Exploring factors influencing outpatient radiology attendance based on Health Belief Model (HBM): A qualitative study.

INTRODUCTION: Non-attendance for radiology outpatient appointments is a global issue and is associated with adverse clinical outcomes and operational inefficiencies. This paper aims to understand the underlying factors influencing outpatient radiology attendances based on the Health Belief Model (HBM). METHODS: Purposive sampling was used to recruit patients (n=30) for in-depth semi-structured telephone interviews. Inclusion criteria comprised participants who were above 21 years old and fluent in English, while participants reliant on third-party assistance (e.g., nursing homes and prison services), to attend the appointment were excluded. The interviews were recorded and transcribed verbatim. The COREQ (Consolidated Criteria for Reporting Qualitative Research) was utilised to guide the reporting of this study. The data analysis involved a hybrid thematic analysis approach using NVivo. RESULTS: Six key themes associated with appointment adherence in radiology were identified. These themes included: 1) prioritising health and acceptance of current medical conditions; 2) the impact of perceived severity on non-attendance; 3) perceived benefits of attending appointments; 4) perceived barriers to attendance; 5) influential prompts; and 6) confidence in attendance. CONCLUSION: This is the first study of its kind to utilise the HBM to examine factors influencing attendance adherence among radiology outpatients in Singapore. Costs, prompts, and the perceived severity of the condition play pivotal roles in shaping the health-seeking behaviours of these outpatients while professionalism of healthcare staff and barriers to attendance present opportunities for providers to address patients' lack of interest towards their appointments. IMPLICATIONS FOR PRACTICE: Findings of this study will contribute to the development of personalised, targeted interventions for improving patient engagement and attendance in radiology settings.

Efficacy of Oral SERDs in the treatment of ER+, HER2 - metastatic breast cancer, a stratified analysis of the ESR1 wild type and mutant subgroups.

BACKGROUND: Oral SERDs are a novel drug class that have been developed to counteract resistance due to ESR1 mutations. Several SERDs have emerged from phase 2 and 3 trials, with the FDA limiting approval for Elacestrant to patients with ESR1mt tumours despite PFS benefit in the overall population. However, questions remain on whether patients with ESR1wt tumours stand to benefit from oral SERDs. PATIENTS AND METHODS: Manuscripts and conference presentations of Randomised Controlled Trials were extracted after a systematic search of Embase, PubMed and Cochrane from inception until January 21,2023. RCTs investigating the efficacy of oral SERDs versus endocrine therapy for ER positive, HER2 negative advanced breast cancer, and which reported the Kaplan Meier (KM) curves of PFS in the overall and ESR1 mutant (ESR1mt) population were selected. A graphical reconstructive algorithm was applied to estimate time-to-event outcomes from reported KM curves in all overall and ESR1mt cohorts. A bipartite matching algorithm, KMSubtraction, was used to derive survival data for unreported (ESR1wt) subgroups. An individual patient data (IPD) meta-analysis was then pursued, pooling data by ESR1 mutation status in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Cochrane Guidelines for IPD. RESULTS: The randomized clinical trials ACELERA, AMEERA-3, EMERALD and SERENA-2 were included, totalling 1290 patients. In the pooled analysis of the overall cohort, PFS benefit was observed with oral SERDs when compared with treatment of physicians choice (TPC) (HR 0.783, 95%CI 0.681-0.900, p<0.001). In the ESR1mt subgroup, oral SERDs demonstrated improved PFS (HR 0.557, 95%CI 0.440-0.705, p<0.001) compared to TPC. In the ESR1wt subgroup, oral SERDs demonstrated no significant PFS benefit (HR 0.944, 95%CI 0.783-1.138, p=0.543) when compared to TPC. CONCLUSIONS: The results of this IPD meta-analysis suggests that PFS benefit in the overall population is mainly driven by the ESR1mt subgroup.

Cosmic-ray antinuclei as messengers of new physics: status and outlook for the new decade.

The precise measurement of cosmic-ray antinuclei serves as an important means for identifying the nature of dark matter and other new astrophysical phenomena, and could be used with other cosmic-ray species to understand cosmic-ray production and propagation in the Galaxy. For instance, low-energy antideuterons would provide a "smoking gun" signature of dark matter annihilation or decay, essentially free of astrophysical background. Studies in recent years have emphasized that models for cosmic-ray antideuterons must be considered together with the abundant cosmic antiprotons and any potential observation of antihelium. Therefore, a second dedicated Antideuteron Workshop was organized at UCLA in March 2019, bringing together a community of theorists and experimentalists to review the status of current observations of cosmic-ray antinuclei, the theoretical work towards understanding these signatures, and the potential of upcoming measurements to illuminate ongoing controversies. This review aims to synthesize this recent work and present implications for the upcoming decade of antinuclei observations and searches. This includes discussion of a possible dark matter signature in the AMS-02 antiproton spectrum, the most recent limits from BESS Polar-II on the cosmic antideuteron flux, and reports of candidate antihelium events by AMS-02; recent collider and cosmic-ray measurements relevant for antinuclei production models; the state of cosmic-ray transport models in light of AMS-02 and Voyager data; and the prospects for upcoming experiments, such as GAPS. This provides a roadmap for progress on cosmic antinuclei signatures of dark matter in the coming years.

Variants in ACTG2 underlie a substantial number of Australasian patients with primary chronic intestinal pseudo-obstruction.

BACKGROUND: Primary chronic intestinal pseudo-obstruction (CIPO) is a rare, potentially life-threatening disorder characterized by severely impaired gastrointestinal motility. The objective of this study was to examine the contribution of ACTG2, LMOD1, MYH11, and MYLK mutations in an Australasian cohort of patients with a diagnosis of primary CIPO associated with visceral myopathy. METHODS: Pediatric and adult patients with primary CIPO and suspected visceral myopathy were recruited from across Australia and New Zealand. Sanger sequencing of the genes encoding enteric gamma-actin (ACTG2) and smooth muscle leiomodin (LMOD1) was performed on DNA from patients, and their relatives, where available. MYH11 and MYLK were screened by next-generation sequencing. KEY RESULTS: We identified heterozygous missense variants in ACTG2 in 7 of 17 families (~41%) diagnosed with CIPO and its associated conditions. We also identified a previously unpublished missense mutation (c.443C>T, p.Arg148Leu) in one family. One case presented with megacystis-microcolon-intestinal hypoperistalsis syndrome in utero with subsequent termination of pregnancy at 28 weeks' gestation. All of the substitutions identified occurred at arginine residues. No likely pathogenic variants in LMOD1, MYH11, or MYLK were identified within our cohort. CONCLUSIONS AND INFERENCES: ACTG2 mutations represent a significant underlying cause of primary CIPO with visceral myopathy and associated phenotypes in Australasian patients. Thus, ACTG2 sequencing should be considered in cases presenting with hypoperistalsis phenotypes with suspected visceral myopathy. It is likely that variants in other genes encoding enteric smooth muscle contractile proteins will contribute further to the genetic heterogeneity of hypoperistalsis phenotypes.

The contribution of recently identified adult BMI risk loci to paediatric obesity in a Singaporean Chinese childhood dataset.

INTRODUCTION: Recent genome-wide association studies have identified 103 adult obesity risk loci; however, it is unclear if these findings are relevant to East-Asian childhood body mass index (BMI) levels. METHODS AND RESULTS: We evaluated for paediatric obesity associations at these risk loci utilizing genome-wide data from Chinese childhood subjects in the Singapore Cohort study Of the Risk factors for Myopia study (N = 1006). A weighted gene-risk score of all adult obesity risk loci in the Singapore Cohort study Of the Risk factors for Myopia study showed strong associations with BMI at age 9 (p-value = 3.40 × 10-12 ) and 4-year average BMI (age 9 to 12, p-value = 6.67 × 10-8 ). Directionally consistent nominal associations for 15 index single nucleotide polymorphisms (SNPs) (p-value < 0.05) were observed. Pathway analysis with genes from these 15 replicating loci revealed over-representation for the G-protein-coupled receptor (GPCR)-mediated integration of entero-endocrine signalling pathway exemplified by L-cell (adjusted p-value = 0.018). Evaluations of birth weight to modify the effects of BMI risk SNPs in paediatric obesity did not reveal significant interactions, and these SNPs were generally not associated with birth weight. CONCLUSIONS: At least some common adult BMI risk variants predispose to paediatric obesity risk in East-Asians.

TPM3 deletions cause a hypercontractile congenital muscle stiffness phenotype.

OBJECTIVE: Mutations in TPM3, encoding Tpm3.12, cause a clinically and histopathologically diverse group of myopathies characterized by muscle weakness. We report two patients with novel de novo Tpm3.12 single glutamic acid deletions at positions ΔE218 and ΔE224, resulting in a significant hypercontractile phenotype with congenital muscle stiffness, rather than weakness, and respiratory failure in one patient. METHODS: The effect of the Tpm3.12 deletions on the contractile properties in dissected patient myofibers was measured. We used quantitative in vitro motility assay to measure Ca(2+) sensitivity of thin filaments reconstituted with recombinant Tpm3.12 ΔE218 and ΔE224. RESULTS: Contractility studies on permeabilized myofibers demonstrated reduced maximal active tension from both patients with increased Ca(2+) sensitivity and altered cross-bridge cycling kinetics in ΔE224 fibers. In vitro motility studies showed a two-fold increase in Ca(2+) sensitivity of the fraction of filaments motile and the filament sliding velocity concentrations for both mutations. INTERPRETATION: These data indicate that Tpm3.12 deletions ΔE218 and ΔE224 result in increased Ca(2+) sensitivity of the troponin-tropomyosin complex, resulting in abnormally active interaction of the actin and myosin complex. Both mutations are located in the charged motifs of the actin-binding residues of tropomyosin 3, thus disrupting the electrostatic interactions that facilitate accurate tropomyosin binding with actin necessary to prevent the on-state. The mutations destabilize the off-state and result in excessively sensitized excitation-contraction coupling of the contractile apparatus. This work expands the phenotypic spectrum of TPM3-related disease and provides insights into the pathophysiological mechanisms of the actin-tropomyosin complex.

Pharmacogenomic diversity in Singaporean populations and Europeans.

Differences in the frequency of pharmacogenomic variants may influence inter-population variability in drug efficacy and risk of adverse drug reactions (ADRs). We investigated the diversity of ∼ 4500 genetic variants in key drug-biotransformation and -response genes among three South East Asian populations compared with individuals of European ancestry. We compared rates of reported ADRs in these Asian populations to determine if the allelic differentiation corresponded to an excess of the associated ADR. We identified an excess of ADRs related to clopidogrel in Singaporean Chinese, consistent with a higher frequency of a known risk variant in CYP2C19 in that population. We also observed an excess of ADRs related to platinum compounds in Singaporean CHS, despite a very low frequency of known ADR risk variants, suggesting the presence of additional genetic and non-genetic risk factors. Our results point to substantial diversity at specific pharmacogenomic loci that may contribute to inter-population variability in drug response phenotypes.

Knockout of a putative ergothioneine transporter in Caenorhabditis elegans decreases lifespan and increases susceptibility to oxidative damage.

In addition to excretion of metabolic waste products, organic ionic transporters facilitate uptake of specific compounds of physiological importance. In animals, the organic cation transporter, OCTN1 was found to enable the specific uptake of the unique amino acid, ergothioneine (EGT). EGT can accumulate in the body at up to millimolar concentrations and is believed to function as a physiological antioxidant. However the main function of EGT and the reasons for its active accumulation in the body remain obscure. Through bioinformatic approaches, we identified an analogous EGT transporter in the nematode, Caenorhabditis elegans. The present study investigated and characterized deletion mutants of this gene, OCT-1, in the nematodes. Gene deletion mutations of the OCT-1 transporter were shown to decrease overall lifespan of the worms and increase oxidative damage. However the absence of impaired EGT uptake and the inability of excess EGT to rescue the debilitating phenotype indicate that EGT transport does not explain the deleterious effects of the gene deletion.

Utility and safety of procalcitonin in an antimicrobial stewardship program (ASP) in patients with malignancies.

As data on procalcitonin utility in antibiotics discontinuation [under an antimicrobial stewardship program (ASP)] in patients with malignancies are lacking, we aimed to evaluate the utility of procalcitonin in an ASP in patients with malignancies. We conducted a retrospective review of the ASP database of all patients with malignancies in whom at least one procalcitonin level was taken and our ASP had recommended changes in carbapenem regimen, from January to December 2011. We compared clinical outcomes between two groups of patients: patients whose physicians accepted and those whose physicians rejected ASP interventions. There were 749 carbapenem cases reviewed. Ninety-nine were suggested to either de-escalate, discontinue antibiotics, or narrow the spectrum of empiric treatment, based on procalcitonin trends. While there was no statistical difference in the mortality within 30 days post-ASP intervention (accepted: 8/65 patients vs. rejected: 9/34 patients; p = 0.076), the median duration of carbapenem therapy was significantly shorter (5 vs. 7 days; p = 0.002). Procalcitonin use safely facilitates decisions on antibiotics discontinuation and de-escalation in patients with malignancies in the ASP.

Replication of 13 obesity loci among Singaporean Chinese, Malay and Asian-Indian populations.

OBJECTIVE: Recent genome-wide association studies (GWAS) have identified 38 obesity-associated loci among European populations. However, their contribution to obesity in other ethnicities is largely unknown. METHODS: We utilised five GWAS (N=10 482) from Chinese (three cohorts, including one with type 2 diabetes and another one of children), Malay and Indian ethnic groups from Singapore. Data sets were analysed individually and subsequently in combined meta-analysis for Z-score body-mass index (BMI) associations. RESULTS: Variants at the FTO locus showed the strongest associations with BMI Z-score after meta-analysis (P-values 1.16 × 10(-7)-7.95 × 10(-7)). We further detected associations with nine other index obesity variants close to the MC4R, GNPDA2, TMEM18, QPCTL/GIPR, BDNF, ETV5, MAP2K5/SKOR1, SEC16B and TNKS/MSRA loci (meta-analysis P-values ranging from 3.58 × 10(-4)-1.44 × 10(-2)). Three other single-nucleotide polymorphisms (SNPs) from CADM2, PTBP2 and FAIM2 were associated with BMI (P-value ≤ 0.0418) in at least one dataset. The neurotrophin/TRK pathway (P-value=0.029) was highlighted by pathway-based analysis of loci that had statistically significant associations among Singaporean populations. CONCLUSION: Our data confirm the role of FTO in obesity predisposition among Chinese, Malays and Indians, the three major Asian ethnic groups. We additionally detected associations for 12 obesity-associated SNPs among Singaporeans. Thus, it is likely that Europeans and Asians share some of the genetic predisposition to obesity. Furthermore, the neurotrophin/TRK signalling may have a central role for common obesity among Asians.

Recent trends in the intrinsic water-use efficiency of ringless rainforest trees in Borneo.

Stable carbon isotope (δ(13)C) series were developed from analysis of sequential radial wood increments from AD 1850 to AD 2009 for four mature primary rainforest trees from the Danum and Imbak areas of Sabah, Malaysia. The aseasonal equatorial climate meant that conventional dendrochronology was not possible as the tree species investigated do not exhibit clear annual rings or dateable growth bands. Chronology was established using radiocarbon dating to model age-growth relationships and date the carbon isotopic series from which the intrinsic water-use efficiency (IWUE) was calculated. The two Eusideroxylon zwageri trees from Imbak yielded ages of their pith/central wood (±1 sigma) of 670 ± 40 and 759 ± 40 years old; the less dense Shorea johorensis and Shorea superba trees at Danum yielded ages of 240 ± 40 and 330 ± 40 years, respectively. All trees studied exhibit an increase in the IWUE since AD 1960. This reflects, in part, a response of the forest to increasing atmospheric carbon dioxide concentration. Unlike studies of some northern European trees, no clear plateau in this response was observed. A change in the IWUE implies an associated modification of the local carbon and/or hydrological cycles. To resolve these uncertainties, a shift in emphasis away from high-resolution studies towards long, well-replicated time series is proposed to develop the environmental data essential for model evaluation. Identification of old (greater than 700 years) ringless trees demonstrates their potential in assessing the impacts of climatic and atmospheric change. It also shows the scientific and applied value of a conservation policy that ensures the survival of primary forest containing particularly old trees (as in Imbak Canyon and Danum).

Comparing the efficacy of sunitinib with sorafenib in xenograft models of human hepatocellular carcinoma: mechanistic explanation.

Hepatocellular carcinoma (HCC) is the fifth most common and third deadliest malignancy. Sorafenib has demonstrated 44% survival advantage over placebo and has emerged as a standard of care in advanced HCC. The therapeutic effects of sorafenib are however transient and hence additional treatment options are warranted. In this study, we aimed to compare the efficacy of sunitinib relative to sorafenib, two potent inhibitors of protein tyrosine kinases involved in tumor growth, metastasis, or angiogenesis. We reported that sorafenib and sunitinib suppressed tumor growth, angiogenesis, cell proliferation, and induced apoptosis in both orthotopic and ectopic models of HCC. However, the antitumor effect of 50 mg/kg sorafenib was greater than that of 40 mg/kg sunitinib. Sorafenib inhibited p-eIF4E Ser209, p-p38 Thr180/Tyr182 and reduced survivin expression. This was not seen with sunitinib. In addition, the antitumor and apoptotic effects of sorafenib, which are associated with upregulation of fast migrating Bim and ASK1 and downregulation of survivin, were greater than that of sunitinib. These observations explained in part the apparent superior anti-tumor activity of sorafenib compared to sunitinib. In conclusion, sunitinib demonstrated an inferior anti-tumor activity compared to sorafenib in ectopic and orthotopic models of human HCC. It remains to be seen whether such observations would be recapitulated in humans.

Prospective determination of the specificity of a commercial snake venom detection kit in urine samples from dogs and cats.

OBJECTIVE: To determine the specificity of a snake venom detection kit in urine samples from dogs and cats presenting to a referral centre for diseases unrelated to snake envenomation. DESIGN: Urine was collected from 50 dog and 25 cats presented for investigation and treatment of diseases unrelated to snake envenomation. Urine was collected as a voided sample, by cystocentesis or by catheterisation, and routine urinanalysis was performed. Snake venom testing was performed within 2 h of collection using a commercially available snake venom detection kit, which was observed continuously during the 10-min colour reaction phase for evidence of a visible colour indicating a positive test. RESULTS: No false-positive reactions occurred in any sample analysed. CONCLUSION: The snake venom detection kit appears to have 100% specificity for using urine as a test sample.

Radio imaging of the very-high-energy gamma-ray emission region in the central engine of a radio galaxy.

The accretion of matter onto a massive black hole is believed to feed the relativistic plasma jets found in many active galactic nuclei (AGN). Although some AGN accelerate particles to energies exceeding 10(12) electron volts and are bright sources of very-high-energy (VHE) gamma-ray emission, it is not yet known where the VHE emission originates. Here we report on radio and VHE observations of the radio galaxy Messier 87, revealing a period of extremely strong VHE gamma-ray flares accompanied by a strong increase of the radio flux from its nucleus. These results imply that charged particles are accelerated to very high energies in the immediate vicinity of the black hole.

OSETI with STACEE: a search for nanosecond optical transients from nearby stars.

We have used the Solar Tower Atmospheric Cherenkov Effect Experiment (STACEE) high-energy gamma-ray detector to look for fast blue-green laser pulses from the vicinity of 187 stars. The STACEE detector offers unprecedented light-collecting capability for the detection of nanosecond pulses from such lasers. We estimate STACEE's sensitivity to be approximately 10 photons/m(2) at a wavelength of 420 nm. The stars have been chosen because their characteristics are such that they may harbor habitable planets, and they are relatively close to Earth. Each star was observed for 10 minutes, and we found no evidence for laser pulses in any of the data sets. Key Words: Search for extraterrestrial intelligence-Optical search for extraterrestrial intelligence-Interstellar communication-Laser.

Extradural haematoma secondary to brown snake (Pseudonaja species) envenomation.

A 4-year-old Siberian Husky dog was treated with brown snake antivenom by his regular veterinarian after a witnessed episode of brown snake envenomation. The dog was discharged 5 hours post presentation despite an ongoing coagulopathy. The dog was presented to the emergency centre 2 hours later because the owner believed the dog to be in pain. Initial examination revealed an ambulatory but neurologically normal patient with thoracolumbar pain and laboratory evidence of a coagulopathy. Despite correction of the coagulopathy, the signs progressed to bilateral hind limb paresis after approximately 3 hours of hospitalisation, and continued to deteriorate over the next 56 hours to loss of deep pain perception in the right hind limb. Computed tomography imaging identified the presence of an extradural haematoma which was subsequently removed via a hemilaminectomy. Surgical decompression was successful in treating the spinal compression and the dog recovered with minimal complications. To our knowledge this is the first report of extradural haematoma secondary to coagulopathy induced by brown snake envenomation.

Validation of hyperbaric oxygen treatment software for use with monoplace chambers.

Hyperbaric oxygen (HBO2) therapy is increasingly used in the treatment of a wide variety of medical conditions. However, for monoplace chambers, there is some uncertainty when sufficiently high oxygen concentrations are attained, because most chambers are not instrumented to measure oxygen. To remedy this, Microsoft Excel-based software, HBO O2 Smart Guide, was developed to simulate the atmosphere ofmonoplace chambers during treatment. Based upon chamber dimensions, patient weight, oxygen purge rates, desired pressurization, and HBO2 time, the program calculates oxygen concentration, consumption and exposure for each treatment. Software testing was conducted using four different chambers instrumented with an oxygen analyzer. Two purge rate profiles were used: constant, and biphasic (a high initial purge rate was changed to a lower plateau rate when pressurization was reached). Comparison of measured and calculated times to reach 95% oxygen concentration within the chambers demonstrated the software was accurate within 1%. The HBO O2 Smart Guide enables optimum purge profiles to be simulated with resultant potential improvements in HBO2 treatment efficacy, calculation of effective oxygen exposures (actual time during prescribed treatment during which patient breathes > or = 95% oxygen) to enable more accurate comparison of treatment profiles and outcomes, and cost savings in oxygen usage. This software will enable clinicians to provide more consistent HBO2 treatments.

Evaluation of 3D modality-independent elastography for breast imaging: a simulation study.

This paper reports on the development and preliminary testing of a three-dimensional implementation of an inverse problem technique for extracting soft-tissue elasticity information via non-rigid model-based image registration. The modality-independent elastography (MIE) algorithm adjusts the elastic properties of a biomechanical model to achieve maximal similarity between images acquired under different states of static loading. A series of simulation experiments with clinical image sets of human breasts were performed to test the ability of the method to identify and characterize a radiographically occult stiff lesion. Because boundary conditions are a critical input to the algorithm, a comparison of three methods for semi-automated surface point correspondence was conducted in the context of systematic and randomized noise processes. The results illustrate that 3D MIE was able to successfully reconstruct elasticity images using data obtained from both magnetic resonance and x-ray computed tomography systems. The lesion was localized correctly in all cases and its relative elasticity found to be reasonably close to the true values (3.5% with the use of spatial priors and 11.6% without). In addition, the inaccuracies of surface registration performed with thin-plate spline interpolation did not exceed empiric thresholds of unacceptable boundary condition error.