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Hereditary sensory and autonomic neuropathy type 1 is an autosomal dominant neuropathy caused by the SPTLC1 or SPTLC2 variants. These variants modify the preferred substrate of serine palmitoyl transferase, responsible for the first step of de novo sphingolipids synthesis, leading to accumulation of cytotoxic deoxysphingolipids. Diagnosis of HSAN1 is based on clinical symptoms, mainly progressive loss of distal sensory keep, and genetic analysis. Aim: Identifying new SPTLC1 or SPTLC2 "gain-of-function" variants raises the question as to their pathogenicity. This work focused on characterizing six new SPTLC1 variants using in silico prediction tools, new meta-scores, 3D modeling, and functional testing to establish their pathogenicity. Methods: Variants from six patients with HSAN1 were studied. In silico, CADD and REVEL scores and the 3D modeling software MITZLI were used to characterize the pathogenic effect of the variants. Functional tests based on plasma sphingolipids quantification (total deoxysphinganine, ceramides, and dihydroceramides) were performed by tandem mass spectrometry. Results: In silico predictors did not provide very contrasting results when functional tests discriminated the different variants according to their impact on deoxysphinganine level or canonical sphingolipids synthesis. Two SPTLC1 variants were newly described as pathogenic: SPTLC1 NM_006415.4:c.998A>G and NM_006415.4:c.1015G>A. Discussion: The combination of the different tools provides arguments to establish the pathogenicity of these new variants. When available, functional testing remains the best option to establish the in vivo impact of a variant. Moreover, the comprehension of metabolic dysregulation offers opportunities to develop new therapeutic strategies for these genetic disorders. [ABSTRACT FROM AUTHOR]

This article integrates the exposure and adaptation hypotheses concerning gambling engagement by quantitatively modeling, at the community level, the non-linear relationship between gamblers' engagement and their years of gambling experience and identifies the years of experience corresponding to the maximum/minimum engagement. Gambling engagement indicators were based on the odds of three metrics concerning casino visits, gambling budgets, and gambling affordability being beyond predefined thresholds. Empirical data were collected offline and online (n = 206 and 481) in Macao. Curve fitting of these indicators against gamblers' years of experience found that the odds of casino visit frequency being less than daily and the gambling budget being greater than both the first and second quartiles followed up-maximum-down quadratic curves over gamblers' experience. Their maxima were at around 13.3, 22.0, and 22.4 years, respectively. In conclusion, these indicators are non-linearly and bi-directionally related to gamblers' years of experience as per the aforesaid curves, i.e. the two hypotheses take turns to prevail over gamblers' lives and are thus integrated temporally. Unprecedentedly, such curves quantitatively model and quantify the timing, magnitude, maximization, and minimization of these indicators' variations over gamblers' lives, which matter to governments, the public, therapeutic/rehabilitative professionals, and gambling operators. [ABSTRACT FROM AUTHOR]

Introduction: Bracing is one of the first-line treatment for early-onset idiopathic scoliosis (EOIS) to control curves from progression. This study aimed to explore the determinants that govern bracing effectiveness in EOIS. Methods: One hundred and eleven patients with EOIS (mean age of 8.6 ± 1.25 at diagnosis) received bracing treatment and had a final follow-up beyond skeletal maturity were identified from records between 1988 and 2021. Demographic data and clinical features of spinal curvature were obtained for correlation analyses to determine the associations between curve outcomes and clinical features. Results: Most patients were female (85.6%) and had a major curve on the left side (67%). The mean baseline Cobb angle of major curves was 21.73 ± 7.92°, with a mean Cobb angle progression of 18.05 ± 19.11°. The average bracing duration was 5.3 ± 1.9 years. Only 26 (23.4%) of them underwent surgery. The final Cobb angle and curve progression at the final follow-up with a Cobb angle of ≥50° were positively correlated with the initial Cobb angle (r = 0.206 and r = 0.313, respectively) and negatively correlated with maturity parameters. The lumbar curve type was found to correlate with a smaller final Cobb angle. Conclusions: The majority of patients had a final Cobb angle < 50°, which was considered a successful bracing outcome. The final Cobb angle correlated with the initial Cobb angle and curve types observed in EOIS. [ABSTRACT FROM AUTHOR]

We discuss inline electrical testing to monitor the baseline of Analog Computing hardware using Phase Change Memory (PCM) technology. Tightening the PCM resistance distribution is necessary to meet analog computation requirement. A new yield methodology is introduced. A study of heater process variation, which will affect the heater height and the PCM resistance, will be discussed. [ABSTRACT FROM AUTHOR]

Omicron generally causes milder disease than previous strains of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), especially in fully vaccinated individuals. However, incompletely vaccinated children may develop Omicron‐related complications such as those affecting the central nervous system. To characterize the spectrum of clinical manifestations of neuro‐COVID and to identify potential biomarkers associated with clinical outcomes, we recruited 15 children hospitalized for Omicron‐related neurological manifestations in three hospitals in Hong Kong (9 boys and 6 girls aged 1–13 years). All were unvaccinated or incompletely vaccinated. Fourteen (93.3%) were admitted for convulsion, including benign febrile seizure (n = 7), complex febrile seizure (n = 2), seizure with fever (n = 3), and recurrent breakthrough seizure (n = 2), and the remaining nonconvulsive patient developed encephalopathic state with impaired consciousness. None of the seven children with benign febrile seizure and six of eight children with other neurological manifestations had residual deficits at 9‐month follow‐up. SARS‐CoV‐2 RNA was undetectable in the cerebrospinal fluid (CSF) specimens of seven patients who underwent lumbar puncture. Spike‐and‐wave/sharp waves affecting the frontal lobes were detected in four of seven (57.1%) patients who underwent electroencephalogram. Children with Omicron‐related neurological manifestations had significantly higher blood levels of IL‐6 (p < 0.001) and CHI3L1 (p = 0.022) than healthy controls, and higher CSF levels of IL‐6 (p = 0.002) than children with non‐COVID‐19‐related febrile illnesses. Higher CSF‐to‐blood ratios of IL‐8 and CHI3L1 were associated with longer length of stay, whereas higher ratios of IL‐6 and IL‐8 were associated with higher blood tau level. The role of CSF:blood ratio of IL‐6, IL‐8, and CHI3L1 as prognostic markers for neuro–COVID should be further evaluated. [ABSTRACT FROM AUTHOR]

Simple Summary: There is a scarcity of economic analysis on the use of non-invasive biomarkers to inform policy-making with respect to their application in population-based colorectal cancer (CRC) screening programs. The objective of this study is to conduct a comparative cost-effectiveness analysis on using M3CRC (m3 + Fn + Ch + Bc + FIT) as a primary test for population-based screening, when compared with FIT and colonoscopy. The study can provide economic analysis regarding the use of non-invasive biomarkers in population-based CRC screening programs. This study aimed to examine the cost-effectiveness of fecal biomarker M3 panel compared to fecal immunochemical test (FIT) and colonoscopy in an Asian population. In a hypothetical population of 100,000 persons aged 50 years who received FIT yearly, M3 biomarker yearly, or colonoscopy every 10 years until the age of 75 years. Participants with positive FOBT or a result of "high risk" identified using the M3 biomarker are offered colonoscopy. We assumed surveillance colonoscopy is repeated every 3 years, and examined the treatment cost. A comparison of various outcome measures was conducted using Markov modelling. The incremental cost-effectiveness ratio (ICER) of FIT, M3 biomarker, and colonoscopy was USD108,176, USD133,485 and USD159,596, respectively. Comparing with FIT, the use of M3 biomarker could lead to significantly smaller total loss of cancer-related life-years (2783 vs. 5279); a higher number of CRC cases prevented (1622 vs. 146), a higher proportion of CRC cases prevented (50.2% vs. 4.5%), more life-years saved (2852 vs. 339), and cheaper total costs per life-year saved (USD212,553 vs. 773,894). The total costs per life-year saved is more affordable than that achieved by colonoscopy as a primary screening tool (USD212,553 vs. USD236,909). The findings show that M3 biomarkers may be more cost-effective than colonoscopy. [ABSTRACT FROM AUTHOR]

Purpose: This study empirically investigates the influence of students' brand attitudes and perceptions of brand fit on their study intention vis-à-vis international brand alliances and individual brands after alliance. Design/methodology/approach: Structural equation modelling (SEM) was used in data analysis, and a questionnaire was administered to a sample of sub-degree business management students recruited from a self-financing higher education institution in Hong Kong. Findings: The results indicate that students' prior attitudes towards the brands of foreign and local institutions and their perceptions of brand fit positively affect their study intention, providing evidence that post-attitudes towards individual brands fully mediate the relationship between attitudes towards international brand alliances and study intention towards individual institutions. Originality/value: International brand alliances between higher education institutions are becoming increasingly important. In Hong Kong, despite the emerging trend of collaboration between foreign and local universities, an evaluation of the effect of international brand alliances on study intention has been seriously overlooked. [ABSTRACT FROM AUTHOR]

Background Age-specific incidence of acute myocarditis/pericarditis in adolescents following Comirnaty vaccination in Asia is lacking. This study aimed to study the clinical characteristics and incidence of acute myocarditis/pericarditis among Hong Kong adolescents following Comirnaty vaccination. Methods This is a population cohort study in Hong Kong that monitored adverse events following immunization through a pharmacovigilance system for coronavirus disease 2019 (COVID-19) vaccines. All adolescents aged between 12 and 17 years following Comirnaty vaccination were monitored under the COVID-19 vaccine adverse event response and evaluation program. The clinical characteristics and overall incidence of acute myocarditis/pericarditis in adolescents following Comirnaty vaccination were analyzed. Results Between 14 June 2021 and 4 September 2021, 33 Chinese adolescents who developed acute myocarditis/pericarditis following Comirnaty vaccination were identified. In total, 29 (87.88%) were male and 4 (12.12%) were female, with a median age of 15.25 years. And 27 (81.82%) and 6 (18.18%) cases developed acute myocarditis/pericarditis after receiving the second and first dose, respectively. All cases are mild and required only conservative management. The overall incidence of acute myocarditis/pericarditis was 18.52 (95% confidence interval [CI], 11.67–29.01) per 100 000 persons vaccinated. The incidence after the first and second doses were 3.37 (95% CI, 1.12–9.51) and 21.22 (95% CI, 13.78–32.28 per 100 000 persons vaccinated, respectively. Among male adolescents, the incidence after the first and second doses were 5.57 (95% CI, 2.38–12.53) and 37.32 (95% CI, 26.98–51.25) per 100 000 persons vaccinated. Conclusions There is a significant increase in the risk of acute myocarditis/pericarditis following Comirnaty vaccination among Chinese male adolescents, especially after the second dose. [ABSTRACT FROM AUTHOR]

The analog AI core concept is appealing for deep‐learning (DL) because it combines computation and memory functions into a single device. Yet, significant challenges such as noise and weight drift will impact large‐scale analog in‐memory computing. Here, effects of flicker noise and drift on large DL systems are explored using a new flicker‐noise model with memory, which preserves temporal correlations, including a flicker noise figure of merit (FOM) Ar to quantify impacts on system performance. Flicker noise is characterized for Ge2Sb2Te5 (GST) based phase‐change memory (PCM) cells with a discovery of read‐noise asymmetry tied to shape asymmetry of mushroom cells. This experimental read polarity dependence is consistent with Pirovano's trap activation and defect annihilation model in an asymmetric GST cell. The impact of flicker noise and resistance drift of analog PCM synaptic devices on deep‐learning hardware is assessed for six large‐scale deep neural networks (DNNs) used for image classification, finding that the inference top‐1 accuracy degraded with the accumulated device flicker noise and drift as ∝Ar×twait, and ∝twait−ν, respectively, where ν is the drift coefficient. These negative impacts could be mitigated with a new hardware‐aware (HWA) (pre)‐training of the DNNs, which is applied before programming to the analog arrays. [ABSTRACT FROM AUTHOR]

As noted previously, HT ht and B p b SB I j i sb are calculated from HT ht and B r b SB I j i sb . As such, let HT ht and HT ht . Likewise, HT ht ${R} {i}^{t}-{R} {j}^{t}\approx \alpha +\beta {\pi } {ij}$. This is achieved by employing an appropriate paired-comparison model HT ht for I p i SB I ij i sb . [Extracted from the article]

We review the diagnostic criteria of polycystic ovarian syndrome (PCOS) in adolescents. It is important to recognise PCOS early for timely management. Clinicians should be aware of the difficulties in diagnosing PCOS in adolescents. A multi-disciplinary approach for diagnosis and treatment is suggested. For high-risk cases, re-evaluation may avoid under-diagnosing or over-diagnosing PCOS. [ABSTRACT FROM AUTHOR]

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Background and Aim: The reported prevalence and risk factors for sessile serrated lesions (SSLs) show significant variation. We aimed to specifically study the prevalence and potential risk factors of SSLs in an average risk colorectal cancer (CRC) screening population of Chinese subjects. Methods: This is a case–control study of prospectively collected data from a territory‐wide colorectal screening program in Hong Kong. Information on risk factors was obtained from questionnaires completed prior to screening colonoscopy. We compared subjects with SSLs against controls without these lesions to identify potential risk factors using multivariable logistic regression. Results: Of 12 039 asymptomatic screening subjects, 6011 subjects received a screening colonoscopy with 2214 subjects (36.8%) having conventional adenomas, 486 subjects (8.1%) having hyperplastic polyps, and 85 subjects (1.4%) having SSLs only. Of these subjects, three had synchronous advanced adenomas and were excluded from the analysis. More than 60% of these lesions were in the proximal colon. We compared these 82 subjects with SSLs only and 3226 controls without any polyps. After multivariable logistic regression, age ≥ 66 years, smoking, and diabetes mellitus (DM) were significant independent risk factors for SSLs. Conclusion: In this study, we report the prevalence of SSLs to be 1.4%. Age ≥ 66 years, smoking, and DM were independent risk factors for these lesions. Our findings provide relevant new data that should be taken into consideration when designing region‐specific surveillance programs for SSLs with the ultimate goal of reducing the risk of CRC. [ABSTRACT FROM AUTHOR]

Purpose. This study aimed to determine whether untrained observers alter their spine as directed via static images of different lifting techniques. Methods. Ten men and eight women, who had no lifting or visual observation training, performed box lifts. Following a self-selected lifting technique trial, participants performed four experimental lifting trials (in randomized order) wherein they were instructed to execute lifts in accordance with the techniques pictured. These techniques differed by the amount of knee, trunk and spine flexion modeled. Peak lumbar flexion angles and flexion/extension velocities were quantified, and then statistically analyzed via general linear models with two within-participant factors (condition = technique; phase = lift/lower). Results. Lumbar flexion angles and flexion/extension velocities differed between conditions (p < 0.001), although the effects depended on the combination of postural characteristics pictured. A main effect of phase was observed for peak lumbar flexion velocity only (p = 0.001). No condition × phase interaction effects were detected for any dependent variables (p > 0.050). Conclusions. Acute changes in lifting mechanics can be elicited via visual observation of pictured techniques. However, if using pictures to attenuate peak lumbar flexion displacements and velocities when lifting, auxiliary instruction may be needed to direct observers' attention to the spine curvature displayed. [ABSTRACT FROM AUTHOR]

A feruloyl esterase (FAE) gene was isolated from rumen microbial metagenome that consisted of 774 bp encoding 258 amino acid residues. The gene was subcloned into pET 32b vector, expressed in Escherichia. coli, and the enzyme was purified in active form. Homology modeling showed that the FAE contained the catalytic triad composed of Ser80- His236-Asp177, and a classical Gly-X-Ser-X-Gly nucleophile motif commonly found in esterases. Under optimum pH and temperature (pH 7.0, 40 °C), 1 nmole FAE catalyzed the release of 19.75 ± 0.24 µg ferulic acid (FA) from 100 mg corn fiber (CF) in 1 h, which represents 3.5% of FA present in saponified CF. Addition of GH10 endoxylanase (XYN) to 0.5 nmole FAE enhanced the yield by 1.1 fold, equivalent to a 5% increase in FA release. Using CF pretreated with hot water, the synergistic effect of adding XYN resulted in 59.0 ± 0.2 mg FA/100 mg CF (5 nmole XYN, 0.5 nmole FAE), equivalent to a 4-fold increase compared to using the untreated CF substrate under the same reaction conditions. [ABSTRACT FROM AUTHOR]

Objective. We report two cases of carotid dissection revealed by isolated paralysis of the ipsilateral half tongue. Observations. First patient, 52 years old, with no particular medical or surgical history, presented with isolated paralysis of the left half tongue preceded by two weeks of moderate-intensity cervicalgia and having been the subject to cervical manipulation. MRI revealed dissection of the left internal carotid artery in its prepetrous portion. The evolution after 6 weeks of platelet aggregating inhibitors treatment was favorable. The second patient, 74 years old, with no particular medical or chirurgical history, presented with a sudden onset of paralysis of the left half tongue preceded by unusual headaches associated with neck pain. Brain MRI showed aneurysmal ectasia of the left internal carotid with parietal irregularity suggestive of carotid dissection. The evolution after four weeks of treatment with anticoagulant was favorable. Conclusion. Carotid dissection revealed by isolated paralysis of the half tongue is rare. It is generally of good prognosis. However, in paralysis of half tongue, it must be urgently sought and treated to reduce the risk of a transient or constituted ischemic accident. [ABSTRACT FROM AUTHOR]

The systematic offset of Gaia parallaxes has been widely reported with Gaia 's second data release, and it is expected to persist in future Gaia data. In order to use Gaia parallaxes to infer distances to high precision, we develop a hierarchical probabilistic model to determine the Gaia parallax zero-point offset along with the calibration of an empirical model for luminosity of red clump stars by combining astrometric and photometric measurements. Using a cross-matched sample of red clump stars from the Apache Point Observatory Galactic Evolution Experiment and Gaia Data Release 2 (DR2), we report the parallax zero-point offset in DR2 to be |$\varpi _0 = -48 \pm 1\,\mu \text{as}$|⁠. We infer the red clump absolute magnitude to be −1.622 ± 0.004 in Ks , 0.435 ± 0.004 in G , −1.019 ± 0.004 in J , and −1.516 ± 0.004 in H. The intrinsic scatter of the red clump is ∼0.09 mag in J, H , and Ks , or ∼ 0.12 mag in G. We tailor our models to accommodate more complex analyses such as investigating the variations of the parallax zero-point with each source's observed magnitude, observed colour, and sky position. In particular, we find fluctuations of the zero-point across the sky to be of order or less than a few 10s of |$\mu \text{as}$|⁠. [ABSTRACT FROM AUTHOR]

We detail the use of ring oscillators (ROs) for yield learning during the research phase of a CMOS technology generation. Failing circuits are located and classified based on electrical analysis of ROs and FETs (Field Effect Transistor) wired out from RO environments. Based on electrical data and binning methods, we improve detection and classification fault methodologies and form a yield detractor pareto. Inline defect monitoring can help to estimate RO yield and is essential in CMOS technology research. [ABSTRACT FROM AUTHOR]

Feruloyl esterases (FAEs) are a key group of enzymes that hydrolyze ferulic acids ester-linked to plant polysaccharides. The cow's rumen is a highly evolved ecosystem of complex microbial microflora capable of converting fibrous substances to energy. From direct cloning of the rumen microbial metagenome, we identified seven active phagemids conferring feruloyl esterase activity. The genomic inserts ranged from 1633 to 4143 bp, and the ORFs from 681 to 1359 bp. BLAST search reveals sequence homology to feruloyl esterases and esterases/lipases identified in anaerobes. The seven genes were expressed in Escherichia coli, and the proteins were purified to homogeneity. The FAEs were found to cover types B, C, and D in the feruloyl esterase classification system using model hydroxycinnamic acid esters. The release of ferulic acid (FA) catalyzed by these enzymes was established using natural substrates corn fiber (CF) and wheat insoluble arabinoxylan (WIA). Three of the enzymes were demonstrated to cleave diferulates and hence the capability to break down Araf-FA-FA-Araf cross-links. The wide variation in the sequence, activity, and substrate specificity observed in the FAEs discovered in this study is a confirming evidence that combined actions of a full range of FAE enzymes contribute to the high-efficiency fiber digestion in the rumen microbial ecosystem. [ABSTRACT FROM AUTHOR]

A general multi-scale strategy is presented for modeling the mechanical environment of a group of neurons that were embedded within a collagenous matrix. The results of the multi-scale simulation are used to estimate the local strains that arise in neurons when the extracellular matrix is deformed. The distribution of local strains was found to depend strongly on the configuration of the embedded neurons relative to the loading direction, reflecting the anisotropic mechanical behavior of the neurons. More importantly, the applied strain on the surrounding extracellular matrix is amplified in the neurons for all loading configurations that are considered. In the most severe case, the applied strain is amplified by at least a factor of 2 in 10% of the neurons' volume. The approach presented in this paper provides an extension to the capability of past methods by enabling the realistic representation of complex cell geometry into a multi-scale framework. The simulation results for the embedded neurons provide local strain information that is not accessible by current experimental techniques. [ABSTRACT FROM AUTHOR]

Background: Few randomised controlled trials (RCTs) have evaluated the different recalling approaches for enhancing adherence to faecal immunochemical test (FIT)-based screening.Aim: The authors evaluated the effectiveness of two telecommunication strategies on improving adherence to yearly FIT screening.Design and Setting: A randomised, parallel group trial was performed in a primary care screening practice.Method: The authors recruited 629 asymptomatic individuals aged 40-70 years with a negative FIT in 2015 to a population-based screening programme. On participation, they were invited to repeat their second round of FIT in 2016, 12 months after the first test. Each participant was randomly assigned to either interactive telephone reminder (n = 207), short message service reminder (SMS, n = 212), or control, where no additional interventions were delivered after the findings of their first FIT was communicated to the participants (n = 210). Reminders in the intervention groups were delivered 1 month before subjects' expected return. Additional telephone reminders were delivered 2 months after the expected return date to all subjects who defaulted specimen return. The outcomes included rates of FIT collection and specimen return up to 6 months after their expected return.Results: At 6 months, the cumulative FIT collection rate was 95.1%, 90.4%, and 86.5%, respectively, for the telephone, SMS, and control groups (P = 0.010). The corresponding specimen return rate was 94.1%, 90.0%, and 86.0% (P = 0.022). When compared with the control, only subjects in the telephone group were significantly more likely to collect FIT tubes (adjusted odds ratio [AOR] 3.18, 95% confidence interval [CI] = 1.50 to 6.75, P = 0.003) and return completed specimens (AOR = 2.73, 95% CI = 1.35 to 5.53, P = 0.005).Conclusion: Interactive telephone reminders are effective at securing previously screened subjects to repeat screening 1 year after a negative finding. [ABSTRACT FROM AUTHOR]

Radio pulsars scintillate because their emission travels through the ionized interstellar medium along multiple paths, which interfere with each other. It has long been realized that, independent of their nature, the regions responsible for the scintillation could be used as ‘interstellar lenses’ to localize pulsar emission regions [1], [2]. Most such lenses, however, resolve emission components only marginally, limiting results to statistical inferences and detections of small positional shifts [3]- [5]. As lenses situated close to their source offer better resolution, it should be easier to resolve emission regions of pulsars located in high-density environments such as supernova remnants [6] or binaries in which the pulsar’s companion has an ionized outflow. Here we report observations of extreme plasma lensing in the ‘black widow’ pulsar, B1957+20, near the phase in its 9.2-hour orbit at which its emission is eclipsed by its companion’s outflow [7]- [9]. During the lensing events, the observed radio flux is enhanced by factors of up to 70-80 at specific frequencies. The strongest events clearly resolve the emission regions: they affect the narrow main pulse and parts of the wider interpulse differently. We show that the events arise naturally from density fluctuations in the outer regions of the outflow, and we infer a resolution of our lenses that is comparable to the pulsar’s radius, about 10 kilometres. Furthermore, the distinct frequency structures imparted by the lensing are reminiscent of what is observed for the repeating fast radio burst FRB 121102, providing observational support for the idea that this source is observed through, and thus at times strongly magnified by, plasma lenses [10]. Radiation from the ‘black widow’ pulsar B1957+20 is amplified when a companion brown dwarf passes in front of the source, suggesting that plasma flowing from the companion acts as a lens. [ABSTRACT FROM AUTHOR]

Background: Many patients admitted to hospital have an antibiotic allergy (AAL) documented in their medical record. In many of these, the reaction is not a hypersensitivity reaction or may no longer be relevant. Despite this, the label adversely affects patient care directly in terms of antibiotic selection, and indirectly in terms of patient costs and the development of antimicrobial resistance.Aims: To estimate the prevalence of AALs in a cohort of hospitalised patients, to investigate the feasibility of de-labelling through re-challenge based solely upon clinical grounds.Design: This is a cross-sectional study conducted over a 6-month period on adult inpatients. An allergy history was taken from each patient and compared with medical record data regarding allergy. Antibiotic selection data were collected (if relevant). It was then determined whether immediate de-labelling was appropriate, if direct provocation test (DPT) could be relatively safely performed, and if antibiotic selection was appropriate.Results: Three thousand eight hundred and fifty five patients were screened, 553 (14.35%) had an AAL, and 352 were interviewed. There were 426 AALs; 276 (64.8%) towards a penicillin. After taking a detailed clinical history of the type of reaction, approximately 20% could be immediately de-labelled and educated (non-allergic, non-severe reactions) and another 38% with either a definite or vague history of mild cutaneous reaction would be suitable for an attempt at clinical de-labelling DPT.Conclusions: These simple measures to 'de-label' patients appropriately, would increase the quality of care of this group known to have higher costs, infection with more resistant bacteria and worse health outcomes that 'non-labelled' patients. [ABSTRACT FROM AUTHOR]

Microglia, the brain's innate immune cells, have highly motile processes which constantly survey the brain to detect infection, remove dying cells, and prune synapses during brain development. ATP released by tissue damage is known to attract microglial processes, but it is controversial whether an ambient level of ATP is needed to promote constant microglial surveillance in the normal brain. Applying the ATPase apyrase, an enzyme which hydrolyzes ATP and ADP, reduces microglial process ramification and surveillance, suggesting that ambient ATP/ADP maintains microglial surveillance. However, attempting to raise the level of ATP/ADP by blocking the endogenous ecto-ATPase (termed NTPDase1/CD39), which also hydrolyzes ATP/ADP, does not affect the cell's ramification or surveillance, nor their membrane currents, which respond to even small rises of extracellular [ATP] or [ADP] with the activation of K+ channels. This indicates a lack of detectable ambient ATP/ADP and ecto-ATPase activity, contradicting the results with apyrase. We resolve this contradiction by demonstrating that contamination of commercially available apyrase by a high K+ concentration reduces ramification and surveillance by depolarizing microglia. Exposure to the same K+ concentration (without apyrase added) reduced ramification and surveillance as with apyrase. Dialysis of apyrase to remove K+ retained its ATP-hydrolyzing activity but abolished the microglial depolarization and decrease of ramification produced by the undialyzed enzyme. Thus, applying apyrase affects microglia by an action independent of ATP and no ambient purinergic signaling is required to maintain microglial ramification and surveillance. These results also have implications for hundreds of prior studies that employed apyrase to hydrolyze ATP/ADP. [ABSTRACT FROM AUTHOR]

Background and Aim We validated a modified risk algorithm based on the Asia-Pacific Colorectal Screening (APCS) score that included body mass index (BMI) for prediction of advanced neoplasia. Methods Among 5744 Chinese asymptomatic screening participants undergoing a colonoscopy in Hong Kong from 2008 to 2012, a random sample of 3829 participants acted as the derivation cohort. The odds ratios for significant risk factors identified by binary logistic regression analysis were used to build a scoring system ranging from 0 to 6, divided into 'average risk' (AR): 0; 'moderate risk' (MR): 1-2; and 'high risk' (HR): 3-6. The other 1915 subjects formed a validation cohort, and the performance of the score was assessed. Results The prevalence of advanced neoplasia in the derivation and validation cohorts was 5.4% and 6.0%, respectively ( P = 0.395). Old age, male gender, family history of colorectal cancer, smoking, and BMI were significant predictors in multivariate regression analysis. A BMI cut-off at > 23 kg/m2 had better predictive capability and lower number needed to screen than that of > 25 kg/m2. Utilizing the score developed, 8.4%, 57.4%, and 34.2% in the validation cohort were categorized as AR, MR, and HR, respectively. The corresponding prevalence of advanced neoplasia was 3.8%, 4.3%, and 9.3%. Subjects in the HR group had 2.48-fold increased prevalence of advanced neoplasia than the AR group. The c-statistics of the modified score had better discriminatory capability than that using predictors of APCS alone (c-statistics = 0.65 vs 0.60). Conclusions Incorporating BMI into the predictors of APCS score was found to improve risk prediction of advanced neoplasia and reduce colonoscopy resources. [ABSTRACT FROM AUTHOR]

The gene RmGH28 from the organism Rhodothermus marinus, a putative glycosyl hydrolase family 28 polygalacturonase, was expressed in Escherichia coli and biochemically characterized. The gene was found to encode an exopolygalacturonase termed RmGH28, with galacturonic acid monomer and the polymer substrate (n-1) as the products released when acting on de-esterified polygalacturonic acid from citrus pectin. The enzyme at 25 °C had k ∼6 s when acting on polygalacturonic acid, with K ∼0.7 μM and a substrate inhibition constant K ∼70 μM. The enzyme was hyperthermophilic, with one half initial enzyme activity remaining after 1-h incubation at 93.9 °C. Since the enzyme can function at high temperatures where reaction rates are increased and the risk of bacterial contamination is decreased, this indicates that RmGH28 can be useful in industry for generating galacturonic acid from pectin. The amino acid sequence of RmGH28 is highly homologous to the known hyperthermophilic exopolygalacturonases TtGH28 and Tm0437, which together can serve as starting points for structure-function studies and molecular breeding enzyme engineering approaches. [ABSTRACT FROM AUTHOR]

Workup following retinal artery occlusion-experience from an outpatient retina clinic and the delay in workup. CT scan, CT angiogram, MRI, diffusion-weighed MRI, and MR angiogram are all reasonable, but likely low-value investigations for secondary prevention of stroke. Workup following retinal artery occlusion-experience from an outpatient retina clinic and the delay in workup. [Extracted from the article]

Divalent metal-activated glycoside hydrolase family 43 (GH43) β-xylosidases have been found to have high k / K for xylooligosaccharides and may demonstrate high efficacy in industrial reactors digesting hemicellulose. By searching an amino acid database, we found a Bacteroides ovatus GH43 β-xylosidase termed BoXA that is 81% identical in overall amino acid sequence to a GH43, divalent metal-activated β-xylosidase with high k / K , and also it has 19 of 20 residues in the active site conserved. However, unlike its metal-activated homolog, the B. ovatus enzyme does not lose activity after extensive EDTA treatment nor does it gain activity by addition of divalent metal ions. Thus, either it cannot be activated by divalent metal or it maintains a tightly bound, non-exchangeable metal ion. At 25 °C and pH 6.0, the k is 69 s for xylobiose and k / K is 210 s mM for xylotriose, with the latter being 0.7 that of the highest known value. The determined K for d-glucose is 4.9 M, which is the highest known for a β-xylosidase. The enzyme has potential utility operating in bioreactors digesting plant biomass. [ABSTRACT FROM AUTHOR]

Individuals hold different epistemic beliefs at different ages, and these beliefs can affect a wide range of reasoning tasks. The present study examined Chinese secondary school students' epistemic beliefs at different grade levels, and how these related to the students' abilities to identify various forms of fallacy with the use of a cross-sectional design. One hundred and forty-six Chinese secondary school students (Grade 7 N = 32, Grade 9 N = 40, Grade 10 N = 36, and Grade 11 N = 38) completed a 14-item Epistemic Beliefs Questionnaire and a set of fallacy tasks. CFA showed that the questionnaire measured the four dimensions of the secondary school student samples adequately. A non-linear trend of epistemic beliefs across different grades was found and analyses using MANOVA showed significant grade differences in the dimension of Certainty (Grade 7 vs. 10 vs. 11). χ tests showed only significant grade difference in the fallacy of Appeal to Authority (Grade 7 vs Grade 9; Grade 7 vs. 10). Finally, only grade, but not epistemic beliefs, predicted fallacy identification (Appeal to Authority) when all variables were considered in the ordinal logistic regression model. The issue of epistemic dimensions change and students' informal reasoning ability are discussed in light of the Chinese culture. [ABSTRACT FROM AUTHOR]

D-galacturonic acid is a potential platform chemical comprising the principal component of pectin in the citrus processing waste stream. Several enzyme activities are required for the enzymatic production of galacturonic acid from pectin, including exo- and endo-polygalacturonases. The gene TtGH28 encoding a putative GH28 polygalacturonase from Pseudothermotoga thermarum DSM 5069 (Theth_0397, NCBI# AEH50492.1) was synthesized, expressed in Escherichia coli, and characterized. Alignment of the amino acid sequence of gene product TtGH28 with other GH28 proteins whose structures and details of their catalytic mechanism have been elucidated shows that three catalytic Asp residues and several other key active site residues are strictly conserved. Purified TtGH28 was dimeric and hyperthermostable, with K = 86.3 °C. Kinetic parameters for activity on digalacturonic acid, trigalacturonic acid, and polygalacturonic acid were obtained. No substrate inhibition was observed for polygalacturonate, while the K values for the oligogalacturonides were in the low mM range, and K for product galacturonic acid was in the low μM range. Kinetic modeling of the progress of reaction showed that the enzyme is both fully exo- and fully non-processional. [ABSTRACT FROM AUTHOR]

Patients with nonalcoholic fatty liver disease (NAFLD) and family history of colorectal cancer (CRC) are at higher risks but how they should be screened remains uncertain. Hence, we evaluated the cost-effectiveness of CRC screening among patients with NAFLD and family history by different strategies. A hypothetical population of 100,000 subjects aged 40-75 years receive: (i) yearly fecal immunochemical test (FIT) at 50 years; (ii) flexible sigmoidoscopy (FS) every 5 years at 50 years; (iii) colonoscopy 10 yearly at 50 years; (iv) colonoscopy 10 yearly at 50 years among those with family history/NAFLD and yearly FIT at 50 years among those without; (v) colonoscopy 10 yearly at 40 years among those with family history/NAFLD and yearly FIT at 50 years among those without and (vi) colonoscopy 10 yearly at 40 years among those with family history/NAFLD and colonoscopy 10 yearly at 50 years among those without. The incremental cost-effectiveness ratio (ICER) was studied by Markov modeling. It was found that colonoscopy, FS and FIT reduced incidence of CRC by 49.5, 26.3 and 23.6%, respectively. Using strategies 4, 5 and 6, the corresponding reduction in CRC incidence was 29.9, 30.9 and 69.3% for family history, and 33.2, 34.7 and 69.8% for NAFLD. Compared with no screening, strategies 4 (US$1,018/life-year saved) and 5 (US$7,485) for family history offered the lowest ICER, whilst strategy 4 (US$5,877) for NAFLD was the most cost-effective. These findings were robust when assessed with a wide range of deterministic sensitivity analyses around the base case. These indicated that screening patients with family history or NAFLD by colonoscopy at 50 years was economically favorable. [ABSTRACT FROM AUTHOR]

We report the X-ray crystal structure of a glycoside hydrolase family 43 β-xylosidase, RS223BX, which is strongly activated by the addition of divalent metal cations. The 2.69 Å structure reveals that the Ca cation is located at the back of the active-site pocket. The Ca is held in the active site by the carboxylate of D85, an 'extra' acid residue in comparison to other GH43 active sites. The Ca is in close contact with a histidine imidazole, which in turn is in contact with the catalytic base (D15) thus providing a mechanism for stabilizing the carboxylate anion of the base and achieve metal activation. The active-site pocket is mirrored by an 'inactive-site' pocket of unknown function that resides on the opposite side of the monomer. [ABSTRACT FROM AUTHOR]

Objective To compare the performance of existing sigmoidoscopy-based strategies in predicting advanced proximal neoplasia (APN) in an asymptomatic Chinese cohort. Design We included all screening participants aged 50-70 years who received colonoscopy between 2008 and 2014 in Hong Kong. Sigmoidoscopy yield was estimated from the colonoscopic findings based on the: (1) UK flexible sigmoidoscopy; (2) Screening for COlon REctum (SCORE); (3) NORwegian Colorectal Cancer Prevention (NORCCAP) trials and (4) US clinical index based on age, gender and distal findings. The sensitivity, specificity, the number of subjects needed to screen (NNS) and the number of subjects needed to refer (NNR) for colonoscopy to detect one APN were evaluated. Binary logistic regression modelling identified the distal findings associated with APN. Results From 5879 eligible subjects, 132 (2.2%) had APN. The US strategy achieved the highest sensitivity for APN detection (42.0%) and the UK criteria attained the highest specificity (96%). The US criteria led to the lowest NNS (92 vs 103-267) and the UK criteria required the least NNR (12 vs 16-21). Using the US strategy, the rates of APN detected were 1.4% (low-risk group), 2.2% (intermediate risk) and 5.9% (high risk). The c-statistics of the UK, SCORE, NORCCAP and the US criteria were 0.55±0.03; 0.59±0.03; 0.59±0.03 and 0.62±0.05 respectively. Conclusions The US criteria had the highest sensitivity for detection of APN and lowest NNS and the UK score had the highest specificity and the lowest NNR. The performance of all these four criteria to predict APN is limited, highlighting an urgent need to devise a novel APN prediction system for Asian subjects. [ABSTRACT FROM AUTHOR]

Purpose: Very few studies examined the issue of regret on choosing colorectal cancer (CRC) screening tests. We evaluated the determinants of regret and tested the hypothesis that regret over screening choices was associated with poorer screening compliance. Methods: A bowel cancer screening centre invited all Hong Kong citizens aged 50-70 years who were asymptomatic of CRC to participate in free-of-charge screening programmes. Upon attendance they attended health seminars on CRC and its screening, and were offered an option to choose yearly faecal immunochemical test (FIT) for up to four years vs. one direct colonoscopy. They were not allowed to switch the screening option after decision. A self-administered, four-item validated survey was used to assess whether they regretted over their choice (> 2 = regretful from a scale of 0 [no regret]-5 [extreme regret]). A binary logistic regression model evaluated if initial regret over their choice was associated with poorer programme compliance. Results: From 4,341 screening participants who have chosen FIT or colonoscopy, 120 (2.8%) regretted over their decision and 1,029 (23.7%) were non-compliant with the screening programme. Younger subjects and people who felt pressure when making their decision were associated with regret. People who regretted their decision were 2.189 (95% C.I. 1.361-3.521, p = 0.001) times more likely to be non-compliant with the programme. Conclusions: This study is the first to show that regret over the initial CRC screening choice was associated with later non-compliance. Screening participants who expressed regret over their choice should receive additional reminders to improve their programmatic compliance. [ABSTRACT FROM AUTHOR]