Fine Mapping of the NRG1 Hirschsprung's Disease Locus

The primary pathology of Hirschsprung's disease (HSCR, colon aganglionosis) is the absence of ganglia in variable lengths of the hindgut, resulting in functional obstruction. HSCR is attributed to a failure of migration of the enteric ganglion precursors along the developing gut. RET is a key regulator of the development of the enteric nervous system (ENS) and the major HSCR-causing gene. Yet the reduced penetrance of RET DNA HSCR-associated variants together with the phenotypic variability suggest the involvement of additional genes in the disease. Through a genome-wide association study, we uncovered a ∼350 kb HSCR-associated region encompassing part of the neuregulin-1 gene (NRG1). To identify the causal NRG1 variants contributing to HSCR, we genotyped 243 SNPs variants on 343 ethnic Chinese HSCR patients and 359 controls. Genotype analysis coupled with imputation narrowed down the HSCR-associated region to 21 kb, with four of the most associated SNPs (rs10088313, rs10094655, rs4624987, and rs3884552) mapping to the NRG1 promoter. We investigated whether there was correlation between the genotype at the rs10088313 locus and the amount of NRG1 expressed in human gut tissues (40 patients and 21 controls) and found differences in expression as a function of genotype. We also found significant differences in NRG1 expression levels between diseased and control individuals bearing the same rs10088313 risk genotype. This indicates that the effects of NRG1 common variants are likely to depend on other alleles or epigenetic factors present in the patients and would account for the variability in the genetic predisposition to HSCR

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Evaluation in community development projects in Hong Kong

published_or_final_versionSocial WorkMasterMaster of Social Wor

Social sustainability in urban renewal: an assessment of community aspirations

The lack of a proper building care culture has led to serious problems of urban decay in most developed cities, threatening community health and safety. To arrest urban decay, redevelopment is a commonly adopted approach for regenerating rundown areas. Redevelopment often results in negative outcomes such as disturbances to existing social networks and burgeoning construction and demolition waste. On the other hand, building rehabilitation is a more socially and environmentally friendly alternative to redevelopment, but its success depends much on residents’ active participation. With a view towards a sustainable strategy for urban renewal, it is necessary to balance the interests of different stakeholders regarding the choice between these two mainstream approaches to renewal. Although economic and physical issues are important decision making considerations, this study explores the aspirations and preferences of local residents in relation to the two options through a structured survey. The findings are conducive to the development of a balanced and socially sustainable strategy of urban renewal

Socialna zdržnost pri urbani prenovi: ocena želja skupnosti

Pomanjkanje prave kulture skrbi za stavbe je v večini razvitih mest pripeljalo do resnih težav zaradi propadanja mestnih predelov, in to ogroža zdravje in varnost mestnih skupnosti. Sanacija je pristop, s katerim navadno ustavimo propadanje in obnovimo propadajoča območja. Pogosto pa ima tudi negativne posledice; zmoti lahko delovanje obstoječih socialnih mrež in pretirano poveča količino odpadkov, ki nastanejo pri gradnji in rušenju zgradb. Po drugi strani je obnova stavb socialno in okolju prijaznejša izbira v primerjavi s prenovo, vendar je njen uspeh kar najbolj odvisen od sodelovanja stanovalcev. Če želimo doseči trajnostno strategijo urbane prenove, moramo najti ravnotežje med interesi različnih déležnikov za enega od obeh glavnih pristopov k prenovi. Čeprav je pomembno, da pri sprejemanju odločitev upoštevamo ekonomska in fizična vprašanja, se v tej raziskavi s strukturirano anketo preučujejo želje in preference lokalnih prebivalcev glede teh dveh možnosti. Ugotovitve prispevajo k razvoju uravnotežene in socialno trajnostne strategije urbane prenove

Urban renewal in Hong Kong: a community aspiration study

Coupled with the growing number of aged private residential buildings, the lack of proper building care culture has led to serious problems of building dilapidation and urban decay in Hong Kong, particularly in the old urban areas. Not only is the cityscape ruined, but also the health and safety of the residents and general public as a whole are jeopardized. To arrest urban decay, redevelopment has long been adopted to renew rundown areas. However, the approach usually has a negative impact on the existing social fabric and causes a reduction in social capital. Given that older buildings usually have a larger proportion of older residents, and that the elderly population tends to be financially less well-off, this group of residents is more adversely affected by the negative impact of social destruction due to redevelopment. Recently, building rehabilitation has been gaining popularity. Yet, with a view to a sustainable strategy for urban renewal, it is necessary to balance the interests of different stakeholders. The alternative ways the community perceives different approaches to urban renewal in Hong Kong is a worthwhile topic to study. In this paper, the community\u27s attitudes towards redevelopment and rehabilitation as urban renewal options are examined through a structured questionnaire survey. The survey findings are discussed with emphases on their policy implications. Recommendations will be drawn with respect to the community engagement process that enhances the likelihood of arriving at a more balanced urban renewal strategy

Emphysematous pyelonephritis: An 8-year retrospective review across four acute hospitals

To retrospectively review our experience of managing patients with emphysematous pyelonephritis (EPN). Case notes of patients with EPN were reviewed. The patients' demographic data, clinical presentation, investigation findings, treatment, and outcome were studied. Twelve patients were diagnosed with EPN. Majority (66.7%) of them had diabetes mellitus. All patients had been evaluated by computed tomography (CT). Using the classification proposed by Wan et al, five patients had type 1 EPN, whereas six, two, and four patients had Huang and Tseng CT class 2, 3a, and 3b EPN, respectively. Immediate nephrectomy was performed in six patients, whereas conservative treatment was adopted in the other six. In the nephrectomy group, one patient died of disseminated sepsis after a protracted course. Conservative treatment failed in three patients, who succumbed despite salvage nephrectomy in two of them. Analysis revealed that severe hyperglycemia and radiological CT class (both Wan and Huang systems) were significant predictors of mortality from EPN. Severe hyperglycemia and CT class of EPN are significant risk factors for death. CT is the investigation of choice for correct diagnosis of EPN. Additional intervention should be offered to EPN patients with Wan type 1 and Huang and Tseng class 3 CT features

Emphysematous pyelonephritis: An 8-year retrospective review across four acute hospitals

Objective: To retrospectively review our experience of managing patients with emphysematous pyelonephritis (EPN). Methods: Case notes of patients with EPN were reviewed. The patients' demographic data, clinical presentation, investigation findings, treatment, and outcome were studied. Results: Twelve patients were diagnosed with EPN. Majority (66.7%) of them had diabetes mellitus. All patients had been evaluated by computed tomography (CT). Using the classification proposed by Wan et al, five patients had type 1 EPN, whereas six, two, and four patients had Huang and Tseng CT class 2, 3a, and 3b EPN, respectively. Immediate nephrectomy was performed in six patients, whereas conservative treatment was adopted in the other six. In the nephrectomy group, one patient died of disseminated sepsis after a protracted course. Conservative treatment failed in three patients, who succumbed despite salvage nephrectomy in two of them. Analysis revealed that severe hyperglycemia and radiological CT class (both Wan and Huang systems) were significant predictors of mortality from EPN. Conclusion: Severe hyperglycemia and CT class of EPN are significant risk factors for death. CT is the investigation of choice for correct diagnosis of EPN. Additional intervention should be offered to EPN patients with Wan type 1 and Huang and Tseng class 3 CT features

Overcoming Abdominal and Pelvic Cavity Workspace Constraints in Robotic-Assisted NOTES

Despite early enthusiasm in robotic-assisted NOTES, several technical challenges exist. Various spinopelvic anatomical constraints can significantly act as obstacles and affect entry and space availability for the deployment of straight and rigid transvaginal/transanal NOTES instruments. Anatomical constraints such as the sacral slope, position, and distance to the target organs are defined. Transvaginal access to the surgical site required a high insertion angle between 20° and 30° to overcome the pronounced sacral slope resulting in dexterity and reachability limitations. A new set of robotic parameters was generated to introduce a 7 degrees of freedom robotic arm. Workspace simulation and phantom precision measurements have shown a significant improvement in the reachability and maneuverability of the robotic platform. While the robotic arms provided stable dexterity, it is constrained when reaching target sites in larger patients. This study has provided an insight and a solution in rigid instrument design, paving a safe route for transvaginal/transanal access for abdominal surgeries towards robotic-assisted NOTES