Accounting for Soil Aging When Assessing Liquefaction Potential

It has been recognized that liquefaction resistance of sand increases with age due to processes such as cementation at particle contacts and increasing frictional resistance resulting from particle rearrangement and interlocking. As such, the currently available empirical correlations derived from liquefaction of young Holocene sand deposits, and used to determine liquefaction resistance of sand deposits from in situ soil indices [standard penetration test (SPT), cone penetration test (CPT), shear wave velocity test (Vs)], are not applicable for old sand deposits. To overcome this limitation, a methodology was developed to account for the effect of aging on the liquefaction resistance of old sand deposits. The methodology is based upon the currently existing empirical boundary curves for Holocene age soils and utilizes correction factors presented in the literature that comprise the effect of aging on the in situ soil indices as well as on the field cyclic strength (CRR). This paper describes how to combine currently recorded SPT, CPT, and Vs values with corresponding CRR values derived for aged soil deposits to generate new empirical boundary curves for aged soils. The method is illustrated using existing geotechnical data from four sites in the South Carolina Coastal Plain (SCCP) where sand boils associated with prehistoric earthquakes have been found. These sites involve sand deposits that are 200,000?to?450,000?years in age. This work shows that accounting for aging of soils in the SCCP yields less conservative results regarding the current liquefaction potential than when age is not considered. The modified boundary curves indicate that old sand deposits are more resistant to liquefaction than indicated by the existing empirical curves and can be used to evaluate the liquefaction potential at a specific site directly from the current in situ properties of the soil.     

GnRH Analogues as a Co-Treatment to Therapy in Women of Reproductive Age with Cancer and Fertility Preservation

In this review, we analyzed existing literature regarding the use of Gonadotropin-releasing Hormone (GnRH) analogues (agonists, antagonists) as a co-treatment to chemotherapy and radiotherapy. There is a growing interest in their application as a prophylaxis to gonadotoxicity caused by chemotherapy and/or radiotherapy due to their ovarian suppressive effects, making them a potential option to treat infertility caused by such chemotherapy and/or radiotherapy. They could be used in conjunction with other fertility preservation options to synergistically maximize their effects. GnRH analogues may be a valuable prophylactic agent against chemotherapeutic infertility by inhibiting rapid cellular turnover on growing follicles that contain types of cells unintentionally targeted during anti-cancer treatments. These could create a prepubertal-like effect in adult women, limiting the gonadotoxicity to the lower levels that young girls have. The use of GnRH agonists was found to be effective in hematological and breast cancer treatment whereas for ovarian endometrial and cervical cancers the evidence is still limited. Studies on GnRH antagonists, as well as the combination of both agonists and antagonists, were limited. GnRH antagonists have a similar protective effect to that of agonists as they preserve or at least alleviate the follicle degradation during chemo-radiation treatment. Their use may be preferred in cases where treatment is imminent (as their effects are almost immediate) and whenever the GnRH agonist-induced flare-up effect may be contra-indicated. The combination treatment of agonists and antagonists has primarily been studied in animal models so far, especially rats. Factors that may play a role in determining their efficacy as a chemoprotective agent that limits gonadal damage, include the type and stage of cancer, the use of alkylating agents, age of patient and prior ovarian reserve. The data for the use of GnRH antagonist alone or in combination with GnRH agonist is still very limited. Moreover, studies evaluating the impact of this treatment on the ovarian reserve as measured by Anti-Müllerian Hormone (AMH) levels are still sparse. Further studies with strict criteria regarding ovarian reserve and fertility outcomes are needed to confirm or reject their role as a gonadal protecting agent during chemo-radiation treatments.     

Angiogenesis and Anti-Angiogenic Treatment in Prostate Cancer: Mechanisms of Action and Molecular Targets

Prostate cancer (PC) is the most common cancer in men and the second leading cause of cancer-related death worldwide. Many therapeutic advances over the last two decades have led to an improvement in the survival of patients with metastatic PC, yet the majority of these patients still succumb to their disease. Antiagiogenic therapies have shown substantial benefits for many types of cancer but only a marginal benefit for PC. Ongoing clinical trials investigate antiangiogenic monotherapies or combination therapies. Despite the important role of angiogenesis in PC, clinical trials in refractory castration-resistant PC (CRPC) have demonstrated increased toxicity with no clinical benefit. A better understanding of the mechanism of angiogenesis may help to understand the failure of trials, possibly leading to the development of new targeted anti-angiogenic therapies in PC. These could include the identification of specific subsets of patients who might benefit from these therapeutic strategies. This paper provides a comprehensive review of the pathways involved in the angiogenesis, the chemotherapeutic agents with antiangiogenic activity, the available studies on anti-angiogenic agents and the potential mechanisms of resistance.     

Predominant Role of mTOR Signaling in Skin Diseases with Therapeutic Potential

The serine/threonine kinase mechanistic target of rapamycin (mTOR) plays a pivotal role in the regulation of cell proliferation, survival, and motility in response to availability of energy and nutrients as well as mitogens. The mTOR signaling axis regulates important biological processes, including cellular growth, metabolism, and survival in many tissues. In the skin, dysregulation of PI3K/AKT/mTOR pathway may lead to severe pathological conditions characterized by uncontrolled proliferation and inflammation, including skin hyperproliferative as well as malignant diseases. Herein, we provide an update on the current knowledge regarding the pathogenic implication of the mTOR pathway in skin diseases with inflammatory features (such as psoriasis, atopic dermatitis, pemphigus, and acne) and malignant characteristics (such as cutaneous T cell lymphoma and melanoma) while we critically discuss current and future perspectives for therapeutic targeting of mTOR axis in clinical practice.     

The Role of Exosomal Non-Coding RNAs in Colorectal Cancer Drug Resistance

Background: Colorectal cancer (CRC) is one of the most common types of cancer diagnosed worldwide with high morbidity; drug resistance is often responsible for treatment failure in CRC. Non-coding RNAs (ncRNAs) play distinct regulatory roles in tumorigenesis, cancer progression and chemoresistance. Methods: A literature search was conducted in PubMed database in order to sum up and discuss the role of exosomal ncRNAs (ex-ncRNAs) in CRC drug resistance/response and their possible mechanisms. Results: Thirty-six (36) original research articles were identified; these included exosome or extracellular vesicle (EV)-containing microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs) and small-interfering (siRNAs). No studies were found for piwi-interacting RNAs. Conclusions: Exosomal transfer of ncRNAs has been documented as a new mechanism of CRC drug resistance. Despite being in its infancy, it has emerged as a promising field for research in order to (i) discover novel biomarkers for therapy monitoring and/or (ii) reverse drug desensitization.     

Burnout and work engagement: A thorough investigation of the independency of both constructs.

This study among 528 South African employees working in the construction industry examined the dimensionality of burnout and work engagement, using the Maslach Burnout Inventory-General Survey, the Oldenburg Burnout Inventory, and the Utrecht Work Engagement Scale. On the basis of the literature, we predicted that cynicism and dedication are opposite ends of one underlying attitude dimension (called “identification”), and that exhaustion and vigor are opposite ends of one “energy” dimension. Confirmatory factor analyses showed that while the attitude constructs represent opposite ends of one continuum, the energy constructs do not—although they are highly correlated. These findings are also supported by the pattern of relationships between burnout and work engagement on the one hand, and predictors (i.e., work pressure, autonomy) and outcomes (i.e., organizational commitment, mental health) on the other hand. Implications for the measurement and conceptualization of burnout and work engagement are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Job resources boost work engagement, particularly when job demands are high.

This study of 805 Finnish teachers working in elementary, secondary, and vocational schools tested 2 interaction hypotheses. On the basis of the job demands-resources model, the authors predicted that job resources act as buffers and diminish the negative relationship between pupil misbehavior and work engagement. In addition, using conservation of resources theory, the authors hypothesized that job resources particularly influence work engagement when teachers are confronted with high levels of pupil misconduct. In line with these hypotheses, moderated structural equation modeling analyses resulted in 14 out of 18 possible 2-way interaction effects. In particular, supervisor support, innovativeness, appreciation, and organizational climate were important job resources that helped teachers cope with demanding interactions with students. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Circulating miRNA Expression Profiles and Machine Learning Models in Association with Response to Irinotecan-Based Treatment in Metastatic Colorectal Cancer

Colorectal cancer represents a leading cause of cancer-related morbidity and mortality. Despite improvements, chemotherapy remains the backbone of colorectal cancer treatment. The aim of this study is to investigate the variation of circulating microRNA expression profiles and the response to irinotecan-based treatment in metastatic colorectal cancer and to identify relevant target genes and molecular functions. Serum samples from 95 metastatic colorectal cancer patients were analyzed. The microRNA expression was tested with a NucleoSpin miRNA kit (Machnery-Nagel, Germany), and a machine learning approach was subsequently applied for microRNA profiling. The top 10 upregulated microRNAs in the non-responders group were hsa-miR-181b-5p, hsa-miR-10b-5p, hsa-let-7f-5p, hsa-miR-181a-5p, hsa-miR-181d-5p, hsa-miR-301a-3p, hsa-miR-92a-3p, hsa-miR-155-5p, hsa-miR-30c-5p, and hsa-let-7i-5p. Similarly, the top 10 downregulated microRNAs were hsa-let-7d-5p, hsa-let-7c-5p, hsa-miR-215-5p, hsa-miR-143-3p, hsa-let-7a-5p, hsa-miR-10a-5p, hsa-miR-142-5p, hsa-miR-148a-3p, hsa-miR-122-5p, and hsa-miR-17-5p. The upregulation of microRNAs in the miR-181 family and the downregulation of those in the let-7 family appear to be mostly involved with non-responsiveness to irinotecan-based treatment.