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PubMed2005

X-linked genes evolve higher codon bias in Drosophila and Caenorhabditis.

Comparing patterns of molecular evolution between autosomes and sex chromosomes (such as X and W chromosomes) can provide insight into the forces underlying genome evolution. Here we investigate patterns of codon bias evolution on the X chromosome and autosomes in Drosophila and Caenorhabditis. We demonstrate that X-linked genes have significantly higher codon bias compared to autosomal genes in both Drosophila and Caenorhabditis. Furthermore, genes that become X-linked evolve higher codon bias gradually, over tens of millions of years. We provide several lines of evidence that this elevation in codon bias is due exclusively to their chromosomal location and not to any other property of X-linked genes. We present two possible explanations for these observations. One possibility is that natural selection is more efficient on the X chromosome due to effective haploidy of the X chromosomes in males and persistently low effective numbers of reproducing males compared to that of females. Alternatively, X-linked genes might experience stronger natural selection for higher codon bias as a result of maladaptive reduction of their dosage engendered by the loss of the Y-linked homologs.

Animals↗
PubMed1986

Complete and delayed reversal of a large dyskinetic area with early spontaneous reperfusion during evolving myocardial infarction.

Sequential angiographic studies have shown that spontaneous reperfusion occurs in approximately 30 to 40% of patients during evolving myocardial infarction. However, it is difficult to establish the effects of spontaneous reperfusion on left ventricular function. We report the case of a 65 year old woman with clinical features of acute myocardial infarction with early spontaneous reperfusion and complete recovery of ventricular function 1 year later.

Aged↗
PubMed2007

Intraoperative neurophysiological monitoring technology: recent advances and evolving uses.

Intraoperative neurophysiological monitoring has evolved over the last 25 years to become an important component of many types of orthopedic and neurosurgical procedures. From its foundations in VIII cranial nerve surgeries and scoliosis corrections surgeries, intraoperative neurophysiological monitoring has expanded to incorporate nearly all spine procedures and many involving the brain and brainstem. Fundamental to this growth in the use of intraoperative neurophysiological monitoring has been the development of the technology used to perform the neurophysiological tests. Advancements in electronics and computer technology have resulted in significant improvements in the capacity, ease of use, quality and reliability of the equipment as well as the quality of and control over the acquired data. These technological advancements have resulted in remarkable improvements in not only the quality and availability of intraoperative neurophysiological monitoring, but also, as a consequence, patient care, and have arguably propelled the expansion of the use that intraoperative neurophysiological monitoring has seen over the last 10 years.

Biomedical Technology↗
PubMed2004

[Group psychotherapy: how it emerged and evolved].

This study aims to offer a historical overview of the emergence and evolution of group psychotherapy, tracing its roots, main models and theoretical bases. Its origin goes back to the beginning of the past century (1905), after which it evolved for five decades: the formative years. Further on, during the 50's and 60's, group psychotherapy went through a period of theoretical expansion, followed by a period of consolidation in the 70's, and maturation in the 80's and 90's. Finally, the study examines its recent evolution, highlighting the construction of new models. In the last few years, several treatment techniques have been developed to attend specific patient populations, with a variety of medical and psychosocial conditions, which suggests an increasing tendency towards a greater specificity of its application.

History, 20th Century↗
PubMed2001

Evidence of evolving carbaryl resistance in western corn rootworm (Coleoptera: Chrysomelidae) in areawide-managed cornfields in north central Kansas.

Susceptibility of adult populations of the western corn rootworm, Diabrotica virgifera virgifera LeConte, to carbaryl was determined by a survey in 1996 before the implementation of an areawide management program near Scandia in north central Kansas. Subsequently, the susceptibility of western corn rootworm adults to carbaryl has been monitored throughout the program from 1997 to 2000 in both control and managed areas. In 1996, adults were highly susceptible to carbaryl with a mean LC50 value of 0.64 microg/vial. This value was comparable to those for adults collected from other regions within Kansas. However, adult susceptibility to carbaryl decreased rapidly within the managed area, where the cucurbitacin- carbaryl-based bait SLAM has been used as the primary tool to control adults in this project since 1997. In 1999, adults collected from the managed area were 9- and 20-fold less susceptible to carbaryl at the LC50 and LC90 levels, respectively, than those evaluated in 1996. In contrast, adults collected from the control area were only 2- and 3-fold less susceptible to carbaryl at the LC50 and LC90 levels, respectively, than adults evaluated in 1996. Although field adult populations of western corn rootworm were relatively low in 2000, evaluations showed trends similar to those in 1999 regarding their carbaryl susceptibility in the managed and control areas. These results provide evidence that western corn rootworm has been evolving carbaryl resistance rapidly in response to the use of SLAM in areawide-managed cornfields near Scandia.

Animals↗
PubMed1998

The evolving epidemiology of chlamydial and gonococcal infections in response to control programs in Winnipeg, Canada.

OBJECTIVES: The purpose of this study was to describe and compare the transmission dynamics of chlamydia and gonorrhea in Winnipeg, Manitoba, Canada, and to assess implications for control programs. METHODS: Chlamydia and gonorrhea surveillance case reports (1988 through 1995) and contact-tracing reports (1991 through 1995) were examined. RESULTS: High incidence rates of both chlamydia and gonorrhea clustered in geographic core areas characterized by low socioeconomic status. A decline in the number of reported cases of chlamydia (61%) and gonorrhea (64%) occurred between 1988 and 1995. For chlamydia, the decline was most prominent in non-core area cases, while for gonorrhea it was similar in core and non-core areas. CONCLUSIONS: Chlamydia and gonorrhea appear to be evolving through different epidemic phases, with chlamydia transmission, in response to a newly introduced control program, becoming more core dependent and gonorrhea transmission becoming more sporadic in the face of a sustained control effort. Focused control programs, based on an understanding of the transmission dynamics of chlamydia and gonorrhea, may make their elimination a feasible goal.

Adolescent↗
PubMed2006

Pharmacovigilance during the pre-approval phases: an evolving pharmaceutical industry model in response to ICH E2E, CIOMS VI, FDA and EMEA/CHMP risk-management guidelines.

Pharmacovigilance science has traditionally been a discipline focussed on the postmarketing or post-authorisation period, with due attention directed towards pre-clinical safety data, clinical trials and adverse events. As the biological sciences have evolved, pharmacovigilance has slowly shifted toward earlier, proactive consideration of risks and potential benefits of drugs in the pre- and peri-approval stages of drug development, leading to a maturing of drug safety risk management. Further advances in biology, pharmacology and improvements in computational applications to medicine have led to the development of more complex medicines previously unobtainable and have also permitted a more thorough assessment of risks and potential benefits even earlier in the development process. Elevated public concern with the safety of more sophisticated medicines, combined with new science, have led pharmaceutical innovators, regulators and healthcare professionals to collaborate to develop guidelines, which drive enhanced pharmacovigilance and safety risk management earlier in drug development. In this paper, we review international guidelines on pharmacovigilance planning applicable to the pre-approval phases of medicines development and provide author opinion on these guidelines' potential drug safety implications. We discuss the possible evolution of a pharmaceutical industry model to respond to these guidelines; a view on multidisciplinary safety management teams is provided to encourage refinement of safety-signal identification and risk assessment early in drug development and to communicate important safety concerns to internal research efforts, patients, investigators and regulators. We further describe these functions in the context of the complexities of vulnerable populations, including the example of medicines research for paediatric populations. We also discuss the special role of epidemiology in pre-approval drug development and the impact on epidemiological science of changes to the pharmacovigilance paradigm.

Adverse Drug Reaction Reporting Systems↗
PubMed1987

Intravenous anisoylated plasminogen streptokinase activator complex versus intravenous streptokinase in evolving myocardial infarction. Preliminary data from a randomised multicentre study.

The efficacy of a single intravenous bolus of anisoylated plasminogen streptokinase activator complex (APSAC 30U in 4 to 5 minutes) versus an intravenous infusion of streptokinase (1.5 X 10(6) U in 60 minutes) was assessed in 86 patients with evolving myocardial infarction of less than 6 hours duration in a cooperative randomised study. The patency of the infarct-related artery was assessed by coronary angiography at, on average, 90 minutes after therapy (mean time: APSAC 95 minutes, streptokinase 105 minutes). The treatment groups were similar with respect to sex, age, location of myocardial infarction and the delay from onset of pain to treatment. The 90-minute patency rate (grade 2 to 3) was 71.8% in the APSAC group and 55.8% in the streptokinase group; the difference was not statistically significant. There was no difference between the drop in fibrinogen concentrations in the 2 groups at 3 or 24 hours. The minimal concentration obtained at the first assessment was +/- 0.2 g/L in the streptokinase group and 0.5 g/L in the APSAC group. One patient in the APSAC group, who had a previous meningeal bleeding, had a non-fatal cerebrovascular accident. In a subgroup of 38 patients who had 3 control coronary angiograms at 90 minutes, 24 hours and 3 weeks, the patency rate was 63, 82 and 93%, respectively, in the APSAC group and 48, 88 and 92%, respectively, in the streptokinase group (the difference was not statistically significant). None of the patients in the APSAC group presented with reocclusion, whilst 3 patients in the streptokinase group had reocclusions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2004

Antipsychotic drugs: evolving mechanisms of action with improved therapeutic benefits.

One of the conundrums of neuropharmacology is to understand the therapeutic mechanisms of action of antipsychotic drugs. Every drug with antipsychotic activity is a dopamine (DA) D(2)-like receptor antagonist and therefore this function is critical to reducing psychotic symptoms. However, the actions of the archetypal atypical antipsychotic drug clozapine go beyond antipsychotic effects because the drug is efficacious in treating psychotic symptoms that do not respond to drugs mainly directed at antagonizing the DA D(2) receptor, has benefits in cognition and has recently been shown to reduce levels of suicide. A growing understanding of the mechanisms of clozapine and other atypical antipsychotic drugs suggests that both partial and inverse agonism, as well as receptor antagonism, at specific neurotransmitter receptors is required to give full therapeutic benefits. It is, therefore, timely to review the evolving nature of the mechanisms of action of different antipsychotic drugs.

Animals↗
PubMed2002

Particle retention and flow in the pharynx of the enteropneust worm Harrimania planktophilus: the filter-feeding pharynx may have evolved before the chordates.

An investigation of the feeding behavior of the acorn worm Harrimania planktophilus suggests a novel form of enteropneust feeding with significant phylogenetic implications. H. planktophilus is a holoinfaunal worm that feeds on deposited sediments, and filter feeds on suspended particles in interstitial pore water. To visualize the particle retention behavior involved in filter feeding, adult animals were held in chilled seawater under low light and fed food coloring and fluorescent particles. The behavior was recorded by videography. Most particles ingested were drawn into the mouth by an incurrent flow created by cilia on the pharyngeal bars and without the aid of mucus. Particles that passed freely through the gill pores averaged 3.04 microm, whereas particles retained in the gut and defecated in the feces averaged 13.9 microm. Food coloring entered the mouth and was pumped through the pharynx at a rate of 0.5-2.0 mm/s. There is no evidence of an endostyle or mucus-net capture mechanism in H. planktophilus, but instead particles are filtered and manipulated by a dense covering of cilia on the pharyngeal gill bars. This study suggests that the filter-feeding pharynx is not an innovation of the chordates, but evolved prior to the evolutionary divergence of the hemichordate-echinoderm clade from the chordates.

Animals↗
PubMed2006

A novel recently evolved gene C19orf24 encodes a non-classical secreted protein.

Secreted proteins play important roles in many crucial biological processes, and can be new agents or targets for drug therapies. Here, we report on the isolation and characterization of a novel human non-classical secreted protein which is encoded by the hypothetical gene C19orf24 (chromosome 19 open reading frame 24). It has no signal peptide, but can still secrete extracellularly despite the presence of the inhibitor brefeldin A (BFA), proving its non-classical secreted protein status. Via subcellular localization using C19orf24 in vivo and transfected pEYFP-Golgi plasmid in Hela cells, C19orf24 was shown not to co-localize in the Golgi apparatus, which suggested that it secretes via a new and unknown pathway. Deglycosylation analysis with PNGase F verified that it has no N-glycosylation modification sites. Via the reverse transcription-PCR method, it was found to be expressed only in the human liver, and preferentially in normal tissue. In addition, C19orf24 was shown to be a recently evolved gene, found only in Homo sapiens and Pan troglodytes. By calculating its synonymous and non-synonymous substitution rate (d (S)/d (N)), we found that it experienced a purifying selection, which suggests that C19orf24 may have a special, irreplaceable biological function in the human organism.

Amino Acid Sequence↗
PubMed1998

Evaluation of fast disintegrants in terfenadine tablets containing a gas-evolving disintegrant.

Effects of four fast disintegrants on the dissolution of terfenadine tablets containing the gas-evolving disintegrant, CaCO3, were evaluated. In addition, effects of presence of starch along with the fast disintegrants on the dissolution of the tablets were examined. Dissolution data were treated to give dissolution parameters which reflected efficiency of the disintegrant combinations. The four fast disintegrants improved disintegration/dissolution of the original formulation. The relative efficiency of improvement was in the order crospovidone > Ac-Di-Sol > Primojel > low substituted hydroxypropylcellulose. The presence of starch advertently affected the role of the fast disintegrants. Scanning electron microscope studies revealed that starch covered the drug-containing granules and other particles of the tablet. pH changes during dissolution of representative tablets in 0.1 N HCl solutions were determined at specific time intervals. The progressive decrease in rates of acid consumption as a function of the amount of starch, along with the SEM studies, suggested that a barrier existed around the tablet particles. The barrier was generated by the swelled starch grains and was responsible for the loss of the dissolution-improving capacity of the fast disintegrants. Furthermore, the barrier interfered with the diffusion of the hydronium ions and therefore, impaired the function of the disintegrant combination.

Calcium Carbonate↗
PubMed2004

[CD5- CD11c+ CD23- small lymphocytic lymphoma evolving from aplastic anemia].

A 91-year-old woman was hospitalized with acute respiratory distress syndrome due to pneumonia in June 1997. Since she had pancytopenia and a bone marrow aspirate indicated hypocellularity with no increase in myeloblasts, dysplasia or abnormal chromosomes, aplastic anemia (AA) was diagnosed. Pulse therapy with methylprednisolone and antibiotics proved successful, and blood cell numbers stabilized. In June 2001, she was readmitted to our hospital with persistent low grade fever and leukopenia. A bone marrow aspirate from the sternum and iliac bone biopsy revealed compact proliferation of small lymphocytes, and the surface marker CD5- CD10- CD11c+ CD19+ CD20+ CD23- was detected through immune staining and flowcytometry. CD30+, CD34+and CD56+cells were scarce. Tests for surface immunoglobulins, IgG, IgA, IgM and IgD, were negative. No nodal or extranodal lesions were evident. Since Southern blot analysis of bone marrow cells indicated rearrangement of the immunoglobulin heavy chain and abnormal chromosomes were evident, small lymphocytic lymphoma (SLL) was diagnosed. Four intravenous infusions of rituximab (375mg/m2) were administered without critical adverse effects. Tests conducted four weeks later revealed saturation of CD20+ antigens of lymphoma cells and chromosomal abnormalities and rearrangement of the immunoglobulin heavy chain were still apparent. Though complete remission of the pancytopenia was not achieved, serum concentrations of lactate dehydrogenase and soluble interleukin-2 receptor decreased, and the numbers of platelets and erythrocytes increased. There was also an improvement in systemic condition. This was a rare case of SLL having the surface marker of CD5- CD10- CD11c+ CD19+ CD20+ CD23-, which had evolved from AA and infiltrated bone marrow.

Aged↗
PubMed2006

Comparison of conference abstracts and presentations with full-text articles in the health technology assessments of rapidly evolving technologies.

OBJECTIVES: To assess the extent of use of data from conference abstracts and presentations in health technology assessments (HTAs) provided as part of the National Institute for Health and Clinical Excellence (NICE) appraisal process. Also to assess the methodological quality of trials from conference abstracts and presentations, the consistency of reporting major outcomes between these sources and subsequent full-length publications, the effect of inclusion or exclusion of data from these sources on the meta-analysis pooled effect estimates, and the timeliness of availability of data from these sources and full articles in relation to the development of technology assessment reviews (TARs). DATA SOURCES: A survey of seven TAR groups. An audit of published TARs: included all NICE TARs published between January 2000 and October 2004. Case studies of selected TARs. REVIEW METHODS: Analyses of the results of the survey and audit were presented as a descriptive summary and in a tabular format. Sensitivity analyses were carried out to compare the effect of inclusion of data from abstracts and presentations on the meta-analysis pooled effect estimates by including data from both abstracts/presentations and full papers, and data from only full publications, included in the original TAR. These analyses were then compared with meta-analysis of data from trials that have subsequently been published in full. RESULTS: All seven TAR groups completed and returned the survey. Five out of seven groups reported a general policy that included searching for and including studies available as conference abstracts/presentations. Five groups responded that if they included data from these sources they would carry out methodological quality assessment of studies from these sources using the same assessment tools as for full publications, and manage the data from these sources in the same way as fully published reports. All groups reported that if relevant outcome data were reported in both an abstract/presentation and a full publication, they would only consider the data in the full publication. Conversely, if data were only available in conference abstract/presentation, all but two groups reported that they would extract and use the data from the abstract/presentation. In total, 63 HTA reports for NICE were identified. In 20 of 63 TARs (32%) explicit statements were made with regards to inclusion and assessment of data from abstracts/presentations. Thirty-eight (60%) identified at least one randomised controlled trial (RCT) available as a conference abstract or presentation. Of these, 26 (68%) included trials available as abstracts/presentations. About 80% (20/26) of the 26 TARs that included RCTs in abstract/presentation form carried out an assessment of the methodological quality of such trials. In 16 TARs full reports of these trials were used for quality assessment where both abstracts/presentations and subsequent full publications were available. Twenty-three of 63 TARs (37%) carried out a quantitative analysis of results. Of these, ten (43%) included trials that were available as abstracts/presentations in the review; however, only 60% (6/10) of these included data from abstracts/presentations in the data analysis of results. Thirteen TARs evaluated rapidly evolving technologies and only three of these identified and included trial data from conference abstracts/presentations and carried out a quantitative analysis where abstract/presentation data were used. These three TARs were used as case studies. In all three case studies the overall quality of reporting in abstracts/presentations was generally poor. In all case studies abstracts and presentations failed to describe the method of randomisation or allocation concealment. Overall, there was no mention of blinding in 66% (25/38) of the abstracts and in 26% (7/27) of the presentations included in case studies, and one presentation (4%) explicitly stated use of intention-to-treat analysis. Results from one case study demonstrated discrepancies in data made available in abstracts or online conference presentations. Not only were discrepancies evident between these sources, but also comparison of conference abstracts/presentations with subsequently published full-length articles demonstrates data discrepancies in reporting of results. Sensitivity analyses based on one case study indicated a change in significance of effect in two outcome measures when only full papers published to date were included. CONCLUSIONS: There are variations in policy and practice across TAR groups regarding searching for and inclusion of studies available as conference abstracts/presentations. There is also variation in the level of detail reported in TARs regarding the use of abstracts/presentations. Therefore, TAR teams should be encouraged to state explicitly their search strategies for identifying conference abstracts and presentations, their methods for assessing these for inclusion, and where appropriate how the data were used and their effect on the results. Comprehensive searching for trials available as conference abstracts/presentations is time consuming and may be of questionable value. However, there may be a case for searching for and including abstract/presentation data if, for example, other sources of data are limited. If conference abstracts/presentations are to be included, the TAR teams need to allocate additional time for searching and managing data from these sources. Incomplete reporting in conference abstracts and presentations limits the ability of reviewers to assess confidently the methodological quality of trials. Where conference abstracts and presentations are considered for inclusion in the review, the TAR teams should increase their efforts to obtain further study details by contacting trialists. Where abstract/presentation data are included, reviewers should discuss the effect of including data from these sources. Any data discrepancies identified across sources in TARs should be highlighted and their impact discussed in the review. In addition, there is a need to carry out, for example, a sensitivity analysis with and without abstract/presentation data in the analysis. There is a need for research into the development of search strategies specific to identification of studies available as conference abstracts and presentations in TARs. Such strategies may include guidance with regard to identification of relevant electronic databases and appropriate conference sites relevant to certain clinical areas. As there are limited case studies included in this report, analyses should be repeated as more TARs accrue, or include the work of other international HTA groups.

Adult↗
PubMed2003

Heterozygous mutations of the gene for Kir 1.1 (ROMK) in antenatal Bartter syndrome presenting with transient hyperkalemia, evolving to a benign course.

Bartter-like syndrome encompasses a set of inherited renal tubular disorders associated with hypokalemic metabolic alkalosis, renal salt wasting, hyperreninemic hyperaldosteronism, and normal blood pressure. Antenatal Bartter syndrome, a subtype of Bartter-like syndrome, is characterized by polyhydramnios, premature delivery, life-threatening episodes of fever and dehydration during the early weeks of life, growth retardation, hypercalciuria, and early-onset nephrocalcinosis. Mutations in the bumetanide-sensitive Na-K-2Cl cotransporter (NKCC2) and ATP-sensitive inwardly rectifying potassium channel (ROMK) of the thick ascending limb of Henle's loop have been identified in the antenatal Bartter syndrome. We report the identification of two heterozygous mutations of the gene for Kir 1.1 (ROMK) from an antenatal Bartter syndrome patient who presented at birth with mild salt wasting and a biochemical findings that mimicked primary pseudohypoaldosteronism type 1, such as hyperkalemia and hyponatremia, and evolved to a relatively benign course. We have identified amino acid exchanges Arg338Stop and Met357Thr in the gene exon 5 for ROMK by PCR and direct sequencing. Both mutations alter the C-terminus of the ROMK protein, and can affect channel function.

Amino Acid Substitution↗
PubMed2003

A model of spatially evolving herpesvirus epidemics causing mass mortality in Australian pilchard Sardinops sagax.

In 1995 mass mortality of pilchards Sardinops sagax occurred along >5000 km of Australian coast; similar events occurred in 1998/99. This mortality was closely associated with a herpesvirus. The pilchard is an important food source for larger animals and supports commercial fisheries. Both epidemics originated in South Australian waters and spread as waves with velocities of 10 to 40 km d(-1). Velocity was constant for a single wave, but varied between the epidemics and between the east- and west-bound waves in each epidemic. The pattern of mortality evolved from recurrent episodes to a single peak with distance from the origin. A 1-dimensional model of these epidemics has been developed. The host population is divided into susceptible, infected and latent, infected and infectious, and removed (recovered and dead) phases; the latent and infectious periods are of fixed duration. This model produces the mortality patterns observed locally and during the spread and evolution of the epidemic. It is consistent with evidence from pathology. The wave velocity is sensitive to diffusion coefficients, viral transmission rates and latent period. These parameters are constrained using the local and large-scale patterns of epidemic spread. The relative roles of these parameters in explaining differences between epidemics and between east- and west-bound waves within epidemics are discussed. The model predicts very high levels of infection, indicating that many surviving pilchards recovered following infection. Control appears impracticable once epidemics are initiated, but impact can be minimised by protecting juvenile stocks.

Animals↗
PubMed2000

Evolving faces from principal components.

A system that uses an underlying genetic algorithm to evolve faces in response to user selection is described. The descriptions of faces used by the system are derived from a statistical analysis of a set of faces. The faces used for generation are transformed to an average shape by defining locations around each face and morphing. The shape-free images and shape vectors are then separately subjected to principal components analysis. Novel faces are generated by recombining the image components (eigenfaces) and then morphing their shape according to the principal components of the shape vectors (eigenshapes). The prototype system indicates that such a statistical analysis of a set of faces can produce plausible, randomly generated photographic images.

Biological Evolution↗
PubMed2005

The evolving role of aromatase inhibitors in adjuvant breast cancer therapy.

The development of third-generation aromatase inhibitors (AIs) has brought about a major change in the therapeutic approach to patients with hormone-sensitive breast cancer. In randomized clinical trials, each of the third-generation AIs has demonstrated efficacy in the adjuvant treatment of postmenopausal women with receptor-positive tumors. Anastrozole has been shown to improve disease-free survival when compared with standard first-line tamoxifen, letrozole has been shown to further reduce the rate of breast cancer events when given as extended adjuvant therapy in women completing between 4.5 and 6 years of tamoxifen, and exemestane has been shown to improve disease-free survival when substituted for tamoxifen after an initial 2-3 years of adjuvant therapy. Although long-term follow-up for safety and overall survival continues in each of these trials, currently available data suggest that an AI should now be included as part of adjuvant endocrine therapy for the great majority of receptor-positive postmenopausal patients. To address these rapidly evolving issues related to the endocrine adjuvant treatment of postmenopausal women, an expert panel met in March 2004 in Hamburg, Germany, the site of the Fourth European Breast Cancer Conference. The panel's overview of recent endocrine data is presented along with updated results where available. In addition, case-based discussions are included to provide direction on how to integrate recent endocrine adjuvant clinical trial findings into everyday practice.

Antineoplastic Agents↗