The verification of wildland-urban interface fire evacuation models.

This paper introduces a protocol for the verification of multi-physics wildfire evacuation models, including a set of tests used to ensure that the conceptual modelling representation of each modelling layer is accurately implemented, as well as the interactions between different modelling layers and sub-models (wildfire spread, pedestrian movement, traffic evacuation, and trigger buffers). This work presents a total of 24 verification tests, including (1) 4 tests related to pedestrians, (2) 15 tests for traffic evacuation, (3) 5 tests concerning the interaction between different modelling layers, along with 5 tests for wildfire spread and trigger buffers. The evacuation tests are organized in accordance with different core components related to evacuation modelling, namely Population, Pre-evacuation, Movement, Route/destination selection, Flow constraints, Events, Wildfire spread and Trigger buffers. A reporting template has also been developed to facilitate the application of the verification testing protocol. An example application of the testing protocol has been performed using an open wildfire evacuation modelling platform called WUI-NITY and its associated trigger buffer model k-PERIL. The verification testing protocol is deemed to improve the credibility of wildfire evacuation model results and stimulate future modelling efforts in this domain. Supplementary Information: The online version contains supplementary material available at 10.1007/s11069-023-05913-2.

A scoping review of public building accessibility.

BACKGROUND: The built environment needs to be designed so that all people can participate in the activities they want and need to do. Yet, accessibility is difficult to put into practice, and accessibility issues tend to be overlooked in the building and planning processes. OBJECTIVES: The aim of this scoping review was to summarize the research front in the area of accessibility to public buildings. Specific aims were to identify knowledge gaps, to identify access activities in relation to environmental features and to link to predominant activities in terms of the International Classification of Functioning, Disability and Health (ICF). METHODS: A literature search was performed in PubMed, PsycINFO, Inspec, Embase and Cochrane databases. Articles in English based on original empirical studies investigating accessibility of public buildings for adults aged ≥18 years with functional limitations were considered. RESULTS: Of the 40 articles included, ten involved study participants, while 30 only examined buildings using instruments to assess accessibility. In addition, the psychometric properties were only tested for a few of them. All articles concerned mobility and several visual limitations, while few addressed cognitive or hearing limitations. Ten main access activities were identified, from using parking/drop-off area to exiting building. CONCLUSIONS: By using the ICF and theoretically relating the accessibility problems to activities, the results revealed that there are large knowledge gaps about accessibility to public buildings for older people and people with functional limitations and that there is a need for more methodological considerations in this area of research.

Multipolar symmetric squaraines with large two-photon absorption cross-sections in the NIR region.

The two-photon absorption (TPA) properties of two extended symmetric squaraine dyes are thoroughly characterized from the experimental and quantum-chemical point of view. The two molecules are specially engineered to have a multipolar structure with increasing complexity, D-π-A-π-D and A'-π-D-π-A-π-D-π-A', respectively. The experimental TPA spectra, measured by means of the Z-scan technique in the femtoseconds regime, display considerably high values of TPA cross sections (σ(TPA)) for both molecules. In particular, the squaraine with the more extended structure shows the highest value of σ(TPA) ever reported for this class of molecules. CIS and TDDFT calculations of the one and two-photon absorption properties are carried out to clarify the origin of the observed TPA properties and fully characterize the electronic properties of these compounds. The calculations, in good agreement with the experimental data, suggest that the origin of this exceptionally high σ(TPA) can be ascribed to the presence of a peripheral A' group, that increases the density of excited states involved in the TPA process.

Comparison of immunochemical and radioligand binding assays for estrogen receptors in human breast tumors.

We have compared a new enzyme immunoassay (EIA) for estrogen receptors (ER) with our conventional radioligand binding assays (multipoint dextran-coated charcoal assay for cytoplasmic ER and hydroxylapatite exchange assay for nuclear ER). Cytoplasmic ERs were measured in 76 human breast cancer specimens by EIA and by five-point Scatchard analysis. The correlation between the two assays yielded a straight line with a slope of 0.92 (r = 0.95; P less than 0.001); conversely, in 31 nuclear salt extracts, linear regression analysis of hydroxylapatite exchange assay data with EIA showed a clear correlation (r = 0.93; P less than 0.001) but a slope of 1.7, demonstrating that EIA detects more ER sites. The binding of the antibody to the cytoplasmic ER molecules was investigated by sucrose density gradient analysis, which showed that EIA recognizes both cytoplasmic forms (9 and 3S), but does not distinguish between them. Advantages and drawbacks of this method are discussed with respect to its application for routine receptor determination for clinical management of breast cancer patients.

Promoter-specific regulation of gene expression by an exogenously added homedomain that promotes neurite growth.

pAntp, a 60 amino acid long peptide corresponding to the homeodomain of the Drosophila Antennapedia protein, translocates through neuronal membranes when added exogenously to neurons in culture, where it accumulates in the nucleus and promotes neurite outgrowth. We proposed that the peptide, once internalized, may compete for homeoprotein DNA binding sites. To investigate this point, we have produced a permanent fibroblast cell line which carries a luciferase reporter gene under the control of a 93 bp genomic region of the HOXD9 promoter with binding sites for homeoproteins. Externally added pAntp specifically down-regulates the expression of the reporter gene, suggesting that the neurotrophic effects observed previously are mediated by direct binding of pAntp to homeoprotein target sites.

Expression of P-glycoprotein in breast cancer tissue and in vitro resistance to doxorubicin and vincristine.

Expression of P-glycoprotein was evaluated by C219 monoclonal antibody immunoblots in 34 previously untreated and 14 pretreated breast cancers and in benign breast lesions or histologically normal breast glands. P-glycoprotein was not detectable in the few cases of normal or benign tissue. P-glycoprotein was expressed in the 170 kD areas of 29% (10/34) of untreated and 64% (9/14) of previously treated tumours (P = 0.02). In treated tumours, high intensity expression was observed more frequently than in untreated breast cancer (40% vs. 9%). Moreover, there was a significant association between P-glycoprotein expression and in vitro resistance to doxorubicin and vincristine. Simultaneous resistance was observed in all of the P-glycoprotein positive and in only 56% of the P-glycoprotein negative tissues (P less than 0.01). Some aspects of the typical multidrug resistant phenotype, such as P-glycoprotein expression and simultaneous resistance to doxorubicin and vincristine, could be detected in small subsets of breast cancer patients. No relation between P-glycoprotein expression and the type of previous clinical treatment was observed.

Genistein in the control of breast cancer cell growth: insights into the mechanism of action in vitro.

Genistein significantly inhibited cell growth (IC50 around 10 microM) of MCF-7, MDAMB-231 and HBL-100 cell lines, but not of skin-derived fibroblasts and counteracted the growth-stimulatory effects exerted by estradiol and growth factors. It abolished the paracrine stimulation observed in MCF-7 cells in co-culture with MDAMB-231 or fibroblasts. Genistein-treated cells accumulated in the S and G2/M phases of the cell cycle and underwent apoptosis. Genistein decreased tyrosine phosphorylation induced upon treatment with transforming growth factor-alpha. Finally, genistein bound the estrogen receptor (ER) (relative affinity constant Kd = 4 nM), induced pS2 and cathepsin-D transcription and increased nuclear ER levels.

Effects of vitamin E on clinic and ambulatory blood pressure in treated hypertensive patients. Collaborative Group of the Primary Prevention Project (PPP)--Hypertension study.

A randomized controlled open trial studied the effect of vitamin E supplementation (300 mg/day) on clinic and 24-h ambulatory blood pressure (BP) in 142 treated hypertensive patients. After 12 weeks, clinic BP decreased whether or not patients were randomized to vitamin E. Ambulatory BP showed no change in systolic BP and a small decrease in diastolic BP (-1.6 mm Hg, 95% confidence intervals from -2.8 to -0.4 mm Hg), approaching statistical significance in comparison to the control group (P = .06). Vitamin E supplementation thus seems to have no clinically relevant effect on BP in hypertensive patients already under controlled treatment.

Effects of low-dose aspirin on clinic and ambulatory blood pressure in treated hypertensive patients. Collaborative Group of the Primary Prevention Project (PPP)--Hypertension study.

Nonsteroidal antiinflammatory drugs may affect blood pressure (BP) control in hypertensive patients receiving drug treatment, but data on the effects of low-dose aspirin are scanty. This study assessed the effects of chronic treatment with low doses of aspirin (100 mg/day) on clinic and ambulatory systolic (SBP) and diastolic (DBP) BP in hypertensives on chronic, stable antihypertensive therapy. The study was conducted in the framework of the Primary Prevention Project (PPP), a randomized, controlled factorial trial on the preventive effect of aspirin or vitamin E in people with one or more cardiovascular risk factors. Fifteen Italian hypertension units studied 142 hypertensive patients (76 men, 66 women; mean age 59 +/- 5.9 years) treated with different antihypertensive drugs: 71 patients were randomized to aspirin and 71 served as controls. All patients underwent a clinic BP evaluation with an automatic sphygmomanometer and a 24-h ambulatory BP monitoring, at baseline and after 3 months of aspirin treatment. At the end of the study the changes in clinic SBP and DBP were not statistically different in treated and untreated subjects. Ambulatory SBP and DBP after 3 months of aspirin treatment were similar to baseline: deltaSBP -0.5 mmHg (95% confidence intervals [CI] from -1.9 to +2.9 mm Hg) and deltaDBP -1.1 mm Hg (95% CI from -2.5 to +0.3 mm Hg). The pattern was similar in the control group. No interaction was found between aspirin and the most used antihypertensive drug classes (angiotensin converting enzyme inhibitors and calcium antagonists). Despite the relatively small sample size our results seem to exclude any significant influence of low-dose aspirin on BP control in hypertensives under treatment.

Evaluation of cardiac activity and pharmacokinetic analysis of 3H-adriamycin in patients pretreated with beta-methyldigoxin.

The consequences at the cardiac level of adriamycin treatment alone or in association with the cardiac glycoside beta-methyldigoxin, were evaluated with reference to the PEP/LVET ratio, heart rate, and minimum blood pressure. The variation usually seen in the PEP/LVET ratio when adriamycin is administered alone was not observed when pretreatment with beta-methyldigoxin was also given. A similar situation is found with variations in blood pressure and heart rate. From a pharmacokinetic point of view, this treatment scheme does not seem to affect the general behavior of the antibiotic.

Effects of photoperiod on brain corticosteroid receptors and the stress response in the golden hamster (Mesocricetus auratus).

Following exposure to short daylengths, in golden hamsters, changes in basal adrenal glucocorticoid secretion are associated with a significant increase in Type I receptor binding, and are preceded by alterations in the stress-induced release of glucocorticoids, which is one of the major modes of operation of the hypothalamo-pituitary-adrenocortical axis (HPA). These results lend support to the hypothesis that corticosteroid receptors, and in particular the Type I receptor subtype, play a central role in the regulation of circadian and circannual rhythms of the HPA.

Expression of exogenous genes transferred into the avian limb in ovo.

We report on a simple method of direct gene transfer which allows the ectopic expression of proteins and the study of mesoderm-specific genes in the chick embryo. We microinjected into the avian embryonic limb several plasmids containing reporter genes under the control of various promoter sequences, including a minimal chicken muscle acetylcholine receptor alpha-subunit promoter [Klarsfeld, A., Daubas, A., Bourachot, B. and Changeux, J.P., Mol. Cell. Biol., 7 (1987) 951-955]. Gene expression is detectable for 3 days, is reproducible, is restricted to the site of injection, and correlates with the amount of DNA injected. Our observations indicate that it is possible to transfer and express genes in ectodermal and mesodermal cells of the chick limb by direct DNA injection and that the method can be used to analyze promoter sequences in vivo during specific windows of development.

Effect of medroxyprogesterone acetate on the growth of mouse transplanted tumors: relation with hormone sensitivity.

The effect of high and low doses of medroxyprogesterone acetate (MPA) was investigated on three transplanted murine tumors (MXT mammary carcinoma, colon 38, and colon 26) in relation to receptor status and sensitivity of the tumors to ovariectomy and treatment with dexamethasone. MPA had no inhibitory activity on the growth of these tumors. It had no effect on the ovarian-sensitive MXT tumor; it significantly enhanced the growth of an MXT tumor line, selected through serial transplantations, which was stimulated also in ovariectomized animals. MPA, as well as ovariectomy, stimulated the growth of the colon 38 tumor, but this hormone sensitivity was lost during serial transplantations. No correlation was found between the effects of MPA and ovariectomy and the steroid receptor status of these tumors. MPA effects on these tumors do not seem contingent upon a glucocorticoid-like action since dexamethasone was highly effective on all the tested tumors. The combined treatment of the colon 26 tumor with a cytotoxic drug, 4'-deoxydoxorubicin, and MPA, which administered alone stimulated tumor growth and increased life span, caused a slight increase in the life span compared to single agents alone.

Oral doxophylline in patients with chronic obstructive pulmonary disease.

Doxophylline, or 2-(7'-theophyllinemethyl)1,3-dioxolane, is a theophylline derivative which has shown interesting bronchodilating activity, and it appears to determine few adverse effects. The aim of the present investigation was to evaluate clinical therapeutic effects of the drug in the treatment of 2 groups of patients suffering from moderate to severe chronic obstructive pulmonary disease differing in acute response to the inhaled beta 2-agonist salbutamol and to compare changes of lung function tests to serum concentration of doxophylline. We studied 67 patients with chronic obstructive pulmonary disease (median age 63 years, 9 females and 58 males) who were all clinically stable at the time of the study. Patients were separated into 2 groups on the basis of their reaction to inhalation of 200 micrograms of salbutamol: those with an increased FEV1 of more than 20% from baseline value (group 1), and those with no increase (group 2). Doxophylline was administered orally at the dose of 400 mg 3 times daily. Serum levels of doxophylline were determined by high-pressure liquid chromatography. Spirometry and blood gas analysis were performed before and 10 days after treatment. Four patients stopped drug assumption because of side effects (3 for dyspepsia and 1 for anxiety). In group 1 (34 patients), a significant increase in SVC, FVC, FEV1, FEF 25-75% and PEFR was observed. In group 1 (29 patients), only PEFR significantly increased. No modifications in blood gas analysis were observed. The mean serum level of doxophylline was 14 micrograms/ml in group 1 and 9 micrograms/ml in group 2: the difference was statistically significant. The relation between serum levels of doxophylline and FVC showed an increase in the parameter up to the concentration of 12-13 micrograms/ml, after which a plateau phase was observed. On the basis of our data, doxophylline appears to have an interesting bronchodilating effect in patients responsive to the inhaled beta 2-agonist salbutamol. The lower limit of the therapeutic range seems to be 12-13 micrograms/ml. The upper limit of the therapeutic range was not determined because it was not possible to obtain serum samples when side effects occurred.

Wernicke's lethal encephalopathy in voluntary, total, prolonged fasting.

A lethal case of Wernicke's encephalopathy caused by prolonged fasting is reported; the liability of physicians is evaluated.

An improved criterion for the evaluation of estrogen receptor binding data in human breast cancer.

The evaluation of the data is an important step in performing the estrogen receptor test. For this reason an effort has been made to derive a more reliable threshold criteria. Among the parameters considered, Xo, Ka, and BI%, only the former 2 appear to be suitable to allow a proper evaluation of the results. From the analysis of different types of carcinomatous or normal breast specimens, limit values of these parameters have been recovered for positivity and negativity of the estrogen receptor test. We found all the samples showing Ka less than 1.5 x 10(9) M-1 or Xo less than 5 fmol/mg proteins to be negative, those characterized by low values of both the parameters were borderline, and all the remaining ones were positive.

Prognostic significance of progesterone receptors alone or in association with estrogen receptors in human breast cancer.

Estrogen (ER) and progesterone (PgR) receptors were measured simultaneously in 1144 consecutive breast cancer patients to determine the distribution of patients according to receptor and menopausal status when receptor occurrence rates were considered. The prognostic significance of PgR, either alone or in association with ER, was studied on 187 consecutive breast cancer patients treated only by radical mastectomy. All the cases, as regards axillary node status, were pathologically assessed as node negative. These patients did not receive any adjuvant treatment after mastectomy. At 36 months after mastectomy, the follow-up indicated that PgR- patients have a worse prognosis than PgR+ ones. This is evident when PgR alone is considered as a prognostic factor as well as when it is used to identify, within ER+ cases, those with a higher probability of relapse. In conclusion, it can be stated that although PgR status is an independent prognostic factor, it is useful to evaluate ER and PgR simultaneously for better patient management.

Distribution of estrogen and progesterone receptors in primary tumor and lymph nodes in individual patients with breast cancer.

Primary breast cancer tissue and lymph nodes were obtained from 48 patients. Estrogen receptors (ER) and progesterone receptors (PgR) were determined by a dextran-coated charcoal assay. ER were present in 72.9% of the primary tumors and in 62.4% of the malignant lymph nodes, whereas PgR were present in 73.0% and 50.0% of the cases, respectively. The primary tumor and the corresponding malignant lymph nodes showed an identical ER and PgR status, i.e., both tumor sites were receptor positive or both receptor negative in 89.6% and 77.1%, respectively. However, 10.4% of the patients had ER-positive tumors but ER-negative lymph nodes and 22.9% had PgR-positive primaries with PgR-negative lymph nodes. No receptor-positive lymph nodes showed a combination with receptor-negative primary tumor. This preliminary data shows that receptor-positive malignant lymph nodes mostly display the same receptor status as the corresponding primary tumor, whereas receptor-negative lymph nodes may have a receptor-positive primary tumor.

Variations in estrogen and progesterone receptor content in premenopausal breast cancer patients throughout the menstrual cycle.

Estrogen (ER) and progesterone (PgR) receptor content was assayed in 290 premenopausal women with primary breast cancer, in order to investigate the influence of endogenous hormones on cytoplasmic receptor concentrations throughout the menstrual cycle, subdivided into four phases of ovarian function (early and late follicular phase, early and late luteal phase). Of the total population, 231 (79.7%) patients were ER positive and 59 (20.3%) were ER negative; 220 (75.9%) were PgR positive and 70 (24.1%) were PgR negative. The percentages of positive cases were almost constant in each phase. No significant difference in mean values of ER concentration was noted throughout the cycle. Instead, the PgR concentration significantly increased from the first to the third phase (P = 0.02) and decreased from the third to the fourth phase (P = 0.01). Our results suggest that ER- and PgR- cases are homogeneously distributed and not influenced by the phase of the cycle. Moreover, they suggest that PgR measurement in the luteal phase, rather than in other phases, prevents the occurrence of false low PgR levels and, at the same time, improves its prognostic significance and response rate to endocrine therapy.

A double-labeling assay for simultaneous estimation and characterization of estrogen and progesterone receptors using radioiodinated estradiol and tritiated Org 2058.

Estrogen (ER) and progesterone receptors (PgR) appear to be a prerequisite to elicit a biologic response by a hormone-target organ. Current methodologies for analysis of these proteins (e.g., dextran-coated charcoal, DCC) in single-label assay (SLA) require relatively large amounts of tissue material, time and laboriousness. Therefore, we have developed for breast cancer tissue an improved dual-label assay (DLA) for simultaneous titration (by DCC) and/or characterization (by sedimentation properties) of ER and PgR on the same sample, using 125I-E2 and 3H-Org 2058 as tracers. The interaction of 125I-E2 with ER and plasma proteins in comparison to 3H-E2 was studied in terms of specificity, time course, affinity binding and sedimentation pattern. 125I-E2 bound the same molecular forms displayed by 3H-E2 (9 and 3S) but with lower titers (about 1.3-fold), irrespective of the technique used, and did not bind to sex hormone-binding globulin. Simultaneous detection of 125I and 3H was achieved by use of a gamma counter plus a beta counter sequentially. ER and PgR titrations with DCC in DLA were in good agreement with those obtained with SLA, in terms of titers and Ka values. An analogous result was obtained with sucrose density gradient (SDG) analysis. Both the DLA methods were highly reproducible (CV less than 8.0%). Between the rotors available for SDG, the vertical one was preferable because of the larger number of samples processed and of less perturbation of sedimenting receptor molecules. Furthermore, a biochemical application of the method is described. In conclusion, the DLA procedure, by simplifying ER and PgR estimation, makes it possible to study, even on small tumor biopsies, the molecular properties of these proteins in relation to the clinical response of the disease.