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Abstract Background Recent genomics studies of breast cancer in Asian cohorts have found a higher prevalence of TP53 mutations in Asian breast cancer patients relative to Caucasian patients. However, the effect of TP53 mutations on Asian breast tumours has not been comprehensively studied. Methods Here, we report an analysis of 492 breast cancer samples from the Malaysian Breast Cancer cohort where we examined the impact of TP53 somatic mutations in relation to PAM50 subtypes by comparing whole exome and transcriptome data from tumours with mutant and wild-type TP53. Results We found that the magnitude of impact of TP53 somatic mutations appears to vary between different subtypes. TP53 somatic mutations were associated with higher HR deficiency scores as well as greater upregulation of gene expression pathways in luminal A and luminal B tumours compared to the basal-like and Her2-enriched subtypes. The only pathways that were consistently dysregulated when comparing tumours with mutant and wild-type TP53 across different subtypes were the mTORC1 signalling and glycolysis pathways. Conclusion These results suggest that therapies that target TP53 or other downstream pathways may be more effective against luminal A and B tumours in the Asian population.

Epileptic seizures, sleep, and circadian timing share bilateral interactions, but concerted work to characterize these interactions and to leverage them to the advantage of patients with epilepsy remains in beginning stages. To further the field, a multidisciplinary group of sleep physicians, epileptologists, circadian timing experts, and others met to outline the state of the art, gaps of knowledge, and suggest ways forward in clinical, translational, and basic research. A multidisciplinary panel of experts discussed these interactions, centered on whether improvements in sleep or circadian rhythms improve decrease seizure frequency. In addition, education about sleep was lacking in among patients, their families, and physicians, and that focus on education was an extremely important low hanging fruit to harvest. Improvements in monitoring technology, experimental designs sensitive to the rigor required to dissect sleep versus circadian influences, and clinical trials in seizure reduction with sleep improvements were appropriate.

Appendiceal diverticulitis is a rare pathology which is distinctly different to acute appendicitis and associated with higher rates of morbidity and mortality. Furthermore, diagnosis is often retrospective on histopathological analysis of appendicectomy specimens due to the atypical clinical and radiological features. Herein, we present a case of ruptured appendiceal diverticulitis in a young patient with atypical clinical features and a radiologically normal appearing appendix in close proximity to an inflammatory phlegmon. This case highlights the importance of maintaining a high clinical suspicion of surgical pathology and considering atypical diagnosis in patients with inflammatory changes in the right iliac fossa.

Introduction Knife-enabled crime is a UK public health issue leading to substantial impacts on society, victims and their families, as well as additional strain on the healthcare system. Despite the increase in knife-enabled crime and the overwhelming consequences, there is a lack of comprehensive studies exploring the long-term health outcomes of knife crime victims in the UK. The research gap hinders the development of more targeted secondary preventative interventions, resource allocation and public awareness campaigns. This systematic review aims to identify the long-term health outcomes of knife crime victims, therefore providing valuable knowledge for stakeholders, health practitioners and policymakers for a more effective public health response.Methods and analysis A comprehensive search strategy was developed, focusing on four key concepts: study design, knife-related offences, outcomes and risk. Databases being searched include MEDLINE, EMBASE, PsycINFO, ProQuest Criminology Collection, Web of Science Core Collection, Google Scholar and OpenGrey. Reference lists and forward citations will be inspected for further suitable literature. The study selection will involve two independent reviewers screening the studies from the search, with disagreements resolved by a third reviewer. All UK quantitative research on long-term health outcomes of knife crime victims will be included in the review. Covidence will be used to efficiently manage data. A data extraction form has been developed which will summarise key aspects of each study that will be included in the review. Methodological Index for Non-Randomised Studies quality assessment checklist will be used to assess the studies and the Newcastle-Ottawa Scale will assess the risk of bias in each study. Findings will be narratively synthesised, and if heterogeneity is sufficient, a meta-analysis will be conducted.Ethics and dissemination Ethics approval is not required for this study as no original data will be collected. The results will be disseminated through a peer-reviewed publication and conference presentation.

Recently, transition metal doped superlattice has shown an anomalous optical band gap of 1.6 eV, about 1 eV lower than either parent element (Barium) majorly, making it appropriate for several applications including magnetism and superconducting materials. In the current study, the structural, electronic, phonon, thermodynamic, and the magnetic ordering of BaXO3 (X = Cr, Mn, Co, and Ni) has been examined using density functional theory (DFT). From the results, the investigated materials show a ferromagnetic behavior with the band gap of range 0.95–1.04 eV, and average absolute magnetization are 2.64, 3.67, 3.19, and 0.01 Bohr magneton/cell for BaCrO3, BaMnO3, BaCoO3, and BaNiO3, respectively. Furthermore, it is conceivable that the Compton profiles of BaXO3(X= Cr, Mn, Co, and Ni) are magnetic due to the substantial exchange-correlation dependence of their Compton profiles, which is shown from the phonon and X-ray distributions, thermodynamic calculation, and mechanically portrayed features of BaXO3. It was further discovered that doping could increase each TM (Cr, Mn, Co, and Ni) atom's magnetic moment. This study demonstrates a novel method for utilizing this revolutionary kind of cubic ferrites for spintronic applications in solid-state electronics.

Lung cancer is one of the most common cancers and a leading cause of cancer-related mortality in Malaysia. This analysis aimed to evaluate the prevalence of actionable and common mutations, as well as co-mutations frequently occurring with EGFR variants in lung cancer. Mutational profiling of lung tumour samples was performed using next generation sequencing (NGS) panels at the Subang Jaya Medical Centre laboratory. A total of 469 lung tumour samples referred from several medical facilities in Malaysia were analysed and 84% were of the adenocarcinoma subtype. The three most frequent mutations found were EGFR (46.5%), TP53 (37.5%) and KRAS (14.3%). Actionable mutations with approved drug targets for lung cancer were detected in 63.5% of patient samples. Among patients with EGFR mutations, deletions in exon 19 were detected in 44.5% and p.L858R in 38.5% of samples. The most common co-mutations for samples with EGFR mutations were found in the TP53 gene (38.1%). A median turnaround time (TAT) of 3 working days was achievable with an automated NGS platform. NGS testing can provide valuable information on the mutational landscape and the prevalence of common or actionable mutations present in lung cancer patients. This real-world experience demonstrates the high percentage of actionable mutations detected and highlights the value of NGS testing in a clinical diagnostic setting.

This research analyzes the shifting of management of God's Kingdom to focus on saving human resources in the economic site due to COVID-19. The old paradigm of management of God's Kingdom, which is to save human resources biblically, shifts to humans from the low economic condition. This study aims to redefine the shifting of management of God's Kingdom as the form of human resources development from the economic perspective. This study systematically presents the economy's condition due to COVID-19, the Church's response to it, and the redefinition of God's Kingdom management through the descriptive qualitative method. This research confirms the redefinition of management of God's Kingdom as the Church's response to help human resources. Finally, this research aims to give out some charity programs and skill training in saving human resources in responding to the economic downward due to COVID-19.

Abstract Physiological closed-loop controlled (PCLC) medical devices monitor and automatically adjust the patient’s condition by using physiological variables as feedback, ideally with minimal human intervention to achieve the target levels set by a clinician. PCLC devices present a challenge when it comes to evaluating their performance, where conducting large clinical trials can be expensive. Virtual physiological patients simulated by validated mathematical models can be utilized to obtain pre-clinical evidence of safety and assess the performance of the PCLC medical device during normal and worst-case conditions that are unlikely to happen in a limited clinical trial. A physiological variable that plays a major role during fluid resuscitation is heart rate (HR). For in silico assessment of PCLC medical devices regarding fluid perturbation, there is currently no mathematical model of HR validated in terms of its predictive capability performance. This paper develops and validates a mathematical model of HR response using data collected from sheep subjects undergoing hemorrhage and fluid infusion. The model proved to be accurate in estimating the HR response to fluid perturbation, where averaged between 21 calibration datasets, the fitting performance showed a normalized root mean square error (NRMSE) of $$7.41 \pm 2.8 \%$$ 7.41 ± 2.8 % . The model was also evaluated in terms of model predictive capability performance via a leave-one-out procedure (21 subjects) and an independent validation dataset (6 subjects). Two different virtual cohort generation tools were used in each validation analysis. The generated envelope of virtual subjects robustly met the defined acceptance criteria, in which $$95\%$$ 95 % of the testing datasets presented simulated HR patterns that were within a deviation of 50% from the observed data. In addition, out of 16000 and 18522 simulated subjects for the leave-one-out and independent datasets, the model was able to generate at least one virtual subject that was close to the real subject within an error margin of $$9.56 \pm 3.15\%$$ 9.56 ± 3.15 % and $$11.1 \pm 1.22\%$$ 11.1 ± 1.22 % NRMSE, respectively. In conclusion, the model can generate valid virtual HR physiological responses to fluid perturbation and be incorporated into future non-clinical simulated testing setups for assessing PCLC devices intended for fluid resuscitation.

Background: The prostate demonstrates inter- and intra- fractional changes and thus adaptive radiotherapy would be required to ensure optimal coverage. Daily adaptive radiotherapy for MRI-guided radiotherapy can be both time and resource intensive when structure delineation is completed manually. Contours can be auto-generated on the MR-Linac via a deformable image registration (DIR) based mapping process from the reference image. This study evaluates the performance of automatically generated target structure contours against manually delineated contours by radiation oncologists for prostate radiotherapy on the Elekta Unity MR-Linac. Methods: Plans were generated from prostate contours propagated by DIR and rigid image registration (RIR) for forty fractions from ten patients. A two-dose level SIB (simultaneous integrated boost) IMRT plan is used to treat localised prostate cancer; 6000 cGy to the prostate and 4860 cGy to the seminal vesicles. The dose coverage of the PTV 6000 and PTV 4860 created from the manually drawn target structures was evaluated with each plan. If the dose objectives were met, the plan was considered successful in covering the gold standard (clinician-delineated) volume. Results: The mandatory PTV 6000 dose objective (D98% > 5580 cGy) was met in 81 % of DIR plans and 45 % of RIR plans. The SV were mapped by DIR only and for all the plans, the PTV 4860 dose objective met the optimal target (D98% > 4617 cGy). The plans created by RIR led to under-coverage of the clinician-delineated prostate, predominantly at the apex or the bladder-prostate interface. Conclusion: Plans created from DIR propagation of prostate contours outperform those created from RIR propagation. In approximately 1 in 5 DIR plans, dosimetric coverage of the gold standard PTV was not clinically acceptable. Thus, at our institution, we use a combination of DIR propagation of contours alongside manual editing of contours where deemed necessary for online treatments.

A shift of the daily plan can mitigate target position changes that occur between daily MR acquisition and treatment for MR-linac radiotherapy, but increases the session time. We demonstrated that our workflow strategy and decision-making process, to determine whether a subsequent shift is necessary, is appropriate.

Abstract Background Parathyroid carcinoma is an uncommon cause of PTH-dependent hypercalcemia. Only a handful of cases have been reported of parathyroid carcinoma during pregnancy. Case presentation Twenty-four – Year – old female presented with proximal myopathy was found to have hypercalcemia. Her serum corrected total calcium was – 15 mg/dl (8.5 – 10.3), serum phosphate – 2.3 mg/dl (2.5 – 4.5), intact PTH – 118 pg/ml (20 – 80), Vitamin D – 15 ng/ml and Urine Ca/Cr ratio – 2.1 (0.1 – 0.2). Her CECT–neck revealed a well-defined mass lesion posterior to the right lobe of the thyroid – 2.6 cm × 2.5 cm × 2.9 cm in size. She was started on vitamin D supplementation, and she underwent right lower focal parathyroidectomy. Her PTH levels normalized following surgery. Her histology revealed an atypical parathyroid adenoma. She was treated with calcium and vitamin D. Her follow up was uneventful. One year following initial surgery the patient became pregnant and at 16 weeks of POA, the patient presented with a rapidly enhancing neck mass for one week duration. Her biochemical investigations were suggestive of a recurrence of primary hyperparathyroidism. Her ultrasound scan of the neck revealed a well-defined discreate hypoechoic nodule, superior to the thyroid isthmus which was confirmed by a non-contrast MRI scan of the neck. She underwent an uncomplicated second trimester parathyroid tumour excision with normalization of post op PTH. Her histology revealed a parathyroid carcinoma with vascular and capsular invasion. Her genetic studies revealed a novel frameshift mutation of the CDC73 gene. She was treated with calcium and vitamin D supplementation and closely followed up with ionized calcium and PTH levels which were normal throughout the pregnancy. She had an uncomplicated caesarean section at a POA of 37 weeks. Currently she is twelve weeks post-partum, in remission of disease. Conclusion This case shows the importance of stringent follow up of atypical parathyroid adenoma patients, the benefit of second trimester surgery in management of hypercalcemia due to parathyroid carcinoma during pregnancy and the importance of identifying the novel CDC73 gene mutation.

Background The retention of doctors is an important issue for the National Health Service; yet evidence suggests that the proportion of doctors wanting to leave UK medicine is increasing. Some of these doctors chose to continue their medical careers in other countries, however, some decided to leave the profession entirely.Objectives This was the first study to interview a cohort of UK doctors who have left the medical profession to embark on alternative careers. Participants were asked about the reasoning behind their decision to leave medicine.Design Qualitative study using one-to-one, semi-structured virtual interviews.Participants 17 participants, recruited via purposive sampling.Setting Zoom interviews with 17 former UK doctors who had left medicine to pursue alternative careers were conducted between February and July 2021.Findings Data were analysed using thematic analysis and the theory of work adjustment was applied to findings. The most frequently discussed reasons for leaving were associated with factors preventing participants from providing a desired level of patient care, work-life balance, a lack of support, a lack of control over working lives and the pull of alternative careers. While reasons for leaving varied between participants, all participants reported greater satisfaction in their new careers.Conclusion New careers were able to address many of the issues that caused participants to leave UK medicine. Consequently, it is important that some of the key issues raised in this study are addressed to retain more doctors in the UK medical workforce.

Development of rechargeable batteries for electronic appliances requires advancement of synthesizing new anode, cathode, and electrolyte materials. Li2GeO3 is a candidate anode material for use in lithium ion batteries owing to its fast Li-ion conductivity. Using advanced computational simulation techniques based on the classical potentials, we investigate the defect, diffusion, and dopant properties of Li2GeO3. Our simulation finds that the minimum energy defect process is the Li-Frenkel. The Li–Ge anti-site defect cluster is higher in energy by 0.45 eV than the Li-Frenkel. The long-range Li diffusion pathway is along the c-direction with an activation energy of 0.36 eV agreeing with the experimental observation. The most promising isovalent dopants on the Li and the Ge sites are the Na and the Si, respectively. Furthermore, the formation of lithium interstitials and oxygen vacancies can be experimentally verified by doping of Al3+ on the Ge site.

There are a variety of difficulties in evaluating clinical cardiac mapping systems, most notably the inability to record the transmembrane potential throughout the entire heart during patient procedures which prevents the comparison to a relevant “gold standard”. Cardiac mapping systems are comprised of hardware and software elements including sophisticated mathematical algorithms, both of which continue to undergo rapid innovation. The purpose of this study is to develop a computational modeling framework to evaluate the performance of cardiac mapping systems. The framework enables rigorous evaluation of a mapping system’s ability to localize and characterize (i.e., focal or reentrant) arrhythmogenic sources in the heart. The main component of our tool is a library of computer simulations of various dynamic patterns throughout the entire heart in which the type and location of the arrhythmogenic sources are known. Our framework allows for performance evaluation for various electrode configurations, heart geometries, arrhythmias, and electrogram noise levels and involves blind comparison of mapping systems against a “silver standard” comprised of computer simulations in which the precise transmembrane potential patterns throughout the heart are known. A feasibility study was performed using simulations of patterns in the human left atria and three hypothetical virtual catheter electrode arrays. Activation times (AcT) and patterns (AcP) were computed for three virtual electrode arrays: two basket arrays with good and poor contact and one high-resolution grid with uniform spacing. The average root mean squared difference of AcTs of electrograms and those of the nearest endocardial action potential was less than 1 ms and therefore appears to be a poor performance metric. In an effort to standardize performance evaluation of mapping systems a novel performance metric is introduced based on the number of AcPs identified correctly and those considered spurious as well as misclassifications of arrhythmia type; spatial and temporal localization accuracy of correctly identified patterns was also quantified. This approach provides a rigorous quantitative analysis of cardiac mapping system performance. Proof of concept of this computational evaluation framework suggests that it could help safeguard that mapping systems perform as expected as well as provide estimates of system accuracy.

The rising demand for the construction of pavement infrastructure creates great pressure on the production and transportation of virgin aggregates, which consumes high energy and natural resources. Therefore, the possibility of using recycled materials in pavements has generated wide interest in the growing economies of developed and developing countries. The wastes produced by construction and demolition materials such as recycled concrete aggregate (RCA) enter landfills every year. Similarly, wastes generated by end-of-life tyres are non-biodegradable and poses an environmental challenge. However, the research on the mechanical performance of waste tyre rubber (TR) in pavement applications is very limited. Therefore, finding innovative ways to incorporate these solid wastes could improve the sustainability of pavements. Meanwhile, the use of major binder (i.e., portland cement) for stabilisation of pavements contributes to carbon footprint issues. Hence, there is a need to use environmentally friendly binders such as ground granulated blast furnace slag which is a promising way to process these waste materials with significant environmental benefits. Therefore, this study investigates the feasibility of RCA and TR as a substitute for quarried pavement material, stabilised with slag (S) to improve the binding action between waste tyre rubber and surrounding aggregates. The main objective of the study was to evaluate the physical and mechanical characteristics of combined TR + RCA mixes by undertaking extensive laboratory tests. Firstly, unconfined compressive strength (UCS) test studies were conducted at 7 days of curing period at 21 °C to determine the efficacy of mixing two types of wastes by slag stabilisation at three different binder contents (10 %, 15 %, and 20 %). Subsequently, a series of resilient modulus (RLT) tests were performed to determine the stiffness of the mixes using a repeated load triaxial setup. Finally, the hydration mechanism was studied by microstructural studies (SEM) to understand the inter-particle bonding of TR + RCA mixes. It was found that stabilised mixes with 10 %TR could satisfy the minimum road requirements for pavement base layers in terms of compressive and resilient moduli characteristics. Besides, the study provided a mathematical model equation by response surface methodology to predict the values of UCS. Predicted values were found to be in good agreement with experimental values. The research offers a sustainable solution with the help of stabilisation technique in increasing the volume of combined TR + RCA wastes in pavements by satisfying road requirement criteria.

Abstract The investigation on the constant current (CC)/constant voltage (CV) charging for the electric vehicle wireless power transfer (WPT) system has been widely conducted. However, the CC/CV performance under misalignment cases has been scarcely studied especially for the multi‐coil WPT system. The resonant tank compensation methodology for the exciter‐quadrature‐repeaters (EQR) transmitter‐based multi‐coil WPT system is studied to achieve high power factor CC/CV charging with low leakage flux over ±150 mm lateral misalignment range. The EQR transmitter consists of one small exciter coil powered by a single full bridge inverter and two larger decoupled quadrature repeater coils which are magnetically coupled to the exciter coil. A variable switched capacitor is applied on the exciter side to maintain a high power factor in the CV mode. A 3‐kW experimental setup with a 200 mm nominal vertical distance was built and a three‐coil WPT system with a single large repeater coil is chosen as a comparison. Experimental results show that the EQR transmitter‐based WPT system achieves 92% coil‐to‐coil efficiency and reduces the leakage flux density by 70% compared with the existing three‐coil system in the CV mode at 150‐mm lateral misalignment.

Abstract Literature review demonstrated a surprising lack of publications on digital e-learning pathology resources for senior medical undergraduates and interns. An interactive Digital Pathology Repository (iDPR) integrating two- and three-dimensional (2D, 3D) high-resolution anatomical pathology images with correlated digital histopathology was developed. The novel iDPR was rigorously evaluated using mixed methods to assess pathology knowledge gains (pre- and post-tests), quality impact analysis (questionnaire), user feedback (focus group discussions) and user visual behaviour (eye gaze tracking analysis of 2D/ 3D images). Exposure to iDPR appeared to improve user pathology knowledge, as observed by significantly increased test scores on topic-related quizzes (n = 69, p

Intro: Sudden unexpected death in infants (SUDI) is one of major contributors to infant mortality worldwide and bacterial infection is a significant aetiological factor. However, worldwide and in Malaysia specifically, few studies report on post-mortem microbiological (PMM) tests in SUDI cases and the types of causative bacterial agents isolated at specific age range has not been well described. This study aimed to analyse the PMM samplings of bacterial isolates found in

Bushfires are classified as catastrophic disasters capable of inflicting significant destruction. The key detrimental consequences of bushfires include the loss of human lives, trauma within communities, economic losses and environmental damage. For example, the estimated economic loss from the September 2019 to March 2020 bushfires in New South Wales (Australia) was about AUD 110 billion, including more than 3000 burned houses. There has been a notable increase in both the frequency and intensity of bushfires, as clearly demonstrated by recent bushfire events. Bushfires are an intricate phenomenon that transpires across various spatial and temporal scales. Further, the changing circumstances of landscapes, vegetation patterns, weather conditions and ecosystems account for the complexity. Therefore, continual attention is essential for the development of bushfire management strategies. In this context, this paper undertakes a comprehensive literature review of bushfire management strategies, encompassing aspects such as bushfire prediction, detection, suppression and prevention. Based on the review, a bushfire management framework is proposed that can eliminate or successfully mitigate the consequences of bushfires. Further, the paper delves into the domains of fire weather conditions, the initiation of bushfires and the adverse consequences stemming from these fires. Both terrestrial and aerial remote sensing methods have proven to be effective in predicting and detecting bushfires. Nevertheless, a simple unique solution cannot be proposed for bushfire management. Changing weather conditions, topography and the geographic mix of asset types need to be considered when deciding on bushfire management strategies and their breadth and depth of application.

ABSTRACT: Objective: This study aims to investigate the association between smoking and the severity of COVID-19 infection during the initial wave of this pandemic in Malaysia. Methods: This is a multi-center observational study using secondary hospital data collected retrospectively from February 1, 2020, until May 30, 2020. Clinical records of all real-time polymerase chain reaction (RT-PCR)-confirmed COVID-19 cases with smoking status, co-morbidities, clinical features, and disease management were retrieved. Severity was assessed by the presence of complications and outcomes of COVID-19 infection. Logistic regression was used to determine the association between COVID-19 disease severity and smoking status. Results: A total of 5,889 COVID-19 cases were included in the analysis. Ever smokers had a higher risk of having COVID-19 complications, such as acute respiratory distress syndrome (odds ratio [OR] 1.69; 95% confidence interval [CI] 1.09-2.55), renal injury (OR 1.55; 95% CI 1.10-2.14), and acute liver injury (OR 1.33; 95% CI 1.01-1.74), compared with never smokers. However, in terms of disease outcomes, there were no differences between the two groups. Conclusion: Although no significant association was found in terms of disease outcomes, smoking is associated with a higher risk of having complications owing to COVID-19 infection.

Abstract Background Persons living with HIV infection (PLHIV) who are diagnosed in community settings in sub-Saharan Africa are particularly vulnerable to barriers to care that prevent or delay many from obtaining antiretroviral therapy (ART). Methods We conducted a retrospective cohort study to assess if a package of peer-delivered linkage case management and treatment navigation services (CommLink) was more effective than peer-delivered counseling, referral, and telephone follow-up (standard linkage services, SLS) in initiating and retaining PLHIV on ART after diagnosis in community settings in Eswatini. HIV-test records of 773 CommLink and 769 SLS clients aged ≥ 15 years diagnosed between March 2016 and March 2018, matched by urban and rural settings of diagnosis, were selected for the study. CommLink counselors recorded resolved and unresolved barriers to care (e.g., perceived wellbeing, fear of partner response, stigmatization) during a median of 52 days (interquartile range: 35—69) of case management. Results Twice as many CommLink than SLS clients initiated ART by 90 days of diagnosis overall (88.4% vs. 37.9%, adjusted relative risk (aRR): 2.33, 95% confidence interval (CI): 1.97, 2.77) and during test and treat when all PLHIV were eligible for ART (96.2% vs. 37.1%, aRR: 2.59, 95% CI: 2.20, 3.04). By 18 months of diagnosis, 54% more CommLink than SLS clients were initiated and retained on ART (76.3% vs. 49.5%, aRR: 1.54, 95% CI: 1.33, 1.79). Peer counselors helped resolve 896 (65%) of 1372 identified barriers of CommLink clients. Compared with clients with ≥ 3 unresolved barriers to care, 42% (aRR: 1.42, 95% CI: 1.19, 1.68) more clients with 1–2 unresolved barriers, 44% (aRR: 1.44, 95% CI: 1.25, 1.66) more clients with all barriers resolved, and 54% (aRR: 1.54, 95% CI: 1.30, 1.81) more clients who had no identified barriers were initiated and retained on ART by 18 months of diagnosis. Conclusions To improve early ART initiation and retention among PLHIV diagnosed in community settings, HIV prevention programs should consider providing a package of peer-delivered linkage case management and treatment navigation services. Clients with multiple unresolved barriers to care measured as part of that package should be triaged for differentiated linkage and retention services.

Abstract As decisions in drug development increasingly rely on predictions from mechanistic systems models, assessing the predictive capability of such models is becoming more important. Several frameworks for the development of quantitative systems pharmacology (QSP) models have been proposed. In this paper, we add to this body of work with a framework that focuses on the appropriate use of qualitative and quantitative model evaluation methods. We provide details and references for those wishing to apply these methods, which include sensitivity and identifiability analyses, as well as concepts such as validation and uncertainty quantification. Many of these methods have been used successfully in other fields, but are not as common in QSP modeling. We illustrate how to apply these methods to evaluate QSP models, and propose methods to use in two case studies. We also share examples of misleading results when inappropriate analyses are used.

Abstract Background SARS-CoV-2 rapid antigen (Ag) detection kits are widely used in addition to quantitative reverse transcription PCR PCR (RT-qPCR), as they are cheaper with a rapid turnaround time. As there are many concerns regarding their sensitivity and specificity, in different settings, we evaluated two WHO approved rapid Ag kits in a large cohort of Sri Lankan individuals. Methods Paired nasopharangeal swabs were obtained from 4786 participants for validation of the SD-Biosensor rapid Ag assay and 3325 for the Abbott rapid Ag assay, in comparison to RT-qPCR. A short questionnaire was used to record symptoms at the time of testing, and blood samples were obtained from 2721 of them for detection of SARS-CoV-2 specific antibodies. Results The overall sensitivity of the SD-Biosensor Ag kit was 36.5% and the Abbott Ag test was 50.76%. The Abbott Ag test showed specificity of 99.4% and the SD-Biosensor Ag test 97.5%. At Ct values 30 (46.1 to 82.9%). 32.1% of those who gave a positive result with the SD-Biosensor Ag test and 26.3% of those who gave positive results with the Abbott Ag test had SARS-CoV-2 antibodies at the time of detection. Conclusions Both rapid Ag tests appeared to be highly sensitive in detecting individuals at lower Ct values, in a community setting in Sri Lanka, but it will be important to further establish the relationship to infectivity.

Abstract The use of external fixators (EFs) dates back to 377 BC Hippocrates’ time, and it has a wide range of orthopaedic applications. External fixator has expanded its use in the management of fractures and other musculoskeletal conditions. It is widely used all over the world to manage complex musculoskeletal injuries. It has many advantages as compared to internal fixation in some trauma scenarios. However, the cost of the external fixators presents a dilemma to the healthcare system in developing countries. The goals of this review article are to explain the importance of EFs in developing countries in managing fractures, to determine the problems encountered at present during external fixation by developing countries, to identify solutions that could be used to address these issues, expand the use of external fixation into other domains of treatment, the impact of COVID-19 pandemic on fracture management based on existing literature. In conclusion, EFs are very expensive, researches have been conducted to overcome these barriers in developing countries. However, there are limitations in implementing in developing countries. It is important to have affordable and clinically acceptable EFs available in developing countries.

Abstract Introduction Osteoarthritis (OA) is a chronic condition. Physiotherapy is known to be beneficial for people with OA. Patient adherence to physiotherapy exercise is essential for the effective management of OA. Objectives To determine different methods used to enhance physiotherapy exercise adherence for a period of more than 12 months among patients with OA and to report the most effective methods to enhance exercise adherence among people with lower limb OA. Design Systematic review. Methods PubMed, Pedro, Web of Science, and EMBASE databases were searched for randomized controlled trials, cohort studies, case-control studies, and cross-sectional studies published in the English language from 2000 to 2020. The literature search was done on 27 August 2020. Two researchers independently conducted the screening, eligibility assessment, data extraction, methodology quality assessment using the PEDro scale, and risk of bias assessment using RoB2. A narrative synthesis of key outcomes is presented, percentage of adherence rate; Preferred Reporting Items for Systematic Review was used to report the review. Meta-analysis was not performed due to heterogeneity of studies. The study protocol was registered in Prospero (Prospero ID: CRD42020205653). Results The primary search strategy identified 5839 potentially relevant articles, of which 5157 remained after discarding duplicates. After screening based on title and abstract, 40 papers were potentially eligible for inclusion. Five of these papers met all predefined eligibility criteria. Introducing methods to enhance exercise adherence has caused a significant increase in exercise adherence for less than 6 or 12 months. There were no significant differences in adherence for more than 12 months with different methods. The results indicate that booster-sessions (89.69%) and telephone-linked communication (86%) had higher percentages for exercise adherence. Secondary outcomes such as pain, stiffness and function show positive outcomes with increasing exercise adherence. However, there were no significant differences on these secondary outcomes. Conclusion The booster sessions and telephone-linked communication appear to enhance exercise adherence for more than 12 months among patients with OA. However, the number of high-quality studies is inadequate to confirm our findings. Therefore, more studies with higher methodological quality are needed to determine the best strategies to enhance long-term exercise adherence among people with OA.

Purpose Enhanced Recovery After Surgery (ERAS) has become standard of care in colorectal surgery. However, there is not a universally accepted colorectal ERAS protocol and significant variations in care exist between institutions. The aim of this study was to examine the impact of variations in ERAS interventions and complications on length of stay (LOS). Methods This study was a single-center review of the first 200 consecutive patients recruited into our prospectively collected ERAS database. The primary outcome of this study was to examine the rate of compliance to ERAS interventions and the impact of these interventions on LOS. The secondary outcome was to assess the impact of complications (anastomotic leak, ileus, and surgical site infections) on LOS. ERAS interventions, rate of adherence, LOS, readmissions, morbidity, and mortality were recorded, and statistical analysis was performed. Results ERAS variations and complications significantly influenced patient LOS on both univariate and multivariate analysis. ERAS interventions identified as the most important strategies in reducing LOS included laparoscopic surgery, mobilization twice daily postoperative day (POD) 0 to 1, discontinuation of intravenous fluids on POD 0 to 1, upgrading to solid diet by POD 0 to 2, removal of indwelling catheter by POD 0 to 2, avoiding nasogastric tube reinsertion and removing drains early. Both major and minor complications increased LOS. Anastomotic leak and ileus were associated with the greatest increase in LOS. Conclusion Seven high-yield ERAS interventions reduced LOS. Major and minor complications increased LOS. Reducing variations in care and complications can improve outcomes following colorectal surgery.

Mathematical models have been an important tool during the COVID-19 pandemic, for example to predict demand of critical resources such as medical devices, personal protective equipment and diagnostic tests. Many COVID-19 models have been developed. However, there is relatively little information available regarding reliability of model predictions. Here we present a general model validation framework for epidemiological models focused around predictive capability for questions relevant to decision-making end-users. COVID-19 models are typically comprised of multiple releases, and provide predictions for multiple localities, and these characteristics are systematically accounted for in the framework, which is based around a set of validation scores or metrics that quantify model accuracy of specific quantities of interest including: date of peak, magnitude of peak, rate of recovery, and monthly cumulative counts. We applied the framework to retrospectively assess accuracy of death predictions for four COVID-19 models, and accuracy of hospitalization predictions for one COVID-19 model (models for which sufficient data was publicly available). When predicting date of peak deaths, the most accurate model had errors of approximately 15 days or less, for releases 3-6 weeks in advance of the peak. Death peak magnitude relative errors were generally in the 50% range 3-6 weeks before peak. Hospitalization predictions were less accurate than death predictions. All models were highly variable in predictive accuracy across regions. Overall, our framework provides a wealth of information on the predictive accuracy of epidemiological models and could be used in future epidemics to evaluate new models or support existing modeling methodologies, and thereby aid in informed model-based public health decision making. The code for the validation framework is available at https://doi.org/10.5281/zenodo.7102854.

The implementation of MRI-guided online adaptive radiotherapy has enabled extension of therapeutic radiographers’ roles to include contouring. An offline interobserver variability study compared five radiographers’ and five clinicians’ contours on 10 MRIs acquired on a MR-Linac from 10 patients. All contours were compared to a “gold standard” created from an average of clinicians’ contours. The median (range) DSC of radiographers’ and clinicians’ contours compared to the “gold standard” was 0.91 (0.86–0.96), and 0.93 (0.88–0.97) respectively illustrating non-inferiority of the radiographers’ contours to the clinicians. There was no significant difference in HD, MDA or volume size between the groups.