High Target Research Articles

Type 1 diabetes in childhood

<h2>Abstract</h2> Type 1 diabetes mellitus is the most common chronic metabolic condition in children and adolescents. Its incidence is increasing worldwide. It must increasingly be differentiated from type 2 diabetes which is also increasing in prevalence in parallel with the global rise in childhood obesity. Type 1 diabetes presents initially with ketoacidosis (DKA) in 15–67% of cases. Children presenting without DKA can safely be treated on an ambulatory basis. Glycemic and HbA1c targets should be tailored to the child's age and stage of development, with higher targets in young children due to the risk of cognitive impairment secondary to repeated severe hypoglycemia. However with increasing age glycemic targets should be more rigorous given the proven benefit of tight metabolic control on the onset and progression of microvascular complications. Insulin regimens used in children range from basal-bolus approaches to continuous subcutaneous insulin infusion (CSII). CSII offers children and their families an improvement in lifestyle and metabolic control. Self-monitoring of blood glucose (SMBG) is an essential component of management, as is attention to nutritional planning. Care of the child and adolescent with type 1 diabetes should be multidisciplinary and involve professionals experienced in childhood diabetes including a physician, nurse, dietitian and social worker or psychologist. Maintenance of excellent glycemic control and regular screening for complications should be emphasized, all in the context of a healthy and supportive physical and psychosocial environment.

On Target: An Examination of CEO Stock Option Performance Hurdles

In this paper, we have looked at the choice of performance targets using a unique panel database on UK CEO executive option performance targets. Using this data on performance targets along with governance data and financial data for company accounts with year ends from 2001 to 2003, we find that the rate of switch in types of targets and in levels of targets has been slow. Furthermore, those with high levels of institutional shareholding are less likely to use pure EPS targets, perhaps because that pure EPS targets are inconsistent with the relative performance targets predicted by agency theory. We find confirmation of the correlation between levels of targets and average analyst estimates of earnings but at the same time higher forecasts only translate into weakly higher targets. We also conclude it is difficult to predict changes in targets from any variables in our dataset and indeed when changes in target levels occur they tend to be rather large.

677. Generation and Application of an Efficient Chronic Myelogenous Leukemia (CML)-Targeted Recombinant Adeno-Associated Virus (rAAV) Vector: New Therapeutic Options?

Top of pageAbstract Introduction: Despite great advances in vector development, most standard rAAV-2 vectors still lack the target cell specificity required for an efficient in vivo application. In addition, the gene transfer efficiency in many promising target cells (e.g.: peripheral blood progenitor cells (PBPC)) is low. Thus, designing gene therapy protocols for diseases like chronic myelogenous leukemia (CML) remained difficult, as standard rAAV-2-based vectors lack both the required gene transfer efficiency and selectivity. A recent advancement in vector development (Muller et al., 2003) now allows the generation of rAAV capsid mutants that offers higher target cell specificity and transduction efficiency. This method was applied to obtain a CML-targeted rAAV vector and was tested on a panel of leukemic cell lines, as well on primary CML material. Material and Methods: Performing latter method on the CML cell line K562 (4 selection rounds), several mutant CML-targeted rAAV2 capsid clones were obtained, cloned into an rAAV2 helper plasmid and for each of the mutants rAAV2-eGFP vector stocks were produced. Titers were verified using our real time PCR-based titration assay. To determine efficiency and specificity, a panel of leukemic (CML and AML) and non-leukemic cell lines, as well primary human CML and PBPC cells were transduced with these vectors. Mock, normal rAAV2 and random mutant clone-transduced cells served as controls. Transduction of primary human CML and PBPC cells was confirmed using FACS-sorted GFP+ cells with subsequent bcr-abl-FISH or FACS analysis for GFP/CD34+ co- expression, respectively. Results: Transduction of a panel of six leukemic cell lines with the CML-targeted rAAV2 vectors (moi 100 iu) resulted in an over 10-fold increase of gene transfer efficiency compared to random mutant and standard rAAV2 vectors; gene transfer rates of >60% were obtained. In primary human cells, for both CML (n=4) and PBPC (n=2), an increase in gene transfer was observed (CML: AAV2: 2.4 |[plusmn]| 0.2 vs AAV2-cml: 5.1 |[plusmn]| 1.6 (p=0.04). CD34+: AAV2: 3.2 |[plusmn]| 0.9 vs AAV2-cml: 8.5 |[plusmn]| 4.3 (p>0.05)). All transduced cell were positive for either the BCR-ABL fusion gene (CML) or the PBPC marker CD34. In contrast, gene transfer of the mutant CML-targeted rAAV2 vectors into non-leukemic cell lines resulted in a reduction in gene transfer efficiency compared to standard rAAV2 vectors (<50%). Conclusion: In this study, we were able to generate a CML-targeted rAAV2 vector, which was able to transduce leukemic cell lines and primary human CML cells with significant higher efficiency and specificity than standard rAAV2 vectors. The development of these vectors holds promise for future clinical applications.

Pharmacodynamics of Moxifloxacin and Levofloxacin Simulating Human Serum and Lung Concentrations*

Fluoroquinolones are known to penetrate well into the infectious foci such as lung mucosa, epithelial lining fluid and alveolar macrophages achieving higher target site concentrations than the corresponding serum levels. In order to integrate the in vitro antibacterial activity and pharmacokinetics of moxifloxacin and levofloxacin, their bactericidal efficacy was assessed by simulating human serum and lung tissue concentrations using Streptococcus pneumoniae, Staphylococcus aureus and Klebsiella pneumoniae as indicator organisms. The bacteria were exposed to fluctuating moxifloxacin and levofloxacin concentrations simulating the drug levels in serum, lung mucosa, epithelial lining fluid and alveolar macrophages. The following parameters were deduced from the kill curves: area under the bactericidal kill curve normalized to the initial inoculum (AUBKC norm), the time needed to reduce the inoculum by 3 log(10) titers, and the initial bactericidal activity. In general, all these three parameters were for all the bacterial isolates having been exposed to moxifloxacin concentration dependent. In contrast, beyond a levofloxacin concentration of optimal bactericidal effect, higher drug concentrations did not further augment the bactericidal activity of levofloxacin. These data demonstrate that not all fluoroquinolones share the same pharmacodynamic targets needed to maximize their antibacterial effect.

Minimization of Seasonal Sucrose Losses Across Robert's- Type Evaporators in Raw Sugar Manufacture by pH Optimization

Factory staff must consider all costs to make sound economic decisions on how to improve the performance of evaporators, which includes knowing optimum pH levels to minimize sucrose losses. A factory study was conducted to determine the effects of target final evaporator syrup (FES) pH values across the season on sucrose losses. The factory operated Robert's type calandria evaporators, with two (2787 and 2322 m2) preevaporators in parallel and three sets of triple-body evaporators (1148 m2 each) in parallel; Rt values were 11.4 and 9.5 min in the two preevaporators, respectively, and increased from 10.0 to 21.8 min across the triple bodies. Gas chromatography was used to determine sucrose losses as Delta%glucose/%sucrose ratios on a degrees Brix basis. Most sucrose losses to acid hydrolysis occurred in the preevaporators. Increasing the target pH of the FES or clarified juice (CJ) systematically reduced losses of sucrose; however, scaling effects overrode pH effects in later bodies. Seasonal effects on evaporator sucrose losses were dramatic. In the early season when cane quality was lowest, higher amounts of impurities catalyzed further hydrolysis of sucrose. In the late season, resilient scale built-up across the season contributed to higher hydrolysis. An optimum target FES pH of approximately 6.3-6.5 measured at room temperature (equivalent to a CJ pH of approximately 7.1-7.3) is recommended, with a higher target FES pH in the early season or when processing immature cane, to reduce excessive losses. Across the evaporation station, the juice/syrup pH decreased up to the 2nd body with a consistent increase in the 3rd body due to evaporation of volatile acids into the condensate. Equations to assess the economic implications of evaporator sucrose losses are described. A target FES pH of 5.9 caused a season average sucrose loss of 0.55% equivalent to 1.52 lbs sucrose lost/ton of cane and a minimum USD 390,400 loss in profits. In contrast, a target FES pH of 6.5 reduced this sucrose loss to 0.36% and 1.01 lbs sucrose lost/ton of cane and saved the factory a minimum of USD 131,100.

Reduced Complexity I/Q Turbo Detection for Space–Time Trellis-Coded Systems

A reduced-complexity turbo-detection scheme, referred to here as the R-TD arrangement, is proposed for employment in space-time trellis-coded (STTC) systems using the inphase/quadrature-phase (I/Q) cancellation technique that was previously developed for single-transmitter and single-receiver systems. The R-TD scheme decomposes the received signal into its constituent I and Q signal components and detects these components separately; hence, reducing the number of possible signal combinations to be tested by the detector. The R-TD scheme is capable of approaching the performance of the conventional turbo detector (F-TD), while achieving a complexity reduction factor of 3 and 862 for a four-phase-shift-keying 32-state STTC system, denoted as STTC(4,32), communicating over two- and five-path Rayleigh-fading channels, respectively, exhibiting a symbol-spaced and equal-tap-weight channel-impulse response. In order to investigate the benefits of employing channel coding in conjunction with STTC schemes, the R-TD principle was also invoked in convolutional-coding-aided STTC schemes. It was observed that, at a given throughput, the turbo-detected nonchannel-coded STTC(4,32) system required a similar signal-to-noise ratio to that of the R=1/2 and constraint length K=7 convolutional-coded STTC(16,16) scheme for achieving the bit error rate (BER) of 10/sup -5/. At a higher target, BER of 10/sup -3/, the nonchannel-coded STTC(4,16) and STTC(4,32) schemes outperformed the channel-coded STTC(16,16) system by 0.8 and 2.3 dB, despite having a factor of 19 or 11 lower complexity, respectively.

Effect of genetic background on the target fatty acids of acyl‐ACP thioesterase transgenes in Brassica napus

AbstractAcyl‐acyl carrier protein (ACP) thioesterase (TE) is involved in the biosynthetic fatty acid pathway of plants. Conventional canola lines transformed individually with the bay‐TE (Uc FatB1), elm‐TE (Ua FatB1), nutmeg‐TE (Mf FatB1) or Cuphea‐TE transgene (Ch FatB1), produce seed oil with modified fatty acid compositions. This study assessed the effects of genetic background, cytoplasm, maternal parent, and interaction of different TE transgenes, on the target fatty acids using F1 seeds and double haploid (DH) lines. The F1 seeds were produced by crossing four TE transgenic parental lines and three non‐transgenic cultivars with distinct fatty acid compositions. The DH lines were developed from microspores of F1 plants. DH lines from different crosses showed that genetic background does not have an effect on the relative levels of the target fatty acids of the same TE, indicating the stability of the substrate specificity of the TE within canola. However, significant effects of genetic background on the content of the major target fatty acids, lauric acid (C12:0) or palmitic acid (C16:0) depending on the TE, were observed. Expression of the TE in low erucic acid (C22:1) genotypes resulted in higher target fatty acid levels than expression in high C22:1 genotypes. Reciprocal crosses showed maternal effects, but not cytoplasmic effects. In addition, co‐expression of two different TE transgenes in the same seeds was observed. These results indicate the importance of selection for appropriate genetic backgrounds in order to maximize the expression of the target fatty acids of TE transgenes, and also indicate potential uses of TE co‐expression in modifying canola seed oil.

History of acid suppression: focus on the hospital setting.

In the hospital setting, prophylactic acid suppression is an important part of care for many critically ill patients. It may also prevent rebleeding in patients admitted with acute upper gastrointestinal tract bleeding. Effective treatments for these conditions stemmed from our increased understanding of the gastric acid secretory pathway and target pH values. The late 1970s saw the introduction of histamine2-receptor antagonists (H2RAs), which partially suppress basal and meal-stimulated acid secretion. Some of these agents can induce an intragastric pH greater than 3, lasting for approximately 10 hours/day when given twice/day at recommended doses. This level of acid suppression can facilitate healing of duodenal ulcers but has limited efficacy for other indications (e.g., gastrointestinal bleed). In the late 1980s a more potent class of acid-suppressing agents was developed, proton pump inhibitors (PPIs). The PPIs can induce an intragastric pH above 3 lasting for approximately 17 hours/day, and an intragastric pH above 5 for approximately 9 hours/day after once-daily oral administration of recommended doses. It is possible to attain even higher target pH values with large doses and with continuous intravenous infusion. Thus, PPIs are agents of choice for treatment of many acid-related disorders including peptic ulcer disease and moderate-to-severe gastroesophageal reflux disease, and for prevention of rebleeding in patients with upper gastrointestinal bleeding. Availability of an intravenous formulation, pantoprazole, enables hospitalized patients for whom oral administration is not feasible to benefit from the superior potency of PPIs. Preliminary data suggest that intravenous PPIs may be more effective than H2RA prophylaxis against stress-related ulcer bleeding for intensive care patients and should facilitate healing in those with bleeding ulcers of the upper gastrointestinal tract.

Waste recovery using packaging waste recovery notes: a cost-effective way of meeting targets?

To comply with EU recycling targets for packaging waste, the UK relies on an industry run and market based eco-tax levied by reprocessors on obligated businesses. After examining the details of this approach, the use of Packaging Waste Recovery Notes is assessed in terms of its allocative impact and the contribution made to eco-efficiency. The evidence indicates the UK system has minimized the cost of delivering current EU targets, but has not been able to deliver allocative efficiency or to demonstrate dynamic improvements in resource use. Its effectiveness in meeting impending higher targets remains open to question.

The Editor's Department

The Editor’s Department The following is excerpted and adapted from the Editor’s Report that was submitted to the Executive Committee at its annual meeting in Washington in January 2001. This past year was the sixth of my seven-year term as editor of Language. It was very similar to the previous year, fairly quiet and free of editorial, redactional, or technological change. I remarked in my last report that the overall shape of the journal and the mix of articles, book reviews, and book notices had stabilized at realistic proportions, and this year’s data largely bears out that statement. Table 1 provides the relevant figures for the seven years since 1994, the year before I became editor. Click for larger view View full resolution Table 1. Pages and numbers of submissions published, 1994–2000. • This year, the number of pages was somewhat greater than the 900 that has been mandated historically by the society for many years. The increase was occasioned by a backlog of articles, several of which happened to be longer than usual. I fully expect that we will be able to move back closer to the lower number next year, but I believe that there are good reasons for aiming for a somewhat higher target in the future. The current acceptance rate, which has hovered between 15 and 20 percent for many years, is discouraging to even the best potential contributors. If we can increase the total pages gradually to close to 300 per issue, I believe that we will do a service to both the profession and to Language. • In 2000, a little more than 70 percent of the annual allotment of pages was devoted to articles and 25 percent to book reviews and book notices. This was somewhat greater than the 65/35 ratio that has become traditional, again largely because of the number of longer-than-usual articles, but we may want to retain the new ratio. • We published 34 full reviews and 207 notices in 2000. The number of notices was almost identical to the previous year, but the number of reviews was smaller, in large part because we received fewer reviews this year. • The lag time for book reviews and book notices has increased, so that the December issue contained reviews and notices that were received between January and March of the same year. The ideal lag is no more than nine months, which we expect to return to next year. • The number of articles published in the last year was 24, one more than the previous year. I had originally set a goal of 25 articles per year when I became editor. Given the pattern over the last two years, this goal seems to have been correct. In last year’s report, I suggested that the executive committee should endorse the numbers that I reported as guidelines for future editors, not as a straitjacket, but rather as a way of making the editor’s job simpler and clearer. This year’s numbers are similar enough to last year’s that I feel that they add support to my earlier suggestion. Technologically, 2000 was similar to 1999, with no innovations. We have continued to enjoy the benefits of our long-term relationship with both our typesetters (Maryland Composition) and our printers (Cadmus). For the near future, the Postscript typesetting [End Page 425] environment seems to be reasonably stable. One aspect of our operation that surprises some is that we continue to submit copy to the typesetters on paper rather than electronically, and that the typesetters continue to key in the copy the old-fashioned way, even though almost every article submitted to Language is prepared electronically. There are two reasons for this practice. The first is that Language has always maintained a tradition of fairly heavy copy editing. By the time our copy editor is through with the average manuscript, the number of changes on any page is so substantial that the cost of revising the author’s electronic file is about the same as the cost of keying in the entire file. Note that typesetters’ pricing structure is not directly connected to the cost of production: typesetting from...

HEMO equilibrated Kt/V goals are difficult to achieve in large male patients.

The long-term outcome of chronic hemodialysis patients is influenced by the adequacy of dialysis treatment. A major objective of the ongoing US HEMO Study is to determine if a higher target value of treatment as measured by the equilibrated Kt/V (eKt/V), a calculation of dialysis adequacy developed for the study, of 1.45 results in a better outcome than the presently accepted target value for eKt/V of 1.05 (approximately equal to spKt/V of 1.2). eKt/V corrects for urea rebound and gives a better estimate of actual treatment received. To examine the feasibility of achieving the higher eKt/V in large hemodialysis patients, a retrospective analysis of 389 monthly eKt/V values from 65 men on chronic hemodialysis of larger than average size dialyzed at high blood and dialysate flows (QB 400, QD 800 ml/min) with large dialyzers (1.8-2.2 m2) for longer than 4 hours three times weekly was performed. A total of 278 treatments considered optimal by a blood water urea clearance estimate were included in the final analyses. The mean body weight and Chertow water volume were 84.3+/-16.5 kgm and 50.0+/-6.7 L, respectively. The mean sp Kt/V was 1.29+/-0.17. The mean eKt/V was 1.16+/-0.14 and was inversely correlated with weight and water volume (p < 0.0001). Despite the large dialyzers and high blood and dialysate flow rates, no patient weighing more than 80 kgm or with body water volume exceeding 46 liters achieved an eKt/V of 1.45. This study suggests that creative dialyses will be required to achieve the HEMO "high arm" target in large patients.

Novel cancer therapies: more efficacy, less toxicity and improved organ preservation

Novel approaches to the treatment of cancer include techniques such as gene therapy, antiangiogenic therapy, monoclonal antibodies either alone or linked with radioactive isotopes or cytotoxins, cancer immunotherapy and vaccines, oligonucleotides and antisense technologies as well as anticancer drugs targeting single metabolic processes, enzymes or oncoproteins. However, substantial improvements are also being made in more conventional cancer treatment modalities. These comprise radiotherapy given concomitantly with chemotherapy, which appears to improve treatment results in a number of common types of human cancer. Other important advances include conformal and intensity-modulated radiation therapy, which may allow for higher target doses with little or no increase in toxicity. Stereotactic radiation therapy for extracranial targets is also being developed, as well as biologically targeted radiation therapy, in which targeting is based on metabolic pathways or carrier molecules, such as boronated compounds in boron neutron capture therapy or monoclonal antibodies in radioimmunotherapy. Sentinel node biopsy and neoadjuvant chemotherapy for breast cancer represent advances in surgery and cancer chemotherapy, which may also allow for a greater chance for organ and tissue preservation without a loss in treatment efficacy.

Time Course of Location-Cuing Effects With a Probability Manipulation

A location-cuing paradigm was used to study the effects of cue probability on the allocation of visual attention. A cue was used to indicate the likely location of a target (out of 4 possible target locations), with 8 cue-target onset intervals, ranging from 0 to 233 ms. There were 3 blocked proportions of correctly cued trials, 100%, 75%, and 50%. The observers had higher target discrimination accuracy at highly probable locations than at less probable locations, and these differences were maintained across all cue-target onset intervals. Thus, it appeared that the observers were allocating attention as a function of cue probability, with a consistent pattern throughout the time course of the development of attention. The consistent pattern across stimulus onset asynchronies (SOAs) suggests that the effects of time after cue and the effects of probability may rely on independent processes.

U.S. interest groups prefer emission trading: A new perspective

If there is to be environmental regulation, what kind of regulation would the main interest groups then prefer? This political distortion must be taken into account when designing future environmental regulation such as CO2 regulation. The three main interest groups in the U.S. (private business, environmentalist groups and the electricity sector) prefer a grandfathered permit market. Business is attracted by this solution because free initial distribution of permits both favours existing sources financially and, furthermore, creates a barrier to entry for new firms. Environmentalist groups have changed attitudes and promote the idea too as a way of negotiating higher target reduction levels with industry to maintain voluntary contributions from their members. Finally, electric utilities prefer a grandfathered permit market, and this step towards less planned economy may be explained by the rise of competition in the U.S. electricity sector. Therefore, it is suggested that a grandfathered permit market is a more effective policy than a tax in relation to organized interests such as industry, electric utilities and environmental organizations. In perspective, the grandfathered permit market may be mixed with the use of taxes. In the case of CO2 regulation, for example, taxes may be applied to badly organized polluters, such as households and the transport sector, because their lobbying power is weak.

Angular distribution of sputtered atoms in physical vapor deposition and collimated sputtering

Collimated sputtering has been studied for a number of years as a possible technique for improving step coverage and feature fill in integrated circuit (IC) metallization. The collimator is a physical filter which blocks sputtered atoms which possess an incident angle greater than the arc-cotangent of the collimator aspect ratio. Those atoms with angles less than this amount are allowed to pass through and deposit on the wafer, though an angle-dependent fraction are still blocked by the collimator. Atoms with low incident angles are able to get down into high aspect ratio features much more effectively than those with higher angles. Equations are derived for predicting the fraction of incident atoms transmitted through a collimator and the angular distribution of atoms arriving at the wafer for both collimated and uncollimated sputtering. Target utilization for collimated sputtering was found to be only 10 to 15% of that for uncollimated sputtering, even when gas scattering effects are neglected. Long-throw sputtering offers higher target utilization, but is not as effective due to excessive gas scattering.

Meeting the challenges of a new millennium: optimizing the use of recombinant human erythropoietin.

Optimizing the use of recombinant human erythropoietin (r-HuEPO) involves choosing an appropriate dose regimen and target haemoglobin level, addressing factors that inhibit response, and considering appropriate adjuvant therapy. Subcutaneous administration of r-HuEPO two or three times weekly is optimal for most patients. Early detection and treatment of iron deficiency is mandatory. Measurement of the percentage of hypochromic red blood cells is a reliable marker of functional iron deficiency, and the treatment of choice is intravenous iron. Other factors that can affect the response to r-HuEPO include blood loss (sometimes occult), infection, inflammation, hyperparathyroidism with marrow fibrosis, aluminium toxicity, vitamin B12/folate deficiency, haemolysis, bone marrow disorders, haemoglobinopathies, under-dialysis and possibly angiotensin-converting enzyme inhibitors. These factors should be identified and corrected where possible. Ascorbic acid, vitamin D, folic acid, carnitine, other cytokines and growth factors have all been shown to augment the response to r-HuEPO in some patients. Further research is required before any of these adjuvant therapies can be incorporated into routine clinical practice. With regard to target haemoglobin value, the current practice is to aim for a level of 10-12 g/dl, but it may be argued that a higher target would achieve greater benefits in terms of physical performance, quality of life, and possibly cardiac morbidity and mortality. International multicentre trials are currently in progress to address this issue, as are studies on other substances that may be able to stimulate erythropoiesis.

Subsurface detection of a buried object using angular correlation function measurement

A new technique is proposed for subsurface detection of buried objects using the angular correlation function (ACF) measurement of scattered waves. Compared with the traditional detection technique which relies on radar cross section (intensity) measurement, this new ACF-based technique results in better signal-to-clutter ratio and thus higher target visibility. Laboratory experiments were conducted at millimetre-wave (80–105 GHz) and X-band (7–13 GHz) frequencies to illustrate the potential effectiveness of this new correlation approach over the traditional cross section approach.

Intercepting real and path-guided apparent motion targets.

Human subjects were instructed to intercept with a cursor real and apparent motion targets presented on a computer screen. Targets traveled counterclockwise (CCW) in a circle at one of five angular velocities (180, 300, 420, 480 and 540 deg/s), either smoothly (real motion) or in path-guided apparent motion. Subjects operated a computer mouse and were instructed to intercept targets at the 12 o'clock position; there were no constraints on when to initiate the response, which was a movement from the center of the screen towards and past 12 o'clock. We found the following: (a) for both motion conditions and all target velocities, subjects were late in intercepting the target, especially at higher target velocities; (b) for both motion conditions, the directional variability of the response increased as a linear function of the target velocity; (c) the directional variability of the response was systematically higher for the apparent than the real motion condition; there was no significant interaction between target velocity and target motion type; (d) the response time did not vary significantly with velocity, but was consistently longer for apparent than real motion targets; (e) the movement time was very similar for different target velocities; and (f) the moment of initiation of the interception movement was delayed appreciably at higher target velocities, relative to that dictated for perfect interception at a given target velocity. This delay was greater for the apparent motion target. These results demonstrated the following: (a) for both target motion conditions, interception was not fully predictive but lagged the target in spite of the constant target velocity and the unconstrained time allowed for initiating the interception movement; (b) subjects can intercept an apparent motion target but, compared with real motion, the performance is somewhat degraded overall; (c) the similarities in performance between the two target motion conditions, and the fact that target velocity influenced performance in a similar fashion, suggest that the motor system can access the visual information provided by the moving target; and (d) since movement time was similar for different target velocities, the strategy for interception relied on controlling the moment of initiation of the interception movement. This was successful for low target velocities but became unsuccessful at higher target velocities.

REASSESSING THE THERAPEUTIC RANGE FOR THEOPHYLLINE ON LABORATORY REPORT FORMS: ANOTHER VIEWPOINT

The therapeutic utility of theophylline and the recommended range for serum concentrations are debated in a series of three editorials by noted contributors in this area. In the first, it is pointed out that the role of theophylline has evolved into an "adjunctive" therapy for asthma and chronic obstructive pulmonary disease. Serum concentrations of 10 to 15 µg/mL do not sacrifice significant clinical benefit, whereas there is increased risk for adverse effects at higher concentrations. Changing laboratry report forms to designate a lower therapeutic range of 5 to 15 µg/mL for an increased margin of safety (with &amp;gt;20 µg/mL continuing as the lower limit of the toxic range) is advocated and a stepwise approach for implementing this change is proposed. The second paper supports the view that theophylline remains more important than a third- or fourth-line agent in the treatment of asthma, particularly in selected patients. A higher target serum concentration range of 10 to 15 µg/mL may be desirable in more severe asthmatics (requiring oral steroids despite treatment with inhaled steroid), those with nocturnal symptoms, acute exacerbations requiring hospitalization and mechanical ventilation, and in patients for whom this is a more economical or preferable therapy. In these patients a serum concentration of 5 µg/mL may be too low to achieve sufficient benefit. Designation of "10 to 15 µg/mL (5 to 20)" as the therapeutic range is suggested to emphasize the midrange as the target while indicating that levels between 5 and 20 µg/mL are acceptable, although not ideal from either an efficacy or safety standpoint. In the third and final viewpoint presented, much data supporting the efficacy of theophylline in the treatment of chronic asthma and its relationship to serum concentrations are presented. Evidence for potential anti-inflammatory effects of theophylline is also reviewed. Severe toxicity, a rare event, is noted to be not a result of serum concentrations slightly above the therapeutic range, but from massive overdosage and/or drug interactions or concomitant illnesses that alter elimination of the drug. No changes in the recommended therapeutic range of theopylline, which might alter its effectiveness, are proposed. Rather, more careful use and monitoring through education of prescribers is advocated.

REASSESSING THE THERAPEUTIC RANGE FOR THEOPHYLLINE ON LABORATORY REPORT FORMS: ANOTHER PERSPECTIVE

The therapeutic utility of theophylline and the recommended range for serum concentrations are debated in a series of three editorials by noted contributors in this area. In the first, it is pointed out that the role of theophylline has evolved into an "adjunctive" therapy for asthma and chronic obstructive pulmonary disease. Serum concentrations of 10 to 15 µg/mL do not sacrifice significant clinical benefit, whereas there is increased risk for adverse effects at higher concentrations. Changing laboratry report forms to designate a lower therapeutic range of 5 to 15 µg/mL for an increased margin of safety (with &amp;gt;20 µg/mL continuing as the lower limit of the toxic range) is advocated and a stepwise approach for implementing this change is proposed. The second paper supports the view that theophylline remains more important than a third- or fourth-line agent in the treatment of asthma, particularly in selected patients. A higher target serum concentration range of 10 to 15 µg/mL may be desirable in more severe asthmatics (requiring oral steroids despite treatment with inhaled steroid), those with nocturnal symptoms, acute exacerbations requiring hospitalization and mechanical ventilation, and in patients for whom this is a more economical or preferable therapy. In these patients a serum concentration of 5 µg/mL may be too low to achieve sufficient benefit. Designation of "10 to 15 µg/mL (5 to 20)" as the therapeutic range is suggested to emphasize the midrange as the target while indicating that levels between 5 and 20 µg/mL are acceptable, although not ideal from either an efficacy or safety standpoint. In the third and final viewpoint presented, much data supporting the efficacy of theophylline in the treatment of chronic asthma and its relationship to serum concentrations are presented. Evidence for potential anti-inflammatory effects of theophylline is also reviewed. Severe toxicity, a rare event, is noted to be not a result of serum concentrations slightly above the therapeutic range, but from massive overdosage and/or drug interactions or concomitant illnesses that alter elimination of the drug. No changes in the recommended therapeutic range of theopylline, which might alter its effectiveness, are proposed. Rather, more careful use and monitoring through education of prescribers is advocated.