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175 years at The Lancet. The editors.

The founder of The Lancet, Thomas Wakley, is well known as a powerful figure whose outspoken and radical views dominated the journal over many decades. His influence went beyond his own term as editor, as the journal was handed first to one son, then the other, and finally to his grandson. The Wakley dynasty ran the journal for 85 years but the 20th century demanded new approaches, and a series of remarkable men took charge of the journal and steered it through the fast-changing world of medicine and journalism. Continuity was maintained by the practice of appointing, In most cases, from within the existing staff of the journal. The story of the editors is the story of the journal itself. These were men of their time--no women so far--who stamped their own ideas on the journal, but who did so within the framework of reliable and radical reporting which the Wakleys established. There have been only 12 editors during the journal's 175-year existence, and their biographies provide a rare insight into the interface between personal qualities and professional achievements during this period.

England↗

Microcontact printing of novel co-polymers in combination with proteins for cell-biological applications.

Microcontact printing (microcP) is a cost effective and simple method to create chemically micropatterned surfaces for cell biological applications. We have combined the technique with the spontaneous molecular assembly of a polycationic PEG-grafted copolymer, poly-L-lysine-g-poly(ethylene glycol) (PLL-g-PEG). PLL-g-PEG with omega-functionalized PEG chains was print-transferred onto tissue culture polystyrene (TCPS) or glass substrates, resulting in patterns with a lateral resolution down to 1 microm. Subsequently, dipping in an aqueous solution of non-functionalized PLL-g-PEG was used to backfill the non-printed regions of the surface, rendering them highly protein and thus cell resistant. In a second approach, proteins were stamped and a PLL-g-PEG backfill was applied for passivation of the bare surface regions. Printing of peptide(RGD)-functionalized PLL-g-PEG or proteins combined with a subsequent PLL-g-PEG backfill can be applied to a wide variety of substrate materials with negatively charged surfaces such as TCPS, glass and many metal oxides. We have tested the printed surfaces with human foreskin fibroblasts for cell adhesion and long-term performance and with fish epidermal keratocytes for cell motility and short-time behaviour. Both cell types reacted selectively to the surface micropatterns. Fibroblasts adhered to the printed (adhesive) regions only, where they remained attached up to at least 1 week and were even able to proliferate. Keratocyte spreading and motility were also directed by the geometry of the underlying patterns. The results prove that microcP in conjunction with the use of PLL-g-PEG and its derivatives provides a simple and robust alternative to previously reported micropatterning methods for future cell biological and biotechnological applications.

Animals↗

Patterning proteins and cells using soft lithography.

This review describes the pattering of proteins and cells using a non-photolithographic microfabrication technology, which we call 'soft lithography' because it consists of a set of related techniques, each of which uses stamps or channels fabricated in an elastomeric ('soft') material for pattern transfer. The review covers three soft lithographic techniques: microcontact printing, patterning using microfluidic channels, and laminar flow patterning. These soft lithographic techniques are inexpensive, are procedurally simple, and can be used to pattern a variety of planar and non-planar substrates. Their successful application does not require stringent regulation of the laboratory environment, and they can be used to pattern surfaces with delicate ligands. They provide control over both the surface chemistry and the cellular environment. We discuss both the procedures for patterning based on these soft lithographic techniques, and their applications in biosensor technology, in tissue engineering, and for fundamental studies in cell biology.

Animals↗

Critical care nursing education at the baccalaureate level: study of employment and job satisfaction.

OBJECTIVE: To examine the employment patterns of nurses who completed an undergraduate course in critical care nursing (CCN); examine the impact of the course on job satisfaction; and compare the job satisfaction of critical care nurses who completed a course at the baccalaureate level and a control group of nurses in critical care who did not have these educational experiences. DESIGN: Descriptive. SETTING: Ten hospitals in the midwest in which graduates of a CCN course at the BSN level were in practice. SUBJECTS: There were two groups of participants: 42 nurses prepared at the undergraduate level for critical care and 59 critical care nurses from the same units. OUTCOME MEASURES: Employment patterns and job satisfaction measured by Stamps and Piedmonte's Index of Work Satisfaction instrument. RESULTS: Most (n = 33, 78.6%) graduates entered critical care as their first position in nursing. At the time of follow-up, these graduates remained in CCN practice. The findings suggested that completion of an undergraduate course enabled students to enter critical care as new graduates. Results of a Mann-Whitney U test indicated no differences in job satisfaction between nurses who remained in critical care and those practicing in non-critical care units. There were no significant differences in total job satisfaction or in any of its component scores between graduates of the course and the control group of critical care nurses. Both groups were least satisfied with pay and most satisfied with their interactions with others on the unit. CONCLUSIONS: Although educational experiences in critical care at the undergraduate level did not influence job satisfaction, other benefits of this education were suggested by the findings. Completion of an undergraduate CCN course enabled graduates to enter critical care as their first practice position.

Adult↗

The prisoners of despair: right hemisphere deficiency and suicide.

This paper presents an integrative approach to understanding of the inner experience of suicidal persons in terms of hemispheric asymmetry. The right hemisphere is involved in formation of polysemantic context. Polysemantic context is determined by multiple interconnections among its elements, while each concrete element bears the stamp of the whole context. Left hemisphere functioning leads to formation of monosemantic context. It is suggested that due to functional insufficiency of the right hemisphere the suicidal person demonstrates a compensatory shift to left hemisphere functioning. This shift manifests itself in reversed asymmetry of neurotransmitters, tendency to dissociation, alienated and negative perception of the body, lower sensitivity to pain, disintegration of self-representation, cognitive constriction, overly general nature of personal memories, difficulties in affect regulation as well as such personality traits as low openness to experience and personal constriction. This hypothesis raises a number of suggestions for future research.

Brain↗

A new inexpensive customized plaque for choroidal melanoma iodine-125 plaque therapy.

The authors have developed a new inexpensive precious metal alloy plaque for use in customized iodine-125 plaque therapy. Each plaque is formed from two flat circular gold/palladium foils which are used in dental crown work. Using a simple manual mechanism, the two forms are stamped over a customized acrylic die shaped to the dimensions of the tumor base plus a 2-mm margin. Completed plaques consist of a back wall, a 2-mm side wall, and a 1.5-mm wide lip with holes for suture placement. Advantages include: simple construction from inexpensive components, customized shape, and iodine seeds that are readily visible on plane radiographs.

Brachytherapy↗

Digital video: a tool for correlating neuronal firing patterns with hand motor behavior.

This report describes the use of multimedia technology for simultaneous recording of single unit responses in cerebral cortex, and imaging of hand kinematics as monkeys grasp and manipulate objects. These imaging methods allow direct correlation of full-frame, full-field video images with the actual spike trains recorded with microelectrodes. Our implementation of digital video provides high-resolution snapshots of the hand motor behavior every 33.3 ms, and a precise calibration and display of the synchronously recorded electrophysiological activity digitized at rates up to 44.5 kHz on the same platform. These imaging methods permit non-invasive, non-traumatic monitoring of both trained and spontaneous activity in experimental animals, while providing synchronized digitized records of neuronal spike trains. We also describe software instruments that quantify and analyze the digitized spike trains. One instrument employs user-selectable objective criteria for distinguishing spikes from noise, separates individual action potential waveforms by their amplitude and duration, and compiles time stamps for each spike train. A second instrument constructs rasters and histograms of repeated behavioral trials using the timing of the corresponding video frame for alignment. These analyses reveal functional classes of cortical neurons signaling specific stages of prehension.

Animals↗

Development of a novel real-time RT-PCR assay for quantitation of foot-and-mouth disease virus in diverse porcine tissues.

Pigs are more difficult to immunise and more variable in their response to foot-and-mouth disease (FMD) than other livestock species. This has important consequences for FMD control during both prophylactic vaccination programmes in endemic situations and when emergency vaccination may be used as an adjunct to stamping out during outbreaks in countries normally free from the disease. The rapid and effective control of FMD in pigs is especially important in regions of high pig density since infected pigs have the potential to generate plumes of airborne virus and spread infection beyond the immediate control area. Increased knowledge of the kinetics of FMDV replication in pigs, especially in their respiratory tracts, could create opportunities for strategies to improve FMD vaccines for pigs. A fluorogenic TaqMan RT-PCR assay specific for the IRES (internal ribosome entry site) sequence of the O(1) Kaufbeuren/Lausanne strain of FMDV has been developed for this purpose. The assay had a sensitivity of 0.1 TCID(50)/ml, and a dynamic range of at least eight orders of magnitude. It was found that an established method of quantitation, relative to a housekeeping gene, exhibited two significant shortcomings when applied to a set of 16 anatomically highly diverse solid tissues: (i) tissue differences in housekeeping gene expression caused errors of up to 60-fold in estimated FMDV concentrations; and (ii) variability in total RNA yields caused unpredictable saturation of RT reactions, which in turn caused errors of up to 250-fold in the estimated FMDV concentration. A novel quantitation strategy, designated the C(t)(min) method, was developed to overcome these problems. The C(t)(min) method was based on the the RT-PCR examination of a dilution series of spectrophotometrically quantitated total RNA, spanning the optimum for the RT-PCR system used. The new method was influenced minimally by any tissue-specific RT-PCR inhibitors and was used to determine FMDV concentrations in tissues from four experimentally infected pigs. The results suggest that the lungs play a less important role in the replication of FMDV in pigs than was thought previously.

Animals↗

An extended state-transition model for foot-and-mouth disease epidemics in France.

The dynamics of foot-and-mouth disease epidemics in France was examined through simulations based on an extended state-transition model. Contagion modelling depended on specific parameters: the so-called dissemination rates. Estimation of these parameters relied on a specific discrete-event simulation model. We were able to address the problem of the hidden spread of the epidemic, before the first outbreak is diagnosed. Furthermore, we took into account the silent development of the disease in affected herds before the diagnosis. The effect of control measures such as the active search for secondary outbreaks could thus be studied. We used the model to compare the development of FMD epidemics in two very different French regions and for different control strategies implemented by the animal-health authorities. These strategies gave similar results in a low herd density area, whereas in a high herd density area, the slaughter of contact herds greatly improved the stamping-out strategy. Finally, key parameters of the model were detected through a sensitivity analysis.

Animals↗

Simulated economic consequences of foot-and-mouth disease epidemics and their public control in France.

The efficient management of foot-and-mouth disease (FMD) epidemics in France was examined through a simulation model which combines epidemiological and economic modules. From the reactions of the importing countries in terms of the products subject to import bans and the regionalization commitments, the economic module assesses the financial consequences of FMD outbreaks borne not only by the breeding sector but also by the other economic sectors on regional and national levels. Among the control options for FMD, the strategy of stamping out infected herds and dangerous in-contact herds most often contributes to reducing the economic consequences of FMD epidemics. Implementing a campaign of emergency vaccination is socially optimal if the additional export losses associated with the delay of slaughtering the vaccinated animals are offset by the gains of reducing the duration of the FMD epidemic. The importance of reducing as much as possible the total duration of the import bans is stressed by the estimated cost of an extra week of import bans. The optimal control strategy was unaffected by the introduction of stochastic parameters.

Animals↗

A decision-tree to optimise control measures during the early stage of a foot-and-mouth disease epidemic.

A decision-tree was developed to support decision making on control measures during the first days after the declaration of an outbreak of foot-and-mouth disease (FMD). The objective of the tree was to minimise direct costs and export losses of FMD epidemics under several scenarios based on livestock and herd density in the outbreak region, the possibility of airborne spread, and the time between first infection and first detection. The starting point of the tree was an epidemiological model based on a deterministic susceptible-infectious-recovered approach. The effect of four control strategies on FMD dynamics was modelled. In addition to the standard control strategy of stamping out and culling of high-risk contact herds, strategies involving ring culling within 1 km of an infected herd, ring-vaccination within 1 km of an infected herd, and ring-vaccination within 3 km of an infected herd were assessed. An economic model converted outbreak and control effects of farming and processing operations into estimates of direct costs and export losses. Ring-vaccination is the economically optimal control strategy for densely populated livestock areas whereas ring culling is the economically optimal control strategy for sparsely populated livestock areas.

Animal Husbandry↗

A survey of Newcastle disease in Swiss laying-hen flocks using serological testing and simulation modelling.

Newcastle disease (ND) is a highly contagious viral disease of birds particularly domestic poultry. Switzerland is currently declared free from ND; since vaccination is prohibited, the detection of antibodies against ND virus (NDV) results in the destruction of the respective flock (stamping-out policy). However, in 1995 and 1996, antibody-positive flocks were detected and sporadic ND outbreaks even occurred in Switzerland. Therefore, a serosurvey was done to look for evidence of NDV infections in Swiss laying-hen flocks. The survey was designed to provide 95% confidence of detecting at least one seropositive flock if the flock prevalence were 1%. Thirty blood samples from each of 260 commercial laying-hen flocks were collected during 1996 in a central poultry slaughterhouse. Sera were screened for NDV antibodies with a commercial blocking enzyme-linked immunosorbent assay (ELISA). Samples with a questionable or positive test result were retested with the same ELISA. A stochastic computer model was applied to define a cut-off number of test-positive samples to help to differentiate between true- and false-positive flocks and to estimate the true flock prevalence of infection. Four flocks were identified as NDV-seropositive and the NDV true seroprevalence among commercial laying-hen flocks in Switzerland was most likely between 1.35 and 1.55%. This indicates that Swiss laying-hen and parental flocks with more than 150 animals have been in contact with strains of NDV that cause subclinical infection in chicken, because no clinical symptoms have been observed. In this context, computer simulation was a useful technique to interpret survey results.

Animals↗

The classical swine fever epidemic 1997-1998 in The Netherlands: descriptive epidemiology.

The objective of this paper is to describe the severe epidemic of classical swine fever (CSF) in The Netherlands in 1997-1998 under a policy of non-vaccination, intensive surveillance, pre-emptive slaughter and stamping out in an area which has one of the highest pig and herd densities in Europe. The primary outbreak was detected on 4 February 1997 on a mixed sow and finishing pig herd. A total of 429 outbreaks was observed during the epidemic, and approximately 700,000 pigs from these herds were slaughtered. Among these outbreaks were two artificial insemination centres, which resulted in a CSF-suspect declaration of 1680 pig herds (mainly located in the southern part of The Netherlands). The time between introduction of CSF virus (CSFV) into the country and diagnosis of CSF in the primary outbreak was estimated to be approximately 6 weeks. It is presumed that CSFV was spread from The Netherlands to Italy and Spain via shipment of infected piglets in the beginning of February 1997, before the establishment of a total stand-still of transportation. In June 1997, CSFV is presumed to be introduced into Belgium from The Netherlands. Pre-emptive slaughter of herds that had been in contact with infected herds or were located in close vicinity of infected herds, was carried out around the first two outbreaks. However, this policy was not further exercised till mid-April 1997, when pre-emptive slaughter became a standard operational procedure for the rest of the epidemic. In total, 1286 pig herds were pre-emptively slaughtered. (approximately 1.1 million pigs). A total of 44 outbreaks (10%) was detected via pre-emptive slaughter. When there were clinical signs, the observed symptoms in infected herds were mainly atypical: fever, apathy, ataxia or a combination of these signs. In 322 out of 429 outbreaks (75%), detection was bases on clinical signs observed: 32% was detected by the farmer, 25% by the veterinary practitioner, 10% of the outbreaks by tracing teams and 8% by screening teams of the veterinary authorities. In 76% of the outbreaks detected by clinical signs, the farmer reported to have seen clinical symptoms for less than 1 week before diagnosis, in 22% for 1-4 weeks before diagnosis, and in 4 herds (1%) the farmer reported to have seen clinical symptoms for more than 4 weeks before diagnosis. Transportation lorries played a major role in the transmission of CSFV before the primary outbreak was diagnosed. It is estimated that approximately 39 herds were already infected before the first measures of the eradication campaign came into force. After the first measures to stop the spread of CSFV had been implemented, the distribution of the most likely routes of transmission markedly changed. In most outbreaks, a neighbourhood infection was indicated. Basically, there were two reasons for this catastrophe. Firstly, there was the extent of the period between introduction of the virus in the region and detection of the first outbreak. As a result, CSFV had opportunities to spread from one herd to another during this period. Secondly, the measures initially taken did not prove sufficient in the swine- and herd-dense region involved.

Animal Husbandry↗

Classical swine fever in The Netherlands 1997-1998: a description of organisation and measures to eradicate the disease.

The central and regional organisation of the campaign to eradicate the CSF epidemic in The Netherlands in 1997/1998 is described. The main instruments used in the campaign were based on stamping-out and movement restrictions specified by the European Union. Additional instruments were used for the first time, namely, pre-emptive culling of contact and neighbouring farms, compartmentalisation of transport, monthly serological screening in established surveillance areas and supervised repopulation of all farms in the former surveillance zone. Two other measures, the killing of very young piglets and a breeding ban were introduced to reduce production in established surveillance zones. Several factors complicated the eradication campaign, for instance, the late detection of the first infection; artificial insemination as a source of infection; the organisation of pig farming in The Netherlands, with its highly concentrated production and dependence on the transport of stock from one unit to another; insufficient rendering capacity; decreasing sensitivity of clinical inspection; and extremely high costs.

Animal Husbandry↗

Development of an adhesive sheet for direct counting of bacteria on solid surfaces.

An adhesive sheet was developed for direct counting of microorganisms on solid surfaces. The sheet consists of a polyurethane film base and water insoluble adhesive. SYBR Green II (for total direct counting) or 6-carboxyfluorescein diacetate (6CFDA) (for fluorescent vital staining) was used for fluorescent microscopy of bacteria collected on the adhesive face of the sheet. Adhesive sheet sampling showed a higher recovery rate for microbial enumeration than conventional swab method or stamp agar. This method is simple, rapid, inexpensive and reproducible.

Adhesives↗

Preoperative cytodiagnosis of very small-sized peripheral-type primary lung cancer.

To demonstrate the importance of preoperative diagnosis of pulmonary cancers presenting as peripheral small-sized solitary shadows we evaluated the results of morphologic definitive diagnosis together with various clinical factors in 91 tumors with less than 15-mm diameter resected surgically between 1983 and 1999. Histologically, these tumors consisted of 73 adenocarcinomas, nine squamous cell carcinomas, and nine other types. Regarding the pathologic stage, 57 tumors were classified in stage IA, three in IB, six in IIA, seven in IIIA, 14 in IIIB, and four in IV. Comparing various biopsy techniques, the sensitivity of preoperative cytodiagnosis was 43.7% for transbronchial brushing (n = 48), 52.9% for transbronchial forceps biopsy-stamp cytology (n = 51), 66.6% for transbronchial fine needle aspiration (n = 78), and 85.0% for percutaneous fine needle aspiration (n = 20). The overall sensitivity of preoperative cytodiagnosis was 79.0% for transbronchial biopsy (n = 81), and 87.3% for transbronchial and percutaneous biopsy (n = 87). Of 73 clinical N0 cases in which lobectomy was performed, 10 cases (13.6%) were diagnosed as between pathological degrees N1, N2 and N3. However, lung cancer cases with less than 10-mm diameter did not have lymph node metastasis. Our study of histologic differentiation showed that all cases of well-differentiated adenocarcinomas (n = 20) were pathological degree N0. The overall sensitivity of preoperative diagnosis increased to 89.1% in cases (n = 74) of tumors with 11-15-mm diameter. The sensitivity of cytodiagnosis for peripheral small-sized primary lung cancers is high, and we can estimate histological differentiation based on the cytological findings. Therefore, cytodiagnosis is an effective and indispensable diagnostic method for determination of the optimal treatment approach, including approaches such as intentionally limited resection.

Adult↗

[Tissular and mechanical effects observed with an experimental femtosecond laser microkeratome for corneal refractive surgery].

PURPOSE: Despite progress in mechanical microkeratomes used in refractive surgery, mechanical complications during cutting of the cornea still occur. Cutting by laser could reduce these complications and to date, the femtosecond laser is the only potential candidate for this purpose. Our study reports preliminary results with a femtosecond microkeratome for cutting porcine corneas ex vivo. METHODS: We first examined the fundamental principles of the interaction between the femtosecond laser and the corneal stroma, including the volume of tissue lesions, the laser breakdown threshold of the stroma and the laser ablation selectivity. We then analyzed the quality of cutting corneal flaps with the laser, focusing on collateral tissue effects and the roughness of the interfaces observed both histologically and with scanning electron microscopy. RESULTS: The photoablative and photodisruptive effects were very similar with the femtosecond laser. This characteristic is specific to ultrashort impulsion photodisruptor lasers and allows for a very precise surgical procedure. The laser-induced breakdown threshold of porcine corneal stroma was found to be 0.55 J/cm2. Collateral tissue lesions were on the submicrometer level. The roughness of the stromal bed was optimal for postage stamp cutting, providing very many contiguous points of impact which were as spherical as possible. CONCLUSION: Corneal photodisruption with a femtosecond laser is reproducible and extremely accurate. The optomechanical parameters involved with this technique require great technological skill and should be placed in experienced hands.

Animals↗

[Advantages and disadvantages of the femtosecond laser microkeratome].

Laser in situ keratomileusis (LASIK) complications are mainly attributable to imperfect cutting with the mechanical microkeratome. The femtosecond laser is an important challenger because it can provide extremely precise cutting beginning at any corneal point. We analyze the potential of this new tool from the results reported in the literature. The optomechanical control of the impact position provides freer and more effective intrastromal cutting than the blade. The best cutting matrix is obtained with the postage stamp method. If the plasma quality is not perfectly under control, side effects such as tissue streaks and secondary ultraviolet radiations can be observed. For LASIK surgery, femtolaser cutting can offer greater safety, reproducibility, predictability and flexibility. The risk of incomplete or irregular cutting and the free cap risk are reduced. Striae, epithelial defects and interface deposits should be minimized. A better flap congruence can limit the risk of secondary displacement and epithelial ingrowth. The results of making thinner flaps should be more predictable. Other than the high cost of the procedure, laser cutting has very few disadvantages. In 1999, Intralase Corporation introduced the first femtolaser microkeratome on the American market. Approximately 120,000 intra-LASIK procedures have been carried out with fewer cutting complications than with the mechanic blade.

Humans↗