Introduction Of New Class Research Articles

Secondary malignancies after therapy of indolent non-Hodgkin's lymphoma

Indolent non-Hodgkin’s lymphoma remains incurable with standard therapeutic modalities. For three decades between 1970 and 2000, despite the introduction of new classes of agents, new modalities such as autologous stem cell transplantation, and improved supportive care, there was no improvement in

Non-Classical Stems from Classical: N. A. Vasiliev’s Approach to Logic and his Reassessment of the Square of Opposition

In the XIXth century there was a persistent opposition to Aristotelian logic. Nicolai A. Vasiliev (1880–1940) noted this opposition and stressed that the way for the novel – non-Aristotelian – logic was already paved. He made an attempt to construct non-Aristotelian logic (1910) within, so to speak, the form (but not in the spirit) of the Aristotelian paradigm (mode of reasoning). What reasons forced him to reassess the status of particular propositions and to replace the square of opposition by the triangle of opposition? What arguments did Vasiliev use for the introduction of new classes of propositions and statement of existence of various levels in logic? What was the meaning and role of the “method of Lobachevsky” which was implemented in construction of imaginary logic? Why did psychologism in the case of Vasiliev happen to be an important factor in the composition of the new ‘imaginary’ logic, as he called it?

Pharmacological Management of Primary Open-Angle Glaucoma

Glaucoma is one of the leading causes of blindness worldwide. Increased intraocular pressure (IOP) is considered to be the most important risk factor. Major outcome studies from recent years have shown that lowering IOP is beneficial in primary open-angle glaucoma and ocular hypertension. The introduction of new classes of IOP-lowering drugs (alpha(2)-adrenoceptor agonists, topical carbonic anhydrase inhibitors and hypotensive lipids) in the last decade has contributed to a change in the drug prescription pattern. Together with beta-adrenoceptor antagonists (beta-blockers), these drugs are now considered to be first-choice classes, giving ophthalmologists ample opportunities to choose from a broad spectrum of IOP-lowering drugs. The number of possible medical treatment combinations has increased likewise.We review medical treatment combinations of two, three or four drugs from the four major first-choice glaucoma drug classes and provide an overview of the scientific evidence for IOP efficacy of second-line medical options when first-line therapy has been effective but additional IOP lowering is necessary. A systematic search of the literature initially revealed 2729 publications. After a thorough selection process, 42 studies were found to be eligible for inclusion in the review. Publications were excluded if the primary endpoint of the study was not IOP or if glaucoma topics other than IOP lowering of drugs were studied. In addition, studies that reported results for monotherapies only were excluded. The vast majority of study arms reported on combinations of a beta-blocker with either a carbonic anhydrase inhibitor or a hypotensive lipid. For a number of treatment combinations no eligible studies were available or could be included.This review shows that combining drugs from the different first-choice classes results in an additional IOP decrease. The exact magnitude of this additional decrease and the patients to whom it applies remain unclear. In many studies, no information on IOP before the run-in phase was available. However, such data are important in order to determine whether patients with high untreated IOP or patients non-responsive to the run-in drug(s) were preferentially included. Another issue that hampers interpretation is the fact that the timepoints of measurements of IOP before and after adding a drug should be related to the peak and trough times of the drugs. Finally, differences between concomitant use and fixed combined use of drugs may have consequences for the interpretation of results.

Photosensitizing compounds in the treatment of psoriasis.

Photosensitizers were first used to treat psoriasis 15 years ago when the phototoxic reaction of psoralens and UVA was found to induce remissions of the disease. The effect of this reaction on DNA, particularly the formation of cross-links, was thought to be the decisive event. Strong cross-linking agents such as 8-MOP, TMP and 5-MOP are clinically effective whereas most compounds which produce only monofunctional adducts are virtually ineffective. Orally administered 8-methoxypsoralen (8-MOP) is the most widely used compound. 4,5',8-Trimethylpsoralen (TMP) is poorly absorbed from the intestine but has marked efficacy when applied topically. 5-MOP may be a useful alternative to 8-MOP because it is less erythemogenic and does not cause nausea. These three furocoumarins appear to be similar photochemically and may introduce similar risks. However, the photobiological properties of furocoumarins can be modified by altering one or more parts of the molecule. Such modifications might yield effective analogues with reduced cytogenetic hazards. Several psoralens and angular furocoumarins are being tested for effectiveness combined with fewest long-term side-effects, especially carcinogenesis. Encouraging preliminary results have been obtained with 7-methyl-pyridopsoralen and 4,6,4'-trimethylangelicin. Other important approaches to increasing the safety of photochemotherapy may be the use of different photoactivating wavelengths or the introduction of new classes of photosensitizers.

March AB, a state-of-the-art march test for realistic static linked faults and dynamic faults in SRAMs

Memory testing commonly faces two issues: the characterisation of detailed and realistic fault models, and the definition of time-efficient test algorithms able to detect them. Among the different types of algorithms proposed for testing static random access memories (SRAMs), march tests have proven to be faster, simpler and regularly structured. The continuous evolution of the memory technology requires the constant introduction of new classes of faults, such as dynamic and linked faults. Presented here is March AB, a march test targeting realistic memory static linked faults and dynamic unlinked faults. Comparison results show that the proposed march test provides the same fault coverage of already published algorithms reducing the test complexity and therefore the test time.

Calcium Channel Blockers: Their Pharmacologic and Therapeutic Role in Hypertension

The prevalence of hypertension is increasing steadily in the US, particularly among African Americans. It is now clear that a large proportion of patients are inadequately controlled, with many patients requiring at least two agents to achieve their target BP. Calcium channel blockers (CCBs), comprising two subclasses--dihydropyridines and nondihydropyridines--have been for many years one of the mainstays of hypertension therapy. However, the use of CCBs as monotherapy has recently been overshadowed by the introduction of newer classes of agents such as angiotensin receptor blockers. Examining the pharmacologic and clinical effects of CCBs in essential hypertension and among specific patient groups (e.g. African Americans, patients with renal disease) paves the way for understanding why these agents are currently enjoying a resurgence in popularity as the basis for several fixed-dose combination regimens that promise to improve BP control and reduce the risk of cardiovascular events.

New β-Lactamases: A Paradigm for the Rapid Response of Bacterial Evolution in the Clinical Setting

Production of beta-lactamases is one of the most common mechanisms of bacterial resistance to beta-lactam antibiotics. In the clinical setting, the introduction of new classes of beta-lactams has invariably been followed by the emergence of new beta-lactamases capable of degrading them, as a paradigmatic example of rapid bacterial evolution under a rapidly changing selective environment. The scope of this article is to provide an overview on the recent evolution of beta-lactamase-mediated resistance among bacterial pathogens. Focus is on the mechanisms of evolution and dissemination of enzymes of greater clinical impact, including the extended-spectrum beta-lactamases, the AmpC-type beta-lactamases and the carbapenemases, which are currently responsible for emerging resistance to the most recent and powerful beta-lactams (the expanded-spectrum cephalosporins and the carbapenems) among major Gram-negative pathogens such as Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter.

AGENT-BASED MICRO-SIMULATIONS IN IMMUNOLOGY AND FINANCE

In the search for computational models that help to understand the dynamics of Complex Systems, one can take a great advantage from the impressive acceleration of computer tools and techniques. In fact the very structure of computation on digital computers has inspired the introduction of new class of models (algorithms), where interaction among degrees of freedom are expressed by logical rules acting over a discrete state space – something much closer to "biological language" than to standard (floating point) physical models. Starting from the definitions of spin systems, with little changes we reach a definition a new model that is well suited to describe different simulation systems. Such class of models is can be considered a subclass of the Agent-Based systems in vogue nowadays. Moreover, we shortly describe two microscopic simulators of this type, which are being used to study microscopic phenomena in two completely different fields of application, namely immunology and finance. As a final remark, given the lattice representation of space, such computational-modeling paradigm is well suited for efficient and "relatively simple" parallelization. Indeed, both models have been implemented to run on parallel computers adopting the Message Passing paradigm for Distributed Memory machines.

Post‐marketing studies: ensuring the safety of diabetes drugs

Today, there are many more dia- betes drugs on the market than there were 10 or 20 years ago. The last five years alone have seen the introduction of new classes of oral antidiabetic drugs (OADs) includ- ing the glitazones and secreta- gogues. In addition, there is a pipeline of drugs in development including a new range of insulins. This, coupled with the escalating numbers of patients suffering from diabetes, means that the manage- ment of diabetes has never been more challenging. All new drugs undergo a com-

Nuclear translocation as a novel target for anti-HIV drugs

During recent years, remarkable progress has been achieved in the treatment of patients infected with HIV. This progress involves not only the improvement of previously known drugs but also the introduction of new classes of anti-HIV agents. Currently, drugs targeting virus entry, reverse transcription, integration and maturation are either in clinical use or in the late stages of clinical development. Nonetheless, the high mutation rate of the virus and toxicity of the drugs, which become problematic during prolonged treatment regimens characteristic of anti-HIV therapy, drive the necessity to produce new drugs that will allow physicians to keep the virus at bay in patients on lifelong anti-HIV therapy. Ideally, such drugs would target a new step in the HIV life cycle, thus avoiding crossresistance with older compounds. One such new target for anti-HIV therapy is nuclear translocation – a process critical for HIV replication. In this article, the authors will review recent literature on the mechanisms of HIV nuclear import and will describe compounds that inhibit this step of HIV replication.

Considerations in Clinical Trials of Combination Antifungal Therapy

The cure rate for serious fungal diseases with currently available agents used as monotherapy is not optimal. The introduction of new classes of antifungal drugs in the last few years naturally leads to the hypothesis that antifungal drugs used in combination may be more effective than the same drugs used alone. The design and interpretation of combination therapy studies raise challenges beyond those encountered when drugs are studied as monotherapy in the treatment of a disease. The definition of combination therapy, the study design, the selection of appropriate patient populations, and the selection of end points, as well as practical considerations, are all important in the design and interpretation of clinical trials of combination therapies. Although combination therapies hold the promise of improved efficacy, it is important to prove this hypothesis, because they also may be associated with increased toxicity and increased drug costs. A careful consideration of study design factors before the initiation of a trial will help obtain the most useful information for patients in this important area.

Recent antihyperglycemic prescribing trends for US privately insured patients with type 2 diabetes.

The mid-1990s witnessed the introduction of new classes of medications to treat hyperglycemia of type 2 diabetes. There is evidence that these newer classes have found a place in the therapeutic armamentarium, but details of their use patterns are not known. We sought to determine whether antihyperglycemic prescribing patterns changed concurrently with new drug introductions, and whether such changes were related to changes in the underlying patient population. A sample of U.S. privately insured patients with suspected type 2 diabetes was identified from the MarketScan Research Database over the period of 1997-2000. Patients with type 2 diabetes were identified among those continuously enrolled in the database for at least 1 year. Drug therapy episodes were defined by sequential fulfillment of prescriptions implying a continuous supply of a particular drug (or combination) of at least 30 days duration. Univariate analyses were used to explore trends over time in drug prescriptions and patient characteristics. Multivariate logistic regressions were used to isolate the impact of year from other variables on the likelihood of receiving prescriptions for a specific therapy. A total of 232,020 unique diabetic patients had an average of 1.91 diabetes drug therapy episodes between 1997 and 2000. Monotherapy with sulfonylureas decreased, but monotherapy with thiazolidinedione, metformin, and other oral antihyperglycemics increased over time. Combinations of sulfonylureas and metformin; sulfonylureas and thiazolidinedione; metformin and thiazolidinedione; and sulfonylureas, metformin, and thiazolidinedione each increased over the time interval. Insulin monotherapy decreased, as did insulin combination therapy with sulfonylureas. The combination of insulin and metformin increased, whereas insulin and thiazolidinedione was stable. The influence of year on prescribing patterns remained highly significant (P < 0.001) after adjusting for patient characteristics. Antihyperglycemic prescription patterns in the U.S. have changed in recent years in parallel with, and probably as a direct result of, the introduction of different classes of medications to the marketplace. Overall, the prescribing trend has been away from monotherapy with insulins and sulfonylureas and toward combination therapies, presumably in attempts to reduce hypoglycemic symptoms and to achieve better glucose control.

Entry Decisions by Mutual Fund Families

Due to the multiple-class structure of mutual funds, the entry decisions by fund families include two separate decisions: the introduction of new (single-class or multiple-class) portfolios and the introduction of new classes for existing portfolios. The two decisions are based on very different considerations and lead to very different class compositions. New classes in existing portfolios are primarily the results of the expansion of traditional front-end load funds and institutional funds, and are mostly introduced in star portfolios. No-load funds rarely introduce new load classes and no-load classes are never observed to be added to load funds. In addition, fund families starting new multiple-class portfolios appear to follow a very risky introduction strategy.

RECENT ADVANCES IN THE PHARMACOLOGIC MANAGEMENT OF DIABETES MELLITUS

The importance of glucose control in reducing the complications of diabetes mellitus has been clearly demonstrated. The emergency physician routinely is expected to treat a wide range of problems related to this disease, including making the initial diagnosis of type 2 and occasionally type 1 diabetes. Also common are patients with poorly controlled diabetes. The recent introduction of new classes of agents to lower blood glucose, especially in type 2 diabetes, should improve the control in this category of patient and reduce the complication rate. Some of these agents, such as troglitazone, have potentially fatal complications and require careful monitoring. Emergency physicians should be aware of the common complications of these drugs because patients can present to the ED with them. Hypoglycemia, a common cause of 911 calls and emergency visits, is not a side effect of either metformin or acarbose. Insulin lispro has improved postprandial glycemic control for type 1 and some insulin-requiring type 2 diabetics. Hypoglycemia is less of a risk with insulin lispro, and quality of life is better with this rapidly acting insulin. Newer methods of insulin delivery, such as continuous subcutaneous infusion, have greatly improved glucose control, given greater freedom to patients, and reduced the risks of hypoglycemia.

Parallel dynamic programming and automata theory

Following Karp's discrete Dynamic Programming (DP) approach, this work extends the sequential model for monadic DP to the parallel case. We propose general parallel DP algorithms for pipeline and ring networks. The study of the optimality of these algorithms leads us to the introduction of new classes of multistage automata. However, the important class of Polyadic Dynamic Problems is out of the scope of this theory. Based on the concept of tree automaton, a new theory covering both Sequential and Parallel Dynamic Programming Polyadic Programs is presented. Monadic Programs appear as a particular case of this new theory. A large number of experiments have proved that the schemes proposed in this work lead to efficient implementations.

AUTOMATED INTERPRETATION OF GEOPHYSICAL BOREHOLE LOGS FOR OREBODY DELINEATION AND GRADE ESTIMATION

An automatic interpretation tool, LogTrans, for geophysical borehole logs was developed during a recent CMTE/AMIRA Project, The Application of Geophysics to Mine Planning and Operations. LogTrans performs rapid analysis of multi-parameter logs and expedites presentation of interpreted results in a form meaningful to mining engineers and geologists. The algorithm exploits the contrasts in petrophysical signatures between different of rock. The classes may be distinguished by lithology, grade, mechanical properties, or any combination of characteristics. The LogTrans procedure entails two stages: • statistical characterisation, involving determination of the centroids (means or medians) and ranges (standard deviations or spreads) of the distributions of each petrophysical parameter for each class, based on a representative control data set; • discrimination, in which data points are assigned to the nearest control class in multi-parameter space. The LogTrans discrimination algorithm is simple, intuitive, fast and flexible. However, it is not a Black Box. Its performance relies fundamentally on the integrity of the control information: the geological, geochemical, and/or geomechanical data from the control holes, as well as the geophysical logs. In particular, drilling depths must be carefully reconciled with borehole logging depths. Interpretational performance is enhanced when parameter distributions are uni-modal and compact, and when high petrophysical contrasts exist between classes. Critical assessment of the control information can prompt introduction of new classes (by sub-division of existing classes or otherwise) and derivation of new parameters (by mathematical combination of original parameters) to better achieve the interpretational objective. LogTrans has been applied successfully to logging data sets collected from a number of Australian and overseas mines. Prediction accuracy in excess of 90% has been achieved in several cases. Its application for orebody delineation at Century and for grade range interpretation at Rosebery is illustrated in this paper.

EXTENDED-SPECTRUM β-LACTAMASES AND OTHER ENZYMES PROVIDING RESISTANCE TO OXYIMINO-β-LACTAMS

Bacteria have once again demonstrated their remarkably versatility in meeting the introduction of new classes of beta-lactam antibiotics by modifying available plasmid mediated beta-lactamases to expand their spectrum of action and by incorporating chromosomal beta-lactamase genes onto plasmids that permit their spread to new hosts. Such resistance is more common than presently is appreciated because current NCCLS breakpoints for resistance underestimate its prevalence. A number of risk factors for acquisition of ESBL-producing K. pneumoniae have been defined, but most will be no easier to control than those for infection by MRSA or VRE. More clinical and animal model studies are needed to evaluate options for treatment. Most strains remain susceptible to imipenem and other carbapenems, but carbapenem resistance has appeared either by spread of metallo-beta-lactamase or by production of an AmpC enzyme combined with loss of an outer membrane porin channel. Attack on our adversaries' latest biological weapons is likely to require enhanced versatility on our part as well.

Are we making progress in antifungal therapy?

Contrary to the case with bacterial infections, progress in the diagnosis and treatment of invasive mycoses in cancer patients has been unsatisfactory. Amphotericin B deoxycholate has remained the drug of choice for severe invasive fungal infections for nearly 40 years. However, its infusion-related side effects, as well as its toxicity, may at times lead to dose reduction or early discontinuation of the treatment. The introduction of the new triazoles, fluconazole and itraconazole, has improved the therapeutic chances against several fungal infections; however, the need for a broad-spectrum drug in empiric antifungal therapy, the emergence of fluconazole-resistant Candida species, and the limitations of itraconazole in terms of speed action and erratic oral absorption represent important limitations. Recently, laboratory and clinical research has been directed at the development of new formulations of older classes of antifungals, the introduction of new classes of antifungals, and the use of immunomodulation associated with antifungal therapy. This paper reviews the more recent advances in the treatment of fungal infections in cancer patients.

The fate of one forgotten idea: N. A. Vasiliev and his imaginary logic

The fate of scientific ideas is whimsical. Very often time only gives us the opportunity to appraise the strength of forecasting of the scholar, the scale of his ideas, their orientation to the future, and the role and place of the scholar in the intellectual history of mankind. As one aphorism put it: "Time has a difficult delivery, but never a miscarriage" (F. R. Lamenne). Today, the significance of the logical works ? only a few articles ? of Kazan University philosophy professor, N. A. Vasiliev (1880? 1940), is becoming ever more apparent. He was the first to introduce considerations of inconsistency into formal logic, manifesting at that time an understanding of dialectical spirit (in Kant's or Hegel's sense). In his early years, Vasiliev was attracted to poetry. As if predicting the fate of his own logical ideas, he wrote: "We are the quickly dying flame. And again a burning fire". Actually, his ideas, expressed at the very beginning of the 20th century, entitle us to call Vasiliev a thinker who anticipated the development of many parts of contemporary non-classical logic, especially its most pioneering and novel parts. Already in 1910 Vasiliev abandoned the law of contradiction and constructed a logic without this law. That is why he is justifiably considered as a forerunner of para consistent logic, which incarnates the idea of non-Aristotelian logic. Through his critique (and rejection) of the law of excluded middle, Vasiliev anticipated the birth of another alternative to classical logic, viz., intuitionist logic. Moreover, due to introduction of new classes of judgements (and, respectively, new meanings of truth) he may be viewed as the predecessor of many ? valued logic, which expanded the capability of classical logic. All of this enables us to compare cum grano salis the role of Vasiliev in logic with that of N. I. Lobachevsky in geometry: Lobachevsky's ideas gave rise to non-Euclidian, non-classical geometry; Vasiliev's ideas gave rise to non-Aristotelian, non-classical logic. Lobachevskv called his geometry "imaginary"; Vasiliev, too,

Recent developments in hard magnetic materials

Hard magnetic materials find ever-increasing uses in modern technology. Their importance is mainly in the domain of permanent magnets, but a variety of other applications is being offered to this class of materials, especially for what regards the areas of information storage, telecommunications and special electronic devices. These developments are connected to the emphasis that is more and more given to thin films having high magnetic anisotropy. The recernt advancement in the field of hard magnetic materials is among the best examples where technology depends to a great extent upon the continuous progress in the scientific knowledge. The research activity is characterized by the introduction of new classes of materials and continuous improvements in the preparation techniques both for what regards industrial processing and method for obtaining high quality materials in form of crystals, films or amorphous specimens. In this respect a special place must be reserved to rare earth transition metal compounds, a class of materals that attracted enormeous attention after the discovery by Hoffer and Strnat in 1966 of the large uniaxial magnetocrystalline anisotropy of the compound YCo5. Beside the so called 1∶5 phase, other compositions of technical importance are the 2∶17 and the recently discovered Nd2Fe14B, which is a real new ternary phase having tetragonal crystal structure. Great efforts have been done to gain a better understanding of the magnetic anisotropy and its relationship to the coercivity is of leading importance for a further development in this important area of magnetism.