Asthmatic versus healthy child classification based on cough and vocalised /ɑ:/ sounds.

Cough is a common symptom presenting in asthmatic children. In this investigation, an audio-based classification model is presented that can differentiate between healthy and asthmatic children, based on the combination of cough and vocalised /ɑ:/ sounds. A Gaussian mixture model using mel-frequency cepstral coefficients and constant-Q cepstral coefficients was trained. When comparing the predicted labels with the clinician's diagnosis, this cough sound model reaches an overall accuracy of 95.3%. The vocalised /ɑ:/ model reaches an accuracy of 72.2%, which is still significant because the dataset contains only 333 /ɑ:/ sounds versus 2029 cough sounds.

Biological disease-modifying antirheumatic drugs in juvenile idiopathic arthritis of polyarticular course, enthesitis-related arthritis, and psoriatic arthritis: a consensus statement.

OBJECTIVES: Juvenile idiopathic arthritis (JIA) is the most common type of inflammatory arthritis in children. Treatment options have been expanded since the introduction of biologics, which are highly effective. The existing local JIA treatment guideline was published more than a decade ago, when use of biologics was not as common. In this article, we review the latest evidence on using biologics in three JIA subtypes: JIA of polyarticular course (pcJIA), enthesitis-related arthritis (ERA), and psoriatic arthritis (PsA). Based on the latest information, an update on eligibility, response assessment, termination, and safety information for using biologics in these patients was performed. CONSENSUS PROCESS: The JIA Work Group, which consisted of nine paediatricians experienced in managing JIA, was convened in 2016. Publications before July 2017 were screened. Eligible articles were clinical trials, extension studies, systemic reviews, and recommendations from international societies and regulatory agencies about the use of biologics in pcJIA, ERA, and PsA. Evidence extraction, appraisal, and drafting of propositions were performed by two reviewers. Extracted evidence and drafted propositions were presented and discussed at the first two meetings. Overwhelming consensus was obtained at the final meeting in May 2018. Seven practice consensus statements were formulated. Regular review should be performed to keep the practice evidence-based and up-to-date.

Family medicine vocational training and career satisfaction in Hong Kong.

BACKGROUND: Postgraduate vocational training in family medicine (FM) is essential for physicians to build capacity and develop quality primary care. Inadequate standards in training and curriculum development can contribute to poor recruitment and retention of doctors in primary care. This study aimed to investigate: 1) the satisfaction level of doctors regarding vocational training in family medicine and associated demographics; and 2) the satisfaction level of doctors regarding their family medicine career and associated factors. METHOD: This is a cross sectional study of all family medicine physicians across all government-funded primary care clinics (GOPCs). The study questionnaire consisted of items from a standardized and validated physician survey named the Physician Worklife Survey (PWS) (Konrad et al., Med Care, 1999). We selected three scales (7 items) relating to global job satisfaction, global career satisfaction and global specialty (family medicine) satisfaction with additional items on training and demographics. All significant variables in bivariate analyses were further examined using stepwise logistic regression. RESULTS: Out of 424 eligible family medicine physicians, 368 physicians successfully completed the questionnaire. The response rate was 86.8%. Most participants were male (52.6%), were aged between 35 and 44 years (55.5%), were FM specialists (42.4%), graduated locally (86.2%), and had postgraduate qualifications. Eighty-two percent (82%) of participants were satisfied with their training. Having autonomy and protected time for training were associated with satisfaction with FM training. Satisfaction with family medicine as a career was correlated with physicians' satisfaction with their current job. Doctors who did not enroll in training (p < 0.001) and physicians who were older (p = 0.023) were significantly less satisfied. Stepwise multivariate regression showed that doctors who subjectively believed their training as "broad and in depth' had higher career satisfaction (p < 0.001). CONCLUSION: Overall, the satisfaction level of physicians on current family medicine training in Hong Kong was high. Having autonomy and protected time for training is associated with higher training satisfaction levels. Perceiving FM training as "broad and in-depth" is associated with higher family medicine career satisfaction.

Validity and reliability of the Chinese version of the Insulin Treatment Appraisal Scale among primary care patients in Hong Kong.

INTRODUCTION: Patients with diabetes mellitus often delay insulin initiation and titration due to psychological factors. This phenomenon is known as 'psychological insulin resistance'. Tools that identify psychological insulin resistance are valuable for detecting its causes and can lead to appropriate counselling. The Insulin Treatment Appraisal Scale was initially developed for western populations and has been translated and validated to measure psychological insulin resistance in Taiwan (Chinese version of the Insulin Treatment Appraisal Scale, C-ITAS). The current study examined the prevalence of psychological insulin resistance and the validity of the C-ITAS in a local population. METHODS: This cross-sectional study involved 360 patients with diabetes mellitus from a government-funded general out-patient clinic who completed the C-ITAS questionnaire. The total C-ITAS score was compared for patients with psychological insulin resistance and those without, and the internal consistency and test-retest reliability of the C-ITAS were calculated. An exploratory factor analysis was used to identify factors within the C-ITAS. RESULTS: The prevalence of psychological insulin resistance was 44.9%. The internal consistency of the scale was high (Cronbach's alpha=0.78). The test-retest reliability was positive with all C-ITAS questions (0.294-0.725). The mean C-ITAS score was significantly higher among patients with psychological insulin resistance than those without (42.42 vs 35.78; P<0.001). The exploratory factor analysis, however, failed to identify the two clear factors identified in the original validation study. CONCLUSIONS: The C-ITAS appears to be a feasible and potentially useful tool for identifying psychological insulin resistance, but additional validation or translation is required before it can be widely used clinically.

Pharmacokinetic study of meropenem in healthy beagle dogs receiving intermittent hemodialysis.

Meropenem, a second carbapenem antimicrobial agent with a broad spectrum of activity, is used to treat sepsis and resistant-bacterial infections in veterinary medicine. The objective of this study was to identify the pharmacokinetics of meropenem in dogs receiving intermittent hemodialysis (IHD) and to determine the proper dosing in renal failure patients receiving IHD. Five healthy beagle dogs were given a single i.v. dose of 24 mg/kg of meropenem and received IHD. The blood flow rate, dialysate flow, and ultrafiltration rate were maintained at 40 mL/min, 300 mL/min, and 40 mL/h, respectively. Blood samples were collected for 24 h from the jugular vein and from the extracorporeal arterial and venous line. Urine samples and dialysate were also collected. The concentrations of meropenem were assayed using HPLC/MS/MS determination. The peak plasma concentration was 116 ± 37 µg/mL at 15 min. The systemic clearance was 347 ± 117 mL/h/kg, and the steady-state volume of distribution was 223 ± 67 mL/kg. Dialysis clearance was 71.1 ± 34.3 mL/h/kg, and the extraction ratio by hemodialysis was 0.455 ± 0.150. The half-life (T1/2 ) in dogs with IHD decreased compared with those without IHD, and the reduction in T1/2 was greater in renal failure patients than in normal patients. Sixty-nine percent and 21% of the administered drug were recovered by urine and dialysate in the unchanged form, respectively. In conclusion, additional dosing of 24 mg/kg of meropenem after dialysis could be necessary according to the residual renal function of the patient based on the simulated data.

Search for neutrinos from annihilation of captured low-mass dark matter particles in the sun by super-kamiokande.

Super-Kamiokande (SK) can search for weakly interacting massive particles (WIMPs) by detecting neutrinos produced from WIMP annihilations occurring inside the Sun. In this analysis, we include neutrino events with interaction vertices in the detector in addition to upward-going muons produced in the surrounding rock. Compared to the previous result, which used the upward-going muons only, the signal acceptances for light (few-GeV/c^{2}-200-GeV/c^{2}) WIMPs are significantly increased. We fit 3903 days of SK data to search for the contribution of neutrinos from WIMP annihilation in the Sun. We found no significant excess over expected atmospheric-neutrino background and the result is interpreted in terms of upper limits on WIMP-nucleon elastic scattering cross sections under different assumptions about the annihilation channel. We set the current best limits on the spin-dependent WIMP-proton cross section for WIMP masses below 200 GeV/c^{2} (at 10 GeV/c^{2}, 1.49×10^{-39} cm^{2} for χχ→bb[over ¯] and 1.31×10^{-40} cm^{2} for χχ→τ^{+}τ^{-} annihilation channels), also ruling out some fraction of WIMP candidates with spin-independent coupling in the few-GeV/c^{2} mass range.

Search for trilepton nucleon decay via p→e+νν and p→µ+νν in the Super-Kamiokande experiment.

The trilepton nucleon decay modes p→e+νν and p→µ+νν violate |Δ(B-L)| by two units. Using data from a 273.4 kt yr exposure of Super-Kamiokande a search for these decays yields a fit consistent with no signal. Accordingly, lower limits on the partial lifetimes of τp→e+νν>1.7×10(32) years and τp→µ+νν>2.2×10(32) years at a 90% confidence level are obtained. These limits can constrain Grand Unified Theories which allow for such processes.

Search for nucleon decay via n→ν[over ¯]π0 and p→ν[over ¯]π+ in Super-Kamiokande.

We present the results of searches for nucleon decay via n→ν[over ¯]π0 and p→ν[over ¯]π+ using data from a combined 172.8 kt·yr exposure of Super-Kamiokande-I,-II, and-III. We set lower limits on the partial lifetime for each of these modes: τn→ν[over ¯]π0>1.1×10(33) years and τp→ν[over ¯]π+>3.9×10(32) years at a 90% confidence level.

First indication of terrestrial matter effects on solar neutrino oscillation.

We report an indication that the elastic scattering rate of solar B8 neutrinos with electrons in the Super-Kamiokande detector is larger when the neutrinos pass through Earth during nighttime. We determine the day-night asymmetry, defined as the difference of the average day rate and average night rate divided by the average of those two rates, to be [-3.2 ± 1.1(stat) ± 0.5(syst)]%, which deviates from zero by 2.7 σ. Since the elastic scattering process is mostly sensitive to electron-flavored solar neutrinos, a nonzero day-night asymmetry implies that the flavor oscillations of solar neutrinos are affected by the presence of matter within the neutrinos' flight path. Super-Kamiokande's day-night asymmetry is consistent with neutrino oscillations for 4 × 10(-5) eV(2) ≤ Δm 2(21) ≤ 7 × 10(-5) eV(2) and large mixing values of θ12, at the 68% C.L.

Evidence for the appearance of atmospheric tau neutrinos in super-Kamiokande.

Super-Kamiokande atmospheric neutrino data were fit with an unbinned maximum likelihood method to search for the appearance of tau leptons resulting from the interactions of oscillation-generated tau neutrinos in the detector. Relative to the expectation of unity, the tau normalization is found to be 1.42 ± 0.35(stat)(-0.12)(+0.14)(syst) excluding the no-tau-appearance hypothesis, for which the normalization would be zero, at the 3.8σ level. We estimate that 180.1 ± 44.3(stat)(-15.2)(+17.8) (syst) tau leptons were produced in the 22.5 kton fiducial volume of the detector by tau neutrinos during the 2806 day running period. In future analyses, this large sample of selected tau events will allow the study of charged current tau neutrino interaction physics with oscillation produced tau neutrinos.

Independent risk factors for the co-colonization of vancomycin-resistant Enterococcus faecalis and methicillin-resistant Staphylococcus aureus in the region most endemic for vancomycin-resistant Staphylococcus aureus isolation.

In the majority of cases of vancomycin-resistant Staphylococcus aureus (VRSA), vancomycin-resistant Enterococcus faecalis (VR E. faecalis) served as the vanA donor to S. aureus. Previous studies that evaluated the risk factors for co-colonization with VRE and MRSA did not differentiate between VR E. faecalis and VR E. faecium. This study aimed to identify variables associated with VR E. faecalis and MRSA co-colonization. A retrospective case-control study from January 2008 to December 2009 was conducted at the Detroit Medical Center. Data were extracted from charts and pharmacy records. Unique patients co-colonized with VR E. faecalis and MRSA (defined as isolation of MRSA within 7 days of VR E. faecalis isolation) were compared with patients with VR E. faecalis who were not co-colonized with MRSA. A total of 546 patients with VR E. faecalis isolation were identified. 85 (15.6 %) VR E. faecalis patients were co-colonized with MRSA and 461 (84.4 %) VR E. faecalis patients were not co-colonized with MRSA. The mean age of the study cohort was 65.9 ± 16.4 years, 424 (77.7 %) were African-American, and 270 (49.5 %) were residing in long-term care institutions. Independent predictors of co-colonization of VR E. faecalis and MRSA were male gender, impaired consciousness, ICU stay prior to VR E. faecalis isolation, indwelling devices, and isolation of VR E. faecalis from wounds. MRSA was frequently isolated from the same culture specimen as VR E. faecalis (n = 39, 45.9 %), most commonly from wounds. This large study of patients with VR E. faecalis identified the severity of illness, indwelling devices, and chronic wounds as independent predictors of co-colonization with VR E. faecalis and MRSA.

Search for differences in oscillation parameters for atmospheric neutrinos and antineutrinos at Super-Kamiokande.

We present a search for differences in the oscillations of antineutrinos and neutrinos in the Super-Kamiokande-I, -II, and -III atmospheric neutrino sample. Under a two-flavor disappearance model with separate mixing parameters between neutrinos and antineutrinos, we find no evidence for a difference in oscillation parameters. Best-fit antineutrino mixing is found to be at (Δm2,sin2 2θ)=(2.0×10(-3) eV2, 1.0) and is consistent with the overall Super-K measurement.

Protection against lethal toxic shock by targeted disruption of the CD28 gene.

Toxic shock syndrome (TSS) is a multi system disorder resulting from superantigen-mediated cytokine production. Nearly 90% of the clinical cases of TSS arise due to an exotoxin, toxic shock syndrome toxin-1 (TSST-1), elaborated by toxigenic strains of Staphylococcus aureus. It is clearly established that besides antigen-specific signals a variety of costimulatory signals are required for full T cell activation. However, the nature and potential redundancy of costimulatory signals are incompletely understood, particularly with regards to superantigen-mediated T cell activation in vivo. Here we report that CD28-deficient mice (CD28-/-) are completely resistant to TSST-1-induced lethal TSS while CD28 (+/-) littermate mice were partially resistant to TSST-1. The mechanism for the resistance of the CD28 (-/-) mice was a complete abrogation of TNF-alpha accumulation in the serum and a nearly complete (90%) impairment of IFN-gamma secretion in response to TSST-1 injection. In contrast, the serum level of IL-2 was only moderately influenced by the variation of CD28 expression. CD28 (-/-) mice retained sensitivity to TNF-alpha as demonstrated by equivalent lethality after cytokine injection. These findings establish an essential requirement for CD28 costimulatory signals in TSST-1-induced TSS. The hierarchy of TSST-1 resistance among CD28 wild-type (CD28+/+), CD28 heterozygous (CD28+/-), and CD28-/- mice suggests a gene-dose effect, implying that the levels of T cell surface CD28 expression critically regulate superantigen-mediated costimulation. Finally, as these results demonstrate the primary and non-redundant role of CD28 receptors in the initiation of the in vivo cytokine cascade, they suggest therapeutic approaches for superantigen-mediated immunopathology.

Inhalation toxicity study of disk-shaped potassium octatitanate particles (terracess TF) in rats following 90 days of aerosol exposure.

Since fibrous particles such as asbestos and some man-made fibers (MMF) have been known to produce carcinogenic or fibrogenic effects, disk-shaped potassium octatitanate (POT) particles (trade name: Terracess TF) were manufactured as nonfibrous particles. A 90-day inhalation toxicity study of Terracess TF was performed to evaluate comparative inhalation toxicity of the disk shape with a fibrous shape that was previously evaluated. Four groups of 20 male and 15 female rats each were exposed to Terracess TF aerosols at concentrations of 0, 2, 10, or 50 mg/m(3) for 90 days. Ten male and 10 female rats per group were sacrificed at 90 days of exposure. After 90 days of exposure, 5 male rats per group were sacrificed at 3 wk of recovery period and 4-5 male rats per group or 5 female rats per group were sacrificed at 15 wk of recovery for lung clearance and histopathology. The mass median aerodynamic equivalent diameter (MMAED) of the aerosols of test materials ranged from 2.5 to 2.9 microm. There were no test-substance-related adverse effects on clinical observations. At the end of the 90-day exposure, a slight increase in lung-to-body weight ratios was observed at 50 mg/m(3) in male but not in female rats. However, lung weights were within normal limits after 3- or 15-wk recovery periods. Microscopically, inhaled Terracess TF particles were mostly phagocytized by free alveolar macrophages (AMs) in the alveolar airspaces and alveolar walls maintained normal structure at 2 and 10 mg/m(3). At 50 mg/m(3), some alveoli were distended and filled with aggregates of particle-laden AMs. The alveolar walls showed slight type II pneumocyte hyperplasia, but neither proliferative inflammation nor alveolar fibrosis was present at 50 mg/m(3). The clearance half-times for Terracess TF were estimated to be in the order of 6 to 9 mo for the 50-mg/m(3) group and 2 to 3 mo for the 10- and 2-mg/m(3) groups. The lung responses and lung clearance rate were comparable to those of "nuisance" type dusts at these concentrations. Based on interpretation that aggregated particle-laden AMs in alveoli was considered to be an early histopathological sign of lung overloading, an effect level was considered to be 50 mg/m(3) and no-observedadverse- effect level (NOAEL) was 10 mg/m(3). This experiment clearly demonstrated that particle morphology was considered to be an important factor to determine inhaled particle toxicity.

Prevalence of medical students' burnout and its associated demographics and lifestyle factors in Hong Kong.

BACKGROUND: Burnout causes personal suffering and adverse professional consequences. It is prevalent among medical students, although the relationship between burnout and lifestyle factors are understudied in Chinese medical students. Thus, this study aims to (i) estimate the prevalence of burnout among medical students in Hong Kong (HK) and (ii) delineate the relationship between burnout and various lifestyle factors. METHOD: 1,341 students were invited to complete a questionnaire from September to December 2017. Burnout was measured by the Maslach Burnout Inventory. Lifestyle factors including drinking habit, sleep habit and quality, and exercise level were assessed by validated instruments, including Alcohol Use Disorder Identification Test (AUDIT-C), Pittsburgh Sleep Quality Index (PSQI), and Godin-Shephard Leisure-Time Physical Activity (GSLTPA), respectively. Smoking status and use of self-medications were also inquired into, while demographic data was self-reported. Prevalence of burnout with confidence intervals was calculated. Difference in lifestyle and demographic data in students with or without burnout, were compared by t-test and Chi-square/Fisher's exact test. From this, all associations with significant p-value at p<0.1 were entered into the multiple logistic regression model. RESULTS: 731 students (55.6%) responded to the questionnaire. Prevalence of burnout was 27.9% (95%CI: 24.6%-31.5%). Only 3 students in the whole sample smoked; and 6.6% of students drank weekly but rarely drank more than 2 drinks per week. 6.3% and 2.3% self-medicated themselves with medications to improve their sleep and concentration, respectively. Using a multiple logistic regression model, only sleep quality and exercise level were significantly associated with the presence of burnout. CONCLUSION: Around a quarter of medical students in HK suffered from burnout. Burnout was found to be significantly associated with sleep quality and physical exercise. The study also highlighted that HK medical students lived very different lifestyles from those from other countries. More research is needed to design and establish the effectiveness of lifestyle interventional programs that enhance exercise level and sleep quality.

Differential T cell costimulatory requirements in CD28-deficient mice.

T cell receptor stimulation without costimulation is insufficient for the induction of an optimal immune response. It is thought that engagement of the CD28 molecule with its ligand B7 provides an essential costimulatory signal without which full activation of T cells cannot occur. A mouse strain with a defective CD28 gene was established. Development of T and B cells in the CD28-deficient mice appeared normal. However, T lymphocytes derived from CD28-/- mutant mice had impaired responses to lectins. Lectin stimulation did not trigger interleukin-2 (IL-2) production, IL-2 receptor alpha expression was significantly decreased, and exogenous IL-2 only partially rescued the CD28 defect. Basal immunoglobulin (Ig) concentrations in CD28-deficient mice were about one-fifth of those found in wild-type controls, with low titers of IgG1 and IgG2b but an increase in IgG2a. In addition, activity of T helper cells in CD28-/- mice was reduced and immunoglobulin class switching was diminished after infection with vesicular stomatitis virus. However, cytotoxic T cells could still be induced and the mice showed delayed-type hypersensitivity after infection with lymphocytic choriomeningitis virus. Thus, CD28 is not required for all T cell responses in vivo, suggesting that alternative costimulatory pathways may exist.

Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4.

The role of the cell-surface molecule CTLA-4 in the regulation of T cell activation has been controversial. Here, lymph nodes and spleens of CTLA-4-deficient mice accumulated T cell blasts with up-regulated activation markers. These blast cells also infiltrated liver, heart, lung, and pancreas tissue, and amounts of serum immunoglobulin were elevated. The mice invariably became moribund by 3 to 4 weeks of age. Although CTLA-4-deficient T cells proliferated spontaneously and strongly when stimulated through the T cell receptor, they were sensitive to cell death induced by cross-linking of the Fas receptor and by gamma irradiation. Thus, CTLA-4 acts as a negative regulator of T cell activation and is vital for the control of lymphocyte homeostasis.

Urban Chinese midwives' knowledge, attitudes and practices toward umbilical cord blood donation.

OBJECTIVE: This study aimed to assess the knowledge, attitudes and factors associated with promotion of umbilical cord blood (CB) donation by Chinese midwives to expectant mothers. DESIGN: An anonymous cross-sectional survey using self-administered questionnaires. SETTING: Hong Kong, China. PARTICIPANTS: One-hundred-and-forty-seven registered Chinese midwives were recruited by convenience sampling from government obstetric clinics and public and private hospitals. MEASUREMENTS AND FINDINGS: In addition to collecting demographic background information, the study examined the midwives' cord blood-related knowledge and perceptions as well as past-year practices and future intention of giving cord blood advice. Hong Kong midwives generally showed high levels of knowledge about the medical uses of cord blood but they were not as familiar with the administrative, legal and financial aspects of donation and storage. Only about 10% had received formal cord blood training and the majority felt that it should be integrated into midwifery program curricula. Although the midwives showed strong positive attitudes towards cord blood donation, only 10.9% consistently gave information and 7.5% consistently advised cord blood donation to expectant mothers in the preceding year while slightly higher percentages planned to do so in the future. In the multivariable models, higher educational attainment and hospital employment were the most consistent predictors of past-year practices of giving cord blood information and future intention to provide advice. Higher score in cord blood-related attitudes was significantly associated with giving past-year cord-blood advice, future intention to provide advice and future intention to recommend donation in the multivariable models. Key barriers to advising expectant mothers were the lack of a formal work protocol, lack of time in the clinic routine and fear of criticism by peers. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Increasing education, improving perceptions and changing workplace protocols will likely increase cord blood advising by Hong Kong midwives to their patients.

Enhanced photoelectrochemical biosensing performances for graphene (2D) - Titanium dioxide nanowire (1D) heterojunction polymer conductive nanosponges.

In this work, an efficient photoelectrochemical (PEC) biosensing platform has been designed and developed based on graphene (G) through modifying it into an electroconductive polymer nanosponge (EPNS) and with the incorporation of titanium dioxide nanowires (TiO2 NW) (designated as TiO2 (G) NW@EPNS). Functioning as an efficient immobilization matrix for immobilization of the enzyme Cytochrome C (Cyt C), TiO2 (G) NW@EPNS delivers features for an efficient PEC biosensor, such as fast kinetics of direct electron transfer (DET) to the electrode and effective separation of photogenerated holes and electrons. TiO2 (G) NW@EPNS exhibited DET to the electrode with a highly heterogeneous electron transfer rate constant of 6.29±0.002s-1. The existence of TiO2, G and EPNS in conjunction facilitates DET between the electrode surface and the protein. The fabricated PEC nitrite ion (NO2-) biosensor showed superior analytical performances such as wide linear range (0.5-9000µM), lowest detection limit (0.225mM) and excellent specificity for NO2- in the presence other interferences at a very low bias potential (-0.11V). This study opens up the feasibility of fabricating a PEC biosensor for any analyte using a matrix comprising of G and a photoactive material and EPNS, because these components synergistically contribute to effective immobilization of on enzyme, DET to the electrode and simple read-out under the light.