Relationship between magnetic rigidity cutoff and chaotic behavior in cosmic ray time series using visibility graph and network analysis techniques.

Cosmic rays are highly energetic particles originating from astrophysical events outside the Solar System. In this study, we analyze the time series of cosmic ray flux measured by neutron detectors at 16 monitoring stations distributed worldwide. By applying visibility graph analysis, we explore the relationship between the magnetic rigidity cutoff (Rc) and the fractality exhibited from topology of the cosmic ray time series. Our results reveal a significant association between the magnetic rigidity cutoff and the fractality of the cosmic ray time series. Specifically, the analysis of visibility graphs and network properties demonstrates that the magnetic rigidity is inversely related to the magnetic rigidity cutoff. The identified relationship between magnetic rigidity and fractality provides insights into the chaotic nature of cosmic ray variations and their potential uses for predictability.

Predictors of Beta-Hexachlorocyclohexane blood levels among people living close to a chemical plant and an illegal dumping site.

BACKGROUND: Hexachlorocyclohexane is a synthetic chemical with several isomers, including ß-Hexachlorocyclohexane (ß-HCH). In 2005, a large contamination of crude milk from some bovine farms along the Sacco River (Central Italy) was detected; it was related to the illegal disposal of large quantities of processing waste by a chemical industry of the area. A biomonitoring study, conducted in 2007 on a sample of the residing population, found high values of ß-HCH in people living close to the river. These results led to the establishment of a clinical and epidemiological surveillance program on all the exposed population. The aim of the study was to evaluate the determinants of ß-HCH blood levels in people living within 1 Km of the Sacco River, focusing on the role of specific foods, body mass index and risk factors not yet identified. METHODS: The program involved all people living within 1 km of the river. A descriptive analysis of ß-HCH blood levels was done in relation to the potential determinants including specific foods. Regression analysis was used to study the association between potential determinants and (natural log) ß-HCH haematic concentration. The results were expressed as geometric mean ratios (GMR). To take into account similarities within the families we adjusted for family clustering. RESULTS: A total of 602 subjects (87.2%) agreed to participate in the surveillance. The ß-HCH geometric mean serum concentration was 72 ng/g lipid. The regression analysis showed that being female (GMR: 1.32, 95%CI: 1.14-1.53), elderly (GMR> 70yy: 10.04, 95%CI: 6.65-15.15), obese (GMR: 1.63, 95%CI: 1.28-2.08), eating food of local/own production (GMR 1.47, 95%CI: 1.15-1.88) and using water from private wells (GMRdrink:1.47, 95%CI: 1.00-2.14 and GMRwash: 1.48, 95%CI: 1.17-1.87) were associated with higher ß-HCH values. There was inverse association with breastfeeding (GMR: 0.64, 95%CI: 0.47-0.86). The focus on specific foods showed that the most important factors were eggs and beef. CONCLUSIONS: The study indicated a greater contamination for older people, and those drinking and washing with water from private wells and consuming locally produced food, especially eggs and beef.

Phenotyping asthma, rhinitis and eczema in MeDALL population-based birth cohorts: an allergic comorbidity cluster.

BACKGROUND: Asthma, rhinitis and eczema often co-occur in children, but their interrelationships at the population level have been poorly addressed. We assessed co-occurrence of childhood asthma, rhinitis and eczema using unsupervised statistical techniques. METHODS: We included 17 209 children at 4 years and 14 585 at 8 years from seven European population-based birth cohorts (MeDALL project). At each age period, children were grouped, using partitioning cluster analysis, according to the distribution of 23 variables covering symptoms 'ever' and 'in the last 12 months', doctor diagnosis, age of onset and treatments of asthma, rhinitis and eczema; immunoglobulin E sensitization; weight; and height. We tested the sensitivity of our estimates to subject and variable selections, and to different statistical approaches, including latent class analysis and self-organizing maps. RESULTS: Two groups were identified as the optimal way to cluster the data at both age periods and in all sensitivity analyses. The first (reference) group at 4 and 8 years (including 70% and 79% of children, respectively) was characterized by a low prevalence of symptoms and sensitization, whereas the second (symptomatic) group exhibited more frequent symptoms and sensitization. Ninety-nine percentage of children with comorbidities (co-occurrence of asthma, rhinitis and/or eczema) were included in the symptomatic group at both ages. The children's characteristics in both groups were consistent in all sensitivity analyses. CONCLUSION: At 4 and 8 years, at the population level, asthma, rhinitis and eczema can be classified together as an allergic comorbidity cluster. Future research including time-repeated assessments and biological data will help understanding the interrelationships between these diseases.

The persistence of ligature marks: towards a new protocol for victims of abuse and torture.

One of the most frequently observed lesions in clinical forensic practice concerns the patterned abrasion on skin due to constriction by various types of ligature. Detection of ligature marks and their patterns may be fundamental for reconstructing events and supporting testimony of an aggression, sexual abuse, or maltreatment. But very little actually exists in literature concerning their detectability and how long they last. This study aims at evaluating the time of persistence and detectability of skin signs left by different types of ligatures in living persons: on the arms of three volunteers, eight different ligatures were applied; 123 tests were performed, with time of contact ranging between 1 min and 2 h and 45 min. In addition, the persistence of the shape and pattern of the ligature was evaluated 15, 30, and 60 min after a 5- and 15-min compression. Polyvinyl siloxane, applied by a gun dispenser, was used to perform a cast of the skin mark. The results show that the pattern was less distinguishable with the decrease of time of contact, going from 75 % after 10 and 15 min of contact, to 45.8 % after 1 min. Above 15 min, the specific pattern was always recognizable. In addition, a progressive decrease of the detectability of the pattern with time, respectively, up to 12.5 and 37.5 % in 5- and 15-min tests was observed. This study provides useful results for the assessment of patterned injuries in forensic pathology and clinical forensic medicine, both on dead and living persons: in addition, the use of silicone casts seems to be a reliable and cheap method for easily recording and preserving the morphological profile of skin lesions.

Dataset for Sun dynamics from topological features.

The present study presents an extensive dataset meticulously curated from solar images sourced from the Solar and Heliospheric Observatory (SOHO), encompassing a range of spectral bands. This collaborative effort spans multiple disciplines and culminates in a robust and automated methodology that traverses the entire spectrum from solar imaging to the computation of spectral parameters and relevant characteristics. The significance of this undertaking lies in the profound insights yielded by the dataset. Encompassing diverse spectral bands and employing topological features, the dataset captures the multifaceted dynamics of solar activity, fostering interdisciplinary correlations and analyses with other solar phenomena. Consequently, the data's intrinsic value is greatly enhanced, affording researchers in solar physics, space climatology, and related fields the means to unravel intricate processes. To achieve this, an open-source Python library script has been developed, consolidating three pivotal stages: image acquisition, image processing, and parameter calculation. Originally conceived as discrete modules, these steps have been unified into a single script, streamlining the entire process. Applying this script to various solar image types has generated multiple datasets, subsequently synthesised into a comprehensive compilation through a data mining procedures. During the image processing phase, conventional libraries like OpenCV and Python's image analysis tools were harnessed to refine images for analysis. In contrast, image acquisition utilised established URL libraries in Python, facilitating direct access to original SOHO repository images and eliminating the need for local storage. The computation of spectral parameters involved a fusion of standard Python libraries and tailored algorithms for specific attributes. This approach ensures precise computation of a diverse array of attributes crucial for comprehensive analysis of solar images.

Fracture propagation in the human cranium: a re-testing of popular theories.

Bone trauma interpretation is an important area of forensic anthropology. Notwithstanding the recent realization of the validity of fracture pattern interpretation, knowledge of trauma is largely based on case studies and older experimental work. Gurdjian and coauthors conducted a number of studies on blunt force fracture propagation that are still used today. Fracture propagation was noted to initiate in an area other than the point of impact, then radiate back toward it. Gurdjian's results are often used to suggest that the point of impact is at a location other than the fracture epicenter. This study is an examination and retesting of Gurdjian's theories of fracture propagation using current biomechanics research and technology. Specifically, the relationship of impact site and fracture patterning was tested using cadaver heads. The results demonstrate that fractures radiate from the point of impact, contrary to the theories of Gurdjian.

[Protection of health and safety of rescue workers to non-profit organizations]. / Tutela della salute e sicurezza degli operatori del Soccorso di organizzazioni onlus.

74% of accidents to staff assistance is linked to transport activities in both normal and emergency. The accident rate is much higher ambulances during his way to siren (22.2 incidents per 100,000 journeys) than normal distances (1.46 per 100,000). Also 60% of accidents and 58% of accidents with serious outcomes for rescuers is on the move for emergency response. The unknown danger, requiring operator safety of relief, that the normal work clothing becomes a D.P.I. standing and adaptable, modular almost without causing discomfort or inconvenience.

Traffic-related air pollution in relation to respiratory symptoms, allergic sensitisation and lung function in schoolchildren.

BACKGROUND: Urban air pollution can trigger asthma exacerbations, but the effects of long-term exposure to traffic-related air pollution on lung function or onset of airway disease and allergic sensitisation in children is less clear. METHODS: All 2107 children aged 9-14 years from 40 schools in Rome in 2000-1 were included in a cross-sectional survey. Respiratory symptoms were assessed on 1760 children by parental questionnaires (response rate 83.5%). Allergic sensitisation was measured by skin prick tests and lung function was measured by spirometry on 1359 children (77.2%). Three indicators of traffic-related air pollution exposure were assessed: self-reported heavy traffic outside the child's home; the measured distance between the child's home and busy roads; and the residential nitrogen dioxide (NO2) levels estimated by a land use regression model (R2 = 0.69). RESULTS: There was a strong association between estimated NO2 exposure per 10 microg/m3 and lung function, especially expiratory flows, in linear regression models adjusted for age, gender, height and weight: -0.62% (95% CI -1.05 to -0.19) for forced expiratory volume in 1 s as a percentage of forced vital capacity, -62 ml/s (95% CI -102 to -21) for forced expiratory flow between 25% and 75% of forced vital capacity and -85 ml/s (95% CI -135 to -35) for peak expiratory flow. The other two exposure indicators showed similar but weaker associations. The associations appeared stronger in girls, older children, in children of high socioeconomic status and in those exposed to parental smoking. Although lifetime asthma was not an effect modifier, there was a suggestion of a larger effect on lung function in subjects with a positive prick test. Multiple logistic regression models did not suggest a consistent association between traffic-related air pollution exposure and prevalence of respiratory symptoms or allergic sensitisation. CONCLUSION: The results of this study suggest that residential traffic-related air pollution exposure is associated with reduced expiratory flows in schoolchildren.

ErbB2 is necessary for induction of carcinoma cell invasion by ErbB family receptor tyrosine kinases.

The epidermal growth factor (EGF) family of tyrosine kinase receptors (ErbB1, -2, -3, and -4) and their ligands are involved in cell differentiation, proliferation, migration, and carcinogenesis. However, it has proven difficult to link a given ErbB receptor to a specific biological process since most cells express multiple ErbB members that heterodimerize, leading to receptor cross-activation. In this study, we utilize carcinoma cells depleted of ErbB2, but not other ErbB receptor members, to specifically examine the role of ErbB2 in carcinoma cell migration and invasion. Cells stimulated with EGF-related peptides show increased invasion of the extracellular matrix, whereas cells devoid of functional ErbB2 receptors do not. ErbB2 facilitates cell invasion through extracellular regulated kinase (ERK) activation and coupling of the adaptor proteins, p130CAS and c-CrkII, which regulate the actin-myosin cytoskeleton of migratory cells. Overexpression of ErbB2 in cells devoid of other ErbB receptor members is sufficient to promote ERK activation and CAS/Crk coupling, leading to cell migration. Thus, ErbB2 serves as a critical component that couples ErbB receptor tyrosine kinases to the migration/invasion machinery of carcinoma cells.

Beta1-class integrins regulate the development of laminae and folia in the cerebral and cerebellar cortex.

Mice that lack all beta1-class integrins in neurons and glia die prematurely after birth with severe brain malformations. Cortical hemispheres and cerebellar folia fuse, and cortical laminae are perturbed. These defects result from disorganization of the cortical marginal zone, where beta1-class integrins regulate glial endfeet anchorage, meningeal basement membrane remodeling, and formation of the Cajal-Retzius cell layer. Surprisingly, beta1-class integrins are not essential for neuron-glia interactions and neuronal migration during corticogenesis. The phenotype of the beta1-deficient mice resembles pathological changes observed in human cortical dysplasias, suggesting that defective integrin-mediated signal transduction contributes to the development of some of these diseases.

Meta-analysis of determinants for pet ownership in 12 European birth cohorts on asthma and allergies: a GA2LEN initiative.

BACKGROUND: Studies on pet ownership as a risk or protective factor for asthma and allergy show inconsistent results. This may be on account of insufficient adjustment of confounding factors. AIM: The objective of this study was to describe determinants of cat and dog ownership in European families with and without allergies. METHODS: Within the EU-funded network of excellence GA(2)LEN, we performed meta-analyses with data from 12 ongoing European birth cohort studies on asthma and allergy. Each of the birth cohort studies enrolled between 485 and 4089 children. Pet ownership, allergic status (asthma, allergic rhinitis, eczema) of parents and siblings, parental education, access to ground floor, and number of people living at home were assessed by questionnaires. RESULTS: Among the 25 056 families from seven European countries cats (14.9%) were more common than dogs (12.0%). Allergic family history significantly reduced the odds to own a cat (adjusted combined random-effect OR 0.91; 95% CI 0.85-0.99), or dog (0.90; 0.86-0.94). A higher parental educational level had even more pronounced effects on cat (0.84; 0.71-0.98), and dog ownership (0.61; 0.54-0.70). Elder siblings reduced the odds to own cats, but not dogs. Convenient ground access significantly increased the odds, whereas crowding at home was not associated with cat or dog ownership. CONCLUSIONS: The chances to own a cat or dog were significantly reduced in allergic families, in parents with a higher educational level, and in homes without convenient ground access. In addition to parental allergies, social and housing factors should be considered as potential confounders in studies on pet exposure and allergic diseases.

Comparison between various indices of exposure to traffic-related air pollution and their impact on respiratory health in adults.

OBJECTIVE: To evaluate the association of different indices of traffic-related air pollution (self-report of traffic intensity, distance from busy roads from geographical information system (GIS), area-based emissions of particulate matter (PM), and estimated concentrations of nitrogen dioxide (NO(2)) from a land-use regression model) with respiratory health in adults. METHODS: A sample of 9488 25-59-year-old Rome residents completed a self-administered questionnaire on respiratory health and various risk factors, including education, occupation, housing conditions, smoking, and traffic intensity in their area of residence. The study used GIS to calculate the distance between their home address and the closest high-traffic road. For each subject, PM emissions in the area of residence as well as estimated NO2 concentrations as assessed by a land-use regression model (R(2) value = 0.69), were available. Generalised estimating equations (GEE) were used to analyse the association between air pollution measures and prevalence of "ever" chronic bronchitis, asthma, and rhinitis taking into account the effects of age, gender, education, smoking habits, socioeconomic position, and the correlation of variables for members of the same family. RESULTS: Three hundred and ninety seven subjects (4% of the study population) reported chronic bronchitis, 472 (5%) asthma, and 1227 (13%) rhinitis. Fifteen per cent of subjects reported living in high traffic areas, 11% lived within 50 m of a high traffic road, and 28% in areas with estimated NO2 greater than 50 microg/m(3). Prevalence of asthma was associated only with self-reported traffic intensity whereas no association was found for the other more objective indices. Rhinitis, on the other hand, was strongly associated with all traffic-related indicators (eg, OR = 1.13, 95% CI: 1.04 to 1.22 for 10 microg/m(3) NO2, especially among non-smokers. CONCLUSIONS: Indices of exposure to traffic-related air pollution are consistently associated with an increased risk of rhinitis in adults, especially among non-smokers. The results for asthma are weak, possibly due to ascertainment problems.

Single-chain antibody-mediated intracellular retention of ErbB-2 impairs Neu differentiation factor and epidermal growth factor signaling.

ErbB-2 becomes rapidly phosphorylated and activated following treatment of many cell lines with epidermal growth factor (EGF) or Neu differentiation factor (NDF). However, these factors do not directly bind ErbB-2, and its activation is likely to be mediated via transmodulation by other members of the type I/EGF receptor (EGFR)-related family of receptor tyrosine kinases. The precise role of ErbB-2 in the transduction of the signals elicited by EGF and NDF is unclear. We have used a novel approach to study the role of ErbB-2 in signaling through this family of receptors. An ErbB-2-specific single-chain antibody, designed to prevent transit through the endoplasmic reticulum and cell surface localization of ErbB-2, has been expressed in T47D mammary carcinoma cells, which express all four known members of the EGFR family. We show that cell surface expression of ErbB-2 was selectively suppressed in these cells and that the activation of the mitogen-activated protein kinase pathway and p70/p85S6K, induction of c-fos expression, and stimulation of growth by NDF were dramatically impaired. Activation of mitogen-activated protein kinase and p70/p85S6K and induction of c-fos expression by EGF were also significantly reduced. We conclude that in T47D cells, ErbB-2 is a major NDF signal transducer and a potentiator of the EGF signal. Thus, our observations demonstrate that ErbB-2 plays a central role in the type I/EGFR-related family of receptors and that receptor transmodulation represents a crucial step in growth factor signaling.

ErbB-1 and ErbB-2 acquire distinct signaling properties dependent upon their dimerization partner.

The different epidermal growth factor (EGF)-related peptides elicit a diverse array of biological responses as the result of their ability to activate distinct subsets of ErbB receptor dimers, leading to the recruitment of different intracellular signaling networks. To specifically examine dimerization-dependent modulation of receptor signaling, we constructed NIH 3T3 cell lines expressing ErbB-1 and ErbB-2 singly and in pairwise combinations with each other ErbB family member. This model system allowed the comparison of EGF-activated ErbB-1 with ErbB-1 activated by Neu differentiation factor (NDF)-induced heterodimerization with ErbB-4. In both cases, ErbB-1 coupled to the adaptor protein Shc, but only when activated by EGF was it able to interact with Grb2. Compared to the rapid internalization of EGF-activated ErbB-1, NDF-activated ErbB-1 showed delayed internalization characteristics. Furthermore, the p85 subunit of phosphatidylinositol kinase (PI3-K) associated with EGF-activated ErbB-1 in a biphasic manner, whereas association with ErbB-1 transactivated by ErbB-4 was monophasic. The signaling properties of ErbB-2 following heterodimerization with the other ErbB receptors or homodimerization induced by point mutation or monoclonal antibody treatment were also analyzed. ErbB-2 binding to peptides containing the Src homology 2 domain of Grb2 or p85 and the phosphotyrosine binding domain of Shc varied according to the mode of receptor activation. Finally, tryptic phosphopeptide mapping of both ErbB-1 and ErbB-2 revealed that receptor phosphorylation is dependent on the dimerization partner. Differential receptor phosphorylation may, therefore, be the basis for the differences in the signaling properties observed.

Neu differentiation factor activation of ErbB-3 and ErbB-4 is cell specific and displays a differential requirement for ErbB-2.

Neu differentiation factor (NDF)-induced signaling involves the activation of members of the ErbB family of receptor tyrosine kinases. Although ectopic expression of recombinant ErbB receptors has yielded valuable insight into their signaling properties, the biological function and in vivo interplay of these receptors are still poorly understood. We addressed this issue by studying NDF signaling in various human cell lines expressing moderate levels of all known ErbB receptors. NDF-induced phosphorylation of ErbB-2 and ErbB-3 was found in the breast epithelial cell line MCF10A, the breast tumor cell lines T47D and MCF7, and the ovarian tumor cell line OVCAR3. Despite similar expression levels, NDF-induced phosphorylation of ErbB-4 was cell specific and only detected in T47D and OVCAR3 cells. Blocking cell surface expression of ErbB-2 by intracellular expression of a single-chain antibody revealed that in these two cell lines, ErbB-2 significantly enhanced phosphorylation of ErbB-4. Efficient NDF-induced phosphorylation of ErbB-3 was strictly ErbB-2 dependent in the breast tumor cell lines T47D and MCF7, while it was largely ErbB-2 independent in MCF10A and OVCAR3 cells. Consequently, NDF-stimulated intracellular signaling and induction of a biological response displayed a cell-specific requirement for ErbB-2. Thus, while ErbB-2 cooperates with NDF receptors in the breast tumor cell lines, ErbB-2 independent mechanisms seem to prevail in other cellular contexts.

Sensitivity of autopsy and radiological examination in detecting bone fractures in an animal model: implications for the assessment of fatal child physical abuse.

Skeletal injuries are often strong indicators of child abuse and their detection is therefore crucial. The aim of this study was to compare the sensitivity of three diagnostic approaches, namely autopsy, traditional (conventional) radiology, and computed tomography on "battered" piglets, in order to verify the sensitivity of each method, with respect to the true number of bone fractures assessed once the piglet was skeletonised (osteological control). Four newborn cadaver piglets who had died from natural causes were severely beaten post-mortem in every district of the body. Traditional radiography, computed tomography (CT) and autopsy were performed. The piglet was then macerated until skeletonised and the number of all fractures present recorded (osteological control). On the cranium, traditional radiology revealed only 35% circa of actual fractures, autopsy detected only 31% (P<0.01 for both comparisons versus osteological control), whereas CT imaging detected all fractures actually present. For ribs, radiology detected only 47% of all fractures present, and autopsy 65% circa (P>0.05 for both comparisons versus osteological control), while CT scans detected 34% (P<0.01). In suspected cases of fatal child abuse, we suggest that the bones of specific districts be directly analysed either at autopsy or by collecting specific diagnostic sites, such as parts of the rib cage, and subjecting them to maceration. The removed areas could be replaced with artificial material for cosmetic purposes. The authors stress the importance of combined radiological, CT scan, autopsy and osteological survey in the detection of perimortem bone fractures.

Neu differentiation factor induces ErbB2 down-regulation and apoptosis of ErbB2-overexpressing breast tumor cells.

Neu differentiation factor (NDF), a member of the epidermal growth factor (EGF)-related peptide family, activates ErbB2 via heterodimerization with the NDF receptors ErbB3 and ErbB4. In a similar fashion, EGF receptor (EGFR) agonists induce heterodimers of EGFR and ErbB2. In this paper, we show that the ErbB2-overexpressing breast tumor cells SKBR3, AU565, and MDA-MB453 are growth inhibited by NDF. Cells with elevated levels of ErbB2 but little or no NDF receptors (SKOV3 and MDA-MB361) or cells with low levels of ErbB2 (T47D and MCF7) are not growth inhibited. None of the EGFR agonists tested (EGF, beta-cellulin, or heparin-binding EGF) inhibited growth of ErbB2-overexpressing cells. These results suggest that formation of an ErbB2/NDF receptor heterodimer, but not of an ErbB2/EGFR heterodimer, promotes growth inhibition. In addition, NDF caused a down-regulation of ErbB2 but not of ErbB3. The mechanism underlying the inhibitory effect was examined further in SKBR3 cells, which are 95% growth inhibited by NDF. A G2-M arrest is seen 24 h after NDF treatment, and increased apoptosis is detectable from day 2 onward. The results demonstrate for the first time that NDF induces apoptosis of tumor cells overexpressing ErbB2.

NDF/heregulin activates MAP kinase and p70/p85 S6 kinase during proliferation or differentiation of mammary epithelial cells.

Neu differentiation factors (NDF) are a novel family of polypeptide factors which activate sub-class I tyrosine kinase receptors. In all mammary epithelial cells analysed in this study, NDF activates the same signalling pathways while it induces different, cell-specific biological effects. In AU565 cells which are growth inhibited, as well as in T47D or HC11 cells which proliferate in response to NDF, the MAP kinase isoforms p44ERK1 and p42ERK2 and the p70/p85 S6 kinase are activated. NDF stimulates tyrosine phosphorylation and the in vitro kinase activity of ErbB-2. When PKC is activated by TPA, NDF is no longer able to activate ErbB-2 in T47D cells, leading to a blockage of cell proliferation. Activation of ErbB-2 by point mutation, or by monoclonal antibodies, also stimulates both the MAPK and the p70/p85 S6 kinase pathways. The same monoclonal antibodies can induce AU565 cell differentiation. In summary, during growth or differentiation of mammary epithelial cells, NDF stimulates several independent signalling pathways which can also be triggered by ErbB-2 stimulation alone. PKC activation blocks the biological effect induced by NDF through negative modulation of ErbB-2.

Neu differentiation factor/heregulin modulates growth and differentiation of HC11 mammary epithelial cells.

The HC11 mouse mammary epithelial cell line has proven to be a valuable in vitro model to study the roles of peptide factors and hormones involved in the growth and differentiation of mammary cells. Treatment of HC11 cells with the lactogenic hormones, dexamethasone, insulin, and PRL (DIP), leads to cellular differentiation and production of the milk protein beta-casein. We have analyzed the effects of Neu differentiation factor (NDF)/heregulin, a newly described activating ligand for erbB-2 and other members of the epidermal growth factor (EGF) receptor family, on cell growth and the expression of milk proteins in HC11 cells. In these cells, NDF induces tyrosine phosphorylation of erbB-2 and erbB-3. Both NDF and EGF stimulate HC11 cell proliferation and promote the responsiveness of HC11 cells to lactogenic hormones. NDF induces the expression of a 22-kilodalton milk protein. This protein is up-regulated by other factors, including dexamethasone, EGF, and basic fibroblast growth factor, and is controlled in a manner distinct from that of beta-casein. Like EGF, NDF inhibits the DIP-induced expression of beta-casein at the level of transcription. The inhibition is due to the negative effect of NDF on the activation of mammary gland factor (MGF/Stat5), a member of the Stat family of transcription factors, which is essential for beta-casein gene expression.

Changes in survival among people with AIDS in Lazio, Italy from 1993 to 1998. Lazio AIDS Surveillance Collaborative Group.

OBJECTIVES: To investigate temporal changes in survival of persons with AIDS (PWA) diagnosed in Lazio, Italy. DESIGN: Longitudinal study of 2862 PWA registered at the AIDS Surveillance System in the period 1 January 1993 to 30 June 1997 and followed for vital status up to 31 May 1998. METHODS: Hazard ratios (HR) of death were calculated by year of diagnosis and by year of follow-up, adjusting for gender, age, modality of exposure, CD4 cell count at diagnosis, and AIDS-defining illness, using the Cox proportional regression model. RESULTS: In the period 1 January 1993 to 31 May 1998, 1914 PWA died. The multivariate model showed a decrease of the risk of death for patients diagnosed from 1995 onward compared with patients diagnosed in 1993 [1995: HR 0.82; 95% confidence intervals (CI) 0.73-0.93; 1996: HR 0.44; 95% CI 0.38-0.51; first semester of 1997: HR 0.47; 95% CI 0.37-0.59]. The model with the year of follow-up modeled as time-dependent variable showed a statistically significant decline in the risk of death starting from the first quarter of 1997 (HR 0.62; 95% CI 0.48-0.80) and reached the minimum in the first two quarters of 1998 (first quarter: HR 0.13; 95% CI 0.08-0.21; second quarter: HR 0.14, 95% CI 0.08-0.25). There was a small difference in the magnitude of the risk estimates among genders, with a slower improvement in survival among females [first semester of 1997 for males HR was 0.51 (95% CI 0.39-0.66) whereas for females HR was 0.80 (95% CI 0.51-1.27)]. CONCLUSIONS: Survival of PWA in a population-based study improved significantly in the era when highly active antiretroviral therapy became available, but such improvement is not homogeneous among genders.