178 research outputs found
New Tools For Intermodal Analysis And Association Testing In Neuroimaging
In the field of neuroimage analysis two key goals are to understand the association of a high- dimensional imaging variable with a phenotype, and to understand relationships between several high-dimensional imaging variables. Several recent studies have shown that the standard āmass- univariateā methods to test an association of an image with a phenotype have inflated type 1 error rates due to invalid assumptions. Here, we propose two new methods to perform association testing in neuroimaging and illustrate the method in two stages of the lifespan. The first is a para- metric bootstrap testing procedure that estimates the joint distribution of test statistical parametric map in order to control the voxel-wise family-wise error rate (FWER). We illustrate the method by identifying sex differences in nonlinear developmental trajectories of cerebral blood flow through adolescence using the Philadelphia Neurodevelopmental Cohort. The second testing procedure is a generalization of Raoās score test based on projecting the score statistic onto a linear sub- space of a high-dimensional parameter space. The approach provides a way to localize signal in the high-dimensional space by projecting the scores to the subspace where the score test was performed. This allows for inference in the high-dimensional space to be performed on the same degrees of freedom as the score test, effectively reducing the number of comparisons. We illus- trate the method by analyzing a subset of the Alzheimerās Disease Neuroimaging Initiative dataset. Finally, we propose a new tool to study relationships between neuroimaging modalities that we to describe how the spatial association between cortical thickness and sulcal depth changes in adolescent development
Ocjena ekspozicije pesticidima i njihove opasnosti za ljude
Although mammalian toxicity studies are essential in assessing the hazard of any candidate pesticide, the ultimate assessment of the safety in its intended use depends upon studies on exposed people. Those compounds introduced for public health purposes undergo a thorough toxicological scrutiny, and assessment of their safety is made concurrently with their development for a particular use. There is an obvious need to carry out a similar evaluation of hazard to users of agricultural pesticides, in particular those handling pesticides in tropical climates.Premda su u ocjeni opasnosti svakog novog pesticida toksikoloÅ”ka prouÄavanja na pokusnim životinjama od bitne važnosti, konaÄna ocjena njegove sigurnosti za predstojeÄu Å”iroku upotrebu zasniva se na rezultatima prouÄavanja njegovih moguÄih uÄinaka na eksponiranim ljudima. Spojevi Å”to se uvode u upotrebu u javnom zdravstvu podliježu veoma temeljitom toksikoloÅ”kom prouÄavanju i njihova sigurnost pri upotrebi ocjenjuje se uporedo s njihovim usavrÅ”avanjem za odreÄenu primjenu. Postoji oÄita potreba da se sliÄan postupak ocjene moguÄe opasnosti uvede i za one pesticide Å”to se upotrebljavaju u poljoprivredi a napose za one Å”to se primjenjuju u tropskim klimatskim uvjetima
Toxicology of organophosphorus insecticides
Prikazana je biokemija, farmakologija, eksperimentalna i klinika toksikologija, terapija i prevencija otrovanja organofosfornim insekticidima. OpÅ”irnije su iznijeta danaÅ”nja shvaÄanja o mehanizmu djelovanja organofosfornih inhibitora na kolinesterazu i istraživanja s podruÄja reaktivacije inhibirane kolinesteraze pomoÄu nukleofilnih reagensa.A review of the biochemistry, pharmacology, experimental and clinical toxicology, therapy, and prevention of poisonings due to organophosphorus insecticides. The present-day concepts of the mechanism of the effect of organophosphorus inhibitors on cholinesterase are described more in detail, as well as the investigations in the field of the reactivation of inhibited cholinesterase by nucleophilic reagents
Toxicology of dieldrin I. studies of acute toxicity
OdreÄena je peroralna, intraperitonealna i intravenozna LD50 vrijednost za dieldrin na bijelim Å”takorima. Istražen je utjecaj gladovanja u odnosu na brzinu javljanja simptoma nakon peroralne aplikacije dieldrina. OdreÄena je ukupna tolerirana doza otrova pri razliÄitim brzinama intravenozne infuzije dieldrina Å”takorima. Dobiveni rezultati su prodiskutirani, a napose s obzirom na pojavu Ā»zakaÅ”njelihĀ« simptoma nakon jednokratne aplikacije otrova.The peroral, intraperitoneal and intravenous LD50 values of dieldrin are determined in albino rats. The effect of starving in relation to the time of the onset of symptoms after peroral application of dieldrin is studied. The total tolerated dose of dieldrin at various intravenous infusion rates is determined. The results obtained are discussed, particularly with regard to the appearance of Ā»delayedĀ« symptoms after a single application of the poison
Study of dermal toxicity of organophosphorus compounds. I. Parathion toxicity in relation to the skin surface and the technique of application
Istražen je uÄinak pripreme povrÅ”ine kože Å”takora kao i pokrivanje kontaminirane povrÅ”ine na perkutanu otrovnost parationa. Uklanjanje masnog sloja s oÅ”iÅ”ane kože leda 24 sata prije aplikacije otrova nije utjecalo na otrovnost parationa. Pokrivanje kontaminiranog mjesta politenskim listiÄem smanjilo je otrovnost parationa za oko 2 puta, a pokrivanje kontaminiranog mjesta leukoplastom za oko 3,5 puta. Pokusi u kojima je moguÄnost ingestije otrova kod nepokrivenih Å”takora bila djelomiÄno ili potpuno sprijeÄena pokazali su da veÄe LD50 vrijednosti dobivene pokrivanjem kontaminiranog mjesta nisu rezultat sprijeÄenog unoÅ”enja otrova peroralnim putem, veÄ su posljedica smanjenog prodiranja parationa kroz kožu. To se može tumaÄiti adhezijom otrova na politenski listiÄ, odnosno leukoplast, kojima je kontaminirano mjesto bilo pokriveno.The effect of the preparation of the rat\u27s skin surface and the covering of the contaminated area on dermal Parathion toxicity was investigated. The removal of the fatty layer from the clipped back skin area 24 hours prior to the application of the poison had no effect on Parathion toxicity. Parathion toxicity was reduced to about twice when the contaminated area was covered with a polythene sheet, and to about three and a half times when cevered with a leukoplast. The experiments, in which the possibility of ingestion of the poison in uncovered rats was partly or completely avoided, have shown that higher LD50 values obtained by covering the contaminated area were not due to the prevented introduction of the poison by ingestion but to a reduced penetration of Parathion through the skin. This may be explained by the adhesion of the poison to the polythene sheet or leukoplast by which the contaminated area was covered
Warburg apparatus
Prikaz sadržava opis i teoriju Warburgova aparata. U drugom dijelu opÅ”irnije su iznijete praktiÄke upute za rad kao i primjer kalibracije aparata i mjerenja aktivnosti enzima.The description and theory as well as methods of calibration of the Warburg apparatus are given. The review includes a detailed description of Iaboratory techniques and an example of calibration of the apparatus and determination of the enzyme activity
Protection of agricultural workers against pesticide poisoning
Izneseni su specifiÄni uvjeti i priroda ekspozicije pesticidima u poljoprivredi i mjere za spreÄavanje profesionalnih i akcidentalnih otrovanja. U zasebnom poglavlju predložen je nacrt higijensko-tehniÄkih propisa za bezopasnu primjenu pesticida. Na kraju autori daju konkretne prijedloge za rjeÅ”avanje aktuelnih problema u preventivi otrovanja pesticidima.Conditions under which pesticides are used in agriculture, the nature of exposure, and the measures for the prevention of hazards are presented. A draft of suggested safety regulations is given in a separate chapter. The authors also make proposals for the solution of current problems in the prevention of pesticide poisonings
Faster Family-wise Error Control for Neuroimaging with a Parametric Bootstrap
In neuroimaging, hundreds to hundreds of thousands of tests are performed
across a set of brain regions or all locations in an image. Recent studies have
shown that the most common family-wise error (FWE) controlling procedures in
imaging, which rely on classical mathematical inequalities or Gaussian random
field theory, yield FWE rates that are far from the nominal level. Depending on
the approach used, the FWER can be exceedingly small or grossly inflated. Given
the widespread use of neuroimaging as a tool for understanding neurological and
psychiatric disorders, it is imperative that reliable multiple testing
procedures are available. To our knowledge, only permutation joint testing
procedures have been shown to reliably control the FWER at the nominal level.
However, these procedures are computationally intensive due to the increasingly
available large sample sizes and dimensionality of the images, and analyses can
take days to complete. Here, we develop a parametric bootstrap joint testing
procedure. The parametric bootstrap procedure works directly with the test
statistics, which leads to much faster estimation of adjusted \emph{p}-values
than resampling-based procedures while reliably controlling the FWER in sample
sizes available in many neuroimaging studies. We demonstrate that the procedure
controls the FWER in finite samples using simulations, and present region- and
voxel-wise analyses to test for sex differences in developmental trajectories
of cerebral blood flow
Analysing spatial point patterns in digital pathology: immune cells in high-grade serous ovarian carcinomas
Multiplex immunofluorescence (mIF) imaging technology facilitates the study
of the tumour microenvironment in cancer patients. Due to the capabilities of
this emerging bioimaging technique, it is possible to statistically analyse,
for example, the co-varying location and functions of multiple different types
of immune cells. Complex spatial relationships between different immune cells
have been shown to correlate with patient outcomes and may reveal new pathways
for targeted immunotherapy treatments.
This tutorial reviews methods and procedures relating to spatial point
patterns for complex data analysis. We consider tissue cells as a realisation
of a spatial point process for each patient. We focus on proper functional
descriptors for each observation and techniques that allow us to obtain
information about inter-patient variation.
Ovarian cancer is the deadliest gynaecological malignancy and can resist
chemotherapy treatment effective in cancers. We use a dataset of high-grade
serous ovarian cancer samples from 51 patients. We examine the immune cell
composition (T cells, B cells, macrophages) within tumours and additional
information such as cell classification (tumour or stroma) and other patient
clinical characteristics. Our analyses, supported by reproducible software,
apply to other digital pathology datasets
Factors influencing the variability of results in the assessment of acute toxicity
U uvodu je raspravljeno znaÄenje novosintetiziranih supstancija s obzirom na njihovu toksiÄnost i opasnost po zdravlje za ljude i domaÄe životinje. AnalizirajuÄi koriÅ”tenje eksperimentalnih podataka o toksiÄnosti, autori istiÄu, da je primjena tih podataka na ljude i domaÄe životinje moguÄa tek onda, kad dobro poznajemo mehanizam djelovanja istraživane supstancije. Izneseni su faktori, koji uvjetuju varijabilnost rezultata pri ocjeni akutne toksiÄnosti, s naroÄitim osvrtom na odreÄivanje toksiÄnosti organofosfornih spojeva. Autori temelje svoja izlaganja na podacima drugih autora i na vlastitim zapažanjima. Faktore, od kojih zavisi varijabilnost rezultata, autori dijele na one, koji se odnose (1) na istraživanu supstanciju, (2) na pokusnu životinju i (3) na put unoÅ”enja otrova. Od faktora, koji se odnose na istraživanu supstanciju, autori istiÄu nedovoljnu ÄistoÄu spoja i razgradnju uzorka u toku njegova pripremanja ili pohranjivanja. S obzirom na pokusnu životinju prodiskutiran je utjecaj vrste, dobi, spola i genetskih faktora, kao i utjecaj faktora, od kojih zavisi kondicija eksperimentalne životinje. NaroÄito je istaknuto od kojeg je znaÄenja za konaÄan ishod rezultata postupak s tretiranim životinjama u toku opservacije simptoma. Zbog razliÄite brzine apsorpcije put unoÅ”enja Äesto uvjetuje vrlo velike razlike u toksiÄnosti nekog spoja. I medij, u kojem se istraživana supstancija primjenjuje, može znatno utjecati na brzinu apsorpcije otrova. Autori zakljuÄuju, da eksperimentalni podaci o akutnoj toksiÄnosti nekog spoja imaju svoju punu vrijednost tek onda, kad uz osnovne statistiÄke karakteristike sadržavaju i sve podatke o eksperimentalnim uvjetima, koji mogu biti od znaÄenja u vezi s istraživanom supstancijom, putom unoÅ”enja i pokusnom životinjom.The significance of newly synthetized compounds with regard to their toxicity and health hazards both for humans and domestic animals is discussed. It is pointed out that the extrapolation of experimental toxicity data on humans and domestic animals is not possible without a thorough understanding of the mechanism of the action of the substances tested. The factors influencing the variability of results in the assessment of acute toxicity are presented, with special reference to the determination of the toxicity of organophosphorus compounds. The autors\u27 discussion is based on literature data and their own experience. The factors influencing the variability of results are divided into those relating (1) to the test substance, (2) to the experimental animal, and (3) to the route of administration. Amongst the factors relating to the test substance, the presence of impurities and the conversion of the sample in the course of its preparation and storage are specially emphasized. With regard to the factors relating to the experimental animal, the effect of the species, age, sex, and genetic factors is discussed. as well as the effect of the factors influencing the condition of the experimental animal. In this connection it is pointed out that in the assessment of results the treatment of animals under observation plays an important part. Different routes of administration may also be the cause of great variability of the results. They determine how long it will take the poison to attain a certain level in the blood, what kind of the detoxifying mechanism will be put in action and to what extent, and by which route and rate the poison will be eliminated from the body. The vehicle used in the application of the test substance may also produce a considerable effect on the absorption rate of the poison. The authors conclude that experimental data on the acute toxicity of .a compound cannot be considered satisfactory, unless besides basic statistical data they contain all the information on the experimental conditions that may be of significance either to the substance tested, or the experimental animal, or the route of administration
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