Perineural Invasion in Pancreatic Ductal Adenocarcinoma: From Molecules towards Drugs of Clinical Relevance

Pancreatic ductal adenocarcinoma is one of the most threatening solid malignancies. Molecular and cellular mediators that activate paracrine signalling also regulate the dynamic interaction between pancreatic cancer cells and nerves. This reciprocal interface leads to perineural invasion (PNI), defined as the ability of cancer cells to invade nerves, similar to vascular and lymphatic metastatic cascade. Targeting PNI in pancreatic cancer might help ameliorate prognosis and pain relief. In this review, the modern knowledge of PNI in pancreatic cancer has been analysed and critically presented. We focused on molecular pathways promoting cancer progression, with particular emphasis on neuropathic pain generation, and we reviewed the current knowledge of pharmacological inhibitors of the PNI axis. PNI represents a common hallmark of PDAC and correlates with recurrence, poor prognosis and pain in pancreatic cancer patients. The interaction among pancreatic cancer cells, immune cells and nerves is biologically relevant in each stage of the disease and stimulates great interest, but the real impact of the administration of novel agents in clinical practice is limited. It is still early days for PNI-targeted treatments, and further advanced studies are needed to understand whether they could be effective tools in the clinical setting

The impact of psychological abuse on somatic symptoms : A study of older persons aged 60-84 years

Purpose– The purpose of this paper is to examine differences in the experience of somatic symptoms by domain (exhaustion, musculoskeletal, gastrointestinal, heart distress) between psychologically abused and non-abused older persons, and to scrutinize associations between abuse and somatic symptoms while considering other factors (e.g. social support).Design/methodology/approach– The design was cross-sectional. The participants were 4,467 women/men aged 60-84 years living in seven European cities. The data were analysed using bivariate/multivariate methods.Findings– Psychologically abused participants scored higher on all somatic symptom domains than non-abused, and thus were more affected by the symptoms. The regressions confirmed a positive association between psychological abuse and most somatic symptom domains, but other factors (e.g. depression, anxiety) were more salient. Demographics/socio-economics were positively (e.g. marriage/cohabitation) or negatively (e.g. education) associated with somatic symptoms depending on the domain. Social support and family structure "protected" the experience of somatic symptoms.Research limitations/implications– The research focused on psychological abuse. It did not incorporate other abuse types calling for further research on the effects of other abuse types on somatic symptoms. Nevertheless, the findings indicate that psychological abuse is linked to somatic symptoms, but the role of other factors (e.g. depression, anxiety, social support) is also important.Practical implications– Improvements in the older person's situation regarding somatic symptoms need to consider psychological abuse, co-morbidities, social support and living conditions.Originality/value– The paper reports data from the ABUEL Survey, which collected population-based data on elder abuse

Over 15% efficient wide-band-gap Cu(In,Ga)S<inf>2</inf> solar cell: Suppressing bulk and interface recombination through composition engineering

The progress of Cu(In,Ga)S2 remains significantly limited mainly due to photovoltage (Voc) losses in the bulk and at the interfaces. Here, via a combination of photoluminescence, cathodoluminescence, electrical measurements, and ab initio modeling, we address the bulk and interface losses to improve ~ 1.6 eV bandgap (Eg) Cu(In,Ga)S2. The optoelectronic quality of the absorber improves upon reducing the [Cu]/[Ga+In] (CGI) ratio, as manifested by the suppression of deep defects, higher quasi-Fermi level splitting (QFLS), improved charge carrier lifetime, and higher Voc. We identify antisite CuIn/CuGa as a major performance-limiting deep defect by comparing the formation energies of various intrinsic defects. Interface recombination is suppressed using a Zn(O,S) buffer layer in Cu-poor devices, which leads to the activation energy of recombination equal to the Eg. We demonstrate efficiency of 15.2% with Voc of 902 mV from a H2S-free, Cd-free, and KCN-free process.The authors acknowledge Dr. Nathalie Valle and Dr. Brahime El Adib, Luxembourg Institute for Science and Technology (LIST), for SIMS measurement. Mohit and Damilola gratefully acknowledge partial funding of this research through the Luxembourgish Fond National de la Recherche FNR through the MASSENA project (FNR PRIDE/15/10935404). CL studies were supported by the EPSRC under grant number EP/R025193/1. Dr. Christian Monachon of Attolight is thanked for his ongoing support of the CL system. Diana Dahliah was financially supported by the Conseil de l’Action Internationale (CAI) through a doctorate grant ‘‘Coopération au Développment’’. We acknowledge access to various computational resources: the Tier-1 supercomputer of the Fédération Wallonie-Bruxelles funded by the Walloon Region (grant agreement no. 1117545), and all the facilities provided by the Université catholique de Louvain (CISM/UCL) and by the Consortium des Equipements de Calcul Intensif en Fédération WallonieBruxelles (CECI)