On the theory of solitons of fluid pressure and solute density in geologic porous media, with applications to shale, clay and sandstone

In this paper we propose the application of a new model of transients of pore pressure p and solute density \r{ho} in geologic porous media. This model is rooted in the non-linear waves theory, the focus of which is advection and effect of large pressure jumps on strain (due to large p in a non-linear version of the Hooke law). It strictly relates p and \r{ho} evolving under the effect of a strong external stress. As a result, the presence of quick and sharp transients in low permeability rocks is unveiled, i.e. the non-linear Burgers solitons. We therefore propose that the actual transport process in porous rocks for large signals is not the linear diffusion, but could be governed by solitons. A test of an eventual presence of solitons in a rock is here proposed, and then applied to Pierre Shale, Bearpaw Shale, Boom Clay and Oznam-Mugu silt and clay. A quick analysis showing the presence of solitons for nuclear waste disposal and salty water intrusions is also analyzed. Finally, in a kind of "theoretical experiment" we show that solitons could also be present in Jordan and St. Peter sandstones, thus suggesting the occurrence of osmosis in these rocks

Towards a Theory of Solitary Shock Waves of Fluid Pressure and Solute Density in Geologic Porous Media

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Antibody-drug conjugates (ADC) against cancer stem-like cells (CSC) - Is there still room for optimism?

Cancer stem-like cells (CSC) represent a subpopulation of tumor cells with peculiar functionalities that distinguish them from the bulk of tumor cells, most notably their tumor-initiating potential and drug resistance. Given these properties, it appears logical that CSCs have become an important target for many pharma companies. Antibody-drug conjugates (ADC) have emerged over the last decade as one of the most promising new tools for the selective ablation of tumor cells. Three ADCs have already received regulatory approval and many others are in different phases of clinical development. Not surprisingly, also a considerable number of anti-CSC ADCs have been described in the literature and some of these have entered clinical development. Several of these ADCs, however, have yielded disappointing results in clinical studies. This is similar to the results obtained with other anti-CSC drug candidates, including native antibodies, that have been investigated in the clinic. In this article we review the anti-CSC ADCs that have been described in the literature and, in the following, we discuss reasons that may underlie the failures in clinical trials that have been observed. Possible reasons relate to the biology of CSCs themselves, including their heterogeneity, the lack of strictly CSC-specific markers, and the capacity to interconvert between CSCs and non-CSCs; second, inherent limitations of some classes of cytotoxins that have been used for the construction of ADCs; third, the inadequacy of animal models in predicting efficacy in humans. We conclude suggesting some possibilities to address these limitations

MicroRNA-551b expression profile in low and high-grade cervical intraepithelial neoplasia

OBJECTIVE: To evaluate the expression of microRNA (miR)-551b in patients with low and high grade cervical intraepithelial neoplasia (CIN) and to find an association with high-risk Human Papillomavirus (HR-HPV) infection-related prognostic biomarkers. PATIENTS AND METHODS: The expression level of miR-551b was determined in 50 paraffin-embedded cervical specimens (10 normal squamous epithelium, 18 condylomas, 8 CIN1, and 14 CIN2-3) using quantitative Real-time polymerase chain reaction (qRT-PCR). χ2-test compared miR-551b expression in different diagnosis groups. An Ordered Logistic Regression and a Probit correlation were made to correlate miR-551b expression levels with the cervical tissue histological findings. The immunohistochemical distribution of p16 and Ki-67 according to histopathological findings was also assessed. RESULTS: The distribution of the miR-551b expression profile was significantly lower in CIN1-3 samples compared to other histological diagnosis groups (condyloma and negative). The expression levels were inversely correlated to the cervical pathological grade, from negative to CIN2-3. A 1% increase in miR-551b expression level produced an increase of 19% to the probability of a minor histological grade diagnosis in a range from negative to CIN2-3 and an increase of 13% to the probability of a negative histological grade diagnosis. Among the cases with miR-551b expression < 0.02 (considered as cut-off value) a significant statistical correlation was found between p16 and Ki-67 expression and the diagnosis of CIN2-3. CONCLUSIONS: O ur d ata s howed a s ignificant inverse correlation between miR-551b expression and the histological grading of the lesions, suggesting a tumor suppressive function in the different stages of cervical dysplasia

Robustness of solutions to the capacitated facility location problem with uncertain demand

We investigate the properties of robust solutions of the Capacitated Facility Location Problem with uncertain demand. We show that the monotonic behavior of the price of robustness is not guaranteed, and therefore that one cannot discriminate among alternative robust solutions by simply relying on the trade-off price-vs-robustness. Furthermore, we report a computational study on benchmark instances from the literature and on instances derived from a real-world application, which demonstrates the validity in practice of our findings

EFFECT OF RESPIRATION DYNAMICS ON POSTURAL CONTROL FOLLOWING A 5K RUN

Research has shown postural control during upright stance can be diminished for up to twenty minutes following aerobic exercise of different types, intensities, and durations (Lepers et al., 1997; Nagy et al., 2002). Researchers have posited that this is caused by neuromuscular changes associated with aerobic exercise and fatigue such as the reduced excitability and central drive to peripheral muscles (Lepers et al., 2002), vestibular desensitization (Lepers et al., 1997), and peripheral somatosensory desensitization (Lepers et al., 1997). However, no research has measured or attempted to control for the influence that changes in respiration dynamics (e.g., rate and volume) alone might have on postural sway. The aim of the current study was to examine these effects in order decipher whether changes to postural control following intense aerobic exercise (a 5-kilometer run performed with maximal effort) can be attributed to effects of exercise and fatigue or simply changes in respiration

Microfluidic interactions between red blood cells and drug carriers by image analysis techniques

This paper was presented at the 4th Micro and Nano Flows Conference (MNF2014), which was held at University College, London, UK. The conference was organised by Brunel University and supported by the Italian Union of Thermofluiddynamics, IPEM, the Process Intensification Network, the Institution of Mechanical Engineers, the Heat Transfer Society, HEXAG - the Heat Exchange Action Group, and the Energy Institute, ASME Press, LCN London Centre for Nanotechnology, UCL University College London, UCL Engineering, the International NanoScience Community, www.nanopaprika.eu.Blood is a complex biological fluid composed of deformable cells and platelets suspended in plasma, a protein-rich liquid. The peculiar nature of blood needs to be considered when designing a drug delivery strategy based on systemically administered carriers. Here, we report on an in vitro fluid dynamic investigation of the influence of the microcapillary flow of red blood cells (RBCs) on micron sized carriers by high speed imaging methods. The experiments were carried out in a 50μm diameter glass capillary that mimicked the hydrodynamic conditions of human microcirculation. Spherical μ particles (μ-Ps), with sizes ranging between 0.5 and 3μm, were tested. Images of the flowing RBCs and μ-Ps were acquired by a highspeed/ high-magnification microscopy. The transport and distribution of rigid particles in a suspension of RBCs under shear flow were followed for: i) the migration of RBCs towards the vessel centerline due to their deformability; ii) the cross-flow migration of μ-Ps towards the vessel wall due to their hydrodynamic interactions with RBCs; iii) the radial distribution of μ-Ps in the presence of RBCs. This study suggests that the therapeutic efficacy of μ-Ps could be ultimately affected by their interactions with the flowing RBCs in the vasculature

Preterm birth after loop electrosurgical excision procedure (LEEP). how cone features and microbiota could influence the pregnancy outcome

OBJECTIVE: In the last years, the mean age of women who underwent cervical treatment for high-grade cervical intraepithelial neoplasia (CIN 2-3) is similar to the age of women having their first pregnancy. The aim of this study was to evaluate the risk of preterm birth in subsequent pregnancies after loop electrosurgical excision procedure (LEEP). PATIENTS AND METHODS: From January 2013 to January 2016 the study identified a total of 1435 women, nulliparous, who underwent LEEP for CIN 2-3, and who wished to have their first pregnancy. Before surgery, the lengths of the cervix were calculated by transvaginal sonography. After the treatment, the dimension of the removed tissue was evaluated. During the pregnancy, all women carried out periodic transvaginal sonography and vaginal-cervical swabs. RESULTS: The average age of patients was 31.96±5.24 years; the interval between the surgical procedure and pregnancy was 12.04±4.67 months; the gestational age at births was 37.53±2.91 weeks. The first vaginal and cervical swab performed during pregnancy was negative in 81.8% of patients. The most prevalent infections were related to C. Albicans, G. Vaginalis, and Group B Streptococcus (GBS). The rate of preterm delivery was significantly higher in women with a minor cervical length. CONCLUSIONS: The length and the volume of cervical tissue excised have been shown to be directly related to the risk for preterm birth. Furthermore, vaginal infections and their persistence during pregnancy in women with a history of LEEP may be associated with an increased risk for preterm birth, compared with women with no history of LEEP

Maximizing rehabilitation outcomes in geriatric hip fracture patients: the impact of surgical variables

Background and aim: Hip fracture is a major traumatic event with high mortality and disability rate. Its management in the acute setting and in the rehabilitation process is highly debated. This study evaluates the possible determinants of hip fracture rehabilitation outcome, among which surgical intervention type, weight-bearing status and hospitalization length Methods: The data of 738 hip fracture patients, who completed rehabilitation process in our centre, were collected and patients' functional abilities at the time of admission and discharge were analysed. Results: It has been observed that functional recovery depends on several factors: the type of surgery, the post-operative course and related complications, the hospitalisation time, the surgeon's techniques and expertise and the Orthopaedics centre where the operation is performed. Conclusions: In conclusion, data integration in perspective of an individualised rehabilitation program appears crucial for the functional recovery of the hip fracture patient