Do some languages sound more beautiful than others?

Italian is sexy, German is rough-but how about Páez or Tamil? Are there universal phonesthetic judgments based purely on the sound of a language, or are preferences attributable to language-external factors such as familiarity and cultural stereotypes? We collected 2,125 recordings of 228 languages from 43 language families, including 5 to 11 speakers of each language to control for personal vocal attractiveness, and asked 820 native speakers of English, Chinese, or Semitic languages to indicate how much they liked these languages. We found a strong preference for languages perceived as familiar, even when they were misidentified, a variety of cultural-geographical biases, and a preference for breathy female voices. The scores by English, Chinese, and Semitic speakers were weakly correlated, indicating some cross-cultural concordance in phonesthetic judgments, but overall there was little consensus between raters about which languages sounded more beautiful, and average scores per language remained within ±2% after accounting for confounds related to familiarity and voice quality of individual speakers. None of the tested phonetic features-the presence of specific phonemic classes, the overall size of phonetic repertoire, its typicality and similarity to the listener's first language-were robust predictors of pleasantness ratings, apart from a possible slight preference for nontonal languages. While population-level phonesthetic preferences may exist, their contribution to perceptual judgments of short speech recordings appears to be minor compared to purely personal preferences, the speaker's voice quality, and perceived resemblance to other languages culturally branded as beautiful or ugly.

Prominence effects in vocal iconicity: Implications for lexical access and language changea).

This paper explores how three cognitive and perceptual cues, vocal iconicity, resemblance-based mappings between form and meaning, and segment position and lexical stress, interact to affect word formation and language processing. The study combines an analysis of the word-internal positions that iconic segments occur in based on data from 245 language families with an experimental study in which participants representing more than 30 languages rated iconic and non-iconic pseudowords. The pseudowords were designed to systematically vary segment and stress placement across syllables. The results for study 1 indicate that segments used iconically appear approximately 0.26 segment positions closer toward the beginning of words compared to non-iconic segments. In study 2, it was found that iconic segments occurring in stressed syllables and non-iconic segments occurring in the second syllable were rated as significantly more fitting. These findings suggest that the interplay between vocal iconicity and prominence effects increases the predictive function of iconic segments by foregrounding sounds, which intrinsically carry semantic information. Consequently, these results contribute to the understanding of the widespread occurrence of vocal iconicity in human languages.

Assaying Chlamydia pneumoniae Persistence in Monocyte-Derived Macrophages Identifies Dibenzocyclooctadiene Lignans as Phenotypic Switchers.

Antibiotic-tolerant persister bacteria involve frequent treatment failures, relapsing infections and the need for extended antibiotic treatment. The virulence of an intracellular human pathogen C. pneumoniae is tightly linked to its propensity for persistence and means for its chemosensitization are urgently needed. In the current work, persistence of C. pneumoniae clinical isolate CV6 was studied in THP-1 macrophages using quantitative PCR and quantitative culture. A dibenzocyclooctadiene lignan schisandrin reverted C. pneumoniae persistence and promoted productive infection. The concomitant administration of schisandrin and azithromycin resulted in significantly improved bacterial eradication compared to sole azithromycin treatment. In addition, the closely related lignan schisandrin C was superior to azithromycin in eradicating the C. pneumoniae infection from the macrophages. The observed chemosensitization of C. pneumoniae was associated with the suppression of cellular glutathione pools by the lignans, implying to a previously unknown aspect of chlamydia-host interactions. These data indicate that schisandrin lignans induce a phenotypic switch in C. pneumoniae, promoting the productive and antibiotic-susceptible phenotype instead of persistence. By this means, these medicinal plant -derived compounds show potential as adjuvant therapies for intracellular bacteria resuscitation.

Quantum Simulation Logic, Oracles, and the Quantum Advantage.

Query complexity is a common tool for comparing quantum and classical computation, and it has produced many examples of how quantum algorithms differ from classical ones. Here we investigate in detail the role that oracles play for the advantage of quantum algorithms. We do so by using a simulation framework, Quantum Simulation Logic (QSL), to construct oracles and algorithms that solve some problems with the same success probability and number of queries as the quantum algorithms. The framework can be simulated using only classical resources at a constant overhead as compared to the quantum resources used in quantum computation. Our results clarify the assumptions made and the conditions needed when using quantum oracles. Using the same assumptions on oracles within the simulation framework we show that for some specific algorithms, such as the Deutsch-Jozsa and Simon's algorithms, there simply is no advantage in terms of query complexity. This does not detract from the fact that quantum query complexity provides examples of how a quantum computer can be expected to behave, which in turn has proved useful for finding new quantum algorithms outside of the oracle paradigm, where the most prominent example is Shor's algorithm for integer factorization.

Angular dependence of fluorescence from turbid media.

We perform Monte Carlo light scattering simulations to study the angular distribution of the fluorescence emission from turbid media and compare the results to measured angular distributions from fluorescing white paper samples. The angular distribution of fluorescence emission is significantly depending on the concentration of fluorophores. The simulations show also a dependence on the angle of incidence that is however not as evident in the measurements. A detailed analysis of the factors affecting this angular distribution indicates that it is strongly correlated to the mean depth of the fluorescence process. The findings can find applications in fluorescence spectroscopy and are of particular interest when optimizing the impact of fluorescence on e.g. the appearance of paper as the measured values are angle dependent.

Influence of finite-sized detection solid angle on bidirectional reflectance distribution function measurements.

This paper deals with limitations and often overlooked sources of error introduced in compact double-beam goniophotometers. It is shown that relative errors in measured radiance factor, comparable to the total measurement uncertainty, can be introduced if recommended corrections are not carried out. Two different error sources are investigated, both related to the size of the detection solid angle. The first is a geometrical error that occurs when the size of the illuminated area and detector aperture are comparable to the distance between them. The second is a convolution error due to variations in radiant flux over the detector aperture, which is quantified by simulating the full 3D bidirectional reflectance distribution function (BRDF) of a set of samples with different degrees of anisotropic reflectance. The evaluation is performed for a compact double-beam goniophotometer using different detection solid angles, and it is shown that both error sources introduce relative errors of 1%-3%, depending on viewing angle and optical properties of the sample. Commercially available compact goniophotometers, capable of absolute measurements, are becoming more and more common, and the findings in this paper are therefore important for anyone using or planning to use this type of instrument.

TRPA1 Inhibition Effects by 3-Phenylcoumarin Derivatives.

Transient receptor potential ankyrin 1 (TRPA1) protein plays an important role in the inflammatory response, and it has been associated with different pain conditions and pain-related diseases, making TRPA1 a valid target for painkillers. In this study, we identified potential TRPA1 inhibitors and located their binding sites utilizing computer-aided drug design (CADD) techniques. The designed 3-phenylcoumarin-based TRPA1 inhibitors were successfully synthesized using a microwave assisted synthetic strategy. 3-(3-Bromophenyl)-7-acetoxycoumarin (5), 7-hydroxy-3-(3-hydroxyphenyl)coumarin (12) and 3-(3-hydroxyphenyl)coumarin (23) all showed inhibitory activity toward TRPA1 in vitro. Compound 5 also decreased the size and formation of breast cancer cells. Hence, targeting TRPA1 may represent a promising alternative for the treatment of pain and inflammation.

Separation of surface and bulk reflectance by absorption of bulk scattered light.

A method is proposed for separating light reflected from turbid media with a rough surface into a bulk and a surface component. Dye is added to the sample, thereby increasing absorption and canceling bulk scattering. The remaining reflected light is surface reflectance, which can be subtracted from the total reflectance of an undyed sample to obtain the bulk component. The method is applied to paper where the addition of dye is accomplished by inkjet printing. The results show that the bulk scattered light is efficiently canceled, and that both the spectrally neutral surface reflectance and the surface topography of the undyed paper is maintained. The proposed method is particularly suitable for characterization of dielectric, highly randomized materials with significant bulk reflectance and rough surfaces, which are difficult to analyze with existing methods. A reliable separation method opens up for new ways of analyzing, e.g., biological tissues and optical coatings, and is also a valuable tool in the development of more comprehensive reflectance models.

Prevalence and prognostic implications of myocardial injury in patients with influenza.

Aims: Influenza may cause myocardial injury and trigger acute cardiovascular events. The aim of this study was to investigate the prevalence and prognostic implications of elevated high-sensitivity cardiac troponin I (hs-cTnI) in patients with influenza. Methods and results: In this prospective cohort study, we consecutively enrolled patients with influenza-like illness from two emergency departments in Sweden during three seasons of influenza, 2017-20. Ongoing Influenza infection was diagnosed by polymerase chain reaction and blood samples were collected for later analysis of hs-cTnI. All patients were followed-up for a composite endpoint of major adverse cardiovascular events (MACE) including death, myocardial infarction, unstable angina, heart failure, atrial fibrillation, and stroke within 1 year. Of the 466 patients with influenza-like symptoms, 181 (39%) were positive for influenza. Fifty (28%) patients were hospitalized. High-sensitivity cTnI was elevated in 11 (6%) patients and 8 (4%) experienced MACE. In univariate analyses, MACE was associated with age [hazard ratio (HR): 1.14, 95% confidence interval (CI): 1.05-1.23], hypertension (HR 5.56, 95%CI: 1.12-27.53), estimated glomerular filtration rate (HR: 0.94, 95%CI: 0.91-0.97), and elevated hs-cTnI (HR: 18.29, 95%CI: 4.57-73.24), N-terminal prohormone of brain natriuretic peptide (HR: 14.21, 95%CI: 1.75-115.5), hs-CRP (HR: 1.01, 95%CI: 1.00-1.02), and white blood cell count (HR: 1.12, 95%CI: 1.01-1.25). In multivariate analysis, elevated hs-cTnI was independently associated with MACE (HR: 4.96, 95%CI: 1.10-22.41). Conclusion: The prevalence of elevated hs-cTnI is low in unselected patients with influenza. Elevated hs-cTnI was associated with poor prognosis. A limitation is that the estimated associations are uncertain due to few events.

Contribution to the subfamily Ophioninae (Hymenoptera: Ichneumonidae) of Southern Europe with the description of one new genus and 15 new species.

This paper presents the descriptions of four new species of the genus Enicospilus Stephens, 1835 and ten species of Ophion Fabricius, 1798: Enicospilus (Allocamptus) izquierdoae sp. nov., E. borderai sp. nov., E. erebus sp. nov., Ophion albanicus sp. nov., O. anatolicus sp. nov., O. canariensis sp. nov., O. castilloae sp. nov., O. cypriotus sp. nov., O. incarinatus sp. nov., O. trochantellatus sp. nov., O. mediterraneus sp. nov., O. pusillus sp. nov., O. rugipleuris sp. nov. and Ophion ziczac sp. nov. Additionally, a new genus Nyxia gen. nov. and its only known species Nyxia shawi sp. nov. is decribed from Portugal. Enicospilus arcuatus (Brull, 1846) syn. nov. and Enicospilus hannibalis (Kohl, 1905) syn. nov. are junior synonyms of Enicospilus inflexus (Ratzeburg, 1844). Enicospilus ramidulops Scaramozzino, 1986 syn. nov. is a junior synonym of Enicospilus bimaculator Aubert, 1979. The mainly Afrotropical species Enicospilus antefurcalis (Szpligeti, 1908) is a new record for the Palaearctic realm. A short discussion on the presumed diversity of Western Palaearctic Ophioninae is given.

Contribution to the Ophioninae (Hymenoptera: Ichneumonidae) of Iran with the description of 16 new species and an illustrated key to the Eremotylus of the Western Palaearctic.

In this study, material of Iranian Ophioninae was examined. In total, 63 species are recognized as occurring in Iran. Sixteen species are described as new to science: Enicospilus amerii Johansson sp. nov., E. apocalypticus Johansson sp. nov., E. haladai Johansson sp. nov., Enicospilus peri sp. nov., Ophion al Johansson sp. nov., Ophion angustigena Johansson sp. nov., Ophion breviflagellator Johansson sp. nov., Ophion golestanicus Johansson sp. nov., Ophion klimenkoi Johansson sp. nov., Ophion persicus Johansson sp. nov., Ophion schmidti Johansson sp. nov., Ophion sinuosus Johansson sp. nov., Ophion sistanicus Johansson sp. nov., Ophion transcarinatus Johansson sp. nov., Ophion vasi Johansson sp. nov. and Ophion xrafstra Johansson sp. nov. Sixteen species: Enicospilus combustus (Gravenhorst, 1829); E. intermedius (Johansson, 2018); E. undulatus (Gravenhorst, 1829); Ophion angularis Johansson Cederberg, 2019; Ophion bipictor Aubert, 1980; Ophion crassicornis Brock, 1982; Ophion confusus Johansson, 2019; Ophion ellenae Johansson, 2019; Ophion eremita Kokujev, 1906; Ophion kallanderi Johansson, 2019; Ophion rostralis Meyer, 1935; Ophion rufoniger Kohl, 1905; Ophion semipullatus Kokujev, 1909; Ophion tenuicornis Johansson, 2019; Hellwigiella dichromoptera (Costa, 1886) and Eremotylus curvinervis (Kriechbaumer, 1878) are new records for the fauna of Iran. Enicospilus flavocephalus (Kirby, 1900), Enicospilus monostigma (Vollenhoven, 1879) and Eremotylus sibiricus Szpligeti, 1905 are excluded from the Iranian checklist due to previous misidentifications. Enicospilus tarsalis Hedwig, 1957 syn. nov. is excluded from synonymy with E. ahngeri and instead introduced as a junior synonym of E. cruciator Viktorov, 1957. Enicospilus affinis Hedwig, 1957 stat. rev. is excluded from synonymy with E. ocellatus Shestakov, 1926 and reinstated as a valid species. Enicospilus splendidus Rousse, Soliman Gadallah, 2017 syn. nov. is a junior synonym of Enicospilus stenopsis Kohl, 1905. Enicospilus grandiflavus Townes Townes, 1973 (= E. grandis Morley) syn. nov. is synonymized with Enicospilus unicallosus (Vollenhoven, 1878). Enicospilus contributus Shestakov, 1926 is confirmed as a junior synonym of E. merdarius (Gravenhorst, 1829). Ophion fossulatus Hedwig, 1957 stat. rev. is excluded from synonymy with Ophion mocsaryi Brauns, 1899 and reinstated as a valid species close to Ophion parvulus Kriechbaumer. Ophion mocsaryi var. decedens Hedwig, 1961 syn. nov. is a synonym of Ophion bipictor Aubert, 1980. Ophion obscuratus var. heratensis Hedwig, 1961 syn. nov. is treated as a synonym of Ophion turcomanicus Szpligeti, 1905. Ophion pravinervis Kokujev, 1906, previously only known from the lost type collected in Georgia, is redescribed. Despite the relatively high number of new species here presented, the Iranian fauna most likely still harbours additional species awaiting discovery.

Preferred sound groups of vocal iconicity reflect evolutionary mechanisms of sound stability and first language acquisition: evidence from Eurasia.

In speech, the connection between sounds and word meanings is mostly arbitrary. However, among basic concepts of the vocabulary, several words can be shown to exhibit some degree of form-meaning resemblance, a feature labelled vocal iconicity. Vocal iconicity plays a role in first language acquisition and was likely prominent also in pre-historic language. However, an unsolved question is how vocal iconicity survives sound evolution, which is assumed to be inevitable and 'blind' to the meaning of words. We analyse the evolution of sound groups on 1016 basic vocabulary concepts in 107 Eurasian languages, building on automated homologue clustering and sound sequence alignment to infer relative stability of sound groups over time. We correlate this result with the occurrence of sound groups in iconic vocabulary, measured on a cross-linguistic dataset of 344 concepts across single-language samples from 245 families. We find that the sound stability of the Eurasian set correlates with iconic occurrence in the global set. Further, we find that sound stability and iconic occurrence of consonants are connected to acquisition order in the first language, indicating that children acquiring language play a role in maintaining vocal iconicity over time. This article is part of the theme issue 'Reconstructing prehistoric languages'.

Exploration of Pyrazolo[1,5-a]pyrimidines as Membrane-Bound Pyrophosphatase Inhibitors.

Inhibition of membrane-bound pyrophosphatase (mPPase) with small molecules offer a new approach in the fight against pathogenic protozoan parasites. mPPases are absent in humans, but essential for many protists as they couple pyrophosphate hydrolysis to the active transport of protons or sodium ions across acidocalcisomal membranes. So far, only few nonphosphorus inhibitors have been reported. Here, we explore the chemical space around previous hits using a combination of screening and synthetic medicinal chemistry, identifying compounds with low micromolar inhibitory activities in the Thermotoga maritima mPPase test system. We furthermore provide early structure-activity relationships around a new scaffold having a pyrazolo[1,5-a]pyrimidine core. The most promising pyrazolo[1,5-a]pyrimidine congener was further investigated and found to inhibit Plasmodium falciparum mPPase in membranes as well as the growth of P. falciparum in an ex vivo survival assay.

Light-Activated Liposomes Coated with Hyaluronic Acid as a Potential Drug Delivery System.

Light-activated liposomes permit site and time-specific drug delivery to ocular and systemic targets. We combined a light activation technology based on indocyanine green with a hyaluronic acid (HA) coating by synthesizing HA-lipid conjugates. HA is an endogenous vitreal polysaccharide and a potential targeting moiety to cluster of differentiation 44 (CD44)-expressing cells. Light-activated drug release from 100 nm HA-coated liposomes was functional in buffer, plasma, and vitreous samples. The HA-coating improved stability in plasma compared to polyethylene glycol (PEG)-coated liposomes. Liposomal protein coronas on HA- and PEG-coated liposomes after dynamic exposure to undiluted human plasma and porcine vitreous samples were hydrophilic and negatively charged, thicker in plasma (~5 nm hard, ~10 nm soft coronas) than in vitreous (~2 nm hard, ~3 nm soft coronas) samples. Their compositions were dependent on liposome formulation and surface charge in plasma but not in vitreous samples. Compared to the PEG coating, the HA-coated liposomes bound more proteins in vitreous samples and enriched proteins related to collagen interactions, possibly explaining their slightly reduced vitreal mobility. The properties of the most abundant proteins did not correlate with liposome size or charge, but included proteins with surfactant and immune system functions in plasma and vitreous samples. The HA-coated light-activated liposomes are a functional and promising alternative for intravenous and ocular drug delivery.

Discovery of Membrane-Bound Pyrophosphatase Inhibitors Derived from an Isoxazole Fragment.

Membrane-bound pyrophosphatases (mPPases) regulate energy homeostasis in pathogenic protozoan parasites and lack human homologues, which makes them promising targets in e.g. malaria. Yet only few nonphosphorus inhibitors have been reported so far. Here, we explore an isoxazole fragment hit, leading to the discovery of small mPPase inhibitors with 6-10 µM IC50 values in the Thermotoga maritima test system. Promisingly, the compounds retained activity against Plasmodium falciparum mPPase in membranes and inhibited parasite growth.

Risk to human health related to the presence of perfluoroalkyl substances in food.

The European Commission asked EFSA for a scientific evaluation on the risks to human health related to the presence of perfluoroalkyl substances (PFASs) in food. Based on several similar effects in animals, toxicokinetics and observed concentrations in human blood, the CONTAM Panel decided to perform the assessment for the sum of four PFASs: PFOA, PFNA, PFHxS and PFOS. These made up half of the lower bound (LB) exposure to those PFASs with available occurrence data, the remaining contribution being primarily from PFASs with short half-lives. Equal potencies were assumed for the four PFASs included in the assessment. The mean LB exposure in adolescents and adult age groups ranged from 3 to 22, the 95th percentile from 9 to 70 ng/kg body weight (bw) per week. Toddlers and 'other children' showed a twofold higher exposure. Upper bound exposure was 4- to 49-fold higher than LB levels, but the latter were considered more reliable. 'Fish meat', 'Fruit and fruit products' and 'Eggs and egg products' contributed most to the exposure. Based on available studies in animals and humans, effects on the immune system were considered the most critical for the risk assessment. From a human study, a lowest BMDL 10 of 17.5 ng/mL for the sum of the four PFASs in serum was identified for 1-year-old children. Using PBPK modelling, this serum level of 17.5 ng/mL in children was estimated to correspond to long-term maternal exposure of 0.63 ng/kg bw per day. Since accumulation over time is important, a tolerable weekly intake (TWI) of 4.4 ng/kg bw per week was established. This TWI also protects against other potential adverse effects observed in humans. Based on the estimated LB exposure, but also reported serum levels, the CONTAM Panel concluded that parts of the European population exceed this TWI, which is of concern.

Screening for Thermotoga maritima Membrane-Bound Pyrophosphatase Inhibitors.

Membrane-bound pyrophosphatases (mPPases) are dimeric enzymes that occur in bacteria, archaea, plants, and protist parasites. These proteins cleave pyrophosphate into two orthophosphate molecules, which is coupled with proton and/or sodium ion pumping across the membrane. Since no homologous proteins occur in animals and humans, mPPases are good candidates in the design of potential drug targets. Here we present a detailed protocol to screen for mPPase inhibitors utilizing the molybdenum blue reaction in a 96 well plate system. We use mPPase from the thermophilic bacterium Thermotoga maritima (TmPPase) as a model enzyme. This protocol is simple and inexpensive, producing a consistent and robust result. It takes only about one hour to complete the activity assay protocol from the start of the assay until the absorbance measurement. Since the blue color produced in this assay is stable for a long period of time, subsequent assay(s) can be performed immediately after the previous batch, and the absorbance can be measured later for all batches at once. The drawback of this protocol is that it is done manually and thus can be exhausting as well as require good skills of pipetting and time keeping. Furthermore, the arsenite-citrate solution used in this assay contains sodium arsenite, which is toxic and should be handled with necessary precautions.

Asymmetry in catalysis by Thermotoga maritima membrane-bound pyrophosphatase demonstrated by a nonphosphorus allosteric inhibitor.

Membrane-bound pyrophosphatases are homodimeric integral membrane proteins that hydrolyze pyrophosphate into orthophosphates, coupled to the active transport of protons or sodium ions across membranes. They are important in the life cycle of bacteria, archaea, plants, and parasitic protists, but no homologous proteins exist in vertebrates, making them a promising drug target. Here, we report the first nonphosphorus allosteric inhibitor of the thermophilic bacterium Thermotoga maritima membrane-bound pyrophosphatase and its bound structure together with the substrate analog imidodiphosphate. The unit cell contains two protein homodimers, each binding a single inhibitor dimer near the exit channel, creating a hydrophobic clamp that inhibits the movement of ß-strand 1-2 during pumping, and thus prevents the hydrophobic gate from opening. This asymmetry of inhibitor binding with respect to each homodimer provides the first clear structural demonstration of asymmetry in the catalytic cycle of membrane-bound pyrophosphatases.

Phthalate diesters and their metabolites in human breast milk, blood or serum, and urine as biomarkers of exposure in vulnerable populations.

BACKGROUND: Phthalates may pose a risk for perinatal developmental effects. An important question relates to the choice of suitable biological matrices for assessing exposure during this period. OBJECTIVES: This study was designed to measure the concentrations of phthalate diesters or their metabolites in breast milk, blood or serum, and urine and to evaluate their suitability for assessing perinatal exposure to phthalates. METHODS: In 2001, 2-3 weeks after delivery, 42 Swedish primipara provided breast milk, blood, and urine samples at home. Special care was taken to minimize contamination with phthalates (e.g., use of a special breast milk pump, heat treatment of glassware and needles, addition of phosphoric acid). RESULTS: Phthalate diesters and metabolites in milk and blood or serum, if detected, were present at concentrations close to the limit of detection. By contrast, most phthalate metabolites were detectable in urine at concentrations comparable to those from the general population in the United States and in Germany. No correlations existed between urine concentrations and those found in milk or blood/serum for single phthalate metabolites. Our data are at odds with a previous study documenting frequent detection and comparatively high concentrations of phthalate metabolites in Finnish and Danish mothers' milk. CONCLUSIONS: Concentrations of phthalate metabolites in urine are more informative than those in milk or serum. Furthermore, collection of milk or blood may be associated with discomfort and potential technical problems such as contamination (unless oxidative metabolites are measured). Although urine is a suitable matrix for health-related phthalate monitoring, urinary concentrations in nursing mothers cannot be used to estimate exposure to phthalates through milk ingestion by breast-fed infants.

Diachronic Atlas of Comparative Linguistics (DiACL)-A database for ancient language typology.

Feature stability, time and tempo of change, and the role of genealogy versus areality in creating linguistic diversity are important issues in current computational research on linguistic typology. This paper presents a database initiative, DiACL Typology, which aims to provide a resource for addressing these questions with specific of the extended Indo-European language area of Eurasia, the region with the best documented linguistic history. The database is pre-prepared for statistical and phylogenetic analyses and contains both linguistic typological data from languages spanning over four millennia, and linguistic metadata concerning geographic location, time period, and reliability of sources. The typological data has been organized according to a hierarchical model of increasing granularity in order to create datasets that are complete and representative.