Improving Outcomes with Surgical Resection and Other Ablative Therapies in HCC

With rising incidence and emergence of effective treatment options, the management of hepatocellular carcinoma (HCC) is a complex multidisciplinary process. There is still little consensus and uniformity about clinicopathological staging systems. Resection and liver transplantation have been the cornerstone of curative surgical treatments with recent emergence of ablative techniques. Improvements in diagnostics, surgical techniques, and postoperative care have lead to dramatically improved results over the years. The most appropriate treatment plan has to be individualised and depends on a variety of patient and tumour-related factors. Very small HCCs discovered on surveillance have the best outcomes. Patients with advanced cirrhosis and tumours within Milan criteria should be offered transplantation. Resection is best for small solitary tumours with preserved liver function. Ablative techniques are suitable for low volume tumours in patients unfit for either resection or transplantation. The role of downstaging and bridging therapy is not clearly established

Computer generation of photorealistic images using ray tracing

Computer generation of photorealistic images has been the target of computer graphics designers almost since the birth of the computer. Of all methods tried, Ray tracing has proven to be the best at generating computer images that exhibit all the optical features found in a real life photograph. Ray tracing is the subject matter of this thesis. We discuss the various issues involved in the design of a ray tracing system that will model and render complex scenes and we implement such a ray tracing system

Antibiotic use in acute pancreatitis : an audit of current practice in a tertiary centre

Introduction: Intravenous antibiotic prophylaxis is not recommended in acute pancreatitis. According to current international guidelines antibiotics together with further intervention should be considered in the setting of infected necrosis. Appropriate antibiotic therapy particularly avoiding over-prescription is important. This study examines antibiotic use in acute pancreatitis in a tertiary centre using the current IAP/APA guidelines for reference. Methods: Data were collected on a consecutive series of patients admitted with acute pancreatitis over a 12 month period. Data were dichotomized by patients admitted directly to the centre and tertiary transfers. Information was collected on clinical course with specific reference to antibiotic use, episode severity, intervention and outcome. Results: 111 consecutive episodes of acute pancreatitis constitute the reported population. 31 (28%) were tertiary transfers. Overall 65 (58.5%) patients received antibiotics. Significantly more tertiary transfer patients received antibiotics. Mean person-days of antibiotic use was 23.9 (sd 29.7) days in the overall study group but there was significantly more use in the tertiary transfer group as compared to patients having their index admission to the centre (40.9 sd 37.1 vs 10.2 sd 8.9; P < 0.005). Thirty four (44%) of patients with clinically mild acute pancreatitis received antibiotics. Conclusions: There is substantial use of antibiotics in acute pancreatitis, in particular in patients with severe disease. Over-use is seen in mild acute pancreatitis. Better consideration must be given to identification of prophylaxis or therapy as indication. In relation to repeated courses of antibiotics in severe disease there must be clear indications for use

Scoping bullying and cyberbullying victimisation among a sample of gifted adolescents in Ireland

Research has indicated that gifted adolescents experience an increased amount of bullying and cyberbullying compared to their non-gifted peers. However, there has not been a sufficient attempt to investigate the extent of bullying and cyberbullying victimisation among gifted adolescent populations in Ireland. A total of 195 gifted adolescents between the ages of 14 and 18 years completed a comprehensive online survey assessing the bullying and cyberbullying prevalence, wellbeing, indicative mental health, and friendship quality outcomes. The results showed considerably higher prevalence rates of bullying and cyberbullying victimisation among gifted adolescents compared to an all-Ireland national prevalence rate. Bullying and cyberbullying victimisation was associated with higher levels of negative outcomes. Females, LGBTI +, and twiceexceptional participants scored signifcantly lower on satisfaction with life and signifcantly higher on negative outcomes compared to other gifted participants. The results are discussed alongside recommendations for anti-bullying policies and teacher education provision

The c-Rel Subunit of NF-κB Regulates Epidermal Homeostasis and Promotes Skin Fibrosis in Mice

The five subunits of transcription factor NF-κB have distinct biological functions. NF-κB signaling is important for skin homeostasis and aging, but the contribution of individual subunits to normal skin biology and disease is unclear. Immunohistochemical analysis of the p50 and c-Rel subunits within lesional psoriatic and systemic sclerosis skin revealed abnormal epidermal expression patterns, compared with healthy skin, but RelA distribution was unaltered. The skin of Nfkb1−/− and c-Rel−/− mice is structurally normal, but epidermal thickness and proliferation are significantly reduced, compared with wild-type mice. We show that the primary defect in both Nfkb1−/− and c-Rel−/− mice is within keratinocytes that display reduced proliferation both in vitro and in vivo. However, both genotypes can respond to proliferative stress, with 12-O-tetradecanoylphorbol-13-acetate–induced epidermal hyperproliferation and closure rates of full-thickness skin wounds being equivalent to those of wild-type controls. In a model of bleomycin-induced skin fibrosis, Nfkb1−/− and c-Rel−/− mice displayed opposite phenotypes, with c-Rel−/− mice being protected and Nfkb1−/− developing more fibrosis than wild-type mice. Taken together, our data reveal a role for p50 and c-Rel in regulating epidermal proliferation and homeostasis and a profibrogenic role for c-Rel in the skin, and identify a link between epidermal c-Rel expression and systemic sclerosis. Modulating the actions of these subunits could be beneficial for treating hyperproliferative or fibrogenic diseases of the skin

PANasta Trial; Cattell Warren versus Blumgart techniques of panreatico-jejunostomy following pancreato-duodenectomy: Study protocol for a randomized controlled trial

PANasta operative manual. (PDF 520 kb

Cancer-related fatigue and self-care agency: A multicentre survey of patients receiving chemotherapy

Aims and objectives: To measure cancer-related fatigue (CRF), self-care agency (SCA) and fatigue self-care strategies, and to explore the relationship between CRF and SCA. Background: Cancer-related fatigue has been consistently rated as the most elusive, common and severe of symptoms that patients with cancer undergoing chemotherapy experience. Despite its frequency and severity, CRF is poorly managed. A renewed focus on supporting self-care among patients with cancer has been found to reduce symptom burden, empower patients and improve patient satisfaction. Understanding the link between self-care agency (i.e. capability and willingness to self-care) and CRF levels will help practitioners to better support individuals on the cancer journey. Design: A descriptive, correlational survey design was employed. Methods: Patients (n = 362) undergoing chemotherapy with a primary diagnosis of breast, colorectal, Hodgkin's and non-Hodgkin's lymphoma cancers were recruited from four oncology centres in one city in the South of Ireland. Participants completed the Piper Fatigue Scale-Revised, Appraisal of Self-care Agency Scale and a researcher-developed Fatigue Self-Care Survey. Multivariate logistic regression was used to examine the relationship between CRF and self-care agency using a dichotomous dependent variable score of four as the cut-off between those deemed to be fatigued (≥4) and those not fatigued (<4). As recommended by the EQUATOR Network, the STROBE checklist of items for cross-sectional studies is used to report the study. Results: The incidence of CRF was high with 75% of participants scoring clinically relevant CRF. Higher SCA (OR = 0.96, 95% CI = 0.93–0.99, p = .011) was associated with decreased odds of developing CRF. Having non-Hodgkin's lymphoma (OR = 3.02, 95% CI = 1.29–7.07, p = .011) was associated with increased odds of developing CRF. Conclusions: Patient's undergoing chemotherapy experience significant fatigue. Higher capability for self-care is associated with lower fatigue. The promotion of SCA and self-care strategies can impact on CRF. Relevance to clinical practice: Understanding the link between self-care abilities and fatigue can lead to more individualised and tailored approaches to CRF

Radiocarbon dates from jar and coffin burials of the Cardamom Mountains reveal a unique mortuary ritual in Cambodia's late- to post-Angkor period (15th-17th centuries AD)

We present the first radiocarbon dates from previously unrecorded, secondary burials in the Cardamom Mountains, Cambodia. The mortuary ritual incorporates nautical tradeware ceramic jars and log coffins fashioned from locally harvested trees as burial containers, which were set out on exposed rock ledges at 10 sites in the eastern Cardamom Massif. The suite of 28 14C ages from 4 of these sites (Khnorng Sroal, Phnom Pel, Damnak Samdech, and Khnang Tathan) provides the first estimation of the overall time depth of the practice. The most reliable calendar date ranges from the 4 sites reveals a high- land burial ritual unrelated to lowland Khmer culture that was practiced from cal AD 1395 to 1650. The time period is concurrent with the 15th century decline of Angkor as the capital of the Khmer kingdom and its demise about AD 1432, and the subsequent shift of power to new Mekong trade ports such as Phnom Penh, Udong, and Lovek. We discuss the Cardamom ritual relative to known funerary rituals of the pre to post-Angkorian periods, and to similar exposed jar and coffin burial rituals in Mainland and Island Southeast Asia

Nanoscale Chemical Imaging by Photo-Induced Force Microscopy: Technical Aspects and Application to the Geosciences

Photo-induced force microscopy (PiFM) is a new-frontier technique that combines the advantages of atomic force microscopy with infrared spectroscopy and allows for the simultaneous acquisition of 3D topographic data with molecular chemical information at high spatial (~ 5 nm) and spectral (~ 1 cm−1) resolution at the nanoscale. This non-destructive technique is time efficient as it requires only conventional mirror-polishing and has fast mapping rates on the order of a few minutes that allow the study of dynamic processes via time series. Here, we review the method’s historical development, working principle, data acquisition, and evaluation, and provide a comparison with traditional geochemical methods. We review PiFM studies in the areas of materials science, chemistry and biology. In addition, we provide the first applications for geochemical samples including the visualization of faint growth zonation in zircons, the identification of fluid speciation in high-pressure experimental samples, and of nanoscale organic phases in biominerals. We demonstrate that PiFM analysis is a time- and cost-efficient technique combining high-resolution surface imaging with molecular chemical information at the nanoscale and, thus, complements and expands traditional geochemical methods.LMO is grateful for financial support through a Beate Mocek Prize awarded by the German Mineralogical Society. This study was supported by the Australian Research Council (DEJ: DP160102081, EB: FT110100685, SFF and MWF: FL180100134) and Macquarie University (MWF: MQRF0001074-2020). We thank both anonymous reviewers and handling editor Dr. Thomas Meisel for improving the final version of this review with their expert comments

Pancreatic ductal adenocarcinoma cells employ integrin α6β4 to form hemidesmosomes and regulate cell proliferation

Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis due to its aggressive progression, late detection and lack of druggable driver mutations, which often combine to result in unsuitability for surgical intervention. Together with activating mutations of the small GTPase KRas, which are found in over 90% of PDAC tumours, a contributory factor for PDAC tumour progression is formation of a rigid extracellular matrix (ECM) and associated desmoplasia. This response leads to aberrant integrin signalling, and accelerated proliferation and invasion. To identify the integrin adhesion systems that operate in PDAC, we analysed a range of pancreatic ductal epithelial cell models using 2D, 3D and organoid culture systems. Proteomic analysis of isolated integrin receptor complexes from human pancreatic ductal epithelial (HPDE) cells predominantly identified integrin α6β4 and hemidesmosome components, rather than classical focal adhesion components. Electron microscopy, together with immunofluorescence, confirmed the formation of hemidesmosomes by HPDE cells, both in 2D and 3D culture systems. Similar results were obtained for the human PDAC cell line, SUIT-2. Analysis of HPDE cell secreted proteins and cell-derived matrices (CDM) demonstrated that HPDE cells secrete a range of laminin subunits and form a hemidesmosome-specific, laminin 332-enriched ECM. Expression of mutant KRas (G12V) did not affect hemidesmosome composition or formation by HPDE cells. Cell-ECM contacts formed by mouse and human PDAC organoids were also assessed by electron microscopy. Organoids generated from both the PDAC KPC mouse model and human patient-derived PDAC tissue displayed features of acinar-ductal cell polarity, and hemidesmosomes were visible proximal to prominent basement membranes. Furthermore, electron microscopy identified hemidesmosomes in normal human pancreas. Depletion of integrin β4 reduced cell proliferation in both SUIT-2 and HPDE cells, reduced the number of SUIT-2 cells in S-phase, and induced G1 cell cycle arrest, suggesting a requirement for α6β4-mediated adhesion for cell cycle progression and growth. Taken together, these data suggest that laminin-binding adhesion mechanisms in general, and hemidesmosome-mediated adhesion in particular, may be under-appreciated in the context of PDAC. Proteomic data are available via ProteomeXchange with the identifiers PXD027803, PXD027823 and PXD027827