This is a very dull book. Like a dictionary, it contains only facts: facts that are not readily to be found elsewhere. People who are important in the study of caves and karst are known for what they ...did, what they wrote and whom they influenced. But as individuals they are often no more than a name. They may perhaps be recognized for other aspects, as a King perhaps, or a novelist or a famous doctor. Some, like Darwin or Freud, have changed the world in other ways~but very many had only normal quiet lives during which they also explored, studied or wrote about caves. It is they whose wider lives are difficult to trace and it is 4634 of them who are recorded here, with information from birth certificates, obituaries, unpublished letters and mentions by other people. It is their wider lives that help to show them as real people. In some cases their interest in caves was a part of their professional lives. In many others it provides stimulation and relaxation in otherwise busy lives. But in every case it was the same person and the same brain that enjoyed both~and it was both that made them the people they were. It is only from the biographical sources recorded here, that each person can be understood.
In the knowledge economy, the 'creative industries' are recognised as a new paradigm. They are industries which use creativity as an intangible asset to generate wealth. The creative industries are ...described as 'evolving' and their outcomes frequently categorised as 'intangibles'. The thesis outlines what I term a creative industries approach to the engagement of visual artists with industry. The artist-in-industry program, a component of New Possibilities for Paper, was established with an explicit brief to generate creative products and contained an implicit agenda to breed intellectual capital. It was conceived as a means of crossfertilising hitherto siloed sectors -- an arts environment with entrenched attitudes towards the subsidy, proprietorship and authority of creativity and the traditionally conservative paper industry. Establishing creative industries characteristics and indicators to describe and measure creative industries operation in this program required careful consideration, with the characteristics and indicators selected able to recognise trends or changes. The analysis of the seven partnerships confirmed that the artistin-industry program is a creative industries approach upon which future programs between visual artists and the paper industry could be constructed. The research found that the creative industries processes in most need of being addressed, if visual artists are to maximise their benefits, included an understanding and utilisation of intellectual property, knowledge of commercialisation processes and a positive attitude towards commercialisation. For paper companies that invest in R&D, there is recognition that potential tangible and intangible benefits can result from engaging in such partnerships. Additionally, a partnership in which the artist's role (or service) is focused on the industry's customers and contributes to employee knowledge was seen as being of greatest value to the paper industry.
There is limited knowledge about cancer patients' experiences of uncertainty while waiting for genome sequencing results, and whether prolonged uncertainty contributes to psychological factors in ...this context. To investigate uncertainty in patients with a cancer of likely hereditary origin while waiting for genome sequencing results, we collected questionnaire and interview data at baseline, and at three and 12 months follow up (prior to receiving results). Participants (
= 353) had negative attitudes towards uncertainty (
= 4.03, SD 0.68) at baseline, and low levels of uncertainty at three (
= 8.23, SD 7.37) and 12 months (
= 7.95, SD 7.64). Uncertainty about genome sequencing did not change significantly over time
(210) = 0.660,
= 0.510. Greater perceived susceptibility for cancer
(348) = 0.14,
<
.01, fear of cancer recurrence
(348) = 0.19,
<
.01, perceived importance of genome sequencing
(350) = 0.24,
<
.01, intention to change behavior if a gene variant indicating risk is found
(349) = 0.29,
<
.01, perceived ability to cope with results
(349) = 0.36,
<
.01, and satisfaction with decision to have genome sequencing
(350) = 0.52,
<
.01 were significantly correlated with negative attitudes towards uncertainty at baseline. Multiple primary cancer diagnoses B = -2.364 -4.238, -0.491,
= 0.014, lower perceived ability to cope with results B = -0.1.881 -3.403, -0.359,
= 0.016 at baseline, greater anxiety about genome sequencing (avoidance) B = 0.347 0.148, 0.546,
= 0.0012 at 3 months, and greater perceived uncertainty about genome sequencing B = 0.494 0.267, 0.721
= 0.000 at 3 months significantly predicted greater perceived uncertainty about genome sequencing at 12 months. Greater perceived uncertainty about genome sequencing at 3 months significantly predicted greater anxiety (avoidance) about genome sequencing at 12 months B = 0.291 0.072, 0.509,
= 0.009. Semi-structured interviews revealed that while participants were motivated to pursue genome sequencing as a strategy to reduce their illness and risk uncertainty, genome sequencing generated additional practical, scientific and personal uncertainties. Some uncertainties were consistently discussed over the 12 months, while others emerged over time. Similarly, some uncertainty coping strategies were consistent over time, while others emerged while patients waited for their genome sequencing results. This study demonstrates the complexity of uncertainty generated by genome sequencing for cancer patients and provides further support for the inter-relationship between uncertainty and anxiety. Helping patients manage their uncertainty may ameliorate psychological morbidity.
Tumor mutation profiling (MP) is often conducted on tissue from biopsies conducted for clinical purposes (diagnostic tissue). We aimed to explore the views of patients with cancer on who should own ...tumor biopsy tissue, pay for its storage, and decide on its future use; and determine their attitudes to and predictors of undergoing additional biopsies if required for research purposes. In this mixed methods, cross-sectional study, patients with advanced solid cancers enrolled in the Molecular Screening and Therapeutics Program (n = 397) completed a questionnaire prior to undergoing MP (n = 356/397). A subset (n = 23) also completed a qualitative interview. Fifty percent of participants believed they and/or relatives should own and control access to diagnostic tissue. Most (65.5%) believed the government should pay for tissue preparation. Qualitative themes included (1) custodianship of diagnostic tissue, (2) changing value of tissue across time and between cultures, (3) equity regarding payment, and (4) cost-benefit considerations in deciding on additional biopsies. Policy and regulation should consider patient perspectives. Extension of publicly funded health care to include tissue retrieval for clinical trials should be considered.
During hibernation, thirteen-lined ground squirrels (
) regularly cycle between bouts of torpor and interbout arousal (IBA). Most of the brain is electrically quiescent during torpor but regains ...activity quickly upon arousal to IBA, resulting in extreme oscillations in energy demand during hibernation. We predicted increased functional capacity of brain mitochondria during hibernation compared with spring to accommodate the variable energy demands of hibernation. To address this hypothesis, we examined mitochondrial bioenergetics in the ground squirrel brain across three time points: spring (SP), torpor (TOR), and IBA. Respiration rates of isolated brain mitochondria through complex I of the electron transport chain were more than twofold higher in TOR and IBA than in SP (
< 0.05). We also found a 10% increase in membrane potential between hibernation and spring (
< 0.05), and that proton leak was lower in TOR and IBA than in SP. Finally, there was a 30% increase in calcium loading in SP brain mitochondria compared with TOR and IBA (
< 0.01). To analyze brain mitochondrial abundance between spring and hibernation, we measured the ratio of copy number in a mitochondrial gene (
) vs. a nuclear gene (
) in frozen cerebral cortex samples. No significant differences were observed in DNA copies between SP and IBA. These data show that brain mitochondrial bioenergetics are not static across the year and suggest that brain mitochondria function more effectively during the hibernation season, allowing for rapid production of energy to meet demand when extreme physiological changes are occurring.
Purpose
The introduction of comprehensive tumour genomic profiling (CGP) into clinical oncology allows the identification of molecular therapeutic targets. However, the potential complexity of ...genomic results and their implications may cause confusion and distress for patients undergoing CGP. We investigated the experience of advanced cancer patients receiving CGP results in a research setting.
Methods
Semi-structured interviews with 37 advanced cancer patients were conducted within two weeks of patients receiving CGP results. Interviewees were purposively sampled based on CGP result, cancer type, age and gender to ensure diversity. Themes were derived from interview transcripts using a framework analysis approach.
Results
We identified six themes: (1) hoping against the odds; (2) managing expectations; (3) understanding is cursory; (4) communication of results is cursory; (5) genomics and incurable cancer; and (6) decisions about treatment.
Conclusion
Despite enthusiasm regarding CGP about the hope it provides for new treatments, participants experienced challenges in understanding results, and acceptance of identified treatments was not automatic. Support is needed for patients undergoing CGP to understand the implications of testing and cope with non-actionable results.
Germline genome sequencing (GS) holds great promise for cancer prevention by identifying cancer risk and guiding prevention strategies, however research evidence is mixed regarding patient ...preferences for receiving GS results. The aim of this study was to discern preferences for return of results by cancer patients who have actually undergone GS. We conducted a mixed methods study with a cohort of cancer probands (n = 335) and their genetic relatives (n = 199) undergoing GS in a research setting. Both groups completed surveys when giving consent. A subset of participants (n = 40) completed semi-structured interviews. A significantly higher percentage of probands thought people would like to be informed about genetic conditions for which there is prevention or treatment that can change cancer risk compared to conditions for which there is no prevention or treatment (93% 311 versus 65% 216; p < 0.001). Similar results were obtained for relatives (91% 180 versus 61% 121; p < 0.001). Themes identified in the analysis of interviews were: (1) Recognised benefits of GS, (2) Balancing benefits with risks, (3) Uncertain results are perceived as unhelpful and (4) Competing obligations. While utility was an important discriminator in what was seen as valuable for this cohort, there was a variety of responses. In view of varied participant preferences regarding return of results, it is important to ensure patient understanding of test validity and identify individual choices at the time of consent to GS. The nature and value of the information, and a contextual understanding of researcher obligations should guide result return.
Systemic lupus erythematosus (SLE) is a clinically heterogeneous disease in which the risk of disease is influenced by complex genetic and environmental contributions. Alleles of HLA-DRB1, IRF5, and ...STAT4 are established susceptibility genes; there is strong evidence for the existence of additional risk loci.
We genotyped more than 500,000 single-nucleotide polymorphisms (SNPs) in DNA samples from 1311 case subjects with SLE and 1783 control subjects; all subjects were North Americans of European descent. Genotypes from 1557 additional control subjects were obtained from public data repositories. We measured the association between the SNPs and SLE after applying strict quality-control filters to reduce technical artifacts and to correct for the presence of population stratification. Replication of the top loci was performed in 793 case subjects and 857 control subjects from Sweden.
Genetic variation in the region upstream from the transcription initiation site of the gene encoding B lymphoid tyrosine kinase (BLK) and C8orf13 (chromosome 8p23.1) was associated with disease risk in both the U.S. and Swedish case-control series (rs13277113; odds ratio, 1.39; P=1x10(-10)) and also with altered levels of messenger RNA in B-cell lines. In addition, variants on chromosome 16p11.22, near the genes encoding integrin alpha M (ITGAM, or CD11b) and integrin alpha X (ITGAX), were associated with SLE in the combined sample (rs11574637; odds ratio, 1.33; P=3x10(-11)).
We identified and then confirmed through replication two new genetic loci for SLE: a promoter-region allele associated with reduced expression of BLK and increased expression of C8orf13 and variants in the ITGAM-ITGAX region.
Clinical genomic sequencing warrants the investigation and potential development of family-centered communication interventions.
Preference-sensitive family communication strategies about genomic ...testing are needed.
Support needs should be assessed specific to clinical applications of genomic testing.
This study explored family communication about undertaking genomic sequencing, and intentions to communicate pertinent heritable results to family members.
Semi-structured interviews were conducted with cancer patients (n = 53) and their relatives (n = 20) who underwent germline genome sequencing or molecular tumor testing. Interviews were audio-recorded, transcribed and analyzed using thematic analysis.
Key themes relevant to family communication about undertaking sequencing included: perceiving family member interest, delaying discussion until results were received, having shared capacity to understand and cope, and having open communication in the family. Intended communication subsequent to receiving results was affected by: disease severity, risk management options, degree of closeness in the family, sense of responsibility, and potential adverse impacts on family. Resource and support needs varied based on the complexity of test results, health professionals’ availability, and disease severity. Unique subthemes were identified for specific subgroups.
Current findings support the need to assess the impact and resource needs specific to each clinical application of genomic sequencing.
Increasingly sophisticated and complex clinical genomic sequencing warrants development of family-centered interventions and resources to facilitate preference-sensitive communication about genomic sequencing, including disseminating relevant information to family members.
Background: Comprehensive tumor genomic profiling (CGP) offers hope for personalized treatment for cancer patients when other treatment options have been exhausted. However, receipt of nonactionable ...or ambiguous results could be an ongoing source of distress. We investigated patterns of hope, anxiety, depression, and CGP-specific anxiety in advanced cancer patients after receiving CGP results and 2-3 months later. Method: Participants were enrolled in a longitudinal psychosocial substudy, embedded in the Molecular Screening and Therapeutics Program, and had advanced solid cancers of any histological type with sufficient and accessible tissue for CGP. At T0 (before receiving CGP results), 1,431 participants completed sociodemographic, disease and psychosocial measures. At T1 (1-4 weeks after receiving CGP results) and T2 (2-3 months post-T1), 374 participants completed psychological outcome measures. Predictors of outcomes at T2 were identified using multinomial logistic regression. Results: Approximately 75% of participants did not experience significant hopelessness or distress at T1 and T2. Hope decreased by T2, yet general anxiety and CGP-specific anxiety also decreased. Receiving actionable results did not impact psychological outcomes at T2. At T2, lower hope, and higher anxiety, depression and CGP-specific anxiety were associated with lower self-efficacy. Psychological and demographic factors (age, socioeconomic status, language, medical occupation, urban living, family history of cancer) independently predicted one or more psychological trajectories. Worse health status and perceived susceptibility to cancer progression predicted hope and anxiety trajectories. Conclusion: Further research on interventions to best support patients undergoing CGP with high anxiety, hopelessness, fear of cancer progression, and poorer health is urgently needed.
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