICIPANTS: Seventeen healthy term-born and 15 preterm infants at a matched postmenstrual age of 44 weeks. MEASUREMENTS AND RESULTS: We concurrently measured ventilation inhomogeneity by EIT, ventilation inhomogeneity (LCI) and functional residual capacity (FRC) by MBW and tidal breathing variables during unsedated quiet sleep. EIT measurements were highly repeatable (coefficient of variation 3.6%). Preterm infants showed significantly more ventilation of the independent parts of the lungs compared to healthy term-born infants assessed by EIT (mean difference 5.0, 95 CI 1.3-8%). Whereas the two groups showed no differences in lung volumes or ventilation inhomogeneities assessed by MBW, EIT discriminated better between term and preterm infants. (FRC/kg: mean difference 1.1 mL, 95% CI -1.4-3.8 mL; LCI: mean difference 0.03, 95% CI -0.32-0.25). CONCLUSIONS: EIT shows distinct differences in ventilation distribution between preterm and term-born infants, which cannot be detected by MBW. Although preterm infants are capable of dynamically maintaining overall functional residual volume and ventilation distribution, they show some spatial differences from fullterm infants.

IMPROVING STARTABILITY AND REDUCING EMISSIONS IN FLEXFUEL SPARK IGNITION DIRECT INJECTION VARIABLE CAM TIMING ENGINE

Experimental work and analysis was done to investigate engine startup robustness and emissions of a flex-fuel spark ignition (SI) direct injection (DI) engine. The vaporization and other characteristics of ethanol fuel blends present a challenge at engine startup. Strategies to reduce the enrichment requirements for the first engine startup cycle and emissions for the second and third fired cycle at 25°C ± 1°C engine and intake air temperature were investigated. Research work was conducted on a single cylinder SIDI engine with gasoline and E85 fuels, to study the effect on first fired cycle of engine startup. Piston configurations that included a compression ratio change (11 vs 15.5) and piston geometry change (flattop vs bowl) were tested, along with changes in intake cam timing (95,110,125) and fuel pressure (0.4 MPa vs 3 MPa). The goal was to replicate the engine speed, manifold pressure, fuel pressure and testing temperature from an engine startup trace for investigating the first fired cycle for the engine. Results showed bowl piston was able to enable lower equivalence ratio engine starts with gasoline fuel, while also showing lower IMEP at the same equivalence ratio compared to flat top piston. With E85, bowl piston showed reduced IMEP as compression ratio increased at the same equivalence ratio. A preference for constant intake valve timing across fuels seemed to indicate that flattop piston might be a good flex-fuel piston. Significant improvements were seen with higher CR bowl piston with high fuel pressure starts, but showed no improvement with low fuel pressures. Simulation work was conducted to analyze initial three cycles of engine startup in GT-POWER for the same set of hardware used in the experimentations. A steady state validated model was modified for startup conditions. The results of which allowed an understanding of the relative residual levels and IMEP at the test points in the cam phasing space. This allowed selecting additional test points that enable use of higher residual levels, eliminating those with smaller trapped mass incapable of producing required IMEP for proper engine turnover. The second phase of experimental testing results for 2nd and 3rd startup cycle revealed both E10 and E85 prefer the same SOI of 240°bTDC at second and third startup cycle for the flat top piston and high injection pressures. E85 fuel optimal cam timing for startup showed that it tolerates more residuals compared to E10 fuel. Higher internal residuals drives down the Ø requirement for both fuels up to their combustion stability limit, this is thought to be direct benefit to vaporization due to increased cycle start temperature. Benefits are shown for an advance IMOP and retarded EMOP strategy at engine startup. Overall the amount of residuals preferred by an engine for E10 fuel at startup is thought to be constant across engine speed, thus could enable easier selection of optimized cam positions across the startup speeds.

Multi-parametric classification of Alzheimer's disease and mild cognitive impairment: the impact of quantitative magnetization transfer MR imaging

Multi-parametric and quantitative magnetic resonance imaging (MRI) techniques have come into the focus of interest, both as a research and diagnostic modality for the evaluation of patients suffering from mild cognitive decline and overt dementia. In this study we address the question, if disease related quantitative magnetization transfer effects (qMT) within the intra- and extracellular matrices of the hippocampus may aid in the differentiation between clinically diagnosed patients with Alzheimer disease (AD), patients with mild cognitive impairment (MCI) and healthy controls. We evaluated 22 patients with AD (n=12) and MCI (n=10) and 22 healthy elderly (n=12) and younger (n=10) controls with multi-parametric MRI. Neuropsychological testing was performed in patients and elderly controls (n=34). In order to quantify the qMT effects, the absorption spectrum was sampled at relevant off-resonance frequencies. The qMT-parameters were calculated according to a two-pool spin-bath model including the T1- and T2 relaxation parameters of the free pool, determined in separate experiments. Histograms (fixed bin-size) of the normalized qMT-parameter values (z-scores) within the anterior and posterior hippocampus (hippocampal head and body) were subjected to a fuzzy-c-means classification algorithm with downstreamed PCA projection. The within-cluster sums of point-to-centroid distances were used to examine the effects of qMT- and diffusion anisotropy parameters on the discrimination of healthy volunteers, patients with Alzheimer and MCIs. The qMT-parameters T2(r) (T2 of the restricted pool) and F (fractional pool size) differentiated between the three groups (control, MCI and AD) in the anterior hippocampus. In our cohort, the MT ratio, as proposed in previous reports, did not differentiate between MCI and AD or healthy controls and MCI, but between healthy controls and AD.

Removable dentures with implant support in strategic positions followed for up to 8 years

PURPOSE: The aim of this study was to analyze prosthetic maintenance in partially edentulous patients with removable prostheses supported by teeth and strategic implants. MATERIALS AND METHODS: Sixty patients with removable partial prostheses and combined tooth-implant support were identified within the time period from 1998 to 2006. One group consisted of 42 patients (planned group) with a reduced residual dentition and in need of removable partial dentures (RPDs) or overdentures in the maxilla and/or mandible. They were admitted consecutively for treatment. Due to missing teeth in strategic important positions, one or two implants were placed to improve symmetrical denture support and retention. The majority of residual teeth exhibited an impaired structural integrity and therefore were provided with root copings for denture retention. A few vital teeth were used for telescopic crowns. The anchorage system for the strategic implants was selected accordingly. A second group of 18 patients (repair group) wearing RPDs with the loss of one abutment tooth due to biologic or mechanical failure was identified. These abutment teeth were replaced by 21 implants, and patients continued to wear their original prostheses. The observation time for planned and repair groups was 12 months to 8 years. All patients followed a regular maintenance schedule. Technical or biologic complications with supporting teeth or implants and prosthetic service were registered regularly. RESULTS: Three maxillary implants were lost after loading and three roots with copings had to be removed. Biologic problems included caries and periodontal/peri-implant infection with a significantly higher incidence in the repair group (P < .05). Technical complications with the dentures were rather frequent in both groups, mostly related to the anchorage system (matrices) of root copings and implants. Maintenance and complications were observed more frequently in the first year after delivery of the denture than in the following 3 years (P < .05). No denture had to be remade. CONCLUSIONS: The placement of a few implants allows for maintaining a compromised residual dentition for support of RPDs. The combination of root and implant support facilitates treatment planning and enhances designing the removable denture. It also proves to be a practical rescue method. Technical problems with the anchorage system were frequent, particularly in the first year after delivery of the dentures.

Executive Stock Ownership and Performance: Tracking Faint Traces

We examine the relation between managers' financial interests and firm performance. Since the relation could go in either direction, we cast the analysis in a simultaneous equations framework. For firms involved in acquisitions, we find that acquisition performance and Tobin's Q ratios affect the size of managers' stockholdings. We find no evidence, however, that larger stockholdings lead to better performance. Perhaps management is effectively disciplined by competition in product and labor markets. Alternatively, it may not be necessary for top executives to own stock to the residual claimants. And finally, higher ownership might multiply the opportunities to appropriate corporate wealth.

A Routing Protocol Based on Energy and Link Quality for Internet of Things Applications

The Internet of Things (IoT) is attracting considerable attention from the universities, industries, citizens and governments for applications, such as healthcare, environmental monitoring and smart buildings. IoT enables network connectivity between smart devices at all times, everywhere, and about everything. In this context, Wireless Sensor Networks (WSNs) play an important role in increasing the ubiquity of networks with smart devices that are low-cost and easy to deploy. However, sensor nodes are restricted in terms of energy, processing and memory. Additionally, low-power radios are very sensitive to noise, interference and multipath distortions. In this context, this article proposes a routing protocol based on Routing by Energy and Link quality (REL) for IoT applications. To increase reliability and energy-efficiency, REL selects routes on the basis of a proposed end-to-end link quality estimator mechanism, residual energy and hop count. Furthermore, REL proposes an event-driven mechanism to provide load balancing and avoid the premature energy depletion of nodes/networks. Performance evaluations were carried out using simulation and testbed experiments to show the impact and benefits of REL in small and large-scale networks. The results show that REL increases the network lifetime and services availability, as well as the quality of service of IoT applications. It also provides an even distribution of scarce network resources and reduces the packet loss rate, compared with the performance of well-known protocols.

Initial clinical experience with the Coherex FlatStent™ and FlatStent™ EF PFO closure system for in-tunnel PFO closure: Results of the Coherex-EU study

OBJECTIVE The Coherex-EU Study evaluated the safety and efficacy of PFO closure utilizing novel in-tunnel PFO closure devices. BACKGROUND Transcatheter closure of patent foramen ovale (PFO) followed the development of transcatheter closure devices designed to patch atrial septal defects (ASDs). The Coherex FlatStent™ and FlatStent™ EF devices were designed specifically to treat PFO anatomy. METHODS A total of 95 patients with a clinical indication for PFO closure were enrolled in a prospective, multicenter first in man study at six clinical sites. Thirty-six patients received the first-generation FlatStent study device, and 57 patients received the second-generation FlatStent EF study device, which was modified based on clinical experience during the first 38 cases. Two patients enrolled to receive the first generation did not receive a device. RESULTS At 6 months post-procedure, 45% (17/38) of the intention-to-treat (ITT) cohort receiving the first-generation FlatStent device had complete closure, 26% (10/38) had a trivial residual shunt, and 29% (11/38) had a moderate to large residual shunt. In the ITT cohort receiving the second-generation FlatStent EF device, 76% (43/57) had complete closure, 12% (7/57) had a trivial shunt, and 12% had a moderate to large shunt. Five major adverse events occurred, all without sequelae. CONCLUSION This initial study of the Coherex FlatStent/FlatStent EF PFO Closure System demonstrated the potential for in-tunnel PFO closure. The in-tunnel Coherex FlatStent EF may offer an alternative to septal repair devices for PFO closure in appropriately selected patients; however, further investigation will be necessary to establish the best use of this device.

Interactions between dodecyl phosphates and hydroxyapatite or tooth enamel: relevance to inhibition of dental erosion.

Tooth surface modification is a potential method of preventing dental erosion, a form of excessive tooth wear facilitated by softening of tooth surfaces through the direct action of acids, mainly of dietary origin. We have previously shown that dodecyl phosphates (DPs) effectively inhibit dissolution of native surfaces of hydroxyapatite (the type mineral for dental enamel) and show good substantivity. However, adsorbed saliva also inhibits dissolution and DPs did not augment this effect, which suggests that DPs and saliva interact at the hydroxyapatite surface. In the present study the adsorption and desorption of potassium and sodium dodecyl phosphates or sodium dodecyl sulphate (SDS) to hydroxyapatite and human tooth enamel powder, both native and pre-treated with saliva, were studied by high performance liquid chromatography-mass Spectrometry. Thermo gravimetric analysis was used to analyse residual saliva and surfactant on the substrates. Both DPs showed a higher affinity than SDS for both hydroxyapatite and enamel, and little DP was desorbed by washing with water. SDS was readily desorbed from hydroxyapatite, suggesting that the phosphate head group is essential for strong binding to this substrate. However, SDS was not desorbed from enamel, so that this substrate has surface properties different from those of hydroxyapatite. The presence of a salivary coating had little or no effect on adsorption of the DPs, but treatment with DPs partly desorbed saliva; this could account for the failure of DPs to increase the dissolution inhibition due to adsorbed saliva.