EFT strings and emergence

We revisit the Emergence Proposal in 4d ${\cal N}=2$ vector multiplet sectors that arise from type II string Calabi--Yau compactifications, with emphasis on the role of axionic fundamental strings, or EFT strings. We focus on large-volume type IIA compactifications, where EFT strings arise from NS5-branes wrapping internal four-cycles, and consider a set of infinite-distance moduli-space limits that can be classified in terms of a scaling weight $w=1,2,3$. It has been shown before how one-loop threshold effects of an infinite tower of BPS particles made up of D2/D0-branes generate the asymptotic behaviour of the gauge kinetic functions along limits with $w=3$. We extend this result to $w=2$ limits, by taking into account D2-brane multi-wrapping numbers. In $w=1$ limits the leading tower involves EFT string oscillations, and one can reproduce the behaviour of both weakly and strongly-coupled $U(1)$'s independently on whether the EFT string is critical or not, by assuming that charged modes dominate the light spectrum.Comment: 33 pages + appendi

Effects of dietary supplementation with krill meal on pigmentation and quality of flesh of rainbow trout (Oncorhynchus mykiss)

Effects of administration of krill meal and synthetic astaxanthin during the finisher phase of the fattening cycle of rainbow trout on flesh pigmentation and quality traits were studied. The inclusion of krill meal increased the body weight and size and decreased the peri-visceral fat and visceral weight indices. The astaxanthin diet produced the highest accumulation of total carotenoids in the fillet compared to the krill meal diet: the difference was significant after 15 days of feeding (2.50 vs 2.10 mg/kg) till the end of the trial (5.00 vs 4.80 mg/kg). The same pattern was observed for astaxanthin concentration with the highest values in the fillets of fish fed the astaxanthin diet. Fillet lightness (L*) was not affected by trout diets whereas redness (a*) and yellowness (b*) were significantly higher in fish fed the astaxanthin diet until day 30 of the trial. Hue was not affected by feeding, whereas chroma was significantly higher in the fish fed astaxanthin throughout the trial except on day 45 of sampling. Trout fed the krill meal diet had a paler pink-red colour on the SalmoFan scale than those receiving the astaxanthin diet. No significant differences emerged in proximate composition and cholesterol content of trout in the two groups. The fatty acid profile of the fillets reflected the fatty acids of the diets administered to the trout: eicosapentaenoic, docosahexaenoic and docosapentaenoic acids and total n-3 polyunsaturated fatty acids were significantly higher in the fish fed the krill meal

Play like me: Similarity in playfulness promotes social play

Social play is associated with the experience of positive emotions in higher vertebrates and may be used as a measure of animal welfare. Altering motivation to play (e.g., through short-term social isolation) can temporarily affect play levels between familiar individuals, a process which may involve emotional contagion. This study investigated how forming groups based on known differences in the personality trait “playfulness” (i.e., the longer-term propensity of an individual to actively play from adolescence to early adulthood) affects social play. Seventy-six adolescent male Lister Hooded rats underwent a Play-in-Pairs test assessing their playfulness, ranked as high (H), intermediate (I) or low (L). At seven weeks of age, rats were resorted into homogenous groups of similar (LLL, III, HHH), or heterogeneous groups of dissimilar (HII, LII) playfulness. Social play was scored in the home cage at Weeks 8, 10, 12 of age. A second Play-in-Pairs test was performed (Week 11) to assess consistency of playfulness. A Social Preference test investigated whether I rats in heterogeneous groups preferred proximity with I, H or L cage mates. It was found that heterogeneous groups played less than homogeneous ones at adolescence (8 weeks of age), while play levels at early adulthood (Weeks 10 and 12) did not differ between groups. Play in the homogeneous groups decreased with age as expected, while it did not change over time in the heterogeneous groups, which did not compensate for the lower play levels shown at adolescence. Play-in-Pairs scores before and after resorting were mildly correlated, indicating some level of consistency over time despite the resorting procedure. In the Social Preference test, subjects did not prefer one playfulness level over another. We conclude that a mismatch in playfulness may negatively affect social play development, and thus the welfare, of rats. Groups made of animals with similar playfulness, even those initially scoring relatively low in this trait, seemed to be more successful in establishing play relationships during adolescence

Peritoneal carcinomatosis

Several gastrointestinal and gynecological malignancies have the potential to disseminate and grow in the peritoneal cavity. The occurrence of peritoneal carcinomatosis (PC) has been shown to significantly decrease overall survival in patients with liver and/or extraperitoneal metastases from gastrointestinal cancer. During the last three decades, the understanding of the biology and pathways of dissemination of tumors with intraperitoneal spread, and the understanding of the protective function of the peritoneal barrier against tumoral seeding, has prompted the concept that PC is a loco-regional disease: in absence of other systemic metastases, multimodal approaches combining aggressive cytoreductive surgery, intraperitoneal hyperthermic chemotherapy and systemic chemotherapy have been proposed and are actually considered promising methods to improve loco-regional control of the disease, and ultimately to increase survival. The aim of this review article is to present the evidence on treatment of PC in different tumors, in order to provide patients with a proper surgical and multidisciplinary treatment focused on optimal control of their locoregional disease. (C) 2013 Baishideng Publishing Group Co., Limited. All rights reserved

Theratyping of the Rare CFTR Variants E193K and R334W in Rectal Organoid-Derived Epithelial Monolayers

Background: The effect of presently available CFTR modulator combinations, such as elexacaftor (ELX), tezacaftor (TEZ), and ivacaftor (IVA), on rare CFTR alleles is often unknown. Several assays have been developed, such as forskolin-induced swelling (FIS), to evaluate the rescue of such uncommon CFTR alleles both by established and novel modulators in patient-derived primary cell cultures (organoids). Presently, we assessed the CFTR-mediated electrical current across rectal organoid-derived epithelial monolayers. This technique, which allows separate measurement of CFTR-dependent chloride or bicarbonate transport, was used to assess the effect of ELX/TEZ/IVA on two rare CFTR variants. Methods: Intestinal organoid cultures were established from rectal biopsies of CF patients carrying the rare missense mutations E193K or R334W paired with F508del. The effect of the CFTR modulator combination ELX/TEZ/IVA on CFTR-mediated Cl- and HCO3- secretion was assessed in organoid-derived intestinal epithelial monolayers. Non-CF organoids were used for comparison. Clinical biomarkers (sweat chloride, FEV1) were monitored in patients receiving modulator therapy. Results: ELX/TEZ/IVA markedly enhanced CFTR-mediated bicarbonate and chloride transport across intestinal epithelium of both patients. Consistent with the rescue of CFTR function in cultured intestinal cells, ELX/TEZ/IVA therapy improved biomarkers of CFTR function in the R334W/F508del patient. Conclusions: Current measurements in organoid-derived intestinal monolayers can readily be used to monitor CFTR-dependent epithelial Cl- and HCO3- transport. This technique can be explored to assess the functional consequences of rare CFTR mutations and the efficacy of CFTR modulators. We propose that this functional CFTR assay may guide personalized medicine in patients with CF-like clinical manifestations as well as in those carrying rare CFTR mutations

Large Animal Models in Regenerative Medicine and Tissue Engineering: To Do or Not to Do

Rapid developments in Regenerative Medicine and Tissue Engineering has witnessed an increasing drive toward clinical translation of breakthrough technologies. However, the progression of promising preclinical data to achieve successful clinical market authorisation remains a bottleneck. One hurdle for progress to the clinic is the transition from small animal research to advanced preclinical studies in large animals to test safety and efficacy of products. Notwithstanding this, to draw meaningful and reliable conclusions from animal experiments it is critical that the species and disease model of choice is relevant to answer the research question as well as the clinical problem. Selecting the most appropriate animal model requires in-depth knowledge of specific species and breeds to ascertain the adequacy of the model and outcome measures that closely mirror the clinical situation. Traditional reductionist approaches in animal experiments, which often do not sufficiently reflect the studied disease, are still the norm and can result in a disconnect in outcomes observed between animal studies and clinical trials. To address these concerns a reconsideration in approach will be required. This should include a stepwise approach using in vitro and ex vivo experiments as well as in silico modeling to minimize the need for in vivo studies for screening and early development studies, followed by large animal models which more closely resemble human disease. Naturally occurring, or spontaneous diseases in large animals remain a largely untapped resource, and given the similarities in pathophysiology to humans they not only allow for studying new treatment strategies but also disease etiology and prevention. Naturally occurring disease models, particularly for longer lived large animal species, allow for studying disorders at an age when the disease is most prevalent. As these diseases are usually also a concern in the chosen veterinary species they would be beneficiaries of newly developed therapies. Improved awareness of the progress in animal models is mutually beneficial for animals, researchers, human and veterinary patients. In this overview we describe advantages and disadvantages of various animal models including domesticated and companion animals used in regenerative medicine and tissue engineering to provide an informed choice of disease-relevant animal models

In silico analysis and theratyping of an ultra-rare CFTR genotype (W57G/A234D) in primary human rectal and nasal epithelial cells

Mutation targeted therapy in cystic fibrosis (CF) is still not eligible for all CF subjects, especially for cases carrying rare variants such as the CFTR genotype W57G/A234D (c.169T>G/c.701C>A). We performed in silico analysis of the effects of these variants on protein stability, which we functionally characterized using colonoids and reprogrammed nasal epithelial cells. The effect of mutations on cystic fibrosis transmembrane conductance regulator (CFTR) protein was analyzed by western blotting, forskolin-induced swelling (FIS), and Ussing chamber analysis. We detected a residual CFTR function that increases following treatment with the CFTR modulators VX661±VX445±VX770, correlates among models, and is associated with increased CFTR protein levels following treatment with CFTR correctors. In vivo treatment with VX770 reduced sweat chloride concentration to non-CF levels, increased the number of CFTR-dependent sweat droplets, and induced a 6% absolute increase in predicted FEV1% after 27 weeks of treatment indicating the relevance of theratyping with patient-derived cells in CF

Postoperative Delirium after elective and emergency surgery: analysis and checking of risk factors. A study protocol

BACKGROUND: Delirum is common in hospitalized elderly patients and may be associated with increased morbidity, length of stay and patient care costs. Delirium (acute confusional state) is defined as an acute disorder of attention and cognition. In elderly patients, delirium is often an early indicator of patho-physiological disturbances. Despite landmark studies dating back to the 1940s, the pathogenesis of Delirium remains poorly understood. Early investigators noted that Delirium was characterized by global cortical dysfunction that was associated predominantly with specific electroencephalographic changes. It's important to understand the risk factors and incidence of Delirium. Some of the risk factors are already identified in literature and can be summarized in the word "VINDICATE" which stands for: Vascular, Infections, Nutrition, Drugs, Injury, Cardiac, Autoimmune, Tumors, Endocrine. Aims of this study are: to re-evaluate the above mentioned clinical risk factors, adding some others selected from literature, and to test, as risk factors, a pattern of some genes associated to cognitive dysfunction and inflammation possibly related to postoperative Delirium. DESIGN: All patients admitted to our Emergency Unit who are meet our inclusion/exclusion criteria will be recruited. The arising of postoperative Delirium will select incidentally two groups (Delirium/non Delirium) and the forward analysis of correlate risk factors will be performed. As in a typical observational case/control study we will consider all the exposure factors to which our population are submitted towards the outcome (presence of Delirium). Our exposures are the following: ASA, Pain (SVS; VAS), Blood gas analysis (pH; Hb; pO2; pCO2), Residence pharmacological therapy (BDZ; hypnotics; narcotic drugs; alcohol; nitrous derivates), Body temperature, Arterial pressure, Heart frequency, Breath frequency, Na, K, Creatinin, Glicemia, Albumin, Hct, White blood cells, Glasgow Coma Scale (GCS), Cognitive state (SPMSQ), Functional state (ADL and IADL), Psychological Distress (HADS), Cumulative Illness Rating Scale (CIRS), Hypotension (classified in: light; moderate and severe and duration), Blood loss (classified in: < 2 lt and > 2 lt), Blood transfusions (< 2 lt and > 2 lt), Quantity of red cells and plasma transfusions, Visual VAS / SVS (timing: I-II-III post-operative day), Red cells and Plasma transfusions, Blood count evaluation and Saturation (O(2)%), Postoperative analgesia (Emilia-Romagna protocol), Presence of malignant tumoral disease, APACHE Score II. Moreover the presence of some relevant genetic polymorphisms will be studied in different genes such as IL-6, IL-10, TNF-alpha, and IL-1 cluster

The open abdomen in trauma and non-trauma patients : WSES guidelines

Damage control resuscitation may lead to postoperative intra-abdominal hypertension or abdominal compartment syndrome. These conditions may result in a vicious, self-perpetuating cycle leading to severe physiologic derangements and multiorgan failure unless interrupted by abdominal (surgical or other) decompression. Further, in some clinical situations, the abdomen cannot be closed due to the visceral edema, the inability to control the compelling source of infection or the necessity to re-explore (as a "planned second-look" laparotomy) or complete previously initiated damage control procedures or in cases of abdominal wall disruption. The open abdomen in trauma and non-trauma patients has been proposed to be effective in preventing or treating deranged physiology in patients with severe injuries or critical illness when no other perceived options exist. Its use, however, remains controversial as it is resource consuming and represents a non-anatomic situation with the potential for severe adverse effects. Its use, therefore, should only be considered in patients who would most benefit from it. Abdominal fascia-to-fascia closure should be done as soon as the patient can physiologically tolerate it. All precautions to minimize complications should be implemented.Peer reviewe