Short-time mentoring - enhancing female medical students' intentions toward surgical careers.

BACKGROUND: Women pursuing a career in surgery or related disciplines are still in the minority, despite the fact that women compose at least half of the medical student population in most Western countries. Thus, recruiting and retaining female surgeons remains an important challenge to meet the need for surgeons and increase the quality of care. The participations were female medical students between their third and fifth academic year. In this study, we applied the well-established psychological theory of planned behavior (TPB) which suggests that the intention to perform a behavior (e.g. pursuing a career in surgery) is the most critical and immediate predictor of performing the behavior. We investigated whether a two-part short-mentoring seminar significantly increases students' intention to pursue a career in a surgical or related specialty after graduation. METHOD: The mentoring and role-model seminar was conducted at 2 days for 90 minutes by six inspiring female role models with a remarkable career in surgical or related disciplines. Participants (N = 57) filled in an online survey before (T0) and after the seminar (T1). A pre-post comparison of central TPB concept attitude towards the behavior, 2) occupational self-efficacy and 3) social norm) was conducted using a paired sampled t-test. A follow-up survey was administered 12 months later (T2). RESULTS: The mentoring seminar positively impacted female students' attitude towards a career in a surgical specialty. Female students reported a significantly increased positive attitude (p < .001) and significantly higher self-efficacy expectations (p < .001) towards a surgical career after participating in the mentoring seminar. Regarding their career intention after the seminar, female students declared a significantly higher intention to pursue a career in a surgical specialty after graduating (p < .001) and this effect seems to be sustainable after 1 year. CONCLUSION: For the first time we could show that short-mentoring and demonstrating role models in a seminar surrounding has a significant impact on female medical student decision´s to pursue a career in a surgery speciality. This concept may be a practical and efficient concept to refine the gender disparity in surgery and related disciplines.

Influence of process temperature and residence time on the manufacturing of amorphous solid dispersions in hot melt extrusion.

The manufacturing of amorphous solid dispersions via hot melt extrusion is a topic of high interest in pharmaceutical development. By this technique, the drug is dissolved in the molten polymer above solubility temperature within the process time. In this study, an experimental framework is proposed determining the minimum required process temperature and the residence time using particularly low quantities of material. Drug/polymer mixtures in different ratios were processed in a micro-scale extruder while the process temperature and residence time were varied systematically. The phase situation was assessed by the turbidity of the final extrudate. Four different drug/polymer mixtures were investigated in three drug/polymer ratios. The minimum required process temperature was close to solubility temperature for each specific formulation. Moreover, an influence of residence time on the phase situation was found. About three minutes were required in order to dissolve the drug in the polymer at these process conditions.

The relaxation behavior of supercooled and glassy imidacloprid.

Employing dielectric spectroscopy, oscillatory shear rheology, and calorimetry, the present work explores the molecular dynamics of the widely used insecticide imidacloprid above and below its glass transition temperature. In its supercooled liquid regime, the applied techniques yield good agreement regarding the characteristic structural (alpha) relaxation times of this material. In addition, the generalized Gemant-DiMarzio-Bishop model provides a good conversion between the frequency-dependent dielectric and shear mechanical responses in its viscous state, allowing for an assessment of imidacloprid's molecular hydrodynamic radius. In order to characterize the molecular dynamics in its glassy regime, we employ several approaches. These include the application of frequency-temperature superposition (FTS) to its isostructural dielectric and rheological responses as well as use of dielectric and calorimetric physical aging and the Adam-Gibbs-Vogel model. While the latter approach and dielectric FTS provide relaxation times that are close to each other, the other methods predict notably longer times that are closer to those reflecting a complete recovery of ergodicity. This seemingly conflicting dissimilarity demonstrates that the molecular dynamics of glassy imidacloprid strongly depends on its thermal history, with high relevance for the use of this insecticide as an active ingredient in technological applications.

Characterization of Nanoporous Materials.

Detailed analysis of textural properties, e.g., pore size and connectivity, of nanoporous materials is essential to identify correlations of these properties with the performance of gas storage, separation, and catalysis processes. The advances in developing nanoporous materials with uniform, tailor-made pore structures, including the introduction of hierarchical pore systems, offer huge potential for these applications. Within this context, major progress has been made in understanding the adsorption and phase behavior of confined fluids and consequently in physisorption characterization. This enables reliable pore size, volume, and network connectivity analysis using advanced, high-resolution experimental protocols coupled with advanced methods based on statistical mechanics, such as methods based on density functional theory and molecular simulation. If macro-pores are present, a combination of adsorption and mercury porosimetry can be useful. Hence, some important recent advances in understanding the mercury intrusion/extrusion mechanism are discussed. Additionally, some promising complementary techniques for characterization of porous materials immersed in a liquid phase are introduced.

A reference high-pressure CO2 adsorption isotherm for ammonium ZSM-5 zeolite: results of an interlaboratory study.

This paper reports the results of an international interlaboratory study led by the National Institute of Standards and Technology (NIST) on the measurement of high-pressure surface excess carbon dioxide adsorption isotherms on NIST Reference Material RM 8852 (ammonium ZSM-5 zeolite), at 293.15 K (20 °C) from 1 kPa up to 4.5 MPa. Eleven laboratories participated in this exercise and, for the first time, high-pressure adsorption reference data are reported using a reference material. An empirical reference equation n e x = d ( 1 + exp [ - ln ( P ) + a / b ] ) c , [n ex -surface excess uptake (mmol/g), P-equilibrium pressure (MPa), a = -6.22, b = 1.97, c = 4.73, and d = 3.87] along with the 95% uncertainty interval (U k = 2 = 0.075 mmol/g) were determined for the reference isotherm using a Bayesian, Markov Chain Monte Carlo method. Together, this zeolitic reference material and the associated adsorption data provide a means for laboratories to test and validate high-pressure adsorption equipment and measurements. Recommendations are provided for measuring reliable high-pressure adsorption isotherms using this material, including activation procedures, data processing methods to determine surface excess uptake, and the appropriate equation of state to be used.

Granule size distributions after twin-screw granulation - Do not forget the feeding systems.

The aim of this study was to investigate the influence of qualitatively different powder feeder performances on resulting granule size distributions after twin-screw granulation of a highly drug loaded, hydrophobic mixture and a mannitol powder. It was shown that powder feeder related problems usually cannot be identified by trusting in the values given by the feeder. Therefore, a newly developed model for the evaluation of the performance of powder feeders was introduced and it was tried to connect this model to residence time distributions in twin-screw granulation processes. The influence of feeder performances on resulting granule size distributions varied, depending on the applied screw configuration and the used powder. Regarding the hydrophobic and highly drug loaded formulation, which was granulated at an L/S-ratio of 0.5, a pure conveying screw and a medium kneading configuration, consisting of 60° kneading blocks were negatively influenced by poor feeder settings. For optimal settings more narrow distributions could be obtained. For an extensive kneading configuration good and poor settings resulted in mono-modal granule size distributions but were differing in the overall size. Mannitol, a model substance for a liquid sensitive formulation was granulated at an L/S-ratio of 0.075. It was even more important to maintain optimal feeding as mannitol was highly affected by poor feeder performances. Even an extensive kneading configuration could not level the errors in powder feeder performance, resulting in qualitatively different granule size distributions. The results of this study demonstrate the importance of detailed knowledge about applied feeding systems to gain optimal performance in twin-screw granulation.

Anomalous Depletion of Pore-Confined Carbon Dioxide upon Cooling below the Bulk Triple Point: An In Situ Neutron Diffraction Study.

The phase behavior of sorbed CO{2} in an ordered mesoporous silica sample (SBA-15) was studied by neutron diffraction. Surprisingly, upon cooling our sample below the bulk critical point, confined CO{2} molecules neither freeze nor remain liquid as expected, but escape from the pores. The phenomenon has additionally been confirmed gravimetrically. The process is reversible and during heating CO{2} refills the pores, albeit with hysteresis. This depletion was for the first time observed in an ordered mesoporous molecular sieve and provides new insight on the phase behavior of nanoconfined fluids.

Simplified formulations with high drug loads for continuous twin-screw granulation.

As different batches of the same excipients will be intermixed during continuous processes, the traceability of batches is complicated. Simplified formulations may help to reduce problems related to batch intermixing and traceability. Twin-screw granulation with subsequent tableting was used to produce granules and tablets, containing drug, disintegrant and binder (binary and ternary mixtures), only. Drug loads up to 90% were achieved and five different disintegrants were screened for keeping their disintegration suitability after wetting. Granule size distributions were consistently mono-modal and narrow. Granule strength reached higher values, using ternary mixtures. Tablets containing croscarmellose-Na as disintegrant displayed tensile strengths up to 3.1MPa and disintegration times from 400 to 466s, resulting in the most robust disintegrant. Dissolution was overall complete and above 96% within 30 min. Na-starch glycolate offers tensile strengths up to 2.8MPa at disintegration times from 25s to 1031s, providing the broadest application window, as it corresponds in some parts to different definitions of orodispersible tablets. Tablets containing micronized crospovidone are not suitable for immediate release, but showed possibilities to produce highly drug loaded, prolonged release tablets. Tablets and granules from simplified formulations offer great opportunities to improve continuous processes, present performances comparable to more complicated formulations and are able to correspond to requirements of the authorities.

Lipid-based intravesical drug delivery systems with controlled release of trospium chloride for the urinary bladder.

The overactive bladder (OAB) is a common disease with an overactivity of the detrusor muscle in the bladder wall. Besides peroral administration of anticholinergic drugs and bladder irrigations, there is a need for a sustained release formulation in the urinary bladder. In order to realise a local long-term treatment of the overactive urinary bladder, lipidic drug delivery systems were prepared. Requirements for an intravesical application are a long-term controlled release of trospium chloride, a high drug loading and small sized drug carriers to permit an insertion through the urethra into the urinary bladder. The drug delivery systems were manufactured by using compression (mini-tablets), solid lipid extrusion (extrudates) and a melting and casting technique (mini-moulds) with different amounts of trospium chloride and glyceryl tristearate as matrix former. Drug release depended on the drug loading and the preparation method. Mini-tablets and lipidic extrudates showed a drug release over five days, whereas that from mini-moulds was negligibly small. The appearance of polymorphic transformations during processing and storage was investigated by using differential scanning calorimetry and X-ray diffraction. In contrast to mini-tablets and mini-moulds, lipidic extrudates showed no polymorphic transformations. In summary, lipids are suitable matrix formers for a highly water-soluble drug, like trospium chloride. Despite a drug loading of up to 30%, it was feasible to achieve a drug release ranging from several days up to weeks. In addition, small dosage forms with a size of only a few millimetres were realised. Therefore, an insertion and excretion through the urethra is possible and the requirements for an intravesical application are fulfilled.

The water binding behavior of kappa-carrageenan determined by three different methods.

kappa-Carrageenan is a biopolymer extracted from red seaweeds which has been in the focus of pharmaceutical development for many years. Most applications make use of the large water binding capacity of kappa-carrageenan. The primary limitation of kappa-carrageenan is the variation in the substance quality. Therefore, the water binding capacity of different kappa-carrageenan products was investigated by dynamic vapor adsorption, freezing and non-freezing bound water and water retention value. The kappa-carrageenans were observed to have a higher water binding capacity than microcrystalline cellulose (MCC) in all three methods. The amount of adsorbed water is similar for all carrageenans. Differences between the carrageenan types (kappa, iota, and lambda) were remarkable for the freezing bound water and centrifugation bound water as well as between the kappa-carrageenans of different suppliers.

Flow-through pore characteristics of monolithic silicas and their impact on column performance in high-performance liquid chromatography.

In order to elucidate the role of the flow-through characteristics with regard to the column performance in high-performance liquid chromatography (HPLC) native and n-octadecyl bonded monolithic silica rods and columns, respectively of 100 mm length and 4.6 mm ID with mesopores in the range between 10 and 25 nm and macropores in the range between 0.7 and 6.0 microm were examined by mercury intrusion/extrusion, scanning electron microscopy, image analysis and permeability. The obtained data of the flow-through pore sizes and porosity values as well as surface-to-volume ratio of the stationary phase skeleton enabled to predict their influence to the chromatographic separation efficiency. Our data demonstrate that mercury porosimetry is a reliable technique to obtain all the characteristic parameters of the flow-through pores of silica monoliths. An important result of our examination was that the surface-to-volume ratio of monolithic silica skeletons had more significant impact to the separation process, rather than the average flow-through pore sizes. We could also show the essential differences between the particulate and monolithic stationary phases based on theoretical computation. The results, obtained from other characterization methods also indicated the structural complexity of monolithic silica samples. Permeability of columns is a generally applicable parameter to characterize all chromatographic phases no matter the chemistry or format. The correlation coefficient obtained for mercury intrusion and permeability of water was 0.998, though our investigation revealed that the surface modification is more likely influencing the obtained results. Further, the assumption of the cylindrical morphology of flow-through pores is not relevant to the investigated monolithic silica columns. These results on the morphology of the flow-through pores and of the skeletons were confirmed by the image analysis as well. Our main finding is that the flow-through pore sizes are not relevant for the estimation of the chromatographic separation efficiency of monolithic silica columns.

Production of pellets via extrusion-spheronisation without the incorporation of microcrystalline cellulose: a critical review.

Microcrystalline cellulose (MCC) is the golden standard to manufacture spherical particles (pellets) via extrusion-spheronisation since wetted microcrystalline cellulose has the proper rheological properties, cohesiveness and plasticity to yield strong and spherical particles. However, microcrystalline cellulose is not universally applicable due to a number of limitations: prolonged drug release of poorly soluble drugs, chemical incompatibility with specific drugs, drug adsorption onto MCC fibers. Hence, several products have been evaluated to explore their application as extrusion-spheronisation aid, aiming to avoid the disadvantages of MCC and to provide a broad application platform for extrusion-spheronisation: powdered cellulose, starch, chitosan, kappa-carrageenan, pectinic acid, hydroxypropylmethyl cellulose, hydroxyethyl cellulose, polyethylene oxide, cross-linked polyvinylpyrrolidone, glycerol monostearate. To determine the true potential of the proposed alternatives for MCC this review critically discusses the properties of the different materials and the quality of the resulting pellets in relation to the properties required for an ideal extrusion-spheronisation aid.

Textural characterization of native and n-alky-bonded silica monoliths by mercury intrusion/extrusion, inverse size exclusion chromatography and nitrogen adsorption.

Native and n-alkyl-bonded (n-octadecyl) monolithic silica rods with mesopores in the range between 10 and 25 nm and macropores in the range between 1.8 and 6.0 microm were examined by mercury intrusion/extrusion, inverse size exclusion chromatography (ISEC) and nitrogen sorption. Our results reveal very good agreement for the mesopore size distribution obtained from nitrogen adsorption (in combination with an advanced NLDFT analysis) and ISEC. Our studies highlight the importance of mercury porosimetry for the assessment of the macropore size distribution and show that mercury porosimetry is the only method which allows obtaining a combined and comprehensive structural characterization of macroporous/mesoporous silica monoliths. Our data clearly confirm that mercury porosimetry hysteresis and entrapment have different origin, and indicate the intrinsic nature of mercury porosimetry hysteresis in these silica monoliths. Within this context some silica monoliths show the remarkable result of no entrapment of mercury after extrusion from the mesopore system (i.e. for the first intrusion/extrusion cycle). The results of a systematic study of the mercury intrusion/extrusion behavior into native silica monoliths and monoliths with bonded n-alkyl groups reveals that the macro (through) pore structure, which controls the mass transfer to and from the mesopores, here mainly controls the entrapment behavior. Our data suggest that mercury intrusion/extrusion porosimetry does not only allow to obtain a comprehensive pore structure analysis, but can also serve as a tool to estimate the mass transport properties of silica monoliths to be employed in liquid-phase separation processes.

Ammonia adsorption on nanostructured silica materials for hydrogen storage and other applications.

Our focus in the present study is to apply high specific surface area silica nanostructured porous materials (about 2200 m2/g, as synthesized, and 600-700 m2/g, after stabilization) to adsorb ammonia (NH3) for hydrogen storage and other chemical and pollution abatement applications. We describe here the synthesis, and characterization of these silica materials, and the adsorption study of N2 and NH3. These materials were obtained with the help of a modification of the Stöber-Fink-Bohn (SFB) method. The main change, made here to the SFB method, was the use of amines, i.e., triethylamine as catalysts instead of ammonium hydroxide. The silica materials have been characterized with the help of SEM and FTIR Spectrometry. The N2 adsorption study was carried out with the help of the Quantachrome-Autosorb-1 and the NH3 adsorption with the Quantachrome-Autosorb-l-C. The amount of hydrogen adsorbed in the form of NH3 in the studied silica samples at: P=760 [Torr] (1.01325 x 10(5) [Pa]), was 2 [wt.%] and the amount of hydrogen stored in the form of NH3 at about: P=7500 [Torr] (10.0 x 10(5) [Pa]), in the studied stabilized silica samples was 11 wt.%, a magnitude higher than the goal figure of 6.5 [wt.%] established by the United States of America, Department of Energy.

Mercury porosimetry in mesoporous glasses: a comparison of experiments with results from a molecular model.

We present results from experiments and molecular modeling of mercury porosimetry into mesoporous Vycor and controlled pore glass (CPG) solid materials. The experimental intrusion/extrusion curves show a transition from a type H2 hysteresis for the Vycor glass to a type H1 hysteresis for the CPG. Mercury entrapment is observed in both materials, but we find that the amount of entrapped mercury depends on the chosen experimental relaxation time. No additional entrapment is found in a second intrusion/extrusion cycle, but hysteresis is still observed. This indicates that hysteresis and entrapment are of different origin. The experimental observations are qualitatively reproduced in theoretical calculations based on lattice models, which provide significant insights of the molecular mechanisms occurring during mercury porosimetry experiments in these porous glasses.

Modeling mercury porosimetry using statistical mechanics.

We consider mercury porosimetry from the perspective of the statistical thermodynamics of penetration of a nonwetting liquid into a porous material under an external pressure. We apply density functional theory to a lattice gas model of the system and use this to compute intrusion/extrusion curves. We focus on the specific example of a Vycor glass and show that essential features of mercury porosimetry experiments can be modeled in this way. The lattice model exhibits a symmetry that provides a direct relationship between intrusion/extrusion curves for a nonwetting fluid and adsorption/desorption isotherms for a wetting fluid. This relationship clarifies the status of methods that are used for transforming mercury intrusion/extrusion curves into gas adsorption/desorption isotherms. We also use Monte Carlo simulations to investigate the nature of the intrusion and extrusion processes.

In vitro studies on lymphocytotoxicity to synovial cells and Chang cells in rheumatoid arthritis patients and healthy controls.

Lymphocytotoxicity to autologous or allogeneic synovial cells and Chang cells was studied in 27 patients with rheumatoid arthritis (RA), in 5 patients with osteoarthrosis of the hip or knee and in 17 healthy controls. Ficoll gradient-separated lymphocytes from the peripheral blood, T cells and non-T cells were used as effector cells. T lymphocytes were isolated as E-rosette forming cells 10 percent of which carried Fc- receptors. The differential counts for T and B cells in the peripheral blood of the RA and osteoarthrosis patients were approximately the same as in the blood of the healthy controls. The counts of Fc-receptor-bearing cells in the RA patients were, however, significantly higher. Cytotoxic reactivity of lymphocytes from RA patients, osteoarthrosis patients or healthy controls to synovial cells of autologous or allogeneic origin could not be demonstrated in our study, in which 125I-iododeoxyuridine labelled target cells were used in the microcytotoxicity test of Cohen et al. However, lymphocytes of the peripheral blood showed an increased cytotoxicity to Chang cells, an effect for which Fc-receptor bearing cells were responsible. Serum did not affect the cytotoxicity of lymphocytes. The results are interpreted as demonstrating an enhanced natural killer (NK) cell activity in RA patients; they do not indicate a specific cell mediated immune reaction to synovial cells.