185 research outputs found

    Helping Junior Lawyers Thrive

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    There has been increased discussion over the past few years about the mental health of lawyers. Most previous studies have researched the extent and causes of psychological distress in law students and lawyers. There has been less attention on also understanding what helps lawyers to thrive and become happy, healthy and ethical members of the legal profession. Our research project, the Transition to Professional Practice Project, has focused on this latter aspect, looking specifically at Australian lawyers in their first year of practice. This can be a difficult and exciting time, but is always a critical period of discovery and change. We were interested to see how newcomers make the transition from student to legal professional and how they develop their professional identity, in the sense of developing their beliefs and practices about what it means to be a lawyer. Lawyers-to-be are often not given opportunities to explore these issues in law school, sometimes resulting in a collision of expectations and reality when first exposed to legal practice

    Teaching professionalism in legal clinic – what new practitioners say is important

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    Anecdotal evidence suggests new lawyers may struggle as they begin legal practice. Little is known empirically about their actual experiences. This paper provides some insights into what occurs in this transition. It reports on a qualitative study currently underway tracking new lawyers through their first year of practice. Preliminary analysis of data from interviews and from workplace observations suggests clinical legal education can play a significant role in smoothing the transition and helping new lawyers develop their sense of professionalism. into their vocational training year. We track new lawyers in the context of their post-admission practice with a small cohort of recently admitted lawyers interviewed and observed in their day to day practice.We describe what these new lawyers say is important to an effective transition – developing autonomy, learning to deal with uncertainty and finding an accommodation between their developing professional values and those modelled by their firm and colleagues. Clinical programs offer opportunities for an early reflective exposure to these experiences

    Implementing a hybrid cognitive-behavioural therapy for pain-related insomnia in primary care : lessons learnt from a mixed-methods feasibility study

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    Objectives: To test the feasibility of implementing a brief but intensive hybrid cognitive behavioural therapy (Hybrid CBT) for pain-related insomnia. Design: Mixed-methods, with qualitative process evaluation on a two-arm randomised controlled feasibility trial. Setting: Primary care. Participants: Twenty-five adult patients with chronic pain and insomnia. Intervention: Hybrid CBT or self-help control intervention. Primary and secondary outcome measures: Primary outcomes measures were the Insomnia Severity Index and interference scale of the Brief Pain Inventory (BPI). Secondary outcomes measures were the present pain intensity rating from the BPI, Multidimensional Fatigue Inventory, Hospital Anxiety and Depression Scale and EQ-5D-5L. Results: Fourteen participants were randomised to receive Hybrid CBT, 11 to receive the self-help control treatment. Of the 14 in the Hybrid CBT group, 9 (64%) completed all four treatment sessions (4 discontinued due to poor health; 1 due to time constraints). Adherence to the self-help control treatment was not monitored. The total number of participants completing the 12-week and 24-week follow-ups were 12 (6 in each group; Hybrid CBT: 43%; self-help: 55%) and 10 (5 in each group; Hybrid CBT: 36%; self-help: 45%). Based on the data available, candidate outcome measures appeared to be sensitive to changes associated with interventions. Thematic analysis of pre-postintervention interview data revealed satisfaction with treatment content among those who completed the Hybrid CBT, whereas those in the self-help control treatment wanted more contact hours and therapist guidance. Other practical suggestions for improvement included shortening the duration of each treatment session, reducing the amount of assessment paperwork, and minimising the burden of sleep and pain monitoring. Conclusion: Important lessons were learnt with regard to the infrastructure required to achieve better patient adherence and retention. Based on the qualitative feedback provided by a subset of treatment completers, future trials should also consider lowering the intensity of treatment and streamlining the data collection procedure. Trial registration number: ISRCTN17294365

    Brassinin Promotes the Degradation of Tie2 and FGFR1 in Endothelial Cells and Inhibits Triple-Negative Breast Cancer Angiogenesis

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    Brassinin, a phytoalexin derived from cruciferous vegetables, has been reported to exhibit anti-cancer activity in multiple cancer types. However, its effects on triple-negative breast cancer (TNBC) development and the underlying mechanisms have not been elucidated so far. In this study, we demonstrated in vitro that brassinin preferentially reduces the viability of endothelial cells (ECs) when compared to other cell types of the tumor microenvironment, including TNBC cells, pericytes, and fibroblasts. Moreover, brassinin at non-cytotoxic doses significantly suppressed the proliferation, migration, tube formation, and spheroid sprouting of ECs. It also efficiently inhibited angiogenesis in an ex-vivo aortic ring assay and an in-vivo Matrigel plug assay. Daily intraperitoneal injection of brassinin significantly reduced tumor size, microvessel density, as well as the perfusion of tumor microvessels in a dorsal skinfold chamber model of TNBC. Mechanistic analyses showed that brassinin selectively stimulates the degradation of Tie2 and fibroblast growth factor receptor 1 in ECs, leading to the down-regulation of the AKT and extracellular signal-regulated kinase pathways. These findings demonstrate a preferential and potent anti-angiogenic activity of brassinin, which may be the main mechanism of its anti-tumor action. Accordingly, this phytochemical represents a promising candidate for the future anti-angiogenic treatment of TNBC

    Integrated GHz silicon photonic interconnect with micrometer-scale modulators and detectors

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    We report an optical link on silicon using micrometer-scale ring-resonator enhanced silicon modulators and waveguide-integrated germanium photodetectors. We show 3 Gbps operation of the link with 0.5 V modulator voltage swing and 1.0 V detector bias. The total energy consumption for such a link is estimated to be ~120 fJ/bit. Such compact and low power monolithic link is an essential step towards large-scale on-chip optical interconnects for future microprocessors

    Estrone sulfate transport and steroid sulfatase activity in colorectal cancer: implications for Hormone Replacement Therapy

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    Hormone replacement therapy (HRT) affects the incidence and potential progression of colorectal cancer (CRC). As HRT primarily consists of estrone sulfate (E(1)S), understanding whether this conjugated estrogen is transported and metabolized in CRC will define its potential effect in this malignancy. Here, we show that a panel of CRC cell lines (Colo205, Caco2, HCT116, HT-29) have steroid sulfatase (STS) activity, and thus can hydrolyze E(1)S. STS activity is significantly higher in CRC cell lysate, suggesting the importance of E(1)S transport in intracellular STS substrate availability. As E(1)S transport is regulated by the expression pattern of certain solute carrier organic anion transporter polypeptides, we show that in CRC OATP4A1 is the most abundantly expressed transporter. All four CRC cell lines rapidly transported E(1)S into cells, with this effect significantly inhibited by the competitive OATP inhibitor BSP. Transient knockdown of OATP4A1 significantly disrupted E(1)S uptake. Examination of estrogen receptor status showed ERα was present in Colo205 and Caco2 cells. None of the cells expressed ERβ. Intriguingly, HCT116 and HT29 cells strongly expressed the G protein coupled estrogen receptor (GPER), and that stimulation of this receptor with estradiol (E(2)) and G1, a GPER agonist, significantly (p < 0.01) increased STS activity. Furthermore, tamoxifen and fulvestrant, known GPER agonist, also increased CRC STS activity, with this effect inhibited by the GPER antagonist G15. These results suggest that CRC can take up and hydrolyze E(1)S, and that subsequent GPER stimulation increases STS activity in a potentially novel positive feedback loop. As elevated STS expression is associated with poor prognosis in CRC, these results suggest HRT, tamoxifen and fulvestrant may negatively impact CRC patient outcomes

    Multi-scale physical properties of NGC 6334 as revealed by local relative orientations between magnetic fields, density gradients, velocity gradients, and gravity

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    We present ALMA dust polarization and molecular line observations toward 4 clumps (I(N), I, IV, and V) in the massive star-forming region NGC 6334. In conjunction with large-scale dust polarization and molecular line data from JCMT, Planck, and NANTEN2, we make a synergistic analysis of relative orientations between magnetic fields (θB\theta_{\mathrm{B}}), column density gradients (θNG\theta_{\mathrm{NG}}), local gravity (θLG\theta_{\mathrm{LG}}), and velocity gradients (θVG\theta_{\mathrm{VG}}) to investigate the multi-scale (from \sim30 pc to 0.003 pc) physical properties in NGC 6334. We find that the relative orientation between θB\theta_{\mathrm{B}} and θNG\theta_{\mathrm{NG}} changes from statistically more perpendicular to parallel as column density (NH2N_{\mathrm{H_2}}) increases, which is a signature of trans-to-sub-Alfv\'{e}nic turbulence at complex/cloud scales as revealed by previous numerical studies. Because θNG\theta_{\mathrm{NG}} and θLG\theta_{\mathrm{LG}} are preferentially aligned within the NGC 6334 cloud, we suggest that the more parallel alignment between θB\theta_{\mathrm{B}} and θNG\theta_{\mathrm{NG}} at higher NH2N_{\mathrm{H_2}} is because the magnetic field line is dragged by gravity. At even higher NH2N_{\mathrm{H_2}}, the angle between θB\theta_{\mathrm{B}} and θNG\theta_{\mathrm{NG}} or θLG\theta_{\mathrm{LG}} transits back to having no preferred orientation or statistically slightly more perpendicular, suggesting that the magnetic field structure is impacted by star formation activities. A statistically more perpendicular alignment is found between θB\theta_{\mathrm{B}} and θVG\theta_{\mathrm{VG}} throughout our studied NH2N_{\mathrm{H_2}} range, which indicates a trans-to-sub-Alfv\'{e}nic state at small scales as well. The normalised mass-to-flux ratio derived from the polarization-intensity gradient (KTH) method increases with NH2N_{\mathrm{H_2}}.Comment: 35 pages, 18 figures. Accepted by Ap

    Temporal and external validation of the fullPIERS model for the prediction of adverse maternal outcomes in women with pre-eclampsia

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    The fullPIERS model is a risk prediction model developed to predict adverse maternal outcomes within 48 h for women admitted with pre-eclampsia. External validation of the model is required before implementation for clinical use. We assessed the temporal and external validity of the fullPIERS model in high income settings using five cohorts collected between 2003 and 2016, from tertiary hospitals in Canada, the United States of America, Finland and the United Kingdom. The cohorts were grouped into three datasets for assessing the primary external, and temporal validity, and broader transportability of the model. The predicted risks of developing an adverse maternal outcome were calculated using the model equation and model performance was evaluated based on discrimination, calibration, and stratification. Our study included a total of 2429 women, with an adverse maternal outcome rate of 6.7%, 6.6%, and 7.0% in the primary external, temporal, and combined (broader) validation cohorts, respectively. The model had good discrimination in all datasets: 0.81 (95%CI 0.75-0.86), 0.82 (95%CI 0.76-0.87), and 0.75 (95%CI 0.71-0.80) for the primary external, temporal, and broader validation datasets, respectively. Calibration was best for the temporal cohort but poor in the broader validation dataset The likelihood ratios estimated to rule in adverse maternal outcomes were high at a cut-off of >= 30% in all datasets. The fullPIERS model is temporally and externally valid and will be useful in the management of women with pre-eclampsia in high income settings although model recalibration is required to improve performance, specifically in the broader healthcare settings.Peer reviewe
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