The development of fermentation processes for recombinant vaccines requires optimizing expression while maintaining high product quality. Changes to cell fermentation conditions are typically ...evaluated following cell disruption, with expression levels quantified by immunoassay, liquid chromatography or enzyme activity. However, assay titres do not always predict the effects that intracellular aggregation, proteolysis, post‐translational modifications and differences in relative impurity levels can have on purification yield and product purity. Furthermore, heterogeneity in the size and surface properties inherent in viral particles makes unit operations such as chromatography less predictable. In these cases, the purification procedure (or a mimic thereof) must be carried out to give accurate information on the impact of changes in fermentation conditions on purification process performance. This was demonstrated for the development of a recombinant vaccine against human papillomavirus produced in Saccharomyces cerevisiae, where the most informative feedback on fermentation variables was obtained by completing a multistep chromatographic purification to evaluate process yield and product purity. To increase the purification throughput and reduce labour, the chromatography was miniaturized 1000‐fold from the laboratory scale using microlitre volumes of adsorbent in a pipette tip and automated on a robotic workstation. The microscale purification is shown to be predictive of the laboratory‐scale purification in terms of yield and purity, while providing over a 10‐fold increase in throughput and allowing for increased monitoring of fermentation processes. In addition, by reducing the volume of cells needed for this assessment, the fermentation can be correspondingly reduced in scale and carried out in parallel for additional throughput gains.
Surgery for locally extensive carcinomas of the thyroid gland Price, Daniel L., MD; Shah, Jatin P., MD, PhD(Hon), FACS, FRCS(Hon), FDSRCS(Hon), FRACS(Hon)
Operative techniques in otolaryngology--head and neck surgery,
03/2009, Letnik:
20, Številka:
1
Journal Article
Recenzirano
Extrathyroidal extension of well-differentiated thyroid carcinoma has a significant impact on survival, reducing 10 year survival in half, and is associated with high rates of local, regional and ...distant recurrence. Up to 13% of patients with well-differentiated thyroid cancer will have extrathyroidal extension, and many of these will be asymptomatic, making thorough preoperative patient evaluation critical. The most commonly involved structures are the strap muscles, and the recurrent laryngeal nerve. The trachea, esophagus and larynx are involved less frequently. Complete surgical excision is the mainstay of treatment, and there are several important principles which should be followed. All gross disease should be removed, with preservation of functioning and vital structures when feasible. Tumors with extrathyroidal extension frequently harbor more aggressive subtypes such as Hürthle cell carcinoma, tall cell variants of papillary carcinoma or even poorly differentiated carcinoma. Because these variants are frequently less radioactive iodine avid, complete surgical resection is paramount. However, adjuvant therapy with radioactive iodine and external beam radiation are invariably needed. This article describes various surgical techniques for resection of thyroid cancer with extra thyroid extension.
Parallel magnetic resonance imaging (MRI) techniques use spatial information from arrays of radiofrequency (RF) detector coils to accelerate imaging. A number of parallel MRI techniques have been ...described in recent years, and numerous clinical applications are currently being explored. The advent of practical parallel imaging presents various challenges for image reconstruction and RF system design. Recent advances in tailored SiMultaneous Acquisition of Spatial Harmonics (SMASH) image reconstructions are summarized. These advances enable robust SMASH imaging in arbitrary image planes with a wide range of coil array geometries. A generalized formalism is described which may be used to understand the relations between SMASH and SENSE, to derive typical implementations of each as special cases, and to form hybrid techniques combining some of the advantages of both. Accurate knowledge of coil sensitivities is crucial for parallel MRI, and errors in calibration represent one of the most common and the most pernicious sources of error in parallel image reconstructions. As one example, motion of the patient and/or the coil array between the sensitivity reference scan and the accelerated acquisition can lead to calibration errors and reconstruction artifacts. Self-calibrating parallel MRI approaches that address this problem by eliminating the need for external sensitivity references are reviewed. The ultimate achievable signal-to-noise ratio (SNR) for parallel MRI studies is closely tied to the geometry and sensitivity patterns of the coil arrays used for spatial encoding. Several parallel imaging array designs that depart from the traditional model of overlapped adjacent loop elements are described.
Coil-by-coil image reconstruction with SMASH McKenzie, Charles A.; Ohliger, Michael A.; Yeh, Ernest N. ...
Magnetic resonance in medicine,
September 2001, Letnik:
46, Številka:
3
Journal Article
We present the case of a 57-yr-old patient who suffered an unexplained cerebrovascular event 3 days after being struck by a motor vehicle. Workup demonstrated a previously unknown patient foramen ...ovale. The etiologies of paradoxical embolism in trauma are discussed.
To determine the correlates of the lability of peak expiratory flow (PEF) in the elderly.
A community sample of 4,581 persons ≥ 65 years old from the Cardiovascular Health Study completed an asthma ...questionnaire and underwent spirometry. During a follow-up examination of the cohort, 1,836 persons agreed to measure PEF at home twice daily for 2 weeks, and 90% successfully obtained at least 4 days of valid measurements. PEF lability was calculated as the highest daily (PEF maximum − PEF minimum)/mean PEF.
Mean PEF measured at home was accurate when compared to PEF determined by spirometry in the clinic. Mean PEF lability was 18% in those with current asthma (n = 165) vs 12% in healthy nonsmokers (upper limit of normal, 29%). Approximately 26% of those with asthma and 14% of the other participants had abnormally high PEF lability (> 29%). After excluding participants with asthma, other independent predictors of high PEF lability included black race, current and former smoking, airway obstruction on spirometry, daytime sleepiness, recent wheezing, chronic cough, emphysema, and wheezing from lying in a supine position. Despite having a lower mean PEF, those reporting congestive heart failure (n = 82) did not have significantly higher PEF lability.
Measurement of PEF lability at home is highly successful in elderly persons. PEF lability ≥ 30% is abnormal in the elderly and is associated with asthma.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To determine if lesser snow geese (Chen caerulescens caerulescens) are a potential reservoir for the Pasteurella multocida bacterium that causes avian cholera, serum samples and/or pharyngeal swabs ...were collected from >3,400 adult geese breeding on Wrangel Island (Russia) and Banks Island (Canada) during 1993–1996. Pharyngeal swab sampling rarely (>0.1%) detected birds that were exposed to P. multocida in these populations. Geese with serum antibody levels indicating recent infection with P. multocida were found at both breeding colonies. Prevalence of seropositive birds was 3.5% at Wrangel Island, an area that has no recorded history of avian cholera epizootics. Prevalence of seropositive birds was 2.8% at Banks Island in 1994, but increased to 8.2% during 1995 and 1996 when an estimated 40,000–60,000 snow geese were infected. Approximately 50% of the infected birds died during the epizootic and a portion of the surviving birds may have become carriers of the disease. This pattern of prevalence indicated that enzootic levels of infection with P. multocida occurred at both breeding colonies. When no avian cholera epizootics occurred (Wrangel Island, Banks Island in 1994), female snow geese (4.7%) had higher antibody prevalence than males (2.0%).
A 400-MHz S/390 microprocessor Webb, C.F.; Anderson, C.J.; Sigal, L. ...
IEEE journal of solid-state circuits,
1997-Nov., 1997-11-00, 19971101, Letnik:
32, Številka:
11
Journal Article
Recenzirano
A microprocessor implementing IBM S/390 architecture operates in a 10+2 way system at frequencies up to 411 MHz (2.43 ns). The chip is fabricated in a 0.2-/spl mu/m L/sub eff/ CMOS technology with ...five layers of metal and tungsten local interconnect. The chip size is 17.35 mm/spl times/17.30 mm with about 7.8 million transistors. The power supply is 2.5 V and measured power dissipation at 300 MHz is 37 W. The microprocessor features two instruction units (IUs), two fixed point units (FXUs), two floating point units (FPUs), a buffer control element (BCE) with a unified 64-KB L1 cache, and a register unit (RU). The microprocessor dispatches one instruction per cycle. The dual-instruction, fixed, and floating point units are used to check each other to increase reliability and not for improved performance. A phase-locked-loop (PLL) provides a processor clock that runs at 2/spl times/ the system bus frequency. High-frequency operation was achieved through careful static circuit design and timing optimization, along with limited use of dynamic circuits for highly critical functions, and several different clocking/latching strategies for cycle time reduction. Timing-driven synthesis and placement of the control logic provided the maximum flexibility with minimum turnaround time. Extensive use of self-resetting CMOS (SRCMOS) circuits in the on-chip L1 cache provides a 2.0-ns access time and up to 500 MHz operation.
This study investigated the reliability and validity of the Capacity for Dynamic Process Scale (CDPS; Thackrey, Butler, & Strupp, 1993) as well as the relationship of this scale to therapeutic ...alliance and termination in an outpatient sample. The sample consisted of 38 outpatients who were admitted over a 22-month period at a university-based community psychological clinic. The results of this study indicated that the CDPS can be reliably scored and is internally consistent. In addition, the CDPS showed discriminant validity based on Diagnostic and Statistical Manual of Mental Disorders (fourth edition; DSM-IV American Psychiatric Association, 1994) scales of functioning and other self-report measures of psychopathology. The CDPS was also significantly related to clinician-rated therapeutic alliance during evaluation and could be used effectively to differentiate between those patients who terminated psychotherapy and those who continued treatment. These results support the reliability and validity of the CDPS in relation to the engagement of patients in outpatient psychodynamic psychotherapy.
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