Harti Hauora Tamariki: randomised controlled trial protocol for an opportunistic, holistic and family centred approach to improving outcomes for hospitalised children and their families in Aotearoa, New Zealand.

Background: Health and wellbeing inequities between the Indigenous Maori and non-Maori populations in Aotearoa, New Zealand continue to be unresolved. Within this context, and of particular concern, hospitalisations for diseases of poverty are increasing for tamariki Maori (Maori children). To provide hospitalised tamariki Maori, and their whanau (families) comprehensive support, a wellbeing needs assessment; the Harti Hauora Tamariki Tool (The Harti tool) was developed. The purpose of this study is to determine how effective the Harti tool is at identifying wellbeing needs, ensuring the documentation of needs, enabling access to services and improving wellbeing outcomes for tamariki and their whanau. Methods: The study uses a Kaupapa Maori methodology with qualitative and quantitative methods. Qualitative methods include in-depth interviews with whanau. This paper presents an overview of a randomised, two parallel, controlled, single blinded, superiority trial for quantitative evaluation of the Harti programme, and hospital satisfaction with care survey. Participants will be Maori and non-Maori tamariki/children aged 0-4 years admitted acutely to the paediatric medical wards at Waikato Hospital, Hamilton, Aotearoa New Zealand. They will be randomised electronically into the intervention or usual care group. The intervention group will receive usual care in addition to the Harti programme, which includes a 24-section health needs assessment delivered by trained Maori navigators to whanau during the time they are in hospital. The primary endpoint is the relative risk of an acute hospital readmission in the 30 days following discharge for the intervention group patients compared with control group patients. Secondary outcomes include access and utilisation of preventative health services including: oral health care, general practice enrolment, immunisation, healthy home initiatives, smoking cessation and the Well Child Tamariki Ora universal health checks available free of charge for children in Aotearoa New Zealand. Discussion: Randomised controlled trials are a gold standard for measuring efficacy of complex multifaceted interventions and the results will provide high quality evidence for implementing the intervention nationwide. We expect that this study will provide valuable evidence for health services and policy makers who are considering how to improve the configuration of paediatric hospital services. Trial registration: The study is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR), registration number: ACTRN12618001079235.

Early career biomedical grantsmanship self-efficacy: validation of an abbreviated self-assessment tool.

A hallmark of success for early career biomedical researchers is the acquisition of research funding. There are marked disparities among principal investigators who submit grants and the likelihood of receiving national funding. The National Research Mentoring Network was funded by the National Institutes of Health to diversify the biomedical research workforce and included grantsmanship training for early career researchers. Self-efficacy in developing research grant applications is significantly improved over time with training and experience. We created a 19-item self-efficacy assessment inventory. Our aims were to confirm the internal consistency of a three-factor solution for grantsmanship confidence and to test the likelihood that self-efficacy influences grant proposal submission timing. We gathered data from 190 diverse biomedical trainees who completed NRMN grantsmanship training between August 2015 and June 2017. Findings revealed high internal consistency for items in each of three factors. There was a statistically significant association between self-efficacy mean scores and grant submission timing predicting that, for every one-point increase in the mean score, the odds of submitting a grant 6 months post-training increased by 69%. An abbreviated inventory of grantsmanship skills self-efficacy is a promising tool for monitoring changes over time in early career researchers and for promoting tailored grantsmanship interventions.

Equine-related injuries requiring hospitalisation in the Midland Region of New Zealand: a continuous five-year review.

AIM: To examine the pattern and outcomes of equine-related injuries for hospitalised patients in the Midland Region of New Zealand over a five-year period. METHOD: A retrospective review of all patients admitted to hospitals within the Midland region of New Zealand with an injury date 1 January 2012-31 December 2016, as a direct result of equine-related trauma. RESULTS: Seven hundred and one patients were admitted due to equine-related injuries, 6.6% were major trauma events (Injury Severity Scale >12), with nearly half of all injuries (47.3%) to the extremities. Mean age was 36 years (median 38 years), and 69% were females. The most common mechanisms of injury were falls from horse (70.6%), kicked (12.7%) and knocked (6.7%) by the horse. Males were more likely to have a non-fall injury. Average length of stay (all patients) was 3.4 days, and half of all patients required surgery. All patients survived. At Waikato Hospital, the largest district hospital in the region, the average inpatient cost was NZ$7,805/patient. CONCLUSION: The study has identified the demography, injury types, risk factors and outcomes for equine-related injuries in the Midland Region of New Zealand. Indications are that the severity of such injuries may be less than previously reported. However, the volumes and costs of injury represent a significant burden on the health system, individuals and communities. More detailed understanding of causative factors will allow targeting of prevention strategies to address high-risk activities and demographic groups.

Novel oxidatively activated agents modify DNA and are enhanced by ercc1 silencing.

Agents that chemically modify DNA form a backbone of many cancer treatments. A key problem for DNA-modifying agents is lack of specificity. To address this issue, we designed novel molecular scaffolds, termed An-Hq and An-Hq(2), which are activated by a hallmark of some cancers: elevated concentrations of reactive oxygen species. Elevated reactive oxygen species are linked to oncogenesis and are found to increase in several aggressive cancers. The agents are quinones that, upon oxidation, form highly electrophilic species. In vitro studies identified the mode of addition to DNA. The aniline portion of An-Hq serves to enhance nucleophilic addition to the ethyl phenyl ether instead of forming common Michael additions. Structural characterization showed that the agents add to 2'-deoxyguanosine at the N2,N3-positions. The product formed is a bulky hydroxy-N2,3-benzetheno-2'-deoxyguanosine adduct. In addition, the oxidatively activated agents added to 2'-deoxyadenosine and 2'-deoxycytidine but not thymidine or 2'-deoxyinosine. These findings are confirmed by primer extension analysis of a 392 base pair DNA. The full-length primer extension product was reduced by 69.0 ± 0.6% upon oxidative activation of An-Hq(2) as compared to controls. Little sequence dependence was observed with 76% of guanine, adenine, and cytosine residues showing an increase in extension stops between 2- and 4-fold above controls. Benzetheno-nucleobase addition to double-stranded DNA was confirmed by LC/MS of a self-complementary oligonucletide. Experiments were carried out to confirm in vivo DNA damage. Because of the lesion identified in vitro, we reasoned that nucleotide excision repair should be involved in reversing the effects of these oxidatively activated agents and enhance toxicity in Drosophila melanogaster. Using an RNAi-based approach, Ercc1 was silenced, and survival was monitored after injection of an agent. As expected, bulky cross-linking DNA-modifying agents, cisplatin and chlorambucil, showed statistically significant enhanced toxicity in Drosophila with silenced Ercc1. In addition, 5-fluorouracil, which does not produce bulky lesions, showed no selective toxicity. An-Hq and An-Hq(2) showed statistically significant toxicity in Drosophila with silenced Ercc1. Examination of cytotoxicity shows renal carcinoma cell lines as a target of these agents with a median IC(50) of 1.8 µM. Taken together, these data show that the designed oxidatively activated agents form distinct, bulky DNA modifications that prove difficult for cancer cells possessing an elevated reactive oxygen species phenotype to overcome. The modification produced is relatively unique among anticancer agents.

Domestic hen chicks' conditioned place preferences for sound.

Food and sounds (white noise, a food call and the sound of other chicks) were used in an attempt to establish conditioned place preferences with domestic hen chicks. Thirty-two chicks were randomly allocated to one of the 4 groups, and exposed to a 3-compartment apparatus to establish a baseline of their movements across 4 15-min sessions. They were then confined to one compartment and provided with free access to food or exposed to one sound for 15 min and then they were confined to the alternate compartment with no food or sound for 15 min. This process was repeated 3 times. Post-conditioning test sessions showed a conditioned place preference towards the area associated with food and away from the area associated with white noise. After conditioning, chicks showed no preference for spending time in the side associated with the food call or the sounds of other chicks; however, they entered a compartment first more often when it was associated with the food call and less often when it was associated with chick-sounds. Overall, these results showed that it was possible to use the conditioned place preference procedure to assess the effects of sounds and that the procedure has potential use for assessing other environmental stimuli.