Successful treatment of jellyfish sting-induced severe digital ischemia with intravenous iloprost infusion

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Developing Taiwan Studies Teaching Programme in Europe and the United States: the experience of SOAS University of London and University of Texas at Austin

Over the last two decades, there has been a rapid expansion in the number of Taiwan programmes at universities in America and Europe; however, few of these Taiwan programmes have attempted to develop teaching courses. Where Taiwan courses have been introduced, they have tended to be in isolation and not well integrated into existing academic programmes. Among the universities with Taiwan programmes, only two have attempted to create comprehensive teaching programmes through which students can graduate with a degree in Taiwan studies: SOAS University of London and the University of Texas at Austin. The purpose of this paper is to compare the experiences of these two institutions in developing such niche teaching programmes. It begins with a discussion of how these two programmes first emerged and then goes on to review their distinct development trajectories and key features. The paper offers an analysis of how these two programmes were able not only to survive but also to expand their offerings and thrive in an academic environment that should be hostile to such niche programmes. It concludes with a review of the remaining challenges facing these teaching programmes

Study of measured pulsar masses and their possible conclusions

We study the statistics of 61 measured masses of neutron stars (NSs) in binary pulsar systems, including 18 double NS (DNS) systems, 26 radio pulsars (10 in our Galaxy) with white dwarf (WD) companions, 3 NSs with main-sequence companions, 13 NSs in X-ray binaries, and one undetermined system. We derive a mean value of M = 1.46 +/- 0.30 solar masses. When the 46 NSs with measured spin periods are divided into two groups at 20 milliseconds, i.e., the millisecond pulsar (MSP) group and others, we find that their mass averages are, respectively, M=1.57 +/- 0.35 solar masses and M=1.37+/- 0.23 solar masses. In the framework of the pulsar recycling hypothesis, this suggests that an accretion of approximately 0.2 solar mass is sufficient to spin up a neutron star and place it in the millisecond pulsar group. An empirical relation between the accreting mass and MSP spin period is \Delta M=0.43 (solar mass)(P/1 ms)^{-2/3}. UNlike the standard recycling process, if a MSP is formed by the accretion induced collapse (AIC) of a white dwarf with a mass less than Chandrasekha limit, e.g. 1.35 solar mass, then the binary MSPs involved in AICs is not be higher than 20%, which imposes a constraint on the AIC origin of MSPs.Comment: 6 pages, 5 figures, in press, Astronomy and Astrophysics 2011, 527, 8

CRISPR-Cas9 screens in human cells and primary neurons identify modifiers of C9ORF72 dipeptide-repeat-protein toxicity.

Hexanucleotide-repeat expansions in the C9ORF72 gene are the most common cause of amyotrophic lateral sclerosis and frontotemporal dementia (c9ALS/FTD). The nucleotide-repeat expansions are translated into dipeptide-repeat (DPR) proteins, which are aggregation prone and may contribute to neurodegeneration. We used the CRISPR-Cas9 system to perform genome-wide gene-knockout screens for suppressors and enhancers of C9ORF72 DPR toxicity in human cells. We validated hits by performing secondary CRISPR-Cas9 screens in primary mouse neurons. We uncovered potent modifiers of DPR toxicity whose gene products function in nucleocytoplasmic transport, the endoplasmic reticulum (ER), proteasome, RNA-processing pathways, and chromatin modification. One modifier, TMX2, modulated the ER-stress signature elicited by C9ORF72 DPRs in neurons and improved survival of human induced motor neurons from patients with C9ORF72 ALS. Together, our results demonstrate the promise of CRISPR-Cas9 screens in defining mechanisms of neurodegenerative diseases

Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen

The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca's large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells

Outcomes of a radiation sparing approach in medulloblastoma by subgroup in young children: an institutional review.

OBJECTIVE To describe disease outcomes including overall survival and relapse patterns by subgroup in young pediatric patients treated for medulloblastoma with a radiation-sparing approach. METHODS Retrospective analysis of clinical outcomes includes treatment, relapse, and salvage therapy and late effects in children treated for medulloblastoma with a radiation-sparing approach at British Columbia Children's Hospital (BCCH) between 2000 and 2020. RESULTS There were 30 patients (median age 2.8 years, 60% male) treated for medulloblastoma with a radiation-sparing approach at BCCH. Subgroups included Sonic Hedgehog (SHH) (n = 14), group 3 (n = 7), group 4 (n = 6), and indeterminate status (n = 3). Three- and 5-year event-free survival (EFS) were 49.0% (30.2-65.4%) and 42.0% (24.2-58.9%) and overall survival (OS) 66.0% (95% CI 46.0-80.1%) and 62.5% (95% CI 42.5 and 77.2%), respectively, with a median follow-up of 9.5 years. Relapse occurred in 12/25 patients following a complete response, of whom six (group 4: n = 4; group 3: n = 1; unknown: n = 1) were successfully salvaged with craniospinal axis (CSA) RT and remain alive at a median follow-up of 7 years. Disease/treatment-related morbidity included endocrinopathies (n = 8), hearing loss n = 16), and neurocognitive abnormalities (n = 9). CONCLUSIONS This radiation sparing treatment approach for young patients with medulloblastoma resulted in a durable cure in most patients with SHH subgroup medulloblastoma. In those patients with groups 3 and 4 medulloblastoma, relapse rates were high; however, most group 4 patients were salvaged with RT

Validation of the CRAVE-C scale in Chinese adults: a four-study examination of competing motivations for physical activity versus rest

BackgroundThe study aimed to validate the Cravings for Rest and Volitional Energy Expenditure (CRAVE) scale among Chinese adults with different health conditions (healthy control, chronic illnesses, and psychiatric disorders) and skill levels (athletes vs. non-athletes).MethodsIn Study 1, a confirmatory factor analysis (CFA) using the Maximum Likelihood Method (MLM) was performed on a Chinese sample of emerging adults (N = 481) to evaluate the structural validity of the Cravings for Rest and Volitional Energy Expenditure-Chinese version (CRAVE-C). In Study 2, differences in “Move” and “Rest” desires were examined among patients with psychiatric disorders, patients with chronic illnesses, and healthy controls. In study 3, investigated the relationship between cardiorespiratory fitness and exercise motivation using the CRAVE-C (N = 83). In Study 4, the changes in “Move” desire from baseline to post-training were compared between athletes and non-athletes.ResultsResults from Study 1 indicated that the 10-item CRAVE-C showed good fit indices (Chi2 (34) = 118.769, CFI = 0.95, TLI = 0.934, SRMR = 0.053, RMSEA = 0.072). “Move” positively correlated with various factors of the Affective Exercise Experiences Questionnaire-Chinese and the Physical Effort Scale-Chinese, while “Rest” correlated negatively. In Study 2, Patients with psychiatric disorders had a significantly higher “Move” desire than healthy controls. Patients with chronic illnesses had a significantly higher “Rest” desire than healthy controls. In Study 3, higher cardiorespiratory fitness was associated with a slight increase in “Move” desire (3.26% ± 37.35%) and a decrease in “Rest” desire (18.94% ± 66.99%). Lower fitness was linked to a significant decline in “Move” desire (−54.61% ± 111.33%) and an increase in “Rest” desire (43.62% ± 63.64%). In Study 4, the athlete group demonstrated a significant increase in “Move” desire from baseline to post-training, whereas the non-athlete group reported a significant decrease in “Move” desire from baseline to post-training.ConclusionThe 10-item CRAVE-C has good reliability and validity in the Chinese cultural context and can be used among Chinese adults with different health conditions and skill levels

Usability evaluation of a clinical decision support tool for osteoporosis disease management

<p>Abstract</p> <p>Background</p> <p>Osteoporosis affects over 200 million people worldwide at a high cost to healthcare systems. Although guidelines are available, patients are not receiving appropriate diagnostic testing or treatment. Findings from a systematic review of osteoporosis interventions and a series of focus groups were used to develop a functional multifaceted tool that can support clinical decision-making in osteoporosis disease management at the point of care. The objective of our study was to assess how well the prototype met functional goals and usability needs.</p> <p>Methods</p> <p>We conducted a usability study for each component of the tool--the Best Practice Recommendation Prompt (BestPROMPT), the Risk Assessment Questionnaire (RAQ), and the Customised Osteoporosis Education (COPE) sheet--using the framework described by Kushniruk and Patel. All studies consisted of one-on-one sessions with a moderator using a standardised worksheet. Sessions were audio- and video-taped and transcribed verbatim. Data analysis consisted of a combination of qualitative and quantitative analyses.</p> <p>Results</p> <p>In study 1, physicians liked that the BestPROMPT can provide customised recommendations based on risk factors identified from the RAQ. Barriers included lack of time to use the tool, the need to alter clinic workflow to enable point-of-care use, and that the tool may disrupt the real reason for the visit. In study 2, patients completed the RAQ in a mean of 6 minutes, 35 seconds. Of the 42 critical incidents, 60% were navigational and most occurred when the first nine participants were using the stylus pen; no critical incidents were observed with the last six participants that used the touch screen. Patients thought that the RAQ questions were easy to read and understand, but they found it difficult to initiate the questionnaire. Suggestions for improvement included improving aspects of the interface and navigation. The results of study 3 showed that most patients were able to understand and describe sections of the COPE sheet, and all considered discussing the information with their physicians. Suggestions for improvement included simplifying the language and improving the layout.</p> <p>Conclusions</p> <p>Findings from the three studies informed changes to the tool and confirmed the importance of usability testing on all end users to reduce errors, and as an important step in the development process of knowledge translation interventions.</p

Evaluation of a clinical decision support tool for osteoporosis disease management: protocol for an interrupted time series design

<p>Abstract</p> <p>Background</p> <p>Osteoporosis affects over 200 million people worldwide at a high cost to healthcare systems. Although guidelines on assessing and managing osteoporosis are available, many patients are not receiving appropriate diagnostic testing or treatment. Findings from a systematic review of osteoporosis interventions, a series of mixed-methods studies, and advice from experts in osteoporosis and human-factors engineering were used collectively to develop a multicomponent tool (targeted to family physicians and patients at risk for osteoporosis) that may support clinical decision making in osteoporosis disease management at the point of care.</p> <p>Methods</p> <p>A three-phased approach will be used to evaluate the osteoporosis tool. In phase 1, the tool will be implemented in three family practices. It will involve ensuring optimal functioning of the tool while minimizing disruption to usual practice. In phase 2, the tool will be pilot tested in a quasi-experimental interrupted time series (ITS) design to determine if it can improve osteoporosis disease management at the point of care. Phase 3 will involve conducting a qualitative postintervention follow-up study to better understand participants' experiences and perceived utility of the tool and readiness to adopt the tool at the point of care.</p> <p>Discussion</p> <p>The osteoporosis tool has the potential to make several contributions to the development and evaluation of complex, chronic disease interventions, such as the inclusion of an implementation strategy prior to conducting an evaluation study. Anticipated benefits of the tool may be to increase awareness for patients about osteoporosis and its associated risks and provide an opportunity to discuss a management plan with their physician, which may all facilitate patient self-management.</p