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Is hirsutism an evolving syndrome?

The possibility that hirsutism is an evolving syndrome rather than a static condition involving only one gland has been considered. To assess this proposal 60 untreated hirsute patients aged 12-32 years were divided into five groups according to the duration of the hirsutism (less than 1, 1-2, 2-3, 3-5 and greater than 5 years). Peripheral plasma concentrations of LH and FSH, androstenedione, dehydroepiandrosterone sulphate, testosterone, 5 alpha-dihydrotestosterone, 5 alpha-androstane-3 alpha, 17 beta-diol, 5 alpha-androstane-3 beta, 17 beta-diol, cortisol, oestradiol-17 beta and oestrone were determined by radioimmunoassay. When the values obtained were compared with those from normal menstruating women, the results showed that in group I there was a significant increase only in the mean plasma 5 alpha-androstane-3 alpha, 17 beta-diol concentration. The mean concentration of this steroid was also raised in all other groups. In groups II and III mean basal levels of plasma dehydroepiandrosterone sulphate were also significantly increased and showed a marked increase after ACTH stimulation (1 mg tetracosactide acetate, i.m.) as did the concentrations of androstenedione and 17 alpha-hydroxyprogesterone. Finally, in groups IV and V, a significant increase in mean plasma concentrations of LH, androstenedione, oestrone and testosterone was found in the basal condition. The clinical picture also became gradually more severe from group I to group V. These data suggest that hirsutism could be an evolving syndrome progressively involving peripheral androgen metabolism, the adrenal gland and finally the ovary possibly through alterations of hypothalamic-pituitary function.

Adolescent↗

Evolving metacommunities: toward an evolutionary perspective on metacommunities.

The metacommunity framework predicts that local coexistence depends on the outcome of local species interactions and regional migration. In analogous fashion, spatial structure among populations can shape species interactions through evolutionary mechanisms. Yet, most metacommunity theories assume that populations do not evolve. Here, we evaluate how evolution shapes local species coexistence and exclusion within the multiscale and multispecies context embodied by the metacommunity framework. In general, coexistence in joint ecological-evolutionary models requires low to intermediate dispersal rates that can promote maintenance of both regional species and genetic diversity. These conditions support a set of key mechanisms that modify patterns of species coexistence including local adaptation, gene storage effects, genetic rescue effects, spatial genetic subsidies, and metacommunity evolution. Multispecies extensions indicate that correlated selection can further alter the outcome of interspecific interactions depending on the magnitude and direction of correlations and shape of fitness trade-offs. We suggest that an evolving metacommunity perspective has the potential to generate novel predictions about community structure and function by incorporating the genetic and species diversity that characterize natural communities. In adopting such a perspective, we seek to facilitate understanding about the interactions between evolutionary and metacommunity dynamics.

Biological Evolution↗

It is hard to predict the future: the evolving nature of threats and vulnerabilities.

This paper describes the evolving nature of threats and vulnerabilities associated with biological disasters with animal origins, and introduces some of the pitfalls and opportunities associated with anticipating future threats. Evolving threats and vulnerabilities include continued deforestation and encroachment on virgin habitats, the effects of globalisation on trade and transportation, the increased interdependence and social vulnerability of modern society, the commingling of intensive agriculture and traditional farming methods, the periodic appearance of pandemics and epizootics, and indications that numerous human actors are displaying an increasing interest in and capability of using biological agents as weapons. These developments must be viewed in the context of various impediments to accurately gauging future threats, such as the appearance of new elements that depart from current trends and the inherent difficulty in anticipating human, and especially terrorist, behaviour. The paper concludes with some broad recommendations for structuring a policy response to the threat in an environment of uncertainty about the future.

Bioterrorism↗

The evolving science of chemical risk assessment for land-applied biosolids.

Biosolids, effluents, and manures are widely applied to agricultural land and other land with varying degrees of pretreatment or control. Regulations governing land application of biosolids take several broad forms in different countries, including limitations based on rates that do not lead to increases in background chemical concentrations or risk assessment approaches such as those used in the United States. Risk assessment is a process that is inherently limited by currently available information and practices, and consequently, risk-based land application limits must be reevaluated periodically. For complex mixtures such as biosolids, three principal categories of information will be affected by changing practices and scientific advances: (i) chemical constituents present in the material, (ii) the nature of expected exposures, and (iii) toxicity of the chemical constituents. New analytical methods and lower detection limits will affect chemical identification in wastes. Approaches to exposure assessment, such as increasing emphasis on probabilistic analyses, will continue to evolve, and exposure assumptions will change as new studies provide better data on factors such as soil ingestion, plant uptake of chemicals, and bioavailability of chemicals in soil. Similarly, toxicity assessments will be updated as new studies are conducted. The evolving science over the past decade is illustrated by comparing approaches used by the USEPA to assess human health and ecological risks for the Part 503 rule compared with the more recent evaluation of dioxins and related compounds in biosolids. While risks of chemicals in land-applied biosolids and other residuals need to be periodically re-evaluated, such re-evaluations may take forms other than full risk assessments.

Animals↗

Evolving phage vectors for cell targeted gene delivery.

We adapted filamentous phage vectors for targeted gene delivery to mammalian cells by inserting a mammalian reporter gene expression cassette (GFP) into the vector backbone and fusing the pIII coat protein to a cell targeting ligand (i.e. FGF2, EGF). Like transfection with animal viral vectors, targeted phage gene delivery is concentration, time, and ligand dependent. Importantly, targeted phage particles are specific for the appropriate target cell surface receptor. Phage have distinct advantages over existing gene therapy vectors because they are simple, economical to produce at high titer, have no intrinsic tropism for mammalian cells, and are relatively simple to genetically modify and evolve. Initially transduction by targeted phage particles was low resulting in foreign gene expression in 1-2% of transfected cells. We increased transduction efficiency by modifying both the transfection protocol and vector design. For example, we stabilized the display of the targeting ligand to create multivalent phagemid-based vectors with transduction efficiencies of up to 45% in certain cell lines when combined with genotoxic treatment. Taken together, these studies establish that the efficiency of phage-mediated gene transfer can be significantly improved through genetic modification. We are currently evolving phage vectors with enhanced cell targeting, increased stability, reduced immunogenicity and other properties suitable for gene therapy.

Animals↗

Chronic myeloid leukemia: why does it evolve from chronic phase to blast transformation?

Clinically chronic myeloid leukemia is a biphasic or triphasic disease that is usually diagnosed in the initial 'chronic', 'indolent' or 'stable' phase and then spontaneously evolves after some years into an advanced phase. This advanced phase can sometimes be subdivided into an earlier accelerated phase and a later blast phase or blast transformation--in about one-half of patients the chronic phase transforms unpredictably and abruptly to a blast phase, while in the other half of patients, the disease evolves somewhat more gradually, through an accelerated phase, which may last for months or years, before a blast phase ensues; this may have myeloblastic or lymphoblastic features. Although much is now known about the molecular biology of the disease, the molecular basis of disease progression is still obscure. The popular thinking has been that one or more probably a sequence of additional genetic events occurs in the BCR-ABL positive clone. When the critical combination of additional events is achieved, clinically definable transformation occurs. Here we review what is known of the mechanisms underlying the evolution of chronic myeloid leukemia from a chronic phase to a blast transformation.

Animals↗

The evolving treatment of chronic hepatitis C: where we stand a decade out.

The treatment of hepatitis C has evolved rapidly since the identification of the hepatitis C virus (HCV) in 1989. Since the first accepted therapy for HCV infection, recombinant interferon, received marketing approval a little more than a decade ago, it has come to be used in combination with ribavirin for improved rates of sustained virologic response. Recently, pegylated versions of interferon have been developed for use with ribavirin, offering pharmacokinetic advantages and further improvements in response rates over conventional interferon. This article briefly reviews how these evolving regimens for HCV infection have addressed the subtle and singular characteristics of this challenging virus.

Antiviral Agents↗

Posterior thoracic segmental pedicle screw instrumentation: evolving methods of safe and effective placement.

The use of pedicle screw instrumentation in the spine has evolved over the last two decades. The initial use of pedicle screws began in the lumbar spine. As surgeons have become more comfortable with the complex anatomy required for accurate screw placement, the use of pedicle instrumentation has evolved to include their use in the thoracolumbar and thoracic spine. The impetus behind their increased use is a result of the many advantages that pedicle screw anchorage offers over traditional hook and rod constructs. Improved deformity correction and overall construct rigidity are two important advantages of pedicle screw instrumentation due its three-column control over the spinal elements. First, pedicle screw instrumentation obviates the need to place instrumentation within the spinal canal with its inherent risk of neurologic injury. Second, the placement of pedicle screws is independent of facet or laminar integrity and thus has been extremely useful in traumatic, neoplastic, and degenerative conditions. The benefits of pedicle screws in the thoracic spine has been tempered by the potential for catastrophic neurological or soft tissue injuries due to the close proximity of these structures. The narrow and inconsistent shape of the thoracic pedicles, especially in spinal deformity, makes their placement technically challenging. As a result, surgeons have employed a number of techniques to ensure the safe and efficacious placement of thoracic pedicle screws. Detailed anatomic landmarks used to determine pedicle location, intraoperative imaging including navigation, and neurophysiological monitoring are some of the techniques currently used by surgeons. The implementation of these techniques and a thorough understanding of the complex three-dimensional anatomy have allowed surgeons to successfully place thoracic and thoracolumbar pedicle screws.

Bone Screws↗

Rapidly evolving aphid gall effector proteins exhibit saposin-like folds.

Many insects manipulate plants by injecting effector proteins. In one extreme example of this molecular "hijacking", Hormaphis cornu aphids inject bicycle proteins into Hamamelis virginiana (Witch Hazel), contributing to the development of novel organs called galls. Bicycle proteins share no amino acid sequence similarity with proteins of known function. Here, we report the crystal structures of two divergent bicycle proteins. Both proteins contain saposin-like folds: one with multiple disulfide bonds exhibits a helix swap; the other has no disulfide bonds and possesses two tandem domains. To explore the structural evolution of bicycle proteins, we predicted bicycle protein structures with Alphafold2 (AF2). While AF2 did not recover the two experimental structures using existing databases, it succeeded after we provided multiple sequence alignments (MSAs) containing protein sequences encoded in new genome sequences from closely related aphid species. Using this customized approach at scale, we generated 2400 high-confidence predictions for bicycle proteins from seven aphid species. This dataset revealed that bicycle proteins without cysteines are outliers in fold space and appear to have evolved from ancestral proteins with disulfide-bonded saposin-like folds. While all bicycle proteins contain predicted saposin-like folds, they display a vast diversity of structural and physicochemical properties. While this diversity thwarts prediction of conserved functions encoded in structure, it suggests that bicycle proteins have evolved to target diverse plant processes and/or to evade plant immune surveillance.

AlphaFold predictions↗

Performance indicators. Defining and evolving the "right" measures of restructuring success.

In summary, it is important to define the "right" set of performance indicators to monitor the success of your Patient Focused restructuring program. Keep these indicators to the vital few--those reflecting the hospital's quality, service, environment and economic performance--rather than falling into the potential trap of the trivial many. Be sure to define many of these indicators in the customers' terms, not necessarily your own. Your Patient Focused program will mature across four primary eras--The Vision, The Plan, The Reality and The Journey. Several important aspects of your performance indicators must evolve along with it if they are to facilitate rather than hinder progress. This should happen naturally. However, it is always wise to keep an eye on these evolutions to ensure they aren't stifled by traditional paradigms, lingering biases and lack of attention. Defining and evolving the "right" performance indicators for your Patient Focused Care program will not only provide valid measures of success, but actually contribute to greater success as well!

Cost-Benefit Analysis↗

Evolving neurocontrollers for balancing an inverted pendulum.

This paper introduces an evolutionary algorithm that is tailored to generate recurrent neural networks functioning as nonlinear controllers. Network size and architecture, as well as network parameters like weights and bias terms, are developed simultaneously. There is no quantization of inputs, outputs or internal parameters. Different kinds of evolved networks are presented that solve the pole-balancing problem, i.e. balancing an inverted pendulum. In particular, controllers solving the problem for reduced phase space information (only angle and cart position) use a recurrent connectivity structure. Evolved controllers of 'minimal' size still have a very good benchmark performance.

Algorithms↗

Evolving concept of multipurpose workers scheme.

During recent years, a concept of multipurpose worker has been evolved and is being implemented in certain States. The implementation of this scheme requires continuous evaluation, so that job-description and training strategy could be modified in order to suit requirements and effectively solve the problems that may arise. This paper deals with the concept of MPW Scheme as it has been evolved and its operational aspects.

Allied Health Personnel↗

Photoelectric responses of oxygen-evolving complexes of photosystem II

The generation of a transmembrane electric potential difference induced by a series of laser flashes was studied by the direct electrometrical method in proteoliposomes containing oxygen-evolving particles of photosystem II. In addition to the fast stage of generation of the membrane potential, which is due to electron transfer from the redox active tyrosine residue Tyr-161 (YZ) to the primary quinone acceptor QA, electrogenic stages corresponding to the S1 --> S2 (tau = 30 &mgr;sec), S2 --> S3 (tau = 240 &mgr;sec), and S3 --> S4 --> S0 (tau = 6.2 msec) transitions of the oxygen-evolving complex (OEC) were observed. The amplitudes of the photoelectric responses show that the contribution of the OEC to the overall electrogenicity is small. The parameters of the electrogenic reactions of the OEC as measured in photosystem II preparations containing the peripheral proteins of 23 and 17 kD were similar to those of photosystem II preparations devoid of these peptides. It is concluded that neither the 23- nor the 17-kD proteins are involved in the electrogenic reactions of the OEC.

Journal Article↗

Isolation of fibroblast growth factor receptor binding sequences using evolved phage display libraries.

A fusion protein construct consisting of the short form of human fibroblast growth factor (FGFR) fused to the heavy chain of mouse IgG1 was used to screen four phage display libraries displaying 8, 13, 38 and 43 amino acids at the amino terminus of the bacteriophage M13 gene III minor coat protein. Phage with specific FGFR binding activity were isolated from the 13, 38 and 43 mer libraries. One of the highest affinity phage clones from the 13mer library was chosen to be further evolved by oligonucleotide saturation mutagenesis. We have isolated evolved sequences that have approximately 8 times the relative binding affinity of the parent sequence. The phage clones have a minimum consensus sequence of CR/SXLLXGAPFXXXXC, where X represents positions tolerant of several amino acids. A synthetic peptide based on this sequence specifically inhibits FGF from binding to its receptor in an in vitro ELISA.

Amino Acid Sequence↗

Viral RNA and evolved mutational robustness.

Many properties of organisms show great robustness against mutations. Whether this robustness is an evolved property or intrinsic to genetic systems is by and large unknown. An evolutionary origin of robustness would require a rethinking of key concepts in the field of molecular evolution, such as gene-specific neutral mutation rates, or the context-independence of deleterious mutations. We provide evidence that mutational robustness of the genome of RNA viruses to mutational changes in secondary structure has evolved. J. Exp. Zool. ( Mol. Dev. Evol.) 285:119-127, 1999.

Animals↗

The evolving role of radical surgery in the management of regionally advanced transitional cell carcinoma of the bladder.

The management of muscle-invasive transitional cell carcinoma (TCC) of the bladder continues to evolve. The standard treatment for patients presenting with clinical stage T2-4aN0M0 bladder cancer remains radical cystectomy. However, the management of patients who present with more advanced disease on clinical evaluation, such as unresectable pelvic tumor (T4b) or regional pelvic lymph node metastases (N+) remains unclear. In addition, the intraoperative management of unsuspected pelvic adenopathy identified during exploration of a planned radical cystectomy, continues to generate controversy. The following discussion relates to the evolving attitudes towards the role of surgery in the treatment of advanced bladder cancer.

Journal Article↗

Evolving methodologies in bipolar disorder maintenance research.

Background During the development of a new treatment for bipolar disorder, maintenance studies are used to evaluate the ability of the putative mood stabiliser to prevent relapse and recurrence of further episodes. Comparisons with the early bipolar disorder maintenance studies indicate that the methodologies of recent trials have evolved substantially. Aims To review the methods used in the first- and second-generation maintenance studies, highlighting the differences of the various designs. Method Literature review. Results Methods that have evolved the most include patient enrolment, randomisation schemes and the use of outcome measures and statistical analyses. In addition, regulatory and commercial issues have also influenced study design. Conclusion There is little consensus on the methodology of bipolar disorder maintenance studies. As the integration of newer therapies into routine clinical practice is dependent on the evidence from controlled studies, it is essential that future maintenance trials in bipolar disorder achieve adequate methodological rigour without sacrificing overall feasibility.

Journal Article↗

Racial divergence in abdominal bristles among parental races and newly evolved cytoraces of nasuta-albomicans complex of Drosophila.

Cytoraces are the products of interracial hybridization between Drosophila nasuta nasuta and D. nasuta albomicans. These races differ from their parents in the chromosome composition, mating preference, certain fitness phenotypes and also a few morphophenotypic traits. Now, these cytoraces are passing through 330 generations. Racial divergence in the 4th and 5th abdominal bristles among the parental races and the newly evolved cytorace 1 and 2 is reported. The results revealed that the parental races have more number of bristles than newly evolved cytoraces. Thus, these cytoraces are evolved/evolving with reduced abdominal bristle number and better fitness.

Animals↗