Future fertility of women cancer survivors : the progress in fertility preservation

Diminished ovarian reserve (DOR) has devastating implications for the affected female in terms of quality of life, fertility, fecundity and overall well-being. DOR can be exacerbated by the use of chemotherapy and gynaecological surgeries. Analysis of the gonadotoxicity and efficacy of chemotherapeutic regimens currently available and the techniques for gynaecological surgeries, allows for the most appropriate regimen or technique to be selected following a risk-benefit ratio analysis. This should be done in conjunction with fertility preservation strategies including cryopreservation, ovarian transposition and suppression, and pharmacological agents. New approaches using fertoprotective agents need to be evaluated in order to keep up with the demand for oncofertility. This ensures the least possible damage to the ovarian environment and the utmost preservation of the follicular pool.peer-reviewe

The rise of pertussis in Malta in 2011 : a case for adolescent and adult pertussis booster vaccination

Notwithstanding the high rates of pertussis infant vaccination coverage in developed countries, Bortedella pertussis infections are manifesting a changing epidemiological pattern of disease. Of notable concern is the rise of pertussis in adolescents and adults. This changing picture is largely attributable to waning immunity after natural infection or vaccination. The belief that pertussis is chiefly a childhood disease is a common misconception. A significant rise of pertussis cases in Malta in older age groups was recorded in 2011. The addition of an adolescent and/or an adult booster dose against pertussis should be strongly considered.peer-reviewe

Development of health services in Malta : past, present and future

As with other modern health systems, Malta has experienced significant changes in its health care landscape over the past two decades. Major changes have occurred, in the country itself and in its health care system, impacting both the provision and consumption of healthcare. The accession of Malta to the European Union has shaped Malta’s health system by catalysing change, standardising certain processes and bringing new legislation. Investments in the infrastructure and health workforce together with innovative management policies and techniques have enhanced the delivery of healthcare to patients. The digitalisation of healthcare has also had a major boost in the past two decades, revolutionising healthcare provision while narrowing the gap between the patient and the healthcare provider. Various strategies and policies have been published and implemented to enhance the delivery of clinical services with the aim of reducing the disease burden of the Maltese population, from diseases such as cancer and diabetes. This article traces these main developments in a descriptive and analytical manner and provides a number of insights for the future.peer-reviewe

Analysing product development working practices for enhancing innovation through collaboration and simulation

The importance of innovation for success in the 21st century economy is evident from the numerous articles on innovation that begin with the statement “companies must innovate or they will die”. It is not sufficient anymore for companies to compete on the basis of cost or time-to-market – if innovation is not part of the company culture, it is very difficult to survive in today’s fast-paced and competitive market. Furthermore, as stated by[ Adams et al. 2006], companies seeking to be innovative should establish formal processes for innovating and make use of tools that facilitate innovative endeavours. The importance of tools as an input to the innovation process is also highlighted by [Cooper et al. 2004]. These tools fall under various categories such as tools for promoting creativity and tools for quality control [Adams et al. 2006]. This research argues that for the innovation process to be successful, two activities together with their supporting tools are required – stakeholder collaboration and artefact simulation. Stakeholder collaboration here refers to collaboration between product development stakeholders, such as designers, customers and manufacturing engineers, required to develop innovative products. Artefact simulation refers to simulation of both the product being developed as well as the manufacturing processes and systems used to develop the product. Both activities fall within what is termed in this research as the Innovation Cloud. Within this cloud is the product development process that involves multiple experts (e.g. designers, production managers) coming from different areas and who need to collaborate together to develop innovative products and manufacturing systems [Adams et al. 2006], [SDRC 2000]. The innovation process is preferably assisted by means of Innovation Management Techniques (IMTs), which are a range of techniques that help companies adapt to different circumstances and market needs in a systematic way [Phaal et al. 2006]. However, collaboration and IMTs by themselves are not sufficient. One of the main stumbling blocks when it comes to the implementation of innovative ideas is the justification of new capital expenses in the short-term and the prediction of long-term profits and other performance metrics such as assembly time, environmental impacts, etc. Thus, artefact simulation is required to predict the consequences of the innovative ideas generated and compare their feasibility from a performance metric perspective [Westkämper 2007]. In view of these arguments, the ultimate goal of this research project is to develop a framework through which product development stakeholders are able to enhance innovation in the product and its manufacturing process, by the use of innovation tools as well as collaboration and simulation tools. In this paper, the focus is on the problem analysis phase of the research project, more specifically on the data collection carried out at local manufacturing companies and on the generation of as-is and to-be models (Figure 1).peer-reviewe

Can designers be proactively supported as from product specifications?

During the design process, designers are concerned with two main types of issues - issues related to “what needs to be achieved” or “whats” and issues related to “how these needs will be met” or “hows”. A literature review carried out revealed that means which proactively make designers aware of artefact life-cycle consequences (LCCs) arising from both their “whats” and “hows” and which guide them on how to minimise or avoid any negative consequences, are lacking. This research thus contributes an approach framework to meet this aim. The approach framework developed is further implemented as a prototype computer-based tool and subsequently evaluated. Based on the feedback obtained from the evaluation, future research directions are also proposed.peer-reviewe

Intelligent life-oriented design solution space selection

Consideration of design specifications is a vital part of the product design process. When design specifications are met, not only is customer satisfaction increased, but product development times and costs are reduced through less iteration. Product quality is also likely to be higher if these specifications are systematically addressed. However, focusing on the functionality specifications of the product is not enough. For the product to be really successful, design engineers have to take into account the specifications for the whole product life cycle, not only those for the use phase. This means that fabrication and assembly specifications, product servicing, product retirement and other specifications of the product from conception to grave should also be taken into account. Traditional CAD tools tend to provide support for the solution phase of the design process, with the design specifications being overlooked. This is a major limitation of these tools given the vital importance of considering design specifications during the design process. Due to this, specifications management is still very paper-based and is kept separate from the actual solution generation as there is no way for the designer to know, via traditional CAD tools, whether a given specification is satisfied in the solution being developed unless it is manually checked each time the question arises. What engineering designers do in practice is they start off with reading the design specifications from the Product Design Specification (PDS), then move on to generate a Quality Function Deployment (QFD) chart to convert the customer ‘wants’ into technical specifications, then start to take decisions based on what has been stored in their memories from the PDS and QFD [Grech 2009]. Hence, in practice, it is quite difficult to trace whether the design solution satisfies the design specifications or not. [Excerpt]peer-reviewe

Effect of BRCA2 sequence variants predicted to disrupt exonic splice enhancers on BRCA2 transcripts

Background: Genetic screening of breast cancer patients and their families have identified a number of variants of unknown clinical significance in the breast cancer susceptibility genes, BRCA1 and BRCA2. Evaluation of such unclassified variants may be assisted by web-based bioinformatic prediction tools, although accurate prediction of aberrant splicing by unclassified variants affecting exonic splice enhancers (ESEs) remains a challenge

Identification of BRCA1 missense substitutions that confer partial functional activity: potential moderate risk variants?

Introduction: Many of the DNA sequence variants identified in the breast cancer susceptibility gene BRCA1 remain unclassified in terms of their potential pathogenicity. Both multifactorial likelihood analysis and functional approaches have been proposed as a means to elucidate likely clinical significance of such variants, but analysis of the comparative value of these methods for classifying all sequence variants has been limited. Methods: We have compared the results from multifactorial likelihood analysis with those from several functional analyses for the four BRCA1 sequence variants A1708E, G1738R, R1699Q, and A1708V. Results: Our results show that multifactorial likelihood analysis, which incorporates sequence conservation, co-inheritance, segregation, and tumour immunohistochemical analysis, may improve classification of variants. For A1708E, previously shown to be functionally compromised, analysis of oestrogen receptor, cytokeratin 5/6, and cytokeratin 14 tumour expression data significantly strengthened the prediction of pathogenicity, giving a posterior probability of pathogenicity of 99%. For G1738R, shown to be functionally defective in this study, immunohistochemistry analysis confirmed previous findings of inconsistent 'BRCA1-like' phenotypes for the two tumours studied, and the posterior probability for this variant was 96%. The posterior probabilities of R1699Q and A1708V were 54% and 69%, respectively, only moderately suggestive of increased risk. Interestingly, results from functional analyses suggest that both of these variants have only partial functional activity. R1699Q was defective in foci formation in response to DNA damage and displayed intermediate transcriptional transactivation activity but showed no evidence for centrosome amplification. In contrast, A1708V displayed an intermediate transcriptional transactivation activity and a normal foci formation response in response to DNA damage but induced centrosome amplification. Conclusion: These data highlight the need for a range of functional studies to be performed in order to identify variants with partially compromised function. The results also raise the possibility that A1708V and R1699Q may be associated with a low or moderate risk of cancer. While data pooling strategies may provide more information for multifactorial analysis to improve the interpretation of the clinical significance of these variants, it is likely that the development of current multifactorial likelihood approaches and the consideration of alternative statistical approaches will be needed to determine whether these individually rare variants do confer a low or moderate risk of breast cancer

Fibronectin acts as a molecular switch to determine SPARC function in pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest of all solid tumours and more effective therapy is urgently needed. The stroma is thought to play a critical role in tumour development and metastasis, and high stromal expression of the matricellular protein SPARC has been robustly associated with poor patient prognosis. However, the precise role of SPARC has been highly controversial, with multiple studies demonstrating tumour-suppressor properties of this protein 'in vitro'. This conflicting data has been a barrier to the development of new therapeutic approaches targeting SPARC, despite current interest in stromal-therapy. We show conclusively that SPARC acts directly on cancer cells to promote pancreatic cancer cell proliferation. This contradicts previous 'in vitro' studies, but is consistent with the observed clinical association between SPARC expression and poor patient prognosis. However, depletion of fibronectin switches the activity of SPARC from promoting cancer cell proliferation to growth inhibition and induction of apoptosis. Thus, targeting the interaction between SPARC and fibronectin could be used to turn the highly expressed tumour protein SPARC against the tumour to induce tumour cytotoxicity, and is a novel target for PDAC therapy

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection