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PubMed2002

Extremely high exposures in an obese patient receiving high-dose cyclophosphamide, thiotepa and carboplatin.

An obese 53-year-old woman (height 167 cm, weight 130 kg) with metastatic breast cancer received high-dose chemotherapy comprising cyclophosphamide, thiotepa and carboplatin (CTC). The cyclophosphamide (1 g/m(2) per day) and thiotepa (80 mg/m(2) per day) doses were based on body surface area (BSA) calculated using total body weight (TBW). The daily carboplatin dose was calculated based on the Calvert formula, using a target area under the plasma concentration-time curve (AUC) value of 3.25 mg.min/ml and applying the Cockcroft-Gault equation to estimate the glomerular filtration rate. The patient received the three agents as short infusions over four consecutive days. For therapeutic drug monitoring (TDM), blood samples were collected on day 1. Thiotepa and its main metabolite tepa, ultrafilterable platinum, cyclophosphamide and its activated metabolite 4-hydroxycyclophosphamide were determined. Individual pharmacokinetics were assessed using Bayesian analysis. Exposure to the individual compounds was determined by calculating the AUC. Exposures to 4-hydroxycyclophosphamide, the combination of thiotepa/tepa and carboplatin were 94%, 117% and 71% higher than the median respective exposures in a non-obese population of patients ( n=24) receiving similar doses. Because high AUCs of 4-hydroxycyclophosphamide, thiotepa/tepa and carboplatin correlate with increased toxicity, the treatment risk in this obese patient was significantly increased. Therefore doses were adapted on the 3rd day of the course. It is concluded that cyclophosphamide and thiotepa in obese patients should not be dosed on the basis of BSA incorporating TBW since the patient will be overexposed. Moreover, applying the Cockcroft-Gault equation to obese patients leads to an overprediction of creatinine clearance and, when used in the Calvert equation, consequently to a carboplatin dose that is too high. Obese patients represent a unique group of patients in which TDM is extremely valuable in optimizing dosing, particularly in high-dose chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2004

Dexamethasone as a probe for docetaxel clearance.

PURPOSE: A pilot study was conducted in 23 patients in order to assess the correlation between docetaxel clearance (CL) and pharmacokinetics of dexamethasone. Dexamethasone is mainly 6-beta hydroxylated by CYP3A4, and is regularly used as standard docetaxel premedication. Genotyping of known functional single nucleotide polymorphism (SNP) of CYP3A5 (G22893A) and mdr-1 (G2677T, G2677A, and C3435T) have been performed in order to tentatively correlate genotype with docetaxel and dexamethasone pharmacokinetics. PATIENTS AND METHODS: To be eligible for this study, patients were required to have a solid malignancy for which docetaxel was indicated. A population pharmacokinetic approach was used to determine individual pharmacokinetic parameters of both docetaxel and dexamethasone by Bayesian analysis, and to screen relationships between docetaxel CL and patients' demographic, phenotype and genotype covariates. RESULTS: Three different pharmacokinetic parameters of dexamethasone were significantly correlated with docetaxel CL: dexamethasone plasma clearance (DPC) that ranged between 7.7 and 27.2 l/h, urinary amount of 6beta-hydroxydexamethasone, and the ratio between urinary amount of 6beta-hydroxydexamethasone and unchanged dexamethasone. The best covariate model was docetaxel CL (l/h) = 356 x fu(alpha1-AG) x (1-0.17 x HPMT)(1+0.126 x DPC) where fu(alpha1-AG) is the unbound plasma fraction of docetaxel calculated from alpha1-acid glycoprotein plasma level, and HPMT is hepatic metastasis coded as 1 if present or 0 if absent. No significant difference in docetaxel CL was observed between the several genotypes. CONCLUSIONS: Dexamethasone may be used as a probe to predict docetaxel clearances, hence reducing interindividual variability.

Adult↗

PubMed2002

A Bayesian model of stereopsis depth and motion direction discrimination.

The extraction of stereoscopic depth from retinal disparity, and motion direction from two-frame kinematograms, requires the solution of a correspondence problem. In previous psychophysical work [Read and Eagle (2000) Vision Res 40: 3345-3358], we compared the performance of the human stereopsis and motion systems with correlated and anti-correlated stimuli. We found that, although the two systems performed similarly for narrow-band stimuli, broadband anti-correlated kinematograms produced a strong perception of reversed motion, whereas the stereograms appeared merely rivalrous. I now model these psychophysical data with a computational model of the correspondence problem based on the known properties of visual cortical cells. Noisy retinal images are filtered through a set of Fourier channels tuned to different spatial frequencies and orientations. Within each channel, a Bayesian analysis incorporating a prior preference for small disparities is used to assess the probability of each possible match. Finally, information from the different channels is combined to arrive at a judgement of stimulus disparity. Each model system--stereopsis and motion--has two free parameters: the amount of noise they are subject to, and the strength of their preference for small disparities. By adjusting these parameters independently for each system, qualitative matches are produced to psychophysical data, for both correlated and anti-correlated stimuli, across a range of spatial frequency and orientation bandwidths. The motion model is found to require much higher noise levels and a weaker preference for small disparities. This makes the motion model more tolerant of poor-quality reverse-direction false matches encountered with anti-correlated stimuli, matching the strong perception of reversed motion that humans experience with these stimuli. In contrast, the lower noise level and tighter prior preference used with the stereopsis model means that it performs close to chance with anti-correlated stimuli, in accordance with human psychophysics. Thus, the key features of the experimental data can be reproduced assuming that the motion system experiences more effective noise than the stereoscopy system and imposes a less stringent preference for small disparities.

Animals↗

PubMed1999

Germline origins in the human F9 gene: frequent G:C-->A:T mosaicism and increased mutations with advanced maternal age.

The factor IX gene (F9) is an advantageous system for analyzing recent spontaneous germline mutation in humans. Herein, the male:female ratio of mutation ("r") in F9 have been estimated by Bayesian analysis from 59 germline origin families. The overall "r" in F9 was estimated at 3.75. The "r"s varied with the type of mutation. The "r"s ranged from 6.65 and 6.10 for transitions at CpG and A:T to G:C transitions at non-CpG dinucleotides, respectively, to 0.57 and 0.42 for microdeletions/microinsertions and large deletions (>1 kb), respectively. The "r" for the two subtypes of non-CpG transitions differed (6.10 for A:T to G:C vs 0.80 for G:C to A:T). Somatic mosaicism was detected in 11% of the 45 origin individuals for whom the causative mutation was visualized directly by genomic sequencing of leukocyte DNA (estimated sensitivity of approximately one part in 20). Four of the five defined somatic mosaics had G:C to A:T transitions at non-CpG dinucleotides, hinting that this mutation subtype may occur commonly early in embryogenesis. The age at conception was analyzed for 41 US Caucasian families in which the age of the origin parent and the year of conception for the first carrier/hemophiliac were available. No evidence for a paternal age effect was seen. However, an advanced maternal age effect was observed (P=0.03) and was particularly prominent for transversions (average of the 79th percentile when maternal age was normalized for the year of conception). This suggests that an increased maternal age results in a higher rate of transmitted mutation, whereas the increased number of mitotic replications associated with advanced paternal age has little, if any, effect on the rate of transmitted mutation.

Adolescent↗

PubMed2006

Phylogenetics of Chinese Dryopteris (Dryopteridaceae) based on the chloroplast rps4-trnS sequence data.

Dryopteris is one of the largest and most taxonomically complex fern genera in the Dryopteridaceae, with 127 species occurring throughout temperate, sub-temperate, subtropical, and tropical China. Investigations of the evolutionary relationships of a subset of these Chinese Dryopteris species, using DNA sequence-based methods, specifically tested the monophyly of the genus and the validity of the previous subgeneric classifications. Sixty species of Dryopteris, four closely related non-Dryopteris and three species of Arachniodes, were used as outgroup taxa. The rps4-trnS region of the chloroplast genome was sequenced in these species for the first time. Both maximum parsimony (MP) and neighbor-joining (NJ) analyses identified six polyphyletic clades that contained Dryopteris species. These results were supported by a Bayesian analysis of the same data set. The phylogenetic patterns strongly suggest the polyphyletic status of Dryopteris; the monophyletic groupings of the species do not correspond with either Fraser-Jenkins [In: Bull Brit Mus (Nat Hist) Bot 14(3):183-218, 1986} or Wu (In: Flora Reipublica Popularis Sinicae Tomus 5 (1) pp 1-241, 2000] subgeneric classification of Dryopteris, except in a few specific cases. This work represents the first molecular systematic analyses of Chinese Dryopteris, and we propose the next steps necessary to recognize new subgenera of the genus.

Base Sequence↗

PubMed2006

Desmoid tumors -- a characterization of patients seen at Mayo Clinic 1976-1999.

Desmoid tumors occur with high frequency in individuals with Familial Adenomatous Polyposis (FAP). Because of this, individuals developing desmoid tumors may be referred for genetic risk assessment. Determining whether a person has a FAP-related desmoid tumor or a sporadic desmoid can be challenging. We sought to characterize the patients who were seen at our institution to determine if there were clinical differences in presentation between FAP-associated and sporadic desmoid tumors. We searched the Mayo Clinic-modified H-ICDA (Hospital adaptation of the International Classification of Diseases) diagnostic codes for all diagnoses of desmoid tumors in patients seen between 1976 and 1999. Charts were reviewed to determine accuracy of diagnosis, age when seen, gender, site of tumor, and presence of polyposis. A total of 454 patients (174 males and 280 females) met the search criterion. Of the 447 patients on whom all data was obtained, 70 had FAP and 377 had no evidence of FAP. The female/male ratio for FAP cases was 1.12 compared to female/male ratio of 1.71 for non-FAP cases. (P=0.17). Location of development of desmoid tumors was correlated with but not specific for distinguishing FAP from non-FAP desmoids. Abdominal desmoids comprised the majority of FAP desmoids and extra-abdominal desmoids comprised the majority of non-FAP desmoids (P<0.001) but age was not a discriminating factor. Using Bayesian analysis, we demonstrate how these findings can assist genetic professionals in their evaluation of patients with desmoid tumors by providing prior probabilities of FAP based upon clinical presentation.

Adenomatous Polyposis Coli↗

PubMed2006

Are higher vancomycin doses needed in ventricle-external shunted patients?

OBJECTIVE: Hydrocephalus is usually resolved by diverting cerebrospinal fluid through a surgically implanted intra-ventricular catheter (shunt). The aim of this study was to characterize vancomycin pharmacokinetic (PK) parameters and optimal dosage in shunted patients under vancomycin treatment. SETTING: Intensive Care and Neurosurgical Units. University Hospital. METHODS: Retrospective data of vancomycin blood concentrations, demographics and biochemical parameters, from a Therapeutic Drug Monitoring (TDM) program, in ventricle-external shunted patients (Group A) and controls (Group B) were collected. In all subjects, several blood samples at steady state conditions were drawn. Individual PK parameters such as drug clearance (CL) and volume of distribution (V) were estimated by using an one-compartmental PK model and later, dosage regimens were individually adjusted by Bayesian analysis. The obtained CL and V mean +/- standard deviation were compared between both groups (A versus B). Vancomycin dosage regimens between both groups were also compared. MAIN OUTCOME MEASURES: Patients demographics, clinical records, creatinine clearance by Cockcroft-Gault, vancomycin blood levels, vancomycin pK parameters and optimal initial IV vancomycin dosage. RESULTS: Forty-five patients were included in the study: 15 patients in group A and 30 subjects in group B. Significant differences between CL(A) and CL(B) means were observed, while not between V(A) and V(B). In shunted patients, the required vancomycin daily dose to reach target concentrations was significantly higher than the dose needed in the control group (49.25 +/- 12.28 mg/kg/day vs. 31.74 +/- 6.70 mg/kg/day; P < 0.0005). CONCLUSIONS: Greater vancomycin clearance was found in our shunted patients, thus they required higher vancomycin daily doses compared to the control group. Consequently, vancomycin TDM in shunted patients should be advisable in order to guarantee antibiotic blood concentrations within the recommended therapeutic range.

Adult↗

PubMed1984

Quantification of pulmonary thallium-201 activity after upright exercise in normal persons: importance of peak heart rate and propranolol usage in defining normal values.

Fifty-nine normal patients (34 angiographically normal and 25 clinically normal by Bayesian analysis) underwent thallium-201 imaging after maximal upright exercise. Lung activity was quantitated relative to myocardial activity and a lung/myocardial activity ratio was determined for each patient. Stepwise regression analysis was then used to examine the influence of patient clinical characteristics and exercise variables on the lung/myocardium ratio. Peak heart rate during exercise and propranolol usage both showed significant negative regression coefficients (p less than 0.001). No other patient data showed a significant relation. Using the regression equation and the estimated variance, a 95% confidence level upper limit of normal could be determined for a give peak heart rate and propranolol status. Sixty-one other patients were studied to validate the predicted upper limits of normal based on this model. None of the 27 patients without coronary artery disease had an elevated lung/myocardial ratio, compared with 1 of 8 with 1-vessel disease (difference not significant), 6 of 14 with 2-vessel disease (p less than 0.005), and 6 of 12 with 3-vessel disease (p less than 0.0001). Thus, lung activity on upright exercise thallium-201 studies can be quantitated relative to myocardial activity, and is inversely related to peak heart rate and propranolol use. Use of a regression analysis allows determination of a 95% confidence upper limit of normal to be anticipated in an individual patient.

Adult↗

PubMed1987

Computerized classification of congenital malformations using a modified Bayesian approach.

The diagnostic classification of children with dysmorphic features involves over 200 syndromes and 232 findings, with an average of about 15 findings per syndrome. A knowledge base expressed in terms of Boolean combinations of findings is impractical. The normal Bayesian method requires a very large incidence matrix with the vast majority of cells being zero. A modified Bayesian method is proposed in which each syndrome is described in terms of its associated findings, whose incidence P (S/D) are designated as essential (0.90), prevalent (0.90), occasional (0.70) or rare (0.15), whilst P(S/-D) ranged from (0.08) to (0.10). The Bayesian calculation determines the probability of the presence P(D/S) or the absence P(-D/S) of each syndrome. The differential diagnosis consisted of all syndromes whose presence has a probability greater than 0.85. One hundred and thirty-one cases from the Hanna Khoushi Developmental Pediatrics Center at Haifa's Rothschild Hospital were considered. Of the 42 cases for which the center's specialists reached a diagnosis, the system listed the correct diagnosis for 91%. The system reached a diagnosis in about half of the remaining 89 cases. The medical literature is arranged by syndrome whilst the computer allows a case by case approach, thereby avoiding the need for the physician to consider each syndrome to see if it fits his case. This study shows that our modified Bayesian analysis is a valid method for shortening the physician's search in an area of great diagnostic complexity.

Bayes Theorem↗

PubMedDate not supplied

Applications of an inexpensive microcomputer for the general radiologist.

Computer programs of interest to the general radiologist have been written by the author and others for an inexpensive microcomputer. Most of these programs are in the public domain and include: computer-assisted diagnosis; computer-assisted medical education; Bayesian analysis, general statistical analysis; word processing; and radiographic image analysis. Previously, computerized functions such as these have been limited to those with access to a large institutional computer. Due to the general availability of inexpensive microcomputers, the average radiologist or group can now afford the many benefits a computer can add to the practice of radiology.

Computer-Assisted Instruction↗

PubMed2005

Bayesian methodology incorporating expert judgment for ranking countermeasure effectiveness under uncertainty: example applied to at grade railroad crossings in Korea.

Transportation professionals are sometimes required to make difficult transportation safety investment decisions in the face of uncertainty. In particular, an engineer may be expected to choose among an array of technologies and/or countermeasures to remediate perceived safety problems when: (1) little information is known about the countermeasure effects on safety; (2) information is known but from different regions, states, or countries where a direct generalization may not be appropriate; (3) where the technologies and/or countermeasures are relatively untested, or (4) where costs prohibit the full and careful testing of each of the candidate countermeasures via before-after studies. The importance of an informed and well-considered decision based on the best possible engineering knowledge and information is imperative due to the potential impact on the numbers of human injuries and deaths that may result from these investments. This paper describes the formalization and application of a methodology to evaluate the safety benefit of countermeasures in the face of uncertainty. To illustrate the methodology, 18 countermeasures for improving safety of at grade railroad crossings (AGRXs) in the Republic of Korea are considered. Akin to "stated preference" methods in travel survey research, the methodology applies random selection and laws of large numbers to derive accident modification factor (AMF) densities from expert opinions. In a full Bayesian analysis framework, the collective opinions in the form of AMF densities (data likelihood) are combined with prior knowledge (AMF density priors) for the 18 countermeasures to obtain 'best' estimates of AMFs (AMF posterior credible intervals). The countermeasures are then compared and recommended based on the largest safety returns with minimum risk (uncertainty). To the author's knowledge the complete methodology is new and has not previously been applied or reported in the literature. The results demonstrate that the methodology is able to discern anticipated safety benefit differences across candidate countermeasures. For the 18 at grade railroad crossings considered in this analysis, it was found that the top three performing countermeasures for reducing crashes are in-vehicle warning systems, obstacle detection systems, and constant warning time systems.

Accidents, Traffic↗

PubMed2004

Venous Doppler in the prediction of acid-base status of growth-restricted fetuses with elevated placental blood flow resistance.

OBJECTIVE: This study was undertaken to test which venous Doppler parameter offers the best prediction of acid-base status at birth in pregnancies complicated by intrauterine growth restriction (IUGR) caused by placental dysfunction. STUDY DESIGN: A prospective cross-sectional Doppler study of IUGR fetuses with abnormal umbilical artery Doppler and birth weight less than the 10th percentile. Absence of atrial systolic forward velocities in the ductus venosus (DV) (DV-RAV) and umbilical vein (UV) pulsations were noted and multiple venous indices were calculated for the inferior vena cava (IVC) and DV (IVC and DV preload index, peak velocity index [PVIV] and pulsatility index [PIV] and the DV S/a ratio). Doppler indices, UV pulsations, and DV- RAV were related to an umbilical artery cord pH <7.20, and a pH <7.00 and/or base deficit greater than -13 (severe metabolic compromise) in neonates delivered by cesarean section without labor. RESULTS: In 122 fetuses all venous Doppler indices were equally predictive of a pH <7.20, with the exception of the IVC PVIV. No Doppler index predicted severe metabolic compromise. Bayesian analysis of individual Doppler parameters showed comparable outcome prediction with the highest sensitivity for the IVC PIV (76%) and the highest specificity for DV-RAV (96%). Combined assessment of the IVC, DV, and UV provided the most accurate outcome prediction. Doppler abnormality in either vessel identified 89% of neonates with pH <7.20 (negative predictive value 92%) and 10 of 11 neonates with severe metabolic compromise. Prediction was most specific (84%) when Doppler parameters were abnormal in all 3 vessels. CONCLUSION: IVC, DV, and UV Doppler parameters correctly predict acid-base status in a significant proportion of IUGR neonates. Combination, rather than single vessel assessment provides the best predictive accuracy. While the choice of Doppler index can be guided by operator preference, familiarity with the examination technique of all 3 vessels is encouraged to offer the highest flexibility in clinical practice.

Acid-Base Imbalance↗

PubMed2006

Determination of the minimal clinically important difference in the FIM instrument in patients with stroke.

OBJECTIVE: To define the minimal clinically important difference (MCID) for the FIM instrument in patients poststroke. DESIGN: Prospective case series discharged over a 9-month period. SETTING: Long-term acute care hospital. PARTICIPANTS: Patients with stroke (N=113). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Admission, discharge, and change scores were calculated for the total FIM, motor FIM, and cognitive FIM. Assessments of clinical change were rated at discharge on a 15-point (-7 to +7) Likert scale by attending physicians, with MCID defined at a cutoff score of 3. The FIM change scores associated with MCID were identified from receiver operating characteristic curves. Bayesian analysis was used to determine the probability of individual patients achieving MCID. RESULTS: FIM change scores associated with MCID were 22, 17, and 3 for the total FIM, motor FIM, and cognitive FIM, respectively. The accuracy of the MCID was greater when subjects were categorized based on admission FIM scores than when considering the sample as a whole. Larger FIM change scores were related to MCID in subjects with lower admission FIM scores. CONCLUSIONS: These findings will assist in the interpretation of FIM change scores relative to physicians' assessments of important clinical change.

Activities of Daily Living↗

PubMed2005

Relationship between taste thresholds and hunger under debate.

We determined taste recognition thresholds for six compounds (sucrose, fructose, sodium chloride, quinine sulphate, PROP and liquorice) in fasting students and, in the same subjects, after a meal. The testing procedure was the staircase-method in blind conditions. Although taste sensitivity may vary with hormonal status, our results did not show any significant difference in taste recognition thresholds between hunger and satiety. Our Bayesian analysis did not corroborate the hypothesis of increased sensitivity to nutrition-related tastants in the fasting state that was recently supported by data obtained with the two-alternative forced-choice method.

Adult↗

PubMed2004

An evaluation of a system that recommends microarray experiments to perform to discover gene-regulation pathways.

The main topic of this paper is modeling the expected value of experimentation (EVE) for discovering causal pathways in gene expression data. By experimentation we mean both interventions (e.g., a gene knockout experiment) and observations (e.g., passively observing the expression level of a "wild-type" gene). We introduce a system called GEEVE (causal discovery in Gene Expression data using Expected Value of Experimentation), which implements expected value of experimentation in discovering causal pathways using gene expression data. GEEVE provides the following assistance, which is intended to help biologists in their quest to discover gene-regulation pathways: Recommending which experiments to perform (with a focus on "knockout" experiments) using an expected value of experimentation method. Recommending the number of measurements (observational and experimental) to include in the experimental design, again using an EVE method. Providing a Bayesian analysis that combines prior knowledge with the results of recent microarray experimental results to derive posterior probabilities of gene regulation relationships. In recommending which experiments to perform (and how many times to repeat them) the EVE approach considers the biologist's preferences for which genes to focus the discovery process. Also, since exact EVE calculations are exponential in time, GEEVE incorporates approximation methods. GEEVE is able to combine data from knockout experiments with data from wild-type experiments to suggest additional experiments to perform and then to analyze the results of those microarray experimental results. It models the possibility that unmeasured (latent) variables may be responsible for some of the statistical associations among the expression levels of the genes under study. To evaluate the GEEVE system, we used a gene expression simulator to generate data from specified models of gene regulation. The results show that the GEEVE system gives better results than two recently published approaches (1) in learning the generating models of gene regulation and (2) in recommending experiments to perform.

Animals↗

PubMed2005

Acupuncture for tinnitus: a series of six n = 1 controlled trials.

OBJECTIVE: To explore patient perceived benefits of acupuncture for tinnitus. DESIGN: Controlled n=1 trials, with two phases A and B. SUBJECTS: Six patients with tinnitus. OUTCOME MEASURES: Primary outcome was Daily Diary records related to four tinnitus symptoms: loudness of tinnitus; pitch of tinnitus; waking hours affected with tinnitus; quality of sleep. Secondary outcomes were the Tinnitus Handicap Inventory (THI) and Measure Your Medical Outcome Profile (MYMOP). METHODS: Patients received a course of 10 acupuncture treatments over a 2-week period. Daily Diary entries related to the four tinnitus symptoms were recorded by patients for 14 days pre-treatment (phase A) and 14 days post-treatment (phase B). A hierarchical Bayesian model was used to combine the results from the individual patients to obtain estimates of the population and individual patient treatment effects, incorporating random variations at both levels (between patients and within patient). Tinnitus Handicap Inventory (THI) and Measure Your Medical Outcome Profile (MYMOP) were recorded at assessment points pre-treatment and post-treatment. RESULTS: Six patients participated in the trials, each receiving 10 treatments and completing all Daily Diary entries and outcome measures. For the of symptoms of loudness and pitch, there were variable treatment effects between patients, with a trend for the median overall reduction for loudness of -2.49 (-5.04, 0.02) and for pitch -1.39 (-3.74, 0.89), 95% credibility intervals being shown in brackets. For the other two symptoms, the waking hours affected and quality of sleep, patients' responses were more consistent, with amore credible overall median reduction for affected waking hours of -2.76 (-3.94, -1.63) and for quality of sleep -2.72 (-3.45, -2.03). The THI and MYMOP measures showed a trend of improvement after treatment. CONCLUSION: The n=1 trial methodology, with an AB design and Bayesian analysis, can be considered of value in exploring treatment effects for small numbers of patients receiving individualised treatments, as is common within complementary medicine. When the treatment effects from six patients were synthesized, the results of this study suggest that acupuncture may have a beneficial role in the treatment of tinnitus.

Acupuncture Therapy↗

PubMed2005

Fungus-growing termites originated in African rain forest.

Fungus-growing termites (subfamily Macrotermitinae, Isoptera) cultivate fungal crops (genus Termitomyces, Basidiomycotina) in gardens inside their colonies. Those fungus gardens are continuously provided with plant substrates, whereas older parts that have been well decomposed by the fungus are consumed (cf.). Fungus-growing termites are found throughout the Old World tropics, in rain forests and savannas, but are ecologically dominant in savannas. Here, we reconstruct the ancestral habitat and geographical origin of fungus-growing termites. We used a statistical model of habitat switching repeated over all phylogenetic trees sampled in a Bayesian analysis of molecular data. Our reconstructions provide strong evidence that termite agriculture originated in African rain forest and that the main radiation leading to the extant genera occurred there. Because extant savanna species are found in most genera, this moreover suggests that the savanna has repeatedly been colonized by fungus-growing termites. Furthermore, at least four independent "out-of-Africa" migrations into Asia, and at least one independent migration to Madagascar, have occurred. Although fungus growing by termites is ecologically most successful under the variable, unfavorable conditions of the savanna, it seems to have evolved under the more constant and favorable conditions of the rain forest.

Africa↗

PubMed2006

Molecular phylogeny of acantharian and polycystine radiolarians based on ribosomal DNA sequences, and some comparisons with data from the fossil record.

Polycystines (spumellarians, nassellarians, and collodarians), phaeodarians, and acantharians are marine planktonic protists that have been conventionally and collectively called "radiolaria". Recent molecular phylogenetic studies revealed radiolarian polyphyly with phaeodarians being a separate offshoot. Collodarians and nassellarians are also shown to form a monophyletic group, but other aspects of radiolarian phylogeny, such as interrelations among polycystines and acantharians, remained uncertain. Here, we present molecular phylogenetic analyses including new ribosomal RNA sequences from ten spumellarians and nine nassellarians, based on Bayesian and maximum-likelihood methods. Results indicate that the Polycystinea is a paraphyletic group, with Bayesian analysis suggesting that spumellarians form a clade with acantharians. The heliozoan-like protist Sticholonche appears as a sister to the spumellarian clade. The nassellarian Eucyrtidium is located outside the clade including the other nassellarians and collodarians. The mineralogy of the test of extant radiolarians and the tree topology obtained in this work suggest that acantharians and spumellarians evolved from an ancestor with a siliceous skeleton. Collodarians and nassellarians form a well-supported clade and one might infer from the fossil record that they may have diverged between the Jurassic and the Eocene.

Animals↗