Influenza Excess Mortality from 1950–2000 in Tropical Singapore

10.1371/journal.pone.0008096PLoS ONE412

Clinical features and mutational analysis of X-linked agammaglobulinemia patients in Malaysia

BackgroundBruton’s tyrosine kinase (BTK) is a cytoplasmic protein involved in the B cell development. X-linked agammaglobulinemia (XLA) is caused by mutation in the BTK gene, which results in very low or absent B cells. Affected males have markedly reduced immunoglobulin levels, which render them susceptible to recurrent and severe bacterial infections. Methods: Patients suspected with X-linked agammaglobulinemia were enrolled during the period of 2010-2018. Clinical summary, and immunological profiles of these patients were recorded. Peripheral blood samples were collected for monocyte BTK protein expression detection and BTK genetic analysis. The medical records between January 2020 and June 2023 were reviewed to investigate COVID-19 in XLA.ResultsTwenty-two patients (from 16 unrelated families) were molecularly diagnosed as XLA. Genetic testing revealed fifteen distinct mutations, including four splicing mutations, four missense mutations, three nonsense mutations, three short deletions, and one large indel mutation. These mutations scattered throughout the BTK gene and mostly affected the kinase domain. All mutations including five novel mutations were predicted to be pathogenic or deleterious by in silico prediction tools. Genetic testing confirmed that eleven mothers and seven sisters were carriers for the disease, while three mutations were de novo. Flow cytometric analysis showed that thirteen patients had minimal BTK expression (0-15%) while eight patients had reduced BTK expression (16-64%). One patient was not tested for monocyte BTK expression due to insufficient sample. Pneumonia (n=13) was the most common manifestation, while Pseudomonas aeruginosa was the most frequently isolated pathogen from the patients (n=4). Mild or asymptomatic COVID-19 was reported in four patients.ConclusionThis report provides the first overview of demographic, clinical, immunological and genetic data of XLA in Malaysia. The combination of flow cytometric assessment and BTK genetic analysis provides a definitive diagnosis for XLA patients, especially with atypical clinical presentation. In addition, it may also allow carrier detection and assist in genetic counselling and prenatal diagnosis

Engineering Outreach: A Successful Initiative With Gifted Students in Science and Technology in Hong Kong

The primary goal of engineering outreach is to attract prospective students to engineering education and the engineering profession. Gifted students, especially those identified as possessing unusually high abilities in science and technology, are especially promising students to attract to careers in engineering. It is critical to cultivate these students' interests and develop their potential for engineering while encouraging them to pursue engineering studies beyond K-12 education. This article presents examples of the successful learning outcomes of an ongoing University-based Electronics Technology Project Study (UETPS) program, a joint endeavor between the IEEE Hong Kong Section, the Education Bureau of the Hong Kong SAR Government, and the Hong Kong Academy of Gifted Education (HKAGE). The UETPS program promotes electrical, electronic, and computer engineering education in Hong Kong and is aimed particularly at gifted students as well as their parents, teachers, and schools. Project applicants underwent formal identification procedures by the Gifted Education Section of the HKSAR Education Bureau and were identified as being gifted in the area of science and technology. Selected participants then participated in one-year research projects in electronics and computer engineering under the guidance of university professors in their respective engineering departments. This program addresses an urgent need of the engineering education sector by reaching out to highly talented K-12 students and their surrounding communities. According to the evaluation results, the UETPS program has significantly enhanced the participating students' interest in engineering as a career choice and encouraged them to pursue undergraduate studies in engineering. This article also discusses lessons learned and proposes strategies for future potential implementers

Psychometric testing of the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) subscale in a longitudinal study of cancer patients treated with chemotherapy.

BackgroundThe aim of this study was to evaluate the psychometric properties of the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) subscale in a longitudinal study of cancer patients treated with chemotherapy.MethodsPatients were assessed with the FACT/GOG-Ntx subscale, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Chemotherapy-Induced Peripheral Neuropathy Scale 20 (EORTC QLQ-CIPN20), National Cancer Institute -Common Terminology Criteria for Adverse Events (NCI-CTCAE), and light touch test using 10 g monofilament for up to ten assessment points from baseline (prior to initiation of first chemotherapy), after the end of each cycle (up to 6 cycles, 3 weeks per cycle), and at 6, 9, and 12 months after starting chemotherapy. Psychometric analyses included internal consistency reliability, convergent validity, factorial validity, sensitivity to change and responsiveness (minimal clinically important difference, MCID).ResultsCronbach's alpha coefficients of the FACT/GOG-Ntx subscale were 0.82-0.89 across assessment points. The subscale strongly correlated with the EORTC QLQ-CIPN20 (r = 0.79-0.93) but low-to-moderately correlated with the NCI-CTCAE sensory (rs = 0.23-0.45) and motor items (rs = 0.15-0.50) as well as the monofilament test (rs = 0.23-0.47). The hypothesized 4-factor structure of the FACT/GOG-Ntx subscale was not confirmed at assessment points (χ2/df = 2.26-8.50; all P < 0.001). The subscale exhibited small-to-moderate sensitivity to change (r = 0.17-0.37). The MCIDs were between 1.38 and 3.68.ConclusionThe FACT/GOG-Ntx subscale has satisfactory reliability, validity, sensitivity to change and responsiveness to evaluate CIPN in cancer patients. Future research is needed to explore the factorial structure of the FACT/GOG-Ntx subscale as the published four-factor structure was not supported in this study

Additional epidemic periods in Singapore, with corresponding excess deaths and positive influenza isolates, 1972 to 2000*.

<p>*Areas shaded in grey correspond to official reports of influenza epidemics during the time period.</p

Periods with significant excess deaths in Singapore and positive influenza isolates, 1972 to 2000*.

<p>*Areas shaded in grey correspond to official reports of influenza epidemics during the time period.</p

Periods of significant excess deaths in tropical Singapore*.

<p>Panel A–Excess deaths compared to overall deaths, 1950 to 2000. Panel B–Excess deaths compared to positive influenza positive, 1972 to 2000. *Significant excess mortality which occurred over 2 contiguous months (August to September 1951, June to July 1989, and December 1992 to January 1993) was summed to allow for comparisons of overall epidemic magnitude.</p