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SARS-CoV-2 intra-host variation shows evidence of transmission and convergent evolution in a university surveillance cohort.

Monitoring and understanding the transmission and evolution of SARS-CoV-2 remains a significant public health priority. Within-host genetic variation provides insight into viral evolution during infection and may help infer transmission events. In this study, we analysed intra-host variation in SARS-CoV-2 genome sequences from Boston University's testing mandate. Focusing on intra-host single nucleotide variants (iSNVs), we inferred transmission events and assessed the selective forces shaping within-host viral evolution. To minimize false-positive iSNVs resulting from systematic biases, we implemented stringent data filtering and developed a heuristic to exclude contamination-derived artefacts arising from batched sequencing. We find that intra-host variation is limited and infrequently transmitted during acute infections, suggesting that shared iSNVs serve as highly specific but insensitive markers of transmission. We also observed incomplete purifying selection shaping within-host diversity, with the loci most affected changing among variants of concern. Finally, we identified a highly recurrent iSNV (G11083T) which may represent a site of positive selection. Our results highlight that within-host variation provides insight into within-host pathogen evolution, in spite of its limited use in genomic epidemiology.

SARS-CoV-2↗

Classical taxonomy of mosquitoes--a memorial to John N. Belkin.

The major contributions of John N. Belkin to the field of mosquito systematics are noted. Hallmarks of his publications are presented and his hypotheses about the evolution, speciation, competition, distribution and classification of mosquitoes are summarized. The current status of the field of mosquito systematics is examined. It is argued that mosquito systematics is still largely at the alpha taxonomy level, that at best only 25-50% of mosquito species are known, and that we have not even begun to develop a natural classification for the Culicidae. It is concluded that there will be little improvement in the status of mosquito taxonomy unless there is increased support for systematics.

Animals↗

Progression of falls in postmortem-confirmed parkinsonian disorders.

Although falls are known to occur in several parkinsonian disorders, such as Parkinson's disease (PD), multiple system atrophy (MSA), dementia with Lewy bodies (DLB), corticobasal degeneration (CBD), and progressive supranuclear palsy (PSP), differences in the evolution of this feature have not been studied systematically in pathologically confirmed cases. Seventy-seven cases with pathologically confirmed parkinsonian disorders (PD: n = 11, MSA: n = 15, DLB: n = 14, CBD: n = 13, PSP: n = 24), collected up to 1994, formed the basis for a multicenter clinicopathologic study organized by the National Institute of Neurological Disorders and Stroke to improve differential diagnosis of parkinsonian disorders. In the present study, we determined the time course, that is, the duration from first symptom to onset (latency) and duration from onset to death, of recurrent falls. Furthermore, we analyzed the diagnostic validity of a predefined latency to onset of recurrent falls within 1 year of symptom onset. Significant group differences for latency, but not duration, of recurrent falls were observed. Latencies to onset of falls were short in PSP patients, intermediate in MSA, DLB, and CBD, and long in PD. Recurrent falls occurring within the first year after disease onset predicted PSP in 68% of the patients. Our study demonstrates for the first time that latency to onset, but not duration, of recurrent falls differentiates PD from other parkinsonian disorders. Whereas early falls are important for the diagnosis of PSP, the addition of other features increases its diagnostic predictive value.

Accidental Falls↗

Primary pulmonary malignant lymphoma, clinical and pathological findings, immunocytochemical and ultrastructural studies in 15 cases.

Fifteen cases of primary pulmonary malignant lymphoma (M.L.) were studied using strict criteria to distinguish them from secondary pulmonary manifestations. All were M.L.'s of the lymphoid B type. Diagnosis on the basis of non specific clinical, X-ray and endoscopic findings if often difficult but can be facilitated by the systematic use of immunocytochemical and ultrastructural techniques. Their evolution is in good agreement with the prognostic data given by the Kiel-Lennert histopathological classification. 14 of the patients had M.L. of low grade malignancy; the one case of high grade malignancy was quickly fatal. A few cases appeared as a complication of a preexisting dysimmune disease (Pigeon breeder's disease, Gougerot-Sjogren disease, Liebow's lymphomatoid granulomatosis).

Adult↗

Evidence-based estimate of appropriate radiotherapy utilization rate for prostate cancer.

PURPOSE: Current estimates of the proportion of cancer patients who will require radiotherapy (RT) are based almost entirely on expert opinion. The objective of this study was to use an evidence-based approach to estimate the proportion of incident cases of prostate cancer that should receive RT at any point in the evolution of the illness. METHODS AND MATERIALS: A systematic review of the literature was undertaken to identify indications for RT for prostate cancer and to ascertain the level of evidence that supported each indication. An epidemiologic approach was then used to estimate the incidence of each indication for RT in a typical North American population of prostate cancer patients. The effect of sampling error on the estimated appropriate rate of RT was calculated mathematically, and the effect of systematic error using alternative sources of information was estimated by sensitivity analysis. RESULTS: It was estimated that 61.2% +/- 5.6% of prostate cancer cases develop one or more indications for RT at some point in the course of the illness. The plausible range for this rate was 57.3%-69.8% on sensitivity analysis. Of all prostate cancer patients, 32.2% +/- 3.8% should receive RT in their initial treatment and 29.0% +/- 4.1% later for recurrence or progression. The proportion of cases that ever require RT is risk grouping dependent; 43.9% +/- 2.2% in low-risk disease, 68.7% +/- 3.5% in intermediate-risk disease; and 79.0% +/- 3.8% in high-risk locoregional disease. For metastatic disease, the predicted rate was 66.4% +/- 0.3%. CONCLUSION: This method provides a rational starting point for the long-term planning of radiation services and for the audit of access to RT at the population level. By completing such evaluations in major cancer sites, it will be possible to estimate the appropriate RT rate for the cancer population as a whole.

Humans↗

Possible dengue sequential infection: dengue spread in a neighbourhood during the 1996/97 dengue-2 epidemic in French Polynesia.

A DEN-2 epidemic occurred in French Polynesia from August 1996 to April 1997 after 7 years of DEN-3 circulation. The susceptible population constituted all expatriates and Polynesians under 21. In August 1996, two successive DEN-2 cases occurred in Teroma, a Tahitian neighbourhood close to the international airport of Tahiti. A serological prospective study of persons < 21 years living in Teroma was conducted. The study population was bled in September 1996, October 1996 and June 1997. Analysis of dengue spread in Teroma confirmed that dengue transmission occurs primarily in the house, thus vector control campaigns should incorporate focal insecticide spraying and systematic daily use of insecticide in houses. The evolution in time of the disease demonstrated that among a susceptible population, prevalence and incidence rates are related to the time of exposure, and consequently to age. Comparison of dengue incidence or dengue prevalence between populations therefore requires adjusted age rates. Most studies did not adjust for age, leading to the conclusion that DHF is more frequent during secondary than during primary dengue infection. Prospective studies taking into account the time of dengue exposure are necessary to confirm the sequential infection hypothesis.

Adolescent↗

Evidence for a clade composed of molluscs with serially repeated structures: monoplacophorans are related to chitons.

Monoplacophorans are among the rarest members of the phylum Mollusca. Previously only known from fossils since the Cambrian, the first living monoplacophoran was discovered during the famous second Galathea deep-sea expedition. The anatomy of these molluscs shocked the zoological community for presenting serially repeated gills, nephridia, and eight sets of dorsoventral pedal retractor muscles. Seriality of organs in supposedly independent molluscan lineages, i.e., in chitons and the deep-sea living fossil monoplacophorans, was assumed to be a relic of ancestral molluscan segmentation and was commonly accepted to support a direct relationship with annelids. We were able to obtain one specimen of a monoplacophoran Antarctic deep-sea species for molecular study. The first molecular data on monoplacophorans, analyzed together with the largest data set of molluscs ever assembled, clearly illustrate that monoplacophorans and chitons form a clade. This "Serialia" concept may revolutionize molluscan systematics and may have important implications for metazoan evolution as it allows for new interpretations for primitive segmentation in molluscs.

Animals↗

Magnetic resonance imaging findings within 5 days of status epilepticus in childhood.

The nature of the relationships between status epilepticus, acute hippocampal injury, mesial temporal sclerosis (MTS) and temporal lobe epilepsy remains unclear. The aim of this study was to investigate whether generalized status epilepticus is associated with brain abnormalities, especially in the mesial temporal lobe, within 5 days of the acute event. Such changes may be the first part of a causative pathophysiological sequence relating status epilepticus and MTS. Thirty-five children with a history of status epilepticus, including 21 with a history of prolonged febrile convulsion (PFC), underwent qualitative and quantitative MRI investigations within 5 days of the acute episode. Quantitative assessments of the hippocampus included T(2) relaxometry and hippocampal volumetry. Hippocampal volumes were large in patients with PFC when compared with controls. In addition, T(2) relaxation time was elevated in patients with PFC compared with control subjects during the first 2 days of the acute event. No difference was observed in patients examined 3-5 days after the event. Patients with afebrile status epilepticus had a variety of imaging abnormalities including elevated hippocampal T(2) values, but no evidence of hippocampal enlargement. PFC is associated with hippocampal abnormalities, consistent with hippocampal oedema, whilst non-febrile status epilepticus is not. A systematic longitudinal study is required to characterize the evolution of these abnormalities and to determine whether any patient develops MTS.

Brain Edema↗

Infusing critical thinking into the nursing curriculum through faculty development.

An important prerequisite to changes in an educational program's predominant philosophy and culture is systematic faculty development to begin and sustain the evolution. The authors describe how one nursing school implemented a faculty development program with the goal of infusing critical thinking strategies into courses throughout the curriculum.

Curriculum↗

The origin of the Australasian marsupial fauna and the phylogenetic affinities of the enigmatic monito del monte and marsupial mole.

Alternative hypotheses in higher-level marsupial systematics have different implications for marsupial origins, character evolution, and biogeography. Resolving the position of the South American monito del monte (Order Microbiotheria) is of particular importance in that alternate hypotheses posit sister-group relationships between microbiotheres and taxa with disparate temporal and geographic distributions: pediomyids; didelphids; dasyuromorphians; diprotodontians; all other australidelphians; and all other marsupials. Among Australasian marsupials, the placement of bandicoots is critical; competing views associate bandicoots with particular Australasian taxa (diprotodontians, dasyuromorphians) or outside of a clade that includes all other Australasian forms and microbiotheres. Affinities of the marsupial mole are also unclear. The mole is placed in its own order (Notoryctemorphia) and sister-group relationships have been postulated between it and each of the other Australasian orders. We investigated relationships among marsupial orders by using a data set that included mitochondrial and nuclear genes. Phylogenetic analyses provide support for the association of microbiotheres with Australasian marsupials and an association of the marsupial mole with dasyuromorphs. Statistical tests reject the association of diprotodontians and bandicoots together as well as the monophyly of Australasian marsupials. The origin of the paraphyletic Australasian marsupial fauna may be accounted for by (i) multiple entries of australidelphians into Australia or (ii) bidirectional dispersal of australidelphians between Antarctica and Australia.

Animals↗

Methods for constraining fine structure constant evolution with OH microwave transitions.

We investigate the constraints that OH microwave transitions in megamasers and molecular absorbers at cosmological distances may place on the evolution of the fine structure constant alpha=e(2)/ variant Planck's over 2pi c. The centimeter OH transitions are a combination of hyperfine splitting and lambda doubling that can constrain the cosmic evolution of alpha from a single species, avoiding systematic errors in alpha measurements from multiple species which may have relative velocity offsets. The most promising method compares the 18 and 6 cm OH lines, includes a calibration of systematic errors, and offers multiple determinations of alpha in a single object. Comparisons of OH lines to the HI 21 cm line and CO rotational transitions also show promise.

Journal Article↗

Time course of symptomatic orthostatic hypotension and urinary incontinence in patients with postmortem confirmed parkinsonian syndromes: a clinicopathological study.

OBJECTIVE: Although both orthostatic hypotension and urinary incontinence have been reported in a number of parkinsonian syndromes, such as Parkinson's disease (PD), multiple system atrophy (MSA), dementia with Lewy bodies (DLB), corticobasal degeneration (CBD), and progressive supranuclear palsy (PSP), differences in the evolution of these features have not been studied systematically in pathologically confirmed cases. METHODS: 77 cases with pathologically confirmed parkinsonian syndromes (PD, n=11; MSA, n=15; DLB, n=14; CBD, n=13; PSP, n=24), collected up to 1994, formed the basis for a multicentre clinicopathological study organised by the NINDS to improve the differential diagnosis of parkinsonian disorders. The present study determined the time course-that is, latency to onset and duration from onset to death, of symptomatic orthostatic hypotension, and urinary incontinence in the NINDS series. Furthermore, the diagnostic validity of a predefined latency to onset within 1 year of disease onset of symptomatic orthostatic hypotension or urinary incontinence was analysed. RESULTS: Significant group differences for latency, but not duration, of symptomatic orthostatic hypotension and urinary incontinence were found. Latencies to onset of either feature were short in patients with MSA, intermediate in patients with DLB, CBD, and PSP, and long in those with PD. Symptomatic orthostatic hypotension occurring within the first year after disease onset predicted MSA in 75% of cases; early urinary incontinence was less predictive for MSA (56%). CONCLUSION: Latency to onset, but not duration, of symptomatic orthostatic hypotension or urinary incontinence differentiates PD from other parkinsonian syndromes, particularly MSA.

Age of Onset↗

Foundations of a query and simulation system for the modeling of biochemical and biological processes.

The analysis of large amounts of data, produced as (numerical) traces of in vivo, in vitro and in silico experiments, has become a central activity for many biologists and biochemists. Recent advances in the mathematical modeling and computation of biochemical systems have moreover increased the prominence of in silico experiments; such experiments typically involve the simulation of sets of Differential Algebraic Equations (DAE), e.g., Generalized Mass Action systems (GMA) and S-systems. In this paper we reason about the necessary theoretical and pragmatic foundations for a query and simulation system capable of analyzing large amounts of such trace data. To this end, we propose to combine in a novel way several well-known tools from numerical analysis (approximation theory), temporal logic and verification, and visualization. The result is a preliminary prototype system: simpathica/xssys. When dealing with simulation data simpathica/xssys exploits the special structure of the underlying DAE, and reduces the search space in an efficient way so as to facilitate any queries about the traces. The proposed system is designed to give the user possibility to systematically analyze and simultaneously query different possible timed evolutions of the modeled system.

Biochemical Phenomena↗

[The cardiovascular manifestations of Paget's disease].

After reviewing the old ideas (peripheral syndrome and cardiac insufficiency at high outputs) and more recent ideas (arterial and intracardiac vascular calcification), the authors report their experiences based on the study of the histories of 150 patients suffering from Paget's disease followed for several years. First they emphasize the frequent latency of cardiac manifestations looked for systematically by means of the electrocardiogram particularly during evolutive stages of the disease. Electrocardiographic disturbances were observed 91 times and included 43 cases of conduction disorders and 48 of repolarization disorders; their distribution was studied as a function of various inherent parameters, of the patient (age and sex) and of the disease (its evolutive character and its degree of diffusion). On the basis of the anti-arythmic power of calcitonin found during experiments and obtained excellent results three times. Finally the place of cardiovascular manifestations in the pathogenic hypotheses and nosology of Paget's disease is discussed.

Adult↗

[Classification of organisms and structuralism in biology].

Structuralism in biology is the oldest trend oriented to the search for natural "laws of forms" comparable with laws of growth of crystal, was revived at the end of 20th century on the basis of structuralist thought in socio-humanitarian sciences. The development of principal ideas of the linguistic structuralism in some aspects is similar to that of biological systematics, especially concerning the relationships between "system" and "evolution". However, apart from this general similarity, biological structuralism is strongly focused on familiar problems of the origin of diversity in nature. In their striving for the renovation of existing views, biological structuralists oppose the neo-darwinism emphasizing the existence of "law of forms", that are independent on heredity and genetic "determinism". The trend to develop so-called "rational taxonomy" is also characteristic of biological structuralism but this attempt failed being connected neither with Darwin's historicism nor with Plato's typology.

Biological Evolution↗

[Pulmonary arterial hypertension in cirrhosis].

Pulmonary arterial hypertension PAH is one of the rare expressions of cirrhosis and defined by a pressure more than 30 mmHg. We report our results in a Tunisian Seria results: 21 cirrhotic patients (19M/12F) with a median age of 60 years (22 to 85) explored by cardiac echographic with measures of PAH. We observe an elevated PAH in 31% of cases. Conclusion elevated PAH is relatively frequent during the evolution of cirrhosis. This symptom needs to be systematically explored in patients proposed for liver graft because increased PAH is a contraindication for liver transplantation.

Adult↗

[A developmental anomaly of Meckel's cartilage].

An atypical evolution of the mandibular cartilage was recorded in systematic dissections of the neck in the Anatomy Laboratory. This anomaly led to the formation of a supernumerary bony fragment in the concavity of the lower edge of the mandibular arch, with a slight adhesion thereto. This observation is reported by the authors after a recapitulation of the embryology.

Aged↗

The English debate on taxonomy and phylogeny, 1937-1940.

Between 1937 and 1940 the Taxonomic Principles Committee of the newly-founded Association for the Study of Systematics in Relation to General Biology (later the Systematics Association) attempted to define the relationship between evolution and taxonomy. The people who took part in the discussion were W.T. Caleman, C.R.P. Diver, J.S.L. Gilmour, J.S. Huxley, W.D. Lang, J.R. Norman, R. Melville, O.W. Richards, M.A. Smith, T.A. Sprague, H. Hamshaw Thomas, W.B. Turrill, B.P. Uvarov, A.F. Watkins, E.I. White, and A.J. Wilmott. Most of the botanists asserted that taxonomy was a practical matter to be kept distinct from phylogenetic speculation, and most of the zoologists insisted that taxonomists must strive to represent evolution if they wished to be scientific. The disagreement seemed to be hardening rather than approaching compromise when World War Two stopped the committee's work.

Animals↗