Time Will Tell: The Involvement of the Circadian Clock in Colorectal Cancer

A circadian rhythm is a 24 hour recurring biological process. A group of core genes and transcription factors (CLK, BMAL1, PER, CRY) called the circadian clock regulates these 24 hour rhythms through a transcription/translation feedback loop. Over 40% of the genome is transcribed rhythmically implicating the clock in many cellular processes. Recently, it has been shown that WNT, a mediator of intestinal stem cell proliferation is transcribed rhythmically. Uncontrolled cell proliferation can lead to cancer, which is seen with the mutation of APC, a regulator of Wnt mutated in 80% of all colorectal cancer cases. Colorectal cancer incidence has been steadily increasing due to chronic photoperiod disruptions such as shift work. My project will examine how the disruption of the circadian clock in the intestine affects cancer incidence. I hypothesize that a dysfunctional clock will lead to enhanced tumorigenesis. Due to the implication of APC in colorectal cancer, we will use a mouse that is heterozygous for the APC gene, APCmin/+ to model colorectal cancer in a mouse. I will compare APCmin/+; BMAL1+/+ intestines, which have a normal circadian clock, to APCmin/+; BMAL1-/- intestines, where the clock is dysfunctional. I will count polyps, and use H&E stained tissue sections to quantify the size of each tumour. The Wnt pathway, cell cycle activity and the circadian clock will be examined using immunofluorescence to study the potential relationship between cancer development and the clock. PER2, a core clock protein as well as cMYC, a Wnt target will be investigated. I predict that the APCmin/+; BMAL1+/+ mice, will have fewer tumors than the APCmin/+; BMAL1-/-. My preliminary data shows that the APCmin/+; BMAL1+/+ tissue has more tumours than APC+/+; BMAL1+/+ suggesting this colorectal mouse model works. Implicating the circadian clock in colorectal cancer may allow for greater understanding in how to treat or avoid it

Assessing midwives' breastfeeding knowledge: Properties of the Newborn Feeding Ability questionnaire and Breastfeeding Initiation Practices scale

10.1186/1746-4358-3-7International Breastfeeding Journal3

Caring for the older person with cognitive impairment in hospital: Qualitative analysis of nursing personnel reflections on fall events

Aims and objectives To explore nurse and nursing assistant reflections on the care of older patients with cognitive impairment who have experienced a fall. Background While there are evidence‐based clinical guidelines for the prevention and management of falls and for the care of older people with cognitive impairment, the falls rates for older people with cognitive impairment are three times as high as those without. Design Critical incident technique. Methods Eleven registered and two enrolled nurses and four assistants in nursing working in one subacute and two acute wards within two hospitals of a tertiary level health service in south‐east Queensland. Individual semistructured interviews focused on two past events when a patient with cognitive impairment had fallen in hospital: one when there was minimal harm and the second when there was significant harm. Thematic analysis was undertaken. The COREQ checklist was followed. Results Three themes emerged from 23 reflective accounts of fall events: “direct observation is confounded by multiple observers” and “knowing the person has cognitive impairment is not enough,” and “want to rely on the guideline but unsure how to enact it.” While participants were aware of the falls prevention policy and techniques available to prevent falls, the implementation of these was challenging due to the complexity of care required by the older person with cognitive impairment. Conclusions Falls prevention for older people with cognitive impairment is complex and belies the simple application of policy. Relevance to clinical practice To reduce falls, nurses can involve the family to support “knowing the patient” to enable prediction of impulsive actions; shift the focus of in‐service from lectures to specific case presentations, with collaborative analysis on person‐focused strategies to prevent falls in older people with cognitive impairment; and reconsider the sitter role from simple observer to assistant, focused on ambulation and supporting independence in activities of daily living.Full Tex

‘Trimming their lamps’: an analysis and investigation of the participation of women in the Catholic Church in the Anglosphere since the Second Vatican Council

This thesis examines the nature and extent of the participation of women in the Catholic Church and attitudes towards this, from the Second Vatican Council to the present day in the Anglosphere nations. The originality of this contribution to knowledge derives from the analysis of earlier survey data on the subject authorised by the Catholic Bishops’ Conferences in Australia, New Zealand, the USA, Canada, England & Wales, Ireland, and Scotland. A comparative study is made of these findings with those of a parallel qualitative and quantitative study undertaken in 2013 in Scotland. The findings evidence analogous themes running through both the earlier research data and that from 2013. The duty to appreciate the diversity of Catholic women is a key factor. The dangers of a culture of clericalism are evidenced as a serious barrier to any lay participation. The need for education and formation of the laity is identified as crucial, as is the importance of Catholic social teaching in providing a conduit for increased dialogue and respect between women and men. The Church’s emphasis on unity and continuity is acknowledged as both a barrier to, and yet potentially a positive means for, future collaboration between men and women. Proposals are made about how this research could underpin future development in the Catholic Church, particularly in Scotland. These include utilising an oblique methodology and the implementation of a receptive feminism. The facilitation of dialogue would ensure there is true gender equality, allowing the gifts of both women and men to be engaged in meeting the needs of the Church and the world

A Gravitational Theory of the Quantum

The synthesis of quantum and gravitational physics is sought through a finite, realistic, locally causal theory where gravity plays a vital role not only during decoherent measurement but also during non-decoherent unitary evolution. Invariant set theory is built on geometric properties of a compact fractal-like subset $I_U$ of cosmological state space on which the universe is assumed to evolve and from which the laws of physics are assumed to derive. Consistent with the primacy of $I_U$, a non-Euclidean (and hence non-classical) state-space metric $g_p$ is defined, related to the $p$-adic metric of number theory where $p$ is a large but finite Pythagorean prime. Uncertain states on $I_U$ are described using complex Hilbert states, but only if their squared amplitudes are rational and corresponding complex phase angles are rational multiples of $2 \pi$. Such Hilbert states are necessarily $g_p$-distant from states with either irrational squared amplitudes or irrational phase angles. The gappy fractal nature of $I_U$ accounts for quantum complementarity and is characterised numerically by a generic number-theoretic incommensurateness between rational angles and rational cosines of angles. The Bell inequality, whose violation would be inconsistent with local realism, is shown to be $g_p$-distant from all forms of the inequality that are violated in any finite-precision experiment. The delayed-choice paradox is resolved through the computational irreducibility of $I_U$. The Schr\"odinger and Dirac equations describe evolution on $I_U$ in the singular limit at $p=\infty$. By contrast, an extension of the Einstein field equations on $I_U$ is proposed which reduces smoothly to general relativity as $p \rightarrow \infty$. Novel proposals for the dark universe and the elimination of classical space-time singularities are given and experimental implications outlined

Nurses’ education, knowledge and perceptions of peripheral intravenous catheter management: A web-based, cross-sectional survey

Background: Peripheral intravenous catheters (PIVCs) are the most used invasive medical device. Unfortunately, PIVCs fail for a variety of reasons and failure often results in serious adverse events leading to patient discomfort, infection, delays in treatment, increased healthcare costs, and even death. In Australia, qualified nurses assess, manage, and remove a PIVC as part of their clinical role. To date, no study has described the current state of knowledge and confidence (self-efficacy) about PIVCs from the perspectives of qualified nurses working in Australian hospital settings. Aims: To describe the current state of knowledge and confidence (self-efficacy) about PIVC management from the perspectives of qualified nurses working in Australian hospital settings. To explore how these related to the education received by these nurses. Methods: An online cross-sectional survey. Findings: Qualified nurses in Australia thought that education about PIVCs was important and that it should be underpinned by evidence-based guidelines. Knowledge Test score for the sample was 12.4/17 (SD 2.1), this equates to a mean grade of 73.0%. Respondents reported very high levels of confidence about caring for a patient with a PIVC in situ. Conclusion: Despite the frequent and increasing use of PIVCs and importantly the documented adverse events associated with poor assessment, management and inappropriate removal, qualified nurses’ knowledge and confidence remain poorly reported. We demonstrated fundamental gaps in qualified nurses’ knowledge in relation to assessment, management, and removal of PIVCs

The tuberculosis challenge in a rural South African HIV programme.

BACKGROUND: South Africa remains the country with the greatest burden of HIV-infected individuals and the second highest estimated TB incidence per capita worldwide. Within South Africa, KwaZulu-Natal has one of the highest rates of TB incidence and an emerging epidemic of drug-resistant tuberculosis. METHODS: Review of records of consecutive HIV-infected people initiated onto ART between 1st January 2005 and 31st March 2006. Patients were screened for TB at initiation and incident episodes recorded. CD4 counts, viral loads and follow-up status were recorded; data was censored on 5th August 2008. Geographic cluster analysis was performed using spatial scanning. RESULTS: 801 patients were initiated. TB prevalence was 25.3%, associated with lower CD4 (AHR 2.61 p = 0.01 for CD4 25 copies/ml (OR 1.75 p = 0.11). A low-risk cluster for incident TB was identified for patients living near the local hospital in the geospatial analysis. CONCLUSION: There is a large burden of TB in this population. Rate of incident TB stabilises at a rate higher than that of the overall population. These data highlight the need for greater research on strategies for active case finding in rural settings and the need to focus on strengthening primary health care

Need for timely paediatric HIV treatment within primary health care in rural South Africa

<p>Background: In areas where adult HIV prevalence has reached hyperendemic levels, many infants remain at risk of acquiring HIV infection. Timely access to care and treatment for HIV-infected infants and young children remains an important challenge. We explore the extent to which public sector roll-out has met the estimated need for paediatric treatment in a rural South African setting.</p> <p>Methods: Local facility and population-based data were used to compare the number of HIV infected children accessing HAART before 2008, with estimates of those in need of treatment from a deterministic modeling approach. The impact of programmatic improvements on estimated numbers of children in need of treatment was assessed in sensitivity analyses.</p> <p>Findings: In the primary health care programme of HIV treatment 346 children <16 years of age initiated HAART by 2008; 245(70.8%) were aged 10 years or younger, and only 2(<1%) under one year of age. Deterministic modeling predicted 2,561 HIV infected children aged 10 or younger to be alive within the area, of whom at least 521(20.3%) would have required immediate treatment. Were extended PMTCT uptake to reach 100% coverage, the annual number of infected infants could be reduced by 49.2%.</p> <p>Conclusion: Despite progress in delivering decentralized HIV services to a rural sub-district in South Africa, substantial unmet need for treatment remains. In a local setting, very few children were initiated on treatment under 1 year of age and steps have now been taken to successfully improve early diagnosis and referral of infected infants.</p&gt

Efficacy and safety of normal saline instillation and paediatric endotracheal suction: an integrative review

To synthesise research findings regarding the efficacy and safety of normal saline instillation (NSI) during endotracheal suction in the paediatric intensive care unit.The Cochrane Library, PROSPERO, the National Health Service Centre for Reviews and Dissemination, PubMed and Cumulative Index to Nursing and Allied Health (CINAHL) databases were systematically searched. Subject headings included "suctioning, endotracheal", "suction", "sodium chloride", "normal saline" and "paediatrics". Additional references were sourced from hand searches of journal article reference lists and Google Scholar.An integrative, systematic approach was used to qualitatively synthesise study results in the context of paediatric intensive care nursing practice. Data were extracted using a standardised data extraction form. Quality assessment was performed independently by two reviewers.Three studies met pre-defined inclusion criteria. Quality of all study methods was 75% on the Mixed Method Appraisal Tool, although reporting quality varied. Overall, there was a scarcity of high quality evidence examining NSI and paediatric endotracheal suction. Outcome measures included oxygen saturation (SpO2), serious adverse events (author/s defined) and ventilation parameters (author/s defined). Endotracheal suction with NSI was associated with a transient decrease in blood oxygen saturation; research protocols did not include interventions to mitigate alveolar derecruitment. Studies were not powered to detect differences in endotracheal tube (ETT) occlusion or ventilator associated pneumonia (VAP).NSI was associated with a transient decrease in oxygen saturation. In children with obstructive mucous, NSI may have a positive effect. Practices which maximise secretion removal and mitigate the negative physiological interactions of ETS have been poorly evaluated in the paediatric population. High quality, powered, clinical trials are needed to determine the safety and efficacy of normal saline instillation and to inform clinical practice