Mechanical failure of the intramedullary hip screw in a subtrochanteric femoral fracture

The Gamma nail, an implant specifically designed for intertrochanteric and subtrochanteric femoral fractures, has been criticized for its high risk of secondary shaft fractures. A modified design, the intramedullary hip screw has recently been introduced to correct this complication. We present a case of mechanical failure of this new implant that occurred in a pathological subtrochanteric fracture. The centering sleeve of the implant became loose and migrated while the head screw penetrated the acetabulum. Refixation was successful.     

How to construct small probabilistic roadmaps with a good coverage?

We investigate how we can construct small probabilistic roadmaps in a reasonable time while still keeping a good coverage and connectivity. We propose a new neighborhood-based method that can reduce the size of the roadmaps by filtering out unnecessary nodes. We then experimentally test it against a basic probabilistic roadmap planner and a visibility-based planner. We use both a uniform sampling and a bridge test sampling in our tests. The results show that the neighborhood-based method can reduce the number of nodes considerably. The neighborhood-based method is simple to implement, it works well with a uniform sampling, and it does not need any additional parameters when compared with the basic planner.     

Endometrial cancer cell lines are sensitive to paclitaxel

We have previously reported a 24 fold difference in the cisplatin sensitivity and a 12 fold difference in carboplatin sensitivity of endometrial carcinoma cell lines. In this study as evaluate paclitaxel sensitivity of the same cell lines. We tested nine endometrial cancer cell lines with the 96-well plate clonogenic assay using limiting dilution. The chemosensitivity was expressed as IC50 value, the drug concentration causing 50% inhibition of clonogenic survival. IC50 values were obtained from dose-response curves after fitting the data to the linear quadratic equation. The IC50 values for paclitaxel were 0.49 - 2.3 nM showing only a 4.7 fold difference between various cell lines. No correlation could be demonstrated between in vitro paclitaxel and platinum analog sensitivities of endometrial adenocarcinoma cell lines. The variance in paclitaxel sensitivity of different cell lines was little. Our results suggest that endometrial adenocarcinoma cell lines tested with the same methods. The clinical efficacy of paclitaxel in the treatment of endometrial cancer should further be evaluated in clinical trials.     

Visualization of a pharmaceutical unit operation: wet granulation

Recent developments in the field of process engineering and manufacturing sciences enable a new level of process understanding. However, extracting this understanding from increasing amounts of information is challenging. The aim of this study was to create a process vector from a model process describing all relevant information and, by that means, create a tool for combining and visualizing this information. Physical (impeller torque and temperature) and chemical (near-infrared spectroscopy) information from a small-scale high-shear granulation was used in the process vector. The vectors created were visualized by two different methods: principal component analysis (PCA) and the self-organizing map (SOM). None of the individual measurement techniques were able to describe the state of the process alone, although they provided important information about the process. By combining the data and visualizing it, an overview could be achieved. The SOM approach had two advantages over the PCA: it presented the results in terms of the original variables and enabled the analysis of nonlinear responses. However, both visualization methods could be used to describe the progress of the process and to increase the level of process understanding.     

Investigation of the phase separation of PNIPAM using infrared spectroscopy together with multivariate data analysis

The use of vibrational spectroscopy to investigate complex structural changes in polymers yields chemically rich data, but interpretation can be challenging and subtle but meaningful spectral changes may be missed through visual inspection alone. Multivariate analysis is an efficient approach to gain an oversight of small but systematic spectral differences anywhere within the spectra, providing further insight into structural changes and associated transformation mechanisms. In this study, the novel analytical approach of infrared spectroscopy combined with principal component analysis and Gaussian peak fitting was used to investigate the structural changes in aqueous solutions of a polymer, using poly(N-isopropyl acrylamide) (PNIPAM) in the atactic form and with controlled tacticity as a model system. Subtle spectral changes associated with the dehydration and phase separation upon heating included peak shifts, an area ratio change of the amide I band to the amide II band and formation of a new peak in the amide I band were efficiently detected. Dehydration and phase separation of PNIPAM occurred in two temperature ranges, one for the atactic and one for isotactic rich part, both involving a complex re-organization of the hydrogen bonds and change of the hydration layer. The changes agreed with existing results from other techniques, and new insights were gained into the effect of controlled tacticity on phase transformation behaviour. The study demonstrates that infrared spectroscopy combined with the multivariate analytical method principal component analysis and Gaussian peak fitting is an efficient approach to probing structural change in polymers during heating. The simplicity of the presented approach could find excellent use in analysing and understanding the molecular environment of a range of stimuli-responsive polymers, for instance block or grafted types of polymers, as well as those with controlled tacticity.     

600 MHz direct modulation of short external cavity wavelength-tunable diode laser

The current modulation characteristics of a short external cavity tunable laser are presented. The 1540 nm Fabry-Perot diode laser is wavelength-tuned by the electrostatically controlled silicon micromachined Fabry-Perot interferometer device. The measured -3 dB cutoff frequency of 600 MHz is the widest reported direct modulation bandwidth of the external cavity tunable laser.     

Racial differences in muscle strength in disabled older women

This study examines racial differences in muscle strength, and associations of muscle strength to level of physical activity and severity of disability, among a community sample of 254 black and 665 white, moderately to severely disabled women aged 65 and older. Potential confounders that were adjusted for in the models included age, body weight and height, joint pain, number of chronic conditions, and socioeconomic status. Hand grip, hip flexion, and knee extension forces were measured using portable hand-held dynamometers in the participants' homes. Hand grip strength was measured as the maximal isometric force. Hip flexion and knee extension forces were measured as the greatest force the tester had to apply to break the isometric contraction. A declining strength gradient was observed with increasing severity of disability and for decreasing level of physical activity in both races. At equal levels of disability or physical activity, blacks had better hand grip and hip flexion strength, but knee extension strength did not differ by race. The greater hand grip and hip flexion strength found in black women may be related to their greater muscle mass and known racial differences in body dimensions. No consistent racial differences were observed in the relationship between physical activity and muscle strength, or muscle strength and disability, suggesting that the role of muscle strength in the disablement process does not differ between races. Physical activity and exercise programs may be feasible ways to prevent worsening of disability in blacks and whites.     

Implementation of a process analytical technology system in a freeze-drying process using Raman spectroscopy for in-line process monitoring

The aim of the present study was to propose a strategy for the implementation of a Process Analytical Technology system in freeze-drying processes. Mannitol solutions, some of them supplied with NaCl, were used as models to freeze-dry. Noninvasive and in-line Raman measurements were continuously performed during lyophilization of the solutions to monitor real time the mannitol solid state, the end points of the different process steps (freezing, primary drying, secondary drying), and physical phenomena occurring during the process. At-line near-infrared (NIR) and X-ray powder diffractometry (XRPD) measurements were done to confirm the Raman conclusions and to find out additional information. The collected spectra during the processes were analyzed using principal component analysis and multivariate curve resolution. A two-level full factorial design was used to study the significant influence of process (freezing rate) and formulation variables (concentration of mannitol, concentration of NaCl, volume of freeze-dried sample) upon freeze-drying. Raman spectroscopy was able to monitor (i) the mannitol solid state (amorphous, alpha, beta, delta, and hemihydrate), (ii) several process step end points (end of mannitol crystallization during freezing, primary drying), and (iii) physical phenomena occurring during freeze-drying (onset of ice nucleation, onset of mannitol crystallization during the freezing step, onset of ice sublimation). NIR proved to be a more sensitive tool to monitor sublimation than Raman spectroscopy, while XRPD helped to unravel the mannitol hemihydrate in the samples. The experimental design results showed that several process and formulation variables significantly influence different aspects of lyophilization and that both are interrelated. Raman spectroscopy (in-line) and NIR spectroscopy and XRPD (at-line) not only allowed the real-time monitoring of mannitol freeze-drying processes but also helped (in combination with experimental design) us to understand the process.     

Upconversion fluorescence resonance energy transfer in a homogeneous immunoassay for estradiol

We recently described a novel homogeneous assay principle based on upconversion fluorescence resonance energy transfer (UC-FRET), where an upconverting phosphor (UCP) is utilized as a donor. The UC-FRET has now been applied to a competitive homogeneous immunoassay for 17beta-estradiol (E2) in serum, using a small-molecular dye as an acceptor. The assay was constructed by employing an UCP coated with an E2-specific recombinant antibody Fab fragment as a donor and an E2-conjugated small-molecular dye, Oyster-556, as an acceptor. Standard curves for the assay were produced both in buffer and in male serum. Sensitized acceptor emission was measured at 600 nm under continuous laser diode excitation at 980 nm. In buffer, the IC50 value of the assay was 1 nM and in serum 3 nM. The lower limits of detection (mean of zero calibrators, 3 SD) were 0.4 and 0.9 nM, respectively. The measurable concentration range extended up to 3 nM in buffer and 9 nM in serum. Equilibrium in the assay was reached in 30 min. The novel principle of UC-FRET has unique advantages compared to present homogeneous luminescence-based methods and can enable an attractive assay system platform for clinical diagnostics and for high-throughput screening approaches.