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Treatment is an art to which science can contribute: the 2nd James Rankin Oration.

Working models-beliefs-are an essential element of behaviour. Clients' models and non-scientific treatment models, need to be respected. It is contended that, practically and theoretically, scientific models have little validity or relevance for understanding and managing addictive behaviour. The WHO model of drug use, with two added elements (the self and the functions of choice and decision making; and random variation of neurophysiological activities), is used as an example. The scientific method consists of dissecting a complex phenomenon into simpler parts, testing hypotheses about these parts, collecting and summating the data, and applying the conclusions to individual cases. It is presumed that if we know enough about a person then we can predict their future behaviour, including response to therapeutic interventions. Four major arguments are produced against that presumption. The scientific method depends upon the use of meaningful numbers (representing discrete, replicable categories) and its results are presented in statistical formats (with limited individual relevance). Measurement in the behavioural sphere is neither precise nor objective. This is critical with complex interactive systems (such as the WHO model) in which an apparently insignificant change in input can result in dramatic changes in output. Progress may have been made technically, e.g. to reduce relapse, but therapy remains an art. In future, scientific endeavours should be complemented by attention to other disciplines.

Journal Article↗

A control technology evaluation of state-of-the-art, perchloroethylene dry-cleaning machines.

NIOSH researchers evaluated the ability of fifth-generation dry-cleaning machines to control occupational exposure to perchloroethylene (PERC). Use of these machines is mandated in some countries; however, less than 1 percent of all U.S. shops have them. A study was conducted at a U.S. dry-cleaning shop where two fifth-generation machines were used. Both machines had a refrigerated condenser as a primary control and a carbon adsorber as a secondary control to recover PERC vapors during the dry cycle. These machines were designed to lower the PERC concentration in the cylinder at the end of the dry cycle to below 290 ppm. A single-beam infrared photometer continuously monitors the PERC concentration in the machine cylinder, and a door interlock prevents opening until the concentration is below 290 ppm. Personal breathing zone air samples were measured for the machine operator and presser. The operator had time-weighted average (TWA) PERC exposures that were less than 2 ppm. Highest exposures occurred during loading and unloading the machine and when performing routine machine maintenance. All presser samples were below the limit of detection. Real-time video exposure monitoring showed that the operator had peak exposures near 160 ppm during loading and unloading the machine (below the OSHA maximum of 300 ppm). This exposure (160 ppm) is an order of magnitude lower than exposures with more traditional machines that are widely used in the United States. The evaluated machines were very effective at reducing TWA PERC exposures as well as peak exposures that occur during machine loading and unloading. State-of-the-art dry-cleaning machines equipped with refrigerated condensers, carbon adsorbers, drum monitors, and door interlocks can provide substantially better protection than more traditional machines that are widely used in the United States.

Air Pollutants, Occupational↗

Environmental and occupational health hazards associated with the presence of asbestos in brake linings and pads (1900 to present): a "state-of-the-art" review.

Throughout the history of automobile development, chrysotile asbestos has been an essential component of vehicle brake linings and pads. Acceptable alternatives were not fully developed until the 1980s, and these were installed in vehicles produced over the past decade. This article presents a "state-of-the-art" analysis of what was known over time about the potential environmental and occupational health hazards associated with the presence of chrysotile asbestos in brake linings and pads. As part of this analysis, the evolution of automobile brakes and brake friction materials, beginning with the early 1900s, is described. Initial concerns regarding exposures to asbestos among workers involved in the manufacture of friction products were raised as early as 1930. Between 1930 and 1959, eight studies were conducted for which friction product manufacturing workers were part of the population assessed. These studies provided evidence of asbestosis among highly exposed workers, but provided little information on the magnitude of exposure. The U.S. Public Health Service proposed the first occupational guideline for asbestos exposure in 1938. The causal relationship between asbestos exposure and lung cancer was confirmed in 1955 in asbestos textile workers in the United Kingdom, and later, in 1960, in South Africa, mesothelioma was attributed to asbestos exposure to even relatively low airborne concentrations of crocidolite. Between 1960 and 1974, five epidemiology studies of friction product manufacturing workers were conducted. During this same time period, the initial studies of brake lining wear (dust or debris) emissions were conducted showing that automobile braking was not a substantial contributor of asbestos fibers greater than 5 microm in length to ambient air. The first exposure surveys, as well as preliminary health effects studies, for brake mechanics were also conducted during this period. In 1971, the Occupational Safety and Health Administration promulgated the first national standards for workplace exposure to asbestos. During the post-1974 time period, most of the information on exposure of brake mechanics to airborne asbestos during brake repair was gathered, primarily from a series of sampling surveys conducted by the National Institute of Occupational Safety and Health in the United States. These surveys indicated that the time-weighted average asbestos

Air Pollutants, Occupational↗

The quest for an AIDS vaccine: the state of the art and current challenges.

Despite intense efforts worldwide, using state-of-the-art methods and techniques and despite ever-increasing knowledge about the molecular and structural make-up of HIV, a practical vaccine against acquired immunodeficiency syndrome (AIDS) has yet to be developed. The increasing use of recombinant DNA techniques and synthetic peptide technology has allowed many groups to identify at the epitope level the regions of HIV proteins which act as targets for (and stimulate) the immune response. Epitopes which stimulate and bind neutralizing antibodies have been examined in detail and an ever-increasing number of antibody-dependent cellular cytotoxicity (ADCC) and cytotoxic T lymphocytes (CTL) epitopes are being defined, as are potentially harmful (immunosuppressive or enhancing) domains. It still is not clear which of the different immune responses (or combinations thereof) it will be necessary to stimulate in order to protect from infection. Infected humans develop neutralizing antibodies, ADCC-inducing antibodies and CTL responses against a variety of viral proteins but it is not known which of these can control or prevent infection in vivo. The extensive knowledge of HIV and the immune response it elicits is being used to design and produce a wide variety of putative vaccines, ranging from whole inactivated virus, through recombinant organisms/proteins, to synthetic peptides although each has its inherent advantages and disadvantages. The very nature of HIV makes vaccine development difficult at best. However, recent successes using whole inactivated virus or virus-infected cells in the macaque simian immunodeficiency virus (SIVmac) model system at least show that protection against lethal lentivirus infection can be achieved.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗

State-of-the-art magnetic resonance imaging of the kidneys and upper urinary tract.

State-of-the-art magnetic resonance imaging (MRI) is an excellent examination in several clinical contexts of interest to endourologists. First, it offers a one-stop imaging examination of prospective renal donors, obviating the need for arteriography and conventional excretory urography. Second, it reliably depicts urinary tract obstruction and can usually distinguish acute from chronic obstruction, although it is not as sensitive as helical CT in detecting small, nonobstructing stones. Third, it is an excellent examination for characterizing renal masses, especially complex cystic masses, and for surgical planning. Because MRI does not use ionizing radiation and because gadolinium contrast agents are essentially non-nephrotoxic, MRI is especially useful in children, women of childbearing age, and patients with renal insufficiency or renal allografts. Future developments will likely include MR "fluoroscopy," which will provide real-time imaging guidance for interventional procedures in the urinary tract.

Humans↗

Modeling techniques for inhaled particle deposition: the state of the art.

Mathematical modeling of aerosol deposition in the human lung is based on idealized assumptions regarding the morphometry of the lung, the fluid dynamics behavior of the inspired air under defined breathing conditions, the transport of particles through the branching airway system, the physical mechanisms acting upon inhaled particles, and the deposition of particles within airways, airway bifurcations, and alveoli. Current models of particle deposition in the human lung, ranging from experimentally based semi empirical to rather sophisticated stochastic and numerical mathematical models, permit the prediction of particle deposition at different levels of complexity, ranging from total deposition in the whole lung to localized deposition patterns within single airway bifurcations. In this paper, the present state of the art in aerosol deposition modeling will be reviewed, focusing on the discussion of different conceptual ideas rather than on a complete listing of all published modeling efforts. The selection of specific contributions by various authors relevant to our present understanding of particle deposition in the human lung reflects the subjective view of the author. In addition, illustrations of salient features of different modeling approaches are based primarily on the author's own research.

Administration, Inhalation↗

The WWWH of remote homolog detection: the state of the art.

The detection of remote homolog pairs of proteins using computational methods is a pivotal problem in structural bioinformatics, aiming to compute protein folds on the basis of information in the database of known structures. In the last 25 years, several methods have been developed to tackle this problem, based on different approaches including sequence-sequence alignments and/or structure comparison. In this article, we will briefly discuss When, Why, Where and How (WWWH) to perform remote homology search, reviewing some of the most widely adopted computational approaches. The specific aim is highlighting the basic criteria implemented by different research groups and commenting on the status of the art as well as on still-open questions.

Algorithms↗

Wavelets in bioinformatics and computational biology: state of art and perspectives.

MOTIVATION: At a recent meeting, the wavelet transform was depicted as a small child kicking back at its father, the Fourier transform. Wavelets are more efficient and faster than Fourier methods in capturing the essence of data. Nowadays there is a growing interest in using wavelets in the analysis of biological sequences and molecular biology-related signals. RESULTS: This review is intended to summarize the potential of state of the art wavelets, and in particular wavelet statistical methodology, in different areas of molecular biology: genome sequence, protein structure and microarray data analysis. I conclude by discussing the use of wavelets in modeling biological structures.

Algorithms↗

Agentomics: an agentic system that autonomously develops novel state-of-the-art solutions for biomedical machine learning tasks.

MOTIVATION: Extracting knowledge from biomedical data is crucial for advancing our understanding of biological systems and developing novel therapeutics. The quantity, quality, and resolution of biomedical data constantly evolves, requiring the automation of biomedical machine learning (ML). Existing Automated ML tools lack flexibility, while large language models (LLMs) struggle to consistently deliver reproducible machine learning codebases, and existing LLM Agent-powered solutions lag behind human-engineered ML models. RESULTS: Here, we introduce Agentomics, an autonomous LLM-powered agentic system for end-to-end ML experimentation. Given a biomedical dataset, Agentomics implements various ML modeling strategies, and produces a ready-to-use ML model. Agentomics introduces strict validation checkpoints for standard ML development steps, allowing gradual development on top of working code with defined interfaces and validated artifacts. Further, it offers native support for biomedical foundation models that can be leveraged during experimentation. The generic nature of Agentomics allows the user to create ML solutions for a large variety of datasets and use various LLMs. We evaluate Agentomics across 20 datasets from the domains of Protein Engineering, Drug Discovery, and Regulatory Genomics. When benchmarked against other agentic systems, Agentomics outperformed them in all tested domains. When benchmarked against human expert solutions, Agentomics generated novel state-of-the-art models for 11/20 established benchmark datasets. AVAILABILITY AND IMPLEMENTATION: Agentomics is implemented in Python. Source code and documentation are freely available at: https://github.com/BioGeMT/Agentomics-ML.

Machine Learning↗

ARTS: alignment of RNA tertiary structures.

MOTIVATION: A fast growing number of non-coding RNAs have recently been discovered to play essential roles in many cellular processes. Similar to proteins, understanding the functions of these active RNAs requires methods for analyzing their tertiary structures. However, in contrast to the wide range of structure-based approaches available for proteins, there is still a lack of methods for studying RNA structures. RESULTS: We present a new computational method named ARTS (alignment of RNA tertiary structures). The method compares two nucleic acid structures (RNAs or DNAs) and detects a-priori unknown common substructures. These substructures can be either large global folds containing hundreds and even thousands of nucleotides or small local tertiary motifs with at least two successive base pairs. To the best of our knowledge, this is the first method of this type. The method is highly-efficient and was used to conduct an all-against-all comparison of all the RNA structures currently available in the Protein Data Bank. AVAILABILITY: The program, a web-server and supplementary information are available on http://bioinfo3d.cs.tau.ac.il/ARTS

Algorithms↗

GC: a review of the state-of-the-art column technologies for the determination of ppm to ppb levels of oxygenated, sulfur, and hydrocarbon impurities in C1-C5 hydrocarbon streams.

The determination of ppm to ppb levels of sulfur, oxygen-containing, and certain reactive hydrocarbons in bulk hydrocarbon feedstocks is important in the petroleum and petrochemical industry to minimize catalytic deactivation and improve product quality. Gas chromatography, coupled with selective or ultratrace universal detection (or both), is ideal in most cases for such analysis. However, to enhance selectivity and quantitation at the trace levels, optimized stationary phases are required. These phases are usually of the adsorbent type. This paper summarizes the performance of several state-of-the-art phases for the analyses of trace key hydrocarbons, sulfur, and oxygenated components.

Journal Article↗

The state of the art of traditional arab herbal medicine in the eastern region of the mediterranean: a review.

Historical and current studies indicate that the Eastern region of the Mediterranean has been distinguished from other regions by a rich inventory of complementary alternative medicine (CAM), in particular herbal medicine. Data collected from several surveys and studies indicate that there is a flourishing and well-developed trade of herbs. These surveys also reveal that 200-250 herbs are used in treating human diseases and are sold or traded in market places in the Mediterranean region or internationally. In addition, some of these herbs are rare or even endangered species. In regard to the status of the know-how of herbalists, unfortunately, herbal medicine in our region is mostly prescribed by ethnopharmacologists symptomatically-based on signs and symptoms alone, rather than as a result of a full understanding of the underlying disease. In some cases, herbs used today may not even correspond to the plants described originally in the old literature, as the former are cultivated from herbs that went through different breeding procedures throughout several centuries. This article presents a systematic review of both the state of the art of traditional Arab herbal medicine and the status of the know-how of Arab herbalists.

Journal Article↗

Five year clinical effect of coronary stenting and coronary artery bypass grafting in renal insufficient patients with multivessel coronary artery disease: insights from ARTS trial.

AIMS: To compare coronary stent implantation and bypass surgery for multivessel coronary disease in patients with renal insufficiency. METHODS AND RESULTS: In the ARTS trial, 142 moderate renal insufficient patients (Ccr<60 mL/min) with multivessel coronary disease were randomly assigned to stent implantation (n=69) or CABG (n=73). At 5 years, there was no significant difference between the two groups in terms of mortality (14.5% in the stent group vs. 12.3% in the CABG group, P=0.81), or combined endpoint of death, cerebrovascular accident (CVA), or myocardial infarction (MI) (30.4% in the stent group vs. 23.3% in the CABG group, P=0.35). Among patients who survived without CVA or MI, 18.8% in the stent group underwent a second revascularization procedure when compared with 8.2% in the surgery group (P=0.08). The event-free survival at 5 years was 50.7% in the stent group and 68.5% in the surgery group (P=0.04). CONCLUSION: At 5 years, the differences in mortality and combined incidence of death, CVA, and MI between coronary stenting and surgery did not reach statistically significant level. However, the occurrence of MACCE in the stent group was higher than in the CABG group, mainly driven by the higher incidence of repeat revascularization in the stent group.

Aged↗

Quality assurance in general practice: the state of the art in Europe.

Quality assurance' (QA) is an important new development in general practice. In order to describe the state of the art in this field a preliminary survey was performed by the WONCA European Working Party on Quality in General Practice (EQuiP) in 17 European countries. The results revealed considerable differences in the systems and organization of general practice care [such as practice form, list size, the role of the general practitioner (GP), remuneration], which will have an impact on setting up QA. The preliminary findings demonstrated that most countries are only just beginning the implementation of QA. Nevertheless, there are many valuable developments and experiments concerned with the methodology, procedures and structures for it. In order to accelerate the speed of adoption of QA and to avoid the repetition of mistakes, policy makers and GPs from different parts of Europe should study examples in their fellow countries. A clearing house of QA projects in general practice can help to inform them on valuable developments.

Europe↗

Group interviews in primary care research: advancing the state of the art or ritualized research?

BACKGROUND: Focus groups have become an important data gathering technique in primary care research. OBJECTIVES: This study provides an integrated review of recent articles that used focus groups as a data collection method to gather information from family physicians. METHODS: Medline was searched for articles that used focus groups with family physicians in a North American setting during the 1990s. Articles that met this criteria were critically evaluated to determine who participated, the number of groups conducted, setting, length, inclusion and exclusion criteria, sampling technique and whether the groups were used as part of a larger study. RESULTS: The twenty articles discussed herein revealed tremendous variation in how focus group research is conducted and reported. CONCLUSIONS: Focus group research is a popular form of qualitative research in primary care research. Journals reporting qualitative research should require that certain basic information be present, thereby advancing the state of the art and permitting readers to better evaluate these articles.

Canada↗

Nuclear genes of human complex I of the mitochondrial electron transport chain: state of the art.

The mitochondrial electron transport chain (mtETC) consists of four multi-subunit enzyme complexes. Complex I or NADH:ubiquinone oxidoreductase, the largest mtETC multisubunit complex, consists of approximately 41 subunits. Seven of these subunits are encoded by the mitochondrial genome, the remainder by the nuclear genome. Among the mitochondriocytopathies, complex I deficiencies are encountered frequently. Although some complex I deficiencies have been associated with mitochondrial DNA mutations, the genetic defect has not been elucidated in the majority of complex I-deficient patients. It is expected that many of these patients have mutations in the nuclear-encoded subunits of this complex, so vital for cellular energy production. After a brief summary of the current knowledge of complex I from cow, bacteria and fungi, this review presents the state of the art of the knowledge of the human nuclear-encoded complex I genes which, in the last 18 months, has made enormous progress. At present, the complete gene structure of four subunits and the cDNA structure of 18 of the 34 complex I nuclear-encoded subunits are known. Mapping of these subunits shows a random distribution over the chromosomes. The chromosomal localization is known for 14 complex I genes. Recently, the first mutation, a 5 bp duplication in the 18 kDa (AQDQ) subunit, has been reported. We expect that within 1 year all human nuclear-encoded complex I subunits will be cloned. Mutational analysis of these subunits is warranted in complex I-deficient patients and will not only be important for genetic counselling but will also extend the knowledge regarding the functional properties of the individual human complex I subunits.

Animals↗

Registration of congenital anomalies in ART populations: pitfalls.

Various methodological pitfalls preclude simple validation of the ostensible safety of offspring conceived thorough assisted reproductive technologies (ART). These pitfalls include lack of an appropriate comparison group (control), failure to take into account potential confounding variables, anomaly surveillance that is either too rigorous or too lax compared to the way in which anomalies are sought in general population surveys, and inconsistent criteria with respect to classifying anomalies (inclusion or exclusion of minor anomalies, internal anomalies evident only on ultrasound, and anomalies present in terminated pregnancies). To minimise these pitfalls, we recommend prospective surveillance for major anomalies, best defined as defects resulting in death, causing major handicap or necessitating surgery. Surveillance should ideally begin as soon as pregnancy is diagnosed. Data should be gathered allowing potential confounding variables to be taken into account, and systematic neonatal surveillance for anomalies should be performed during a designated time interval.

Confounding Factors, Epidemiologic↗

Molecular diagnosis of Y chromosome microdeletions in Europe: state-of-the-art and quality control.

The polymerase chain reaction (PCR) screening of microdeletions of the Y chromosome has become an important diagnostic step in the work-up of male infertility. However, there is no agreement about how this diagnosis should be performed. There are suggestions that the large variation in deletion frequency reported in the literature could be due to the various selection criteria of the patients analysed, although methodological aspects may play a role as well. As for other genetic diseases, molecular diagnosis of Y chromosome microdeletions should be controlled by adopting strict internal quality control measures and by participating in external quality assessment schemes. Such an external quality assessment project is presently being organized jointly by the European Academy of Andrology and the European Molecular Genetics Quality Network. Three preliminary trials have given a state-of-the-art picture of the diagnostic performance in various European laboratories, showing an overall rate of misdiagnosis of approximately 5% for both AZFb and AZFc regions, and providing data useful in the generation of guidelines for the molecular diagnosis of Y chromosome microdeletions.

Cytogenetic Analysis↗