Rapid quasi-periodic oscillations in the relativistic jet of BL Lacertae.

Blazars are active galactic nuclei (AGN) with relativistic jets whose non-thermal radiation is extremely variable on various timescales1-3. This variability seems mostly random, although some quasi-periodic oscillations (QPOs), implying systematic processes, have been reported in blazars and other AGN. QPOs with timescales of days or hours are especially rare4 in AGN and their nature is highly debated, explained by emitting plasma moving helically inside the jet5, plasma instabilities6,7 or orbital motion in an accretion disc7,8. Here we report results of intense optical and γ-ray flux monitoring of BL Lacertae (BL Lac) during a dramatic outburst in 2020 (ref. 9). BL Lac, the prototype of a subclass of blazars10, is powered by a 1.7 × 108 MSun (ref. 11) black hole in an elliptical galaxy (distance = 313 megaparsecs (ref. 12)). Our observations show QPOs of optical flux and linear polarization, and γ-ray flux, with cycles as short as approximately 13 h during the highest state of the outburst. The QPO properties match the expectations of current-driven kink instabilities6 near a recollimation shock about 5 parsecs (pc) from the black hole in the wake of an apparent superluminal feature moving down the jet. Such a kink is apparent in a microwave Very Long Baseline Array (VLBA) image.

Fish otoliths as biological dosimeter: internal dose calculation.

Otoliths are organs used by fish for hearing and keeping balance. They consist of biogenic crystals of hydroxyapatite and do not contain any living cells. Upon exposure to ionizing radiation, otolith hydroxyapatite accumulates radiation-induced stable CO2- radicals whose amount is proportional to absorbed dose. In electron paramagnetic resonance (EPR) dosimetry, carbonate ions are registered and, hence, the total accumulated dose in the fish otolith can be quantified. Therefore, otoliths can be used as individual fish dosimeters to support radiobiological and radioecological studies. An important aspect of otolith-based EPR dosimetry on fish from contaminated water bodies is the potential presence of bone-seeking 90Sr. Consequently, cumulative absorbed doses measured with EPR in otoliths may reflect the superposition of internal exposure to 90Sr/90Y and external exposure due to radionuclides circulating in soft tissue of the fish as well as due to environmental contamination. The objective of the present study was to develop a method that allows for an assessment of the contribution of 90Sr to the total dose in otolith. The method has been tested using otoliths from seven fish taken from reservoirs located in the Southern Urals contaminated with radionuclides including 90Sr. It has been shown that dose to otoliths is largely determined by 90Sr in the hydroxyapatite. The internal dose component can be calculated using activity concentration-to-dose conversion factors, which vary slightly in the range of 2.0-2.8 × 10-3 Gy year-1 per Bq g-1 depending on fish species and age. Internal doses to fish from water bodies with different levels of 90Sr contamination were calculated in the range from 2 mGy to ~ 200 Gy. External dose contribution was derived for two fish only to be about 100 and 40 Gy. It is concluded that EPR dosimetry on fish otoliths is a promising tool when external exposure prevails or is comparable to internal exposure due to 90Sr.

[Kisspeptins: role in the aging of the reproductive system and the development of comorbid pathology.]

The literature review is devoted to the role of kisspeptins in aging. There are data about the involvement of kisspeptins in the development of menopause and ovarian aging, as well as metabolic syndrome. In addition, the role of kisspeptins in the development of age-related diseases such as diabetes mellitus, coronary heart disease, and Alzheimer's disease is described. Involvement of kisspeptins and kisspeptin receptors in the development of malignant neoplasms are postulated. Evidence of the antimetastatic properties of the kisspeptin protein, as well as the possibility of using it as a tumor marker, is presented.

The software for interactive evaluation of mass spectra stability and reproducibility.

SUMMARY: Mass spectrometry (MS) methods are widely used for the analysis of biological and medical samples. Recently developed methods, such as DESI, REIMS and NESI allow fast analyses without sample preparation at the cost of higher variability of spectra. In biology and medicine, MS profiles are often used with machine learning (classification, regression, etc.) algorithms and statistical analysis, which are sensitive to outliers and intraclass variability. Here, we present spectra similarity matrix (SSM) Display software, a tool for fast visual outlier detection and variance estimation in mass spectrometric profiles. The tool speeds up the process of manual spectra inspection, improves accuracy and explainability of outlier detection, and decreases the requirements to the operator experience. It was shown that the batch effect could be revealed through SSM analysis and that the SSM calculation can also be used for tuning novel ion sources concerning the quality of obtained mass spectra. AVAILABILITY AND IMPLEMENTATION: Source code, example datasets, binaries and other information are available at https://github.com/EvgenyZhvansky/R_matrix. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Value of ultra-high field MRI in patients with suspected focal epilepsy and negative 3 T MRI (EpiUltraStudy): protocol for a prospective, longitudinal therapeutic study.

PURPOSE: Resective epilepsy surgery is a well-established, evidence-based treatment option in patients with drug-resistant focal epilepsy. A major predictive factor of good surgical outcome is visualization and delineation of a potential epileptogenic lesion by MRI. However, frequently, these lesions are subtle and may escape detection by conventional MRI (≤ 3 T). METHODS: We present the EpiUltraStudy protocol to address the hypothesis that application of ultra-high field (UHF) MRI increases the rate of detection of structural lesions and functional brain aberrances in patients with drug-resistant focal epilepsy who are candidates for resective epilepsy surgery. Additionally, therapeutic gain will be addressed, testing whether increased lesion detection and tailored resections result in higher rates of seizure freedom 1 year after epilepsy surgery. Sixty patients enroll the study according to the following inclusion criteria: aged ≥ 12 years, diagnosed with drug-resistant focal epilepsy with a suspected epileptogenic focus, negative conventional 3 T MRI during pre-surgical work-up. RESULTS: All patients will be evaluated by 7 T MRI; ten patients will undergo an additional 9.4 T MRI exam. Images will be evaluated independently by two neuroradiologists and a neurologist or neurosurgeon. Clinical and UHF MRI will be discussed in the multidisciplinary epilepsy surgery conference. Demographic and epilepsy characteristics, along with postoperative seizure outcome and histopathological evaluation, will be recorded. CONCLUSION: This protocol was reviewed and approved by the local Institutional Review Board and complies with the Declaration of Helsinki and principles of Good Clinical Practice. Results will be submitted to international peer-reviewed journals and presented at international conferences. TRIAL REGISTRATION NUMBER: www.trialregister.nl : NTR7536.

New complexes of liquid crystal discotic triphenylenes: induction of the double gyroid phase.

Electron donor-acceptor liquid crystals have been attracting considerable attention due to possible applications in optoelectronics and photonics. The creation of such charge transfer complexes is a powerful and flexible instrument for modifying the structures and properties compared to those of the initial components. In the present work, such an approach is exemplified on new complexes formed via non-covalent interactions of triphenylene discotics, namely, 2,3,6,7,10,11-hexakis(pentyloxy) triphenylene (H5T) and 2-(acryloyloxypropyloxy)-3,6,7,10,11-pentapentylox-triphenylene (TPh-3A), with an electron acceptor, ß-(2,4,7-trinitro-9-fluorenylideneaminooxy) propionic acid (TNF-carb). The structure of thin supported films of H5T, TPh-3A and their blends with TNF-carb was investigated by grazing-incidence wide-angle X-ray scattering using a synchrotron source. At room temperature, the pristine discotics crystallize in orthorhombic unit cells whereas the self-assembly of H5T and TPh-3A with TNF-carb results in a double gyroid and hexagonal phases, respectively. Formation of the double gyroid phase with the lattice parameter of 36.5 Å is driven by phase separation between the aromatic and alkyl regions of the system. It is supposed that the TNF-carb molecules of the complex are positioned in the nodes of the structure while the H5T molecules are located in the struts adjoining the nodes via triple junctions. For the hexagonal crystal of the TPh-3A/TNF-carb complex, the acceptor molecules are likely located in the interstices between the neighboring supramolecular columns of TPh-3A. The molecular structures of the blends were also explored by means of FTIR spectroscopy. A detailed FTIR spectra analysis illustrates fine changes in inter-molecular bonds. For example, the initially dimerized acceptor molecules totally disappear in the complex structures whereas in TPh-3A/TNF-carb additional H-bonds between the carboxylate group in TNF-carb and the ester group of TPh-3A form. The experimental data allows putting forward possible molecular models of the complex structures.

[The new approaches to legal regulation of application of medical technologies in The Russian Federation at present-day period].

The article presents analysis of legal regulation of medical technologies in Russia. The proper development of medicine and health care is impossible without permanent improvement and implementation of new medical technologies. The upcoming decades will be an era of development of bio-technologies, cellular and gene technologies included. The proposed analysis is focused on conceptual set, analysis of actual normative legal base regulating mentioned relationships and identification of perspectives of development of medical technologies. The adequate and competent legal regulation creates enabling environment developing new technological capabilities. The legislation should avoid inhibiting retributive mode and apply particularly permitting and regulating approach determining framework not to be violated. Undoubtedly, these activities should be carried out in conjunction with professional medical community to develop legislation ensuring the highest possible level of development of health care practice.

Feedback-Induced Quantum Phase Transitions Using Weak Measurements.

We show that applying feedback and weak measurements to a quantum system induces phase transitions beyond the dissipative ones. Feedback enables controlling essentially quantum properties of the transition, i.e., its critical exponent, as it is driven by the fundamental quantum fluctuations due to measurement. Feedback provides the non-Markovianity and nonlinearity to the hybrid quantum-classical system, and enables simulating effects similar to spin-bath problems and Floquet time crystals with tunable long-range (long-memory) interactions.

The TRACK-PD study: protocol of a longitudinal ultra-high field imaging study in Parkinson's disease.

BACKGROUND: The diagnosis of Parkinson's Disease (PD) remains a challenge and is currently based on the assessment of clinical symptoms. PD is also a heterogeneous disease with great variability in symptoms, disease course, and response to therapy. There is a general need for a better understanding of this heterogeneity and the interlinked long-term changes in brain function and structure in PD. Over the past years there is increasing interest in the value of new paradigms in Magnetic Resonance Imaging (MRI) and the potential of ultra-high field strength imaging in the diagnostic work-up of PD. With this multimodal 7 T MRI study, our objectives are: 1) To identify distinctive MRI characteristics in PD patients and to create a diagnostic tool based on these differences. 2) To correlate MRI characteristics to clinical phenotype, genetics and progression of symptoms. 3) To detect future imaging biomarkers for disease progression that could be valuable for the evaluation of new therapies. METHODS: The TRACK-PD study is a longitudinal observational study in a cohort of 130 recently diagnosed (≤ 3 years after diagnosis) PD patients and 60 age-matched healthy controls (HC). A 7 T MRI of the brain will be performed at baseline and repeated after 2 and 4 years. Complete assessment of motor, cognitive, neuropsychiatric and autonomic symptoms will be performed at baseline and follow-up visits with wearable sensors, validated questionnaires and rating scales. At baseline a blood DNA sample will also be collected. DISCUSSION: This is the first longitudinal, observational, 7 T MRI study in PD patients. With this study, an important contribution can be made to the improvement of the current diagnostic process in PD. Moreover, this study will be able to provide valuable information related to the different clinical phenotypes of PD and their correlating MRI characteristics. The long-term aim of this study is to better understand PD and develop new biomarkers for disease progression which may help new therapy development. Eventually, this may lead to predictive models for individual PD patients and towards personalized medicine in the future. TRIAL REGISTRATION: Dutch Trial Register, NL7558 . Registered March 11, 2019.

[Clinical and economic comparison of utilization of reslizumab, mepolizumab and benralizumab in the treatment of severe eosinophilic asthma].

During last few years, the approaches to the management of patients with severe asthma have been revised. Monoclonal antibodies (MABs), inhibitors of interleukin-5 (reslizumab, mepolizumab, benralizumab) have been recently introduced for the treatment of severe eosinophilic asthma. The mentioned drugs were approved in Russia and included into the list of Vitally Essential Drugs. AIM: The aim of this study was to compare the clinical and economic consequences of the use of biological agents that antagonize IL-5 in the treatment of severe eosinophilic asthma in adults. MATERIALS AND METHODS: Two methods of clinical and economic research were used: assessment of the cost-effectiveness ratio and analysis of the budget impact. The effectiveness of the drugs was assessed using indirect comparison; special attention was paid to comparability of the patient groups in the studies chosen for such an assessment. Two approaches were used for calculation of the cost of therapy for severe asthma: using DRGs (applicable to most regions of Russia), and without the use of DRGs, which is relevant only for few Russian regions. RESULTS: Basing on the data obtained from a budget impact study without the use of DRG, it was shown that reslizumab was dominating for patients with body mass of up to 70 kg, while for the patients with body mass of 70 to 110 kg, mepolizumab was dominating, while utilization of reslizumab appeared to be somewhat more expensive. In the group of patients with body mass over 110 kg, mepolizumab also was dominating. The calculation of the cost-effectiveness ratio (CER) showed that reslizumab appeared to be dominating over two other MABs, The results of the study using the DRG demonstrated that the cost of an annual course of benralizumab in most cases in Russia would exceed the amount that can be compensated by Territorial Funds for Mandatory Medical Insurance to a healthcare institution for therapy of bronchial asthma in one adult patient with genetically engineered drugs. Therefore, further comparisons were made for reslizumab and mepolizumab only. Analysis of the impact on the budget demonstrated that treatment with reslizumab and mepolizumab would represent a similar burden for the budget. When applying cost-effectiveness analysis, reslizumab was more cost-effective than mepolizumab (regardless of patient body mass). CONCLUSION: Thus, the results of the clinical and economic study suggested that, basing on the cost-effectiveness analysis, reslizumab appeared to be the dominant IL-5 antagonist (regardless of body mass if DRG approach was used and in patients with body mass up to 110 kg, if such an approach was not used). Basing on budget impact analysis, calculations without use of DRG approach showed superiority of reslizumab over mepolizumab and benralizumab for the patients with body mass up to 70 kg and the DRG-based approach showed equal burden for the budget for reslizumab and mepolizumab for the patients with any body mass.

[Initial experience of renal autotransplantation in a child with ureteric rupture secondary to abdominal blunt trauma]. / Autotransplantatsiia pochki u rebenka s razryvom mochetochnika posle zakrytoi travmy zhivota.

A 8-year-old child with multiple skeletal injuries after car accident is presented in the article. Extensive right-sided urohematoma with impaired kidney function was diagnosed after 15 days. External drainage of urohematoma, ureteroscopy and examination of the right kidney were consecutively performed within 1.5 months. A complete rupture of the right ureter at the level of pyeloureterostomy was diagnosed. Right kidney autotransplantation with ureteral resection and pyeloureteral anastomosis were performed in 2 months after injury. Duration of surgery was 7.5 hours, cold ischemia - 55 min. Postoperative examination confirmed satisfactory function of the right kidney. This observation is relatively rare and the first in Russia.

INFLUENCE OF THE ACTING SUBSTANCE SODIUM DICLOFENAC ON BONE MARROW CELLS.

In humans and mammals, the homeostasis system is supported by many organs and systems, but hematopoietic remains one of the most important. A negative effect on the hematopoietic system is rejected by many factors, but the first place remains for drugs, which one in three are non-steroidal anti-inflammatory drugs (NSAIDs). The most popular among them remains the active substance "Diclofenac Sodium", which is part of many drugs. The purpose of the work is to study the action of the active substance Diclofenac sodium and its effect on the erythrocyte series of bone marrow cells of white laboratory mice in an experiment. The studies were conducted on white laboratory mice, males, 6 months old, 60 grams. The animals were divided into three groups, the first received 0.09 mg of Diclofenac sodium in the quadriceps of the thigh, the second - 0.18 mg and the third physiological solution for 96 hours. After observing all the rules of bioethics, the animals were slaughtered and the bone marrow was examined using pure immuno-magnetic separation techniques. During the study, it became known that in the first group the number of erythroblasts increased by 75%, while in the second group by 166.5%, due to the blocking of differentiation into more mature cells. The number of reticular cells decreased by 33.4%, while in the second group by 60%. A decrease in the erythrokaryocyte maturation index in the first group by 42.6% whereas in the second by 32.5%, primarily due to immature red blood cell precursors. In the first group, the leuko-erythrokaryoid ratio decreased by 9.5%, while in the second group by 12.3%. The number of megakaryocytes due to the predominant blockade of cyclooxygenase-2 increased in the first group by 266.6%, while in the second by 733.3%. It was found that the most favorable effect on red bone marrow cells has a dose of 0.09 mg, while 0.18 mg has a toxic effect and contributes to the development of cardiovascular complications.

Impact of the solubility of organic semiconductors for solution-processable electronics on the structure formation: a real-time study of morphology and electrical properties.

The control of structure formation in the active layers of organic solar cells allows for improvement in their processability and enhancement of the efficiency of the final devices. In the present work, in situ studies of film formation from binary toluene solutions of an electron donor, poly(3-hexylthiophene) (P3HT), and an electron acceptor such as [6,6]-phenyl-C-61-butyric acid methyl ester (PCBM) or indene-C60 bisadduct (ICBA) have been conducted. These experiments were carried out using GIWAXS with simultaneous electric current measurements. The comparative analysis of the intensity of the amorphous halo, and the 100 and 020 peaks of P3HT reveals the development of the semicrystalline morphology of the donor through a partly-ordered phase. The experiments show the impact of the chemical structure of the acceptor, as well as that of the donor : acceptor ratio on the kinetics of drying and crystallization. The optimal bulk heterojunction morphology was achieved for P3HT : ICBA 1 : 1, which exhibited the highest value of current. A more efficient phase separation in non-annealed P3HT:ICBA films as compared to P3HT:PCBM was accounted for by the differences in solubility of the components in toluene. The structure formation during solvent evaporation can be subdivided into three stages, including the ordering of the polymer in solution, phase separation during precipitation, and the perfectioning of P3HT crystals in the dry film.

The Time-Resolved Fluorescence Stokes Shift of Cucurbit[6]Uril Complexes with a Pyridinium Styryl Dye.

The time-resolved Stokes shift of fluorescence of styryl dye, trans-4-[4-(dimethylamino)-styryl]-1-methylpyridinium iodide (DASPI), and its host-guest complexes with cucurbit[6]uril (CB[6]) was studied by up-conversion technique on a 5 ps time scale. In all cases, the solvation time correlation function - that describes relaxation of the fluorescent state - contains two components. The time constant of the first component, which is related to the vibrational relaxation of the dye cation, increases from 118 fs without CB[6] to 224 fs in the presence CB[6]. It suggests the production of CB[6] complexes to disturb the hydrogen-bond net in the vicinity of DASPI cation. The time constant of the second component, which is associated with solvation, changes from 0.81 ps without CB[6] to 1.15 ps in the presence of the cavitand. The observed increase can be related to the displacement of the dye cation deeper into CB[6] that allows considering DASPI-CB[6] complexes as a light-controlled molecular machine with a response time on the picosecond scale.

Otoliths as object of EPR dosimetric research.

Otoliths are the organs which fish use for hearing and keeping balance. Otoliths are the most calcified tissues in the fish body. In contrast to bones, otoliths are not affected by remodeling and, therefore, they are expected to accumulate any dose from ionizing radiation during lifetime. Therefore, EPR dosimetry with fish otoliths could be an important tool for dose reconstruction in radiobiology and radioecology. It could also provide useful information remediation actions to de-contaminate waterbodies. Consequently, in the present study, otoliths of three contaminated fish species (roach (Rutilus rutilus), pike (Esox lucius) and perch (Perca Fluviatilis)) were examined with Electron Paramagnetic Resonance (EPR) spectroscopy. The fish were caught at storage reservoirs of liquid radioactive waste from Mayak PA and from the upper reach of the Techa River, which have been contaminated with different levels of radionuclide activity concentrations. It is shown that the radiation-induced EPR signal of otolith is stable and characterized by a linear dose response. However, the slope of the calibration curve (corresponding to the radiation sensitivity of the material) is not the same for different species; this may be caused by differences in mineralization. The reconstructed doses were found to be in the range from undetectable (in fish from the upper stream of the Techa River) up to 265 Gy (in roach from the most contaminated waterbody). In parallel, otoliths were measured with ß-counter to detect 90Sr/90Y. Samples were also tested on the presence of alpha-emitters, but no alpha activity above background could be detected. However, a significant activity concentration of 90Sr was detected (from 1 × 101 to 2 × 104 Bq/g). The EPR doses measured correlated with the 90Sr activity concentration measured in the otolith samples.

Peculiar Effects of Electromagnetic Millimeter Waves on Tumor Development in BALB/c Mice.

The study examined the effects of millimeter electromagnetic waves at a frequency of 130 GHz corresponding to the molecular absorption and radiation spectra of NO and O2 with the total exposition time of 6 h on tumor morphogenesis in 3- and 6-month-old tumor-prone BALB/c mice of both sexes. In experimental mice exposed to electromagnetic radiation, the development of cancer process was slowed down throughout the observation period; moreover, no macroscopic signs of the tumors were revealed. However, in contrast to control mice, experimental animals demonstrated the formation of pathological reactions reflected by hepatic biochemical indices accompanied by the development of dystrophic and microcirculatory alterations in the liver tissue.

Effects of Electromagnetic Fields Modulated by Infralow Frequencies on the Production of Stem Cells.

Experimental validation of the method for regulation of stem cell proliferation and differentiation is carried out. The method consists in exposure to ultrahigh frequency electromagnetic radiation, modulated by infralow frequencies with variable parameters. A specially designed programmer, setting up the parameters of exposure, is connected to the source of radiation. The zones of anatomical location of the red bone marrow of rats were exposed for 15 min to the amplitude-modulated electromagnetic radiation of ultrahigh frequency range. The parameters of exposure were determined in previous studies. The red bone marrow was collected from the sternum and head of the femur. The cellular composition of the red bone marrow was evaluated 1, 2, 3, and 6 days after the exposure. The optimal therapeutic mode of irradiation was then chosen, leading to stem cell activation with subsequent proliferation and differentiation into mature red bone marrow cells.

Next-to-Leading Order Computation of Exclusive Diffractive Light Vector Meson Production in a Saturation Framework.

We perform the first next-to-leading order computation of the γ^{(*)}→V (ρ,ϕ,ω) exclusive impact factor in the QCD shock-wave approach and in the most general kinematics. This paves the way to the very first quantitative study of high-energy nucleon and nucleus saturation beyond the leading order for a whole range of small-x exclusive processes, to be measured in ep, eA, pp, and pA collisions at existing and future colliders.

Humidity-induced formation of water channels in supramolecular assemblies of wedge-shaped amphiphiles: the effect of the molecular architecture on the channel topology.

In supramolecular assemblies, absorption of water can assist the channel formation, similarly to biological systems and Nafion-like commercial ion-selective membranes. In this work, we investigate humidity-induced formation of water channels in wedge-shaped amphiphilic molecules, namely sodium 4'-[3'',4'',5''-tris(alkyloxy)benzoyloxy]azobenzene-4-sulfonates. The studied molecules contain a polar sulfonate group at the tip and a hydrophobic periphery composed of alkyl chains of two different lengths. Upon increasing the relative humidity (RH) the amount of absorbed water significantly increases for the mesogen with dodecyl chains as compared to the one with octyl groups. In the former case, water sorption is accompanied by a considerable enhancement of ionic conductivity and a phase transition. In particular, an increase of RH induces a transition from a lamellar to a columnar phase resulting in the formation of 1D water channels running along the axis of the supramolecular columns. For the compound with shorter alkyl chains the lamellar phase exists in the entire RH-range exhibiting pronounced swelling at high RH-values and thereby forming a 2D water channel structure. NMR diffusometry was used to address the different molecular motions in the lyotropic mesophases of the studied amphiphiles.

[Application of the EPR and FISH Methods to Dose Reconstruction for People Exposed in the Techa River Area].

Release of liquid radioactive waste into the Techa River from the Mayak Production Association during 1949-1956 resulted in a significant exposure of about 30000 people who lived in downstream settlements. The residents were exposed to internal and external radiation. The article discusses the capability of two methods that were used 50 years after the termination of radioactive discharges for the dose reconstruction, namely EPR measurements of tooth enamel, and FISH measurements of stable chromosome aberrations in circulating lymphocytes. The Main issue in the application of these methods for the dose reconstruction was local irradiation from strontium radioisotopes incorporated in teeth and bones. The EPR and FISH assays were supported by measurements of the 90Sr content in the skeleton and teeth in order to estimate and subtract internal doses from incorporated 89, 90Sr. The resulting dose estimates obtained from EPR and FISH mea- surements were found to be consistent The settlement-averaged values in the upper-Techa Region varied from 550-570 mGy to 130-160 mGy and showed a reduction with the distance from the release site. The EPR- and FISH-based dose estimates were in agreement with the doses calculated with the dosimetry system TRDS that uses data on radionuclide contamination of the Techa River floodplain and individual residential histories.