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PubMed2006

Subjective and behavioural consequences of striatal dopamine depletion in schizophrenia--findings from an in vivo SPECT study.

Dysphoria is an integral part of the symptomatology of a variety of clinical states, though there is little empirical data available on the qualitative and quantitative aspects of this phenomenon. The purpose of the study was to administer alphamethyl paratyrosine (AMPT), a catecholamine depleting agent as a chemical probe to induce dysphoria, and document the ensuing changes in mental status. AMPT (4-5 g/day) was administered to a group of medication-free schizophrenic patients (n=13) over a 48 hour period, and changes in their mental status were monitored at 12 hour intervals with the Profile of Mood States (POMS), Addiction Research Center Inventory (ARCI), Drug Attitude Inventory (DAI) and other standardized rating scales. All of the subjects experienced dysphoric responses of variable severity. The profile of changes included blunted pleasure responsivity, clouded thinking, loss of motivation and lowered vigilance. Subtle subjective changes were experienced soon after the first dose of AMPT and the dysphoria steadily worsened, resulting in social withdrawal and personal distress. Subjective responses were the earliest to manifest, followed by akathisia, akinesia and rigidity. We conclude that AMPT induced dopamine depletion is a safe, rapid, reliable and reversible method of studying dysphoric states in humans. The technique is helpful in examining the phenomenology of dysphoria, the temporal relationship between subjective and behavioural consequences of dopamine depletion, and the role of dopamine in mediating subtle aspects of pleasure responsivity, which is in turn crucial to the understanding of treatment non-adherence in schizophrenia and the origins of comorbid substance abuse.

Adult↗
PubMed1987

Clinical features of patients with high-altitude pulmonary edema in Japan.

Clinical studies were performed in 27 consecutive patients with high-altitude pulmonary edema who were transported from the mountains to Shinshu University Hospital, Matsumoto, Japan. The altitude of onset was 2,680 m to 3,190 m above sea level. Symptoms included marked dyspnea, cough, and stridor. Physical findings included cyanosis, tachycardia, and rales. Neurologic disturbances, which were seen in 17 patients, included headache, vomiting, memory disturbance, clouding of consciousness, or coma. Chest roentgenograms revealed patchy infiltrates throughout the pulmonary fields, often in an asymmetric pattern, and enlargement of the right ventricle. Hemodynamic studies by right cardiac catheterization showed that high-altitude pulmonary edema was noncardiogenic. Scintiscans of the lungs with technetium-99m-macroaggregated albumin (99mTc-MAA) performed in one patient showed decreased perfusion of 99mTc-MAA in the area of infiltrates. Pulmonary edema fluid collected through the endotracheal tube in two patients was rich in protein. Computerized tomograms of the brain showed small ventricles and cisterns, disappearance of sulci, and diffuse low density of the cerebrum, indicating cerebral edema in eight of nine cases. Retinal hemorrhage and papilledema were observed in five patients.

Adolescent↗
PubMed2005

Model simulation of meteorology and air quality during the summer PUMA intensive measurement campaign in the UK West Midlands conurbation.

The Regional Atmospheric Modeling System (RAMS) and Urban Airshed Model (UAM IV) have been implemented for prediction of air pollutant concentrations within the West Midlands conurbation of the United Kingdom. The modelling results for wind speed, direction and temperature are in reasonable agreement with observations for two stations, one in a rural area and the other in an urban area. Predictions of surface temperature are generally good for both stations, but the results suggest that the quality of temperature prediction is sensitive to whether cloud cover is reproduced reliably by the model. Wind direction is captured very well by the model, while wind speed is generally overestimated. The air pollution climate of the UK West Midlands is very different to those for which the UAM model was primarily developed, and the methods used to overcome these limitations are described. The model shows a tendency towards under-prediction of primary pollutant (NOx and CO) concentrations, but with suitable attention to boundary conditions and vertical profiles gives fairly good predictions of ozone concentrations. Hourly updating of chemical concentration boundary conditions yields the best results, with input of vertical profiles desirable. The model seriously underpredicts NO2/NO ratios within the urban area and this appears to relate to inadequate production of peroxy radicals. Overall, the chemical reactivity predicted by the model appears to fall well below that occurring in the atmosphere.

Air Pollutants↗
PubMed2001

Evolution of digital organisms at high mutation rates leads to survival of the flattest.

Darwinian evolution favours genotypes with high replication rates, a process called 'survival of the fittest'. However, knowing the replication rate of each individual genotype may not suffice to predict the eventual survivor, even in an asexual population. According to quasi-species theory, selection favours the cloud of genotypes, interconnected by mutation, whose average replication rate is highest. Here we confirm this prediction using digital organisms that self-replicate, mutate and evolve. Forty pairs of populations were derived from 40 different ancestors in identical selective environments, except that one of each pair experienced a 4-fold higher mutation rate. In 12 cases, the dominant genotype that evolved at the lower mutation rate achieved a replication rate >1.5-fold faster than its counterpart. We allowed each of these disparate pairs to compete across a range of mutation rates. In each case, as mutation rate was increased, the outcome of competition switched to favour the genotype with the lower replication rate. These genotypes, although they occupied lower fitness peaks, were located in flatter regions of the fitness surface and were therefore more robust with respect to mutations.

Biological Evolution↗
PubMed2001

Occurrence of thyroid papillary carcinoma in young patients. A Chernobyl connection?

The risk of thyroid papillary carcinoma is increased by external radiation particularly in children under 15 years of age as shown by a marked increase in those exposed to radiation after Chernobyl. We were recently confronted in Belgium over a short period with four patients (3 F, 1 M) with papillary thyroid carcinoma who were aged 10 years, 2 months, 2 years and 6 years when the Chernobyl accident occurred. We thus raise the question of a possible relationship. The patients were aged 17, 11, 10, 19 years at presentation. They all presented fortuitously over 3 years which was a very unusual increase in our extensive experience in thyroid surgery (62 cases of thyroid cancer among 1014 thyroidectomies in adults vs 4 cases in 18 children since the Chernobyl accident in 1986). Two out of the four patients had psammoma bodies (identifiable on CT scanning and ultrasound) and thyroglobulin autoantibodies (TgAb). The first patient had positive lymph nodes at the time of surgery. The incidence of thyroid cancers in Belarus and Ukraine rose just 4 years after the Chernobyl disaster; because radioactive clouds passed over Belgium, we wonder whether the occurrence of thyroid cancer in our patients could be related to this irradiation. The mechanism of increased incidence of radiation-induced thyroid cancer is thought to be due to rearrangement of the tyrosine kinase domains of the RET and TTK genes. The other important similarities in our patients are the presence of psammoma bodies that can be visualized on radiological examination and the presence of TgAb that are more frequent in differentiated thyroid cancers. Whether or not these cases reflect an increased incidence in the population as a whole, clinicians must remain vigilant for this rare but curable cancer in young patients, especially if suggestive radiological features or TgAb are present.

Adolescent↗
PubMed1989

[A case of multiple sclerosis with pure alexia].

We report here a case of multiple sclerosis (MS) showing pure alexia. The patient was a 28 year-old, right-handed male student of medicine. He had been healthy prior to college, but when he tried to read the newspaper one morning in January of 1983, he suddenly became aware that he could not. He could speak fluently and had no disturbances of auditory comprehension. No signs of abnormality were noted in his writing ability. Thereafter, the patient occasionally experienced difficulty in reading, together with right homonymous hemianopsia. These symptoms, however, usually vanished following sleep. In April, 1984, the patient experienced headache and ataxia when walking, followed by repeated remission and exacerbation of the symptoms. Corticosteroid therapy produced complete disappearance of the headache and ataxia. In September of 1985, he was hospitalized at our department due to the clouding of consciousness accompanied by convulsions. Neurologically, no abnormalities of the ocular fundus were noted and Babinski's sign was negative, but left hemiplegia was observed. Neuropsychologically, his intelligence was normal and he had no difficulty in writing, but paralexia was noted. There were no disorders of spontaneous speech or auditory comprehension. Examination by CT scan and magnetic resonance imaging revealed a number of lesions in the white substance of the cerebrum, including the left occipital lobe. The abnormal signs seen radiographically vanished when cortical hormones were administered. It has been thought that the symptoms of multiple sclerosis are due mainly to disorders of the white substance, and that MS seldom produces symptoms of aphasia, due to the fact that the lesions in this disease are generally small.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2003

[Roentgenography and CT appearance in patients with severe acute respiratory syndrome].

OBJECTIVE: To evaluate the appearance and dynamic change of chest roentgenography and CT in patients with severe acute respiratory syndrome (SARS). METHODS: Serial roentgenography and CT of 61 confirmed SARS patients were analyzed. RESULTS: The onset symptom was fever in all patients. In the early phase of SARS, the main abnormal appearance was single or bilateral localized patchy clouding opacity on roentgenography, which progressed rapidly. The area of opacity peaked at about 2 weeks, involving the majority area of the lung in 57% of the patients. The area involved was correlated with the severity of clinical symptoms. The opacity disappeared gradually in 5 weeks in 84% of the patients. Lungs complicated infection were found in 6 patients with a prolonged duration of the illness. Among the 61 patients, 4 died. CT scan was performed in 16 SARS patients in the recovery phase, of whom 13 showed lung fibrosis. CONCLUSIONS: Lung infiltration in early phase develops rapidly and involves most area of the lung in advanced phase in most SARS patients. Lungs fibrosis was found in some patients in the recovery phase.

Adult↗
PubMed2006

A geographically explicit genetic model of worldwide human-settlement history.

Currently available genetic and archaeological evidence is generally interpreted as supportive of a recent single origin of modern humans in East Africa. However, this is where the near consensus on human settlement history ends, and considerable uncertainty clouds any more detailed aspect of human colonization history. Here, we present a dynamic genetic model of human settlement history coupled with explicit geographical distances from East Africa, the likely origin of modern humans. We search for the best-supported parameter space by fitting our analytical prediction to genetic data that are based on 52 human populations analyzed at 783 autosomal microsatellite markers. This framework allows us to jointly estimate the key parameters of the expansion of modern humans. Our best estimates suggest an initial expansion of modern humans approximately 56,000 years ago from a small founding population of approximately 1,000 effective individuals. Our model further points to high growth rates in newly colonized habitats. The general fit of the model with the data is excellent. This suggests that coupling analytical genetic models with explicit demography and geography provides a powerful tool for making inferences on human-settlement history.

Africa, Eastern↗
PubMed1984

In vitro inhibition of 3-methylcholanthrene-induced rat hepatic aryl hydrocarbon hydroxylase by 8-acyl-7-hydroxycoumarins. Structure-activity relationships and metabolite profiles.

A series of 4,5,6-substituted-8-acyl-7-hydroxycoumarins was synthesized, and their inhibitory potencies towards 3-methylcholanthrene-induced rat hepatic microsomal aryl hydrocarbon hydroxylase activity were studied, both qualitatively and quantitatively. Using the Hansch approach to structure-activity relationships and computer analysis of the data, we have shown that the inhibitory potency could be related to the lipophilicity and molecular size of the compounds. 13C NMR spectroscopy was used to determine electron density at particular carbons of the candidate inhibitors. The electron density was used as an additional parameter in the fitting of potency curves and was found to be of significance. Thus, the potency of a candidate inhibitor could be related to its lipophilicity, molecular size, and electron distribution. The existence of a dipole at the enzyme active site is postulated. The distribution of benzo[a]pyrene metabolites, both in the presence and absence of several derivatives, was studied with high pressure liquid chromatography. There was a significant decrease of the 7,8- and 9,10-dihydrodiols in the presence of these inhibitors. The comparative decrease in each of the dihydrodiols was not related to the potency of the inhibitor. The possibility of epoxide hydrolase inhibition by the 4,5,6-substituted-8-acyl-7-hydroxycoumarins was also examined; no epoxide hydrolase inhibition or stimulation was detected at concentrations 10-100 times greater than those which inhibited aryl hydrocarbon hydroxylase by 50%. The decreased formation of the 7,8- and 9,10-arene oxides was therefore postulated to be responsible for the decreased 7,8- and 9,10-dihydrodiol formations in the presence of inhibitor. Inhibition is postulated to have occurred at the enzyme active site, probably by means of a perturbation of the electron cloud density and the active site such that oxygenation at the 7,8- and 9,10-positions was unfavourable.

Animals↗
PubMed2005

First singlet (n,pi*) excited state of hydrogen-bonded complexes between water and pyrimidine.

Hydrogen bonds from water to excited-state formaldehyde and from water to excited-state pyridine have been shown to display novel motifs to traditional hydrogen bonds involving ground states, with, in particular for H2O:pyridine, strong interactions involving the electron-rich pi cloud dominating the (n,pi) excited state. We investigate H2O:pyrimidine and various dihydrated species and reveal another motif, one in which the hydrogen bonding can dramatically alter the electronic structure of the excited state. Such effects are rare for ground-state interactions for which hydrogen bonding usually acts to merely perturb the electronic structure of the participating molecules. It arises as the (n,pi*) excitation of isolated pyrimidine is delocalized over both nitrogens but asymmetric hydrogen bonding causes it to localize on just the noninteracting atom. As a result, the excited-state hydrogen bond in H2O:pyrimidine is suprisingly very similar to the ground-state structure. These results lead to an improved understanding of the spectroscopy of pyrimidine in liquid water, and to the prediction that stable excited-state hydrogen bonds in H2O:pyrimidine should be observable, despite failure of experiments to actually do so. They also provide a simple model for the intricate control over primary charge separation in photosynthesis exerted by hydrogen bonding, and for solvent-induced electron localization in symmetric mixed-valence complexes. All conclusions are based on strong parallels found between the results of calculations performed using density-functional theory (DFT) and time-dependent DFT (TDDFT), complete-active-space self-consistent-field (CASSCF) with second-order perturbation-theory correction (CASPT2) theory, and equation-of-motion coupled cluster (EOM-CCSD) theory, calculations that are verified through detailed comparison of computed properties with experimental data for both the isolated molecules and the ground-state hydrogen bond.

Journal Article↗
PubMed1990

Precambrian evolution of the climate system.

Climate is an important environmental parameter of the early Earth, likely to have affected the origin and evolution of life, the composition and mineralogy of sedimentary rocks, and stable isotope ratios in sedimentary minerals. There is little observational evidence constraining Precambrian climates. Most of our knowledge is at present theoretical. Factors that must have affected the climate include reduced solar luminosity, enhanced rotation rate of the Earth, an area of land that probably increased with time, and biological evolution, particularly as it affected the composition of the atmosphere and the greenhouse effect. Cloud cover is a major uncertainty about the early Earth. Carbon dioxide and its greenhouse effect are the factors that have been most extensively studied. This paper presents a new examination of the biogeochemical cycles of carbon as they may have changed between an Archean Earth deficient in land, sedimentary rocks, and biological activity, and a Proterozoic Earth much like the modern Earth, but lacking terrestrial life and carbonate-secreting plankton. Results of a numerical simulation of this transition show how increasing biological activity could have drawn down atmospheric carbon dioxide by extracting sedimentary organic carbon from the system. Increasing area of continents could further have drawn down carbon dioxide by encouraging the accumulation of carbonate sediments. An attempt to develop a numerical simulation of the carbon cycles of the Precambrian raises questions about sources and sinks of marine carbon and alkalinity on a world without continents. More information is needed about sea-floor weathering processes.

Atmosphere↗
PubMed2002

Two-generation analysis of pollen flow across a landscape. IV. Estimating the dispersal parameter.

The distance of pollen movement is an important determinant of the neighborhood area of plant populations. In earlier studies, we designed a method for estimating the distance of pollen dispersal, on the basis of the analysis of the differentiation among the pollen clouds of a sample of females, spaced across the landscape. The method was based solely on an estimate of the global level of differentiation among the pollen clouds of the total array of sampled females. Here, we develop novel estimators, on the basis of the divergence of pollen clouds for all pairs of females, assuming that an independent estimate of adult population density is available. A simulation study shows that the estimators are all slightly biased, but that most have enough precision to be useful, at least with adequate sample sizes. We show that one of the novel pairwise methods provides estimates that are slightly better than the best global estimate, especially when the markers used have low exclusion probability. The new method can also be generalized to the case where there is no prior information on the density of reproductive adults. In that case, we can jointly estimate the density itself and the pollen dispersal distance, given sufficient sample sizes. The bias of this last estimator is larger and the precision is lower than for those estimates based on independent estimates of density, but the estimate is of some interest, because a meaningful independent estimate of the density of reproducing individuals is difficult to obtain in most cases.

Alleles↗
PubMed1986

[Acute neurologic dysfunction associated with a hypodensity of the basal ganglia].

A previously healthy five years old boy, following a mild nonspecific upper respiratory infection developed, fever (39 degrees C), vomiting, clouding of consciousness and focal seizures. The CSF showed a mononuclear cell reaction with negative bacterial and viral cultures. A cranial CT scan on the 4th day of admission showed bilateral low density lesions on the basal ganglia region. After 30 days of severe involvement of muscle tone (rigidity) which kept the patient immobilized in bed and without a meaningful communication with his surroundings, improvement was noticed. A repeated CT scan 40 days after admission, was considered normal. Two months after the beginning of disease, patient's physical examination was normal. This case shows striking clinical and radiological similarities to the ones described by Aicardi and Goutieres in 1982 and most likely is explained by bilateral basal ganglia edema complicating viral encephalitis. Mumps virus, being so far, the most commonly implicated.

Basal Ganglia Diseases↗
PubMed2001

Essential dynamics of reversible peptide folding: memory-free conformational dynamics governed by internal hydrogen bonds.

A principal component analysis has been applied on equilibrium simulations of a beta-heptapeptide that shows reversible folding in a methanol solution. The analysis shows that the configurational space contains only three dense sub-states. These states of relatively low free energy correspond to the "native" left-handed helix, a partly helical intermediate, and a hairpin-like structure. The collection of unfolded conformations form a relatively diffuse cloud with little substructure. Internal hydrogen-bonding energies were found to correlate well with the degree of folding. The native helical structure folds from the N terminus; the transition from the major folding intermediate to the native helical structure involves the formation of the two most C-terminal backbone hydrogen bonds. A four-state Markov model was found to describe transition frequencies between the conformational states within error limits, indicating that memory-effects are negligible beyond the nanosecond time-scale. The dominant native state fluctuations were found to be very similar to unfolding motions, suggesting that unfolding pathways can be inferred from fluctuations in the native state. The low-dimensional essential subspace, describing 69% of the collective atomic fluctuations, was found to converge at time-scales of the order of one nanosecond at all temperatures investigated, whereas folding/unfolding takes place at significantly longer time-scales, even above the melting temperature.

Computer Simulation↗
PubMed2003

Early diagnosis of Alzheimer's disease: contribution of structural neuroimaging.

To accurately predict the development of Alzheimer's disease (AD) at its predementia stage would be a major breakthrough from both therapeutic and research standpoints. In this review, our focus is on markers obtained with structural imaging--especially magnetic resonance imaging (MRI)--and on studies of subjects at risk of developing AD. Among the latter, amnestic mild cognitive impairment (MCI) is currently the most commonly accepted reference, and therefore is specially targeted in this review. MCI refers to patients with significant but isolated memory impairment relative to subjects of identical age. Consistent with established histopathological data, structural imaging studies comparing patients with early probable AD to healthy aged subjects have shown that the most specific and sensitive features of AD at this stage are hippocampal and entorhinal cortex atrophy, especially when combined with a reduced volume of the temporal neocortex. MCI patients have significant hippocampal atrophy when compared to aged normal controls. When comparing patients with probable AD to MCI subjects, hippocampal region atrophy significantly extends to the neighboring temporal association neocortex. However, only longitudinal studies of MCI subjects are suited to assess (in a retrospective way) the predictive value of initial atrophy measurements for progression to AD. Few such studies have been published so far and for the most they were based on small samples. Furthermore, the comparison among studies is clouded by differences in both populations studied and MRI methodology used. Nevertheless, comparing the initial MRI data of at-risk subjects who convert to AD at follow-up to those of nonconverters suggests that a reduced association temporal neocortex volume combined with hippocampal or anterior cingulate cortex atrophy may be the best predictor of progression to AD. These data, although still preliminary, are consistent with postmortem studies describing the hierarchical progression of tau lesions in normal aging and early stages of AD, such that damage to the medial temporal lobe and association cortex would account for the memory and nonmemory cognitive impairments, respectively, the combination of which is required to operationally define probable AD. Future research in this field should capitalize on thorough methodology for brain structure delineation, and combine atrophy measurements to cognitive and/or functional imaging data.

Aged↗
PubMed1997

Role of pilot instrument proficiency in the safety of helicopter emergency medical services.

OBJECTIVES: To determine whether instrument-proficient pilots would more safely manage a flight into unplanned instrument meteorologic conditions (IMC) than would nonproficient pilots. METHODS: A controlled experimental study was performed using a full-motion helicopter simulator. Participants were emergency medical services (EMS) pilots with commercial licenses and previous simulator experience who were blinded to the study design and hypothesis. During a simulated EMS mission, cloud ceiling and visibility were decreased until IMC prevailed, and pilot actions were recorded. Data included the altitude at which the aircraft entered IMC, and whether the pilots maintained control of the aircraft, flew within aviation standards (i.e., bank angle, airspeed), and safely landed. RESULTS: Twenty-eight pilots (13 instrument-proficient, 15 nonproficient) participated; they had a median of 6,300 hours of helicopter experience. Two pilots crashed, both from the nonproficient group. The instrument-proficient pilots lost control less often (15% vs 67%, p < 0.05), maintained instrument standards more often (77% vs 40%, p < 0.05), and entered IMC at a higher altitude (689 feet vs 517 feet, p < 0.05) compared with the nonproficient pilots. Instructor comments indicated that the nonproficient pilots made more errors than did the instrument-proficient pilots. CONCLUSIONS: Instrument-proficient pilots more safely manage an unexpected encounter with IMC. Helicopter EMS programs should strongly consider maintaining instrument proficiency to enhance safety.

Accidents, Aviation↗
PubMed2001

Automated quantification of sympathetic beat-by-beat activity, independent of signal quality.

Sympathetic nerve activity (SNA) can provide critical information on cardiovascular regulation; however, in a typical laboratory setting, adequate recordings require assiduous effort, and otherwise high-quality recordings may be clouded by frequent baseline shifts, noise spikes, and muscle twitches. Visually analyzing this type of signal can be a tedious and subjective evaluation, whereas objective analysis through signal averaging is impossible. We propose a new automated technique to identify bursts through objective detection criteria, eliminating artifacts and preserving a beat-by-beat SNA signal for a variety of subsequent analyses. The technique was evaluated during both steady-state conditions (17 subjects) and dynamic changes with rapid vasoactive drug infusion (14 recordings from 5 subjects) on SNA signals of widely varied quality. Automated measures of SNA were highly correlated to visual measures of steady-state activity (r = 0.903, P < 0.001), dynamic relation measures (r = 0.987, P < 0.001), and measures of burst-by-burst variability (r = 0.929, P < 0.001). This automated sympathetic neurogram analysis provides a viable alternative to tedious and subjective visual analyses while maximizing the usability of noisy nerve tracings.

Adolescent↗
PubMed2006

Application of a new leaf area index algorithm to China's landmass using MODIS data for carbon cycle research.

An operational system was developed for mapping the leaf area index (LAI) for carbon cycle models from the moderate resolution imaging spectroradiometer (MODIS) data. The LAI retrieval algorithm is based on Deng et al. [2006. Algorithm for global leaf area index retrieval using satellite imagery. IEEE Transactions on Geoscience and Remote Sensing, 44, 2219-2229], which uses the 4-scale radiative transfer model [Chen, J.M., Leblancs, 1997. A 4-scale bidirectional reflection model based on canopy architecture. IEEE Transactions on Geoscience and Remote Sensing, 35, 1316-1337] to simulate the relationship of LAI with vegetated surface reflectance measured from space for various spectral bands and solar and view angles. This algorithm has been integrated to the MODISoft platform, a software system designed for processing MODIS data, to generate 250 m, 500 m and 1 km resolution LAI products covering all of China from MODIS MOD02 or MOD09 products. The multi-temporal interpolation method was implemented to remove the residual cloud and other noise in the final LAI product so that it can be directly used in carbon models without further processing. The retrieval uncertainties from land cover data were evaluated using five different data sets available in China. The results showed that mean LAI discrepancies can reach 27%. The current product was also compared with the NASA MODIS MOD15 LAI product to determine the agreement and disagreement of two different product series. LAI values in the MODIS product were found to be 21% larger than those in the new product. These LAI products were compared against ground TRAC measurements in forests in Qilian Mountain and Changbaishan. On average, the new LAI product agrees with the field measurement in Changbaishan within 2%, but the MODIS product is positively biased by about 20%. In Qilian Mountain, where forests are sparse, the new product is lower than field measurements by about 38%, while the MODIS product is larger by about 65%.

Algorithms↗