Using technology to deliver cancer follow-up : a systematic review

Peer reviewedPublisher PD

Planetary science and exploration in the deep subsurface: results from the MINAR Program, Boulby Mine, UK

The subsurface exploration of other planetary bodies can be used to unravel their geological history and assess their habitability. On Mars in particular, present-day habitable conditions may be restricted to the subsurface. Using a deep subsurface mine, we carried out a program of extraterrestrial analog research – MINe Analog Research (MINAR). MINAR aims to carry out the scientific study of the deep subsurface and test instrumentation designed for planetary surface exploration by investigating deep subsurface geology, whilst establishing the potential this technology has to be transferred into the mining industry. An integrated multi-instrument suite was used to investigate samples of representative evaporite minerals from a subsurface Permian evaporite sequence, in particular to assess mineral and elemental variations which provide small-scale regions of enhanced habitability. The instruments used were the Panoramic Camera emulator, Close-Up Imager, Raman spectrometer, Small Planetary Linear Impulse Tool, Ultrasonic drill and handheld X-ray diffraction (XRD). We present science results from the analog research and show that these instruments can be used to investigate in situ the geological context and mineralogical variations of a deep subsurface environment, and thus habitability, from millimetre to metre scales. We also show that these instruments are complementary. For example, the identification of primary evaporite minerals such as NaCl and KCl, which are difficult to detect by portable Raman spectrometers, can be accomplished with XRD. By contrast, Raman is highly effective at locating and detecting mineral inclusions in primary evaporite minerals. MINAR demonstrates the effective use of a deep subsurface environment for planetary instrument development, understanding the habitability of extreme deep subsurface environments on Earth and other planetary bodies, and advancing the use of space technology in economic mining

A multidisciplinary systematic literature review on frailty: Overview of the methodology used by the Canadian Initiative on Frailty and Aging

<p>Abstract</p> <p>Background</p> <p>Over the past two decades, there has been a substantial growth in the body of literature on frailty in older persons. However, there is no consensus on its definition or the criteria used to identify frailty. In response to this lack of consensus, the Canadian Initiative on Frailty and Aging carried out a set of systematic reviews of the literature in ten areas of frailty research: biological basis; social basis; prevalence; risk factors; impact; identification; prevention and management; environment and technology; health services; health and social policy. This paper describes the methodology that was developed for the systematic reviews.</p> <p>Methods</p> <p>A Central Coordination Group (CCG) was responsible for developing the methodology. This involved the development of search strategies and keywords, article selection processes, quality assessment tools, and guidelines for the synthesis of results. Each review was conducted by two experts in the content area, with the assistance of methodologists and statisticians from the CCG.</p> <p>Results</p> <p>Conducting a series of systematic literature reviews involving a range of disciplines on a concept that does not have a universally accepted definition posed several conceptual and methodological challenges. The most important conceptual challenge was determining what would qualify as literature on frailty. The methodological challenges arose from our goal of structuring a consistent methodology for reviewing literature from diverse fields of research. At the outset, certain methodological guidelines were deemed essential to ensure the validity of all the reviews. Nevertheless, it was equally important to permit flexibility in the application of the proposed methodology to capture the essence of frailty research within the given fields.</p> <p>Conclusion</p> <p>The results of these reviews allowed us to establish the status of current knowledge on frailty and promote collaboration between disciplines. Conducting systematic literature reviews in health science that involve multiple disciplines is a mechanism to facilitate interdisciplinary collaboration and a more integrated understanding of health. This initiative highlighted the need for further methodological development in the performance of multidisciplinary systematic reviews.</p

A Community Study of Factors Related to Poorly Controlled Asthma among Brazilian Urban Children

BACKGROUND: Asthma constitutes a serious public health problem in many regions of the world, including the city of Salvador, State of Bahia-Brazil. The purpose of this study was to analyse the factors associated with poor asthma control. METHODOLOGY/PRINCIPAL FINDINGS: Two definitions were used for asthma: 1) wheezing in the last 12 months; 2) wheezing in the last 12 months plus other asthma symptoms or asthma diagnosis ever. The definition of poorly controlled asthma was: at least one reported hospitalisation due to asthma and/or high frequency of symptoms, in the last year. Children with poorly controlled asthma (N = 187/374) were compared with wheezing children with controlled asthma regarding age, gender, atopy, parental asthma, rhinitis, eczema, exposure to second hand tobacco smoke, presence of moulds, pets and pests in the house, helminth infections and body mass index. Crude and logistic regression adjusted odds ratios were used as measures of association. There was a higher proportion of poorly controlled asthma among children with eczema (OR = 1.55; 95% CI 1.02; 2.37). The strength of the association was greater among children with eczema and rhinitis (42.6%, 53.4% and 57.7%, respectively, in children who had no rhinitis nor eczema, had only one of those, and had both (p = 0.02 for trend test). The presence of mould in the houses was inversely associated with poorly controlled asthma (OR = 0.54; 95% CI 0.34; 0.87). CONCLUSIONS/SIGNIFICANCE: Our results indicate an association between eczema and poor asthma control in this environment, but emphasize the role of various other individual and environmental factors as determinants of poor control

Uptake in cancer screening programmes:a priority in cancer control

Achieving adequate levels of uptake in cancer screening requires a variety of approaches that need to be shaped by the characteristics of both the screening programme and the target population. Strategies to improve uptake typically produce only incremental increases. Accordingly, approaches that combine behavioural, organisational and other strategies are most likely to succeed. In conjunction with a focus on uptake, providers of screening services need to promote informed decision making among invitees. Addressing inequalities in uptake must remain a priority for screening programmes. Evidence informing strategies targeting low-uptake groups is scarce, and more research is needed in this area. Cancer screening has the potential to make a major contribution to early diagnosis initiatives in the United Kingdom, and will best be achieved through uptake strategies that emphasise wide coverage, informed choice and equitable distribution of cancer screening services

Physician Experiences and Understanding of Genomic Sequencing in Oncology

The amount of information produced by genomic sequencing is vast, technically complicated, and can be difficult to interpret. Appropriately tailoring genomic information for nonâ geneticists is an essential next step in the clinical use of genomic sequencing. To initiate development of a framework for genomic results communication, we conducted eighteen qualitative interviews with oncologists who had referred adult cancer patients to a matched tumorâ normal tissue genomic sequencing study. In our qualitative analysis, we found varied levels of clinician knowledge relating to sequencing technology, the scope of the tumor genomic sequencing study, and incidental germline findings. Clinicians expressed a perceived need for more genetics education. Additionally, they had a variety of suggestions for improving results reports and possible resources to aid in results interpretation. Most clinicians felt genetic counselors were needed when incidental germline findings were identified. Our research suggests that more consistent genetics education is imperative in ensuring the proper utilization of genomic sequencing in cancer care. Clinician suggestions for results interpretation resources and results report modifications could be used to improve communication. Cliniciansâ perceived need to involve genetic counselors when incidental germline findings were found suggests genetic specialists could play a critical role in ensuring patients receive appropriate followâ up.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147187/1/jgc40187.pd

Deletion of Genes Implicated in Protecting the Integrity of Male Germ Cells Has Differential Effects on the Incidence of DNA Breaks and Germ Cell Loss

Infertility affects approximately 20% of couples in Europe and in 50% of cases the problem lies with the male partner. The impact of damaged DNA originating in the male germ line on infertility is poorly understood but may increase miscarriage. Mouse models allow us to investigate how deficiencies in DNA repair/damage response pathways impact on formation and function of male germ cells. We have investigated mice with deletions of ERCC1 (excision repair cross-complementing gene 1), MSH2 (MutS homolog 2, involved in mismatch repair pathway), and p53 (tumour suppressor gene implicated in elimination of germ cells with DNA damage).We demonstrate for the first time that depletion of ERCC1 or p53 from germ cells results in an increased incidence of unrepaired DNA breaks in pachytene spermatocytes and increased numbers of caspase-3 positive (apoptotic) germ cells. Sertoli cell-only tubules were detected in testes from mice lacking expression of ERCC1 or MSH2 but not p53. The number of sperm recovered from epididymes was significantly reduced in mice lacking testicular ERCC1 and 40% of sperm contained DNA breaks whereas the numbers of sperm were not different to controls in adult Msh2 -/- or p53 -/- mice nor did they have significantly compromised DNA.These data have demonstrated that deletion of Ercc1, Msh2 and p53 can have differential but overlapping affects on germ cell function and sperm production. These findings increase our understanding of the ways in which gene mutations can have an impact on male fertility

The ROS Scavenger, NAC, Regulates Hepatic Vα14iNKT Cells Signaling during Fas mAb-Dependent Fulminant Liver Failure

Uncontrolled systemic activation of the immune system is an early initiating event that leads to development of acute fulminant liver failure (FLF) in mice after treatment with agonistic Fas mAb. In this study, we demonstrate that treatment of mice with N-acetylcysteine (NAC), an ROS scavenger and glutathione (GSH) precursor, almost completely abolished Fas mAb-induced FLF through suppression of Vα14iNKT cell activation, IFN-γ signaling, apoptosis and nitrotyrosine formation in liver. In addition, enrichment of the liver with GSH due to Vα14iNKT cells deficiency, induced an anti-inflammatory response in the liver of Jα18−/− mice that inhibited apoptosis, nitrotyrosine formation, IFN-γ signaling and effector functions. In summary, we propose a novel and previously unrecognized pro-inflammatory and pro-apoptotic role for endogenous ROS in stimulating Th1 signaling in Vα14iNKT cells to promote the development of FLF. Therefore, our study provides critical new insights into how NAC, a ROS scavenger, regulates Th1 signaling in intrahepatic Vα14iNKT cells to impact inflammatory and pathological responses

Decoding the regulatory network of early blood development from single-cell gene expression measurements.

Reconstruction of the molecular pathways controlling organ development has been hampered by a lack of methods to resolve embryonic progenitor cells. Here we describe a strategy to address this problem that combines gene expression profiling of large numbers of single cells with data analysis based on diffusion maps for dimensionality reduction and network synthesis from state transition graphs. Applying the approach to hematopoietic development in the mouse embryo, we map the progression of mesoderm toward blood using single-cell gene expression analysis of 3,934 cells with blood-forming potential captured at four time points between E7.0 and E8.5. Transitions between individual cellular states are then used as input to develop a single-cell network synthesis toolkit to generate a computationally executable transcriptional regulatory network model of blood development. Several model predictions concerning the roles of Sox and Hox factors are validated experimentally. Our results demonstrate that single-cell analysis of a developing organ coupled with computational approaches can reveal the transcriptional programs that underpin organogenesis.We thank J. Downing (St. Jude Children's Research Hospital, Memphis, TN, USA) for the Runx1-ires-GFP mouse. Research in the authors' laboratory is supported by the Medical Research Council, Biotechnology and Biological Sciences Research Council, Leukaemia and Lymphoma Research, the Leukemia and Lymphoma Society, Microsoft Research and core support grants by the Wellcome Trust to the Cambridge Institute for Medical Research and Wellcome Trust - MRC Cambridge Stem Cell Institute. V.M. is supported by a Medical Research Council Studentship and Centenary Award and S.W. by a Microsoft Research PhD Scholarship.This is the accepted manuscript for a paper published in Nature Biotechnology 33, 269–276 (2015) doi:10.1038/nbt.315