Urban planning in Banda Aceh: supporting local actors after the Tsunami

"There is increasing awareness of the importance of humanitarian agencies supporting and collaborating with local actors in order to restore city functions following humanitarian crises. This research aimed to document learning from UN-Habitat’s experiences of supporting communities and local government to undertake urban planning after the Indian Ocean earthquake and tsunami in Banda Aceh, Indonesia, in 2004. Despite the challenges of urban planning after a complex crisis, in areas devastated by the tsunami, UN-Habitat successfully supported communities and local government to develop village plans, a spatial plan for Meuraxa sub-district, and update the wider spatial plan for Banda Aceh City.

Urban planning in Banda Aceh: supporting local actors after the Tsunami

"There is increasing awareness of the importance of humanitarian agencies supporting and collaborating with local actors in order to restore city functions following humanitarian crises. This research aimed to document learning from UN-Habitat’s experiences of supporting communities and local government to undertake urban planning after the Indian Ocean earthquake and tsunami in Banda Aceh, Indonesia, in 2004. Despite the challenges of urban planning after a complex crisis, in areas devastated by the tsunami, UN-Habitat successfully supported communities and local government to develop village plans, a spatial plan for Meuraxa sub-district, and update the wider spatial plan for Banda Aceh City.

The role and response of primary healthcare services in the delivery of palliative care in epidemics and pandemics : a rapid review to inform practice and service delivery during the COVID-19 pandemic

Background: The increased number of deaths in the community happening as a result of COVID-19 has caused primary healthcare services to change their traditional service delivery in a short timeframe. Services are quickly adapting to new challenges in the practical delivery of end-of-life care to patients in the community including through virtual consultations and in the provision of timely symptom control. Aim: To synthesise existing evidence related to the delivery of palliative and end-of-life care by primary healthcare professionals in epidemics and pandemics. Design: Rapid systematic review using modified systematic review methods, with narrative synthesis of the evidence. Data sources: Searches were carried out in Medline, Embase, PsychINFO, CINAHL and Web of Science on 7th March 2020. Results: Only five studies met the inclusion criteria, highlighting a striking lack of evidence base for the response of primary healthcare services in palliative care during epidemics and pandemics. All were observational studies. Findings were synthesised using a pandemic response framework according to ‘systems’ (community providers feeling disadvantaged in terms of receiving timely information and protocols), ‘space’ (recognised need for more care in the community), ‘staff’ (training needs and resilience) and ‘stuff’ (other aspects of managing care in pandemics including personal protective equipment, cleaning care settings and access to investigations). Conclusions: As the COVID-19 pandemic progresses, there is an urgent need for research to provide increased understanding of the role of primary care and community nursing services in palliative care, alongside hospices and community specialist palliative care providers

Aurora kinase A drives the evolution of resistance to third-generation EGFR inhibitors in lung cancer.

Although targeted therapies often elicit profound initial patient responses, these effects are transient due to residual disease leading to acquired resistance. How tumors transition between drug responsiveness, tolerance and resistance, especially in the absence of preexisting subclones, remains unclear. In epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma cells, we demonstrate that residual disease and acquired resistance in response to EGFR inhibitors requires Aurora kinase A (AURKA) activity. Nongenetic resistance through the activation of AURKA by its coactivator TPX2 emerges in response to chronic EGFR inhibition where it mitigates drug-induced apoptosis. Aurora kinase inhibitors suppress this adaptive survival program, increasing the magnitude and duration of EGFR inhibitor response in preclinical models. Treatment-induced activation of AURKA is associated with resistance to EGFR inhibitors in vitro, in vivo and in most individuals with EGFR-mutant lung adenocarcinoma. These findings delineate a molecular path whereby drug resistance emerges from drug-tolerant cells and unveils a synthetic lethal strategy for enhancing responses to EGFR inhibitors by suppressing AURKA-driven residual disease and acquired resistance

Engaging terminally ill patients in end of life talk: How experienced palliative medicine doctors navigate the dilemma of promoting discussions about dying

Objective: To examine how palliative medicine doctors engage patients in end-of-life (hereon, EoL) talk. To examine whether the practice of “eliciting and responding to cues”, which has been widely advocated in the EoL care literature, promotes EoL talk. Design: Conversation analysis of video- and audio-recorded consultations. Participants: Unselected terminally ill patients and their companions in consultation with experienced palliative medicine doctors. Setting: Outpatient clinic, day therapy clinic, and inpatient unit of a single English hospice. Results: Doctors most commonly promoted EoL talk through open elaboration solicitations; these created opportunities for patients to introduce Ð then later further articulate Ð EoL considerations in such a way that doctors did not overtly ask about EoL matters. Importantly, the wording of elaboration solicitations avoided assuming that patients had EoL concerns. If a patient responded to open elaboration solicitations without introducing EoL considerations, doctors sometimes pursued EoL talk by switching to a less participatory and more presumptive type of solicitation, which suggested the patient might have EoL concerns. These more overt solicitations were used only later in consultations, which indicates that doctors give precedence to patients volunteering EoL considerations, and offer them opportunities to take the lead in initiating EoL talk. There is evidence that doctors treat elaboration of patients’ talk as a resource for engaging them in EoL conversations. However, there are limitations associated with labelling that talk as “cues” as is common in EoL communication contexts. We examine these limitations and propose “possible EoL considerations” as a descriptively more accurate term. Conclusions: Through communicating Ð via open elaboration solicitations Ð in ways that create opportunities for patients to volunteer EoL considerations, doctors navigate a core dilemma in promoting EoL talk: giving patients opportunities to choose whether to engage in conversations about EoL whilst being sensitive to their communication needs, preferences and state of readiness for such dialogue

Breakpoint Associated with a novel 2.3 Mb deletion in the VCFS region of 22q11 and the role of Alu (SINE) in recurring microdeletions

BACKGROUND: Chromosome 22q11.2 region is highly susceptible to rearrangement, specifically deletions that give rise to a variety of genomic disorders including velocardiofacial or DiGeorge syndrome. Individuals with this 22q11 microdeletion syndrome are at a greatly increased risk to develop schizophrenia. METHODS: Genotype analysis was carried out on the DNA from a patient with the 22q11 microdeletion using genetic markers and custom primer sets to define the deletion. Bioinformatic analysis was performed for molecular characterization of the deletion breakpoint sequences in this patient. RESULTS: This 22q11 deletion patient was established to have a novel 2.3 Mb deletion with a proximal breakpoint located between genetic markers RH48663 and RH48348 and a distal breakpoint between markers D22S1138 and SHGC-145314. Molecular characterization of the sequences at the breakpoints revealed a 270 bp shared sequence of the breakpoint regions (SSBR) common to both ends that share >90% sequence similarity to each other and also to short interspersed nuclear elements/Alu elements. CONCLUSION: This Alu sequence like SSBR is commonly in the proximity of all known deletion breakpoints of 22q11 region and also in the low copy repeat regions (LCRs). This sequence may represent a preferred sequence in the breakpoint regions or LCRs for intra-chromosomal homologous recombination mechanisms resulting in common 22q11 deletion

BAMBI Regulates Angiogenesis and Endothelial Homeostasis through Modulation of Alternative TGFβ Signaling

BACKGROUND: BAMBI is a type I TGFβ receptor antagonist, whose in vivo function remains unclear, as BAMBI(-/-) mice lack an obvious phenotype. METHODOLOGY/PRINCIPAL FINDINGS: Identifying BAMBI's functions requires identification of cell-specific expression of BAMBI. By immunohistology we found BAMBI expression restricted to endothelial cells and by electron microscopy BAMBI(-/-) mice showed prominent and swollen endothelial cells in myocardial and glomerular capillaries. In endothelial cells over-expression of BAMBI reduced, whereas knock-down enhanced capillary growth and migration in response to TGFβ. In vivo angiogenesis was enhanced in matrigel implants and in glomerular hypertrophy after unilateral nephrectomy in BAMBI(-/-) compared to BAMBI(+/+) mice consistent with an endothelial phenotype for BAMBI(-/-) mice. BAMBI's mechanism of action in endothelial cells was examined by canonical and alternative TGFβ signaling in HUVEC with over-expression or knock-down of BAMBI. BAMBI knockdown enhanced basal and TGFβ stimulated SMAD1/5 and ERK1/2 phosphorylation, while over-expression prevented both. CONCLUSIONS/SIGNIFICANCE: Thus we provide a first description of a vascular phenotype for BAMBI(-/-) mice, and provide in vitro and in vivo evidence that BAMBI contributes to endothelial and vascular homeostasis. Further, we demonstrate that in endothelial cells BAMBI interferes with alternative TGFβ signaling, most likely through the ALK 1 receptor, which may explain the phenotype observed in BAMBI(-/-) mice. This newly described role for BAMBI in regulating endothelial function has potential implications for understanding and treating vascular disease and tumor neo-angiogenesis

Systematically reviewing and synthesizing evidence from conversation analytic and related discursive research to inform healthcare communication practice and policy: an illustrated guide

Background Healthcare delivery is largely accomplished in and through conversations between people, and healthcare quality and effectiveness depend enormously upon the communication practices employed within these conversations. An important body of evidence about these practices has been generated by conversation analysis and related discourse analytic approaches, but there has been very little systematic reviewing of this evidence. Methods We developed an approach to reviewing evidence from conversation analytic and related discursive research through the following procedures: • reviewing existing systematic review methods and our own prior experience of applying these • clarifying distinctive features of conversation analytic and related discursive work which must be taken into account when reviewing • holding discussions within a review advisory team that included members with expertise in healthcare research, conversation analytic research, and systematic reviewing • attempting and then refining procedures through conducting an actual review which examined evidence about how people talk about difficult future issues including illness progression and dying Results We produced a step-by-step guide which we describe here in terms of eight stages, and which we illustrate from our ‘Review of Future Talk’. The guide incorporates both established procedures for systematic reviewing, and new techniques designed for working with conversation analytic evidence. Conclusions The guide is designed to inform systematic reviews of conversation analytic and related discursive evidence on specific domains and topics. Whilst we designed it for reviews that aim at informing healthcare practice and policy, it is flexible and could be used for reviews with other aims, for instance those aiming to underpin research programmes and projects. We advocate systematically reviewing conversation analytic and related discursive findings using this approach in order to translate them into a form that is credible and useful to healthcare practitioners, educators and policy-makers