Unveiling the Incipient Caries by Quantitative Light-induced Fluorescence

Dental caries is one of the most prevalent chronic diseases of humans worldwide. When different stages of the disease are taken into account, from the initial to the clinically manifesting lesion, very few individuals are truly unaffected. Quantitative light-induced fluorescence (QLF) is a prominent diagnostic technique in dentistry. The purpose of this article is to review the effectiveness of QLF system in early detection of carious lesions as well as its future clinical application in dentistry. The review article has been prepared doing a literature review from the world wide web and PubMed/medline

Comparison of outcomes after open versus robotic kidney transplantation: A systematic review and meta-analysis

INTRODUCTION: This meta-analysis compares the clinical outcomes of robot-assisted kidney transplant (RAKT) to open kidney transplant (OKT). METHODS: A systematic search of Scopus and MEDLINE databases was carried out using a combination of keywords to identify studies comparing RAKT to OKT. Baseline characteristics and preoperative and postoperative data were collected along with data on the short- and long-term outcomes. The study was registered in PROSPERO and Assessing the Methodological Quality of Systematic Reviews and Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines were followed. RESULTS: A total of 16 studies were included with a total of 2555 patients, of which 677 underwent RAKT and 1878 underwent OKT. This meta-analysis shows a significant benefit of RAKT over OKT in terms of less intra-operative blood loss, smaller incision length, less postoperative pain scores at 24 and 48 hours, and a lower incidence of surgical site infections (SSIs), especially in obese patients. In addition, the incidence of postoperative lymphoceles was lower in the RAKT group compared to the OKT group, although not statistically significant. There was no difference between the two groups in terms of short-term graft functional outcomes and overall survival. The number of deceased donor recipients undergoing RAKT was very small. At the time of reporting this meta-analysis, no randomized controlled trials (RCTs) had been published. CONCLUSION: This meta-analysis showed that RAKT is a safe and feasible alternative to OKT, especially in obese individuals. Further trials are needed to confirm the safety, efficacy, and cost-effectiveness of RAKT

Application of multivariate data analysis in the monitoring and control of mammalian cell processes

High throughput (HT) methodologies are increasingly being adopted for bioprocess development activities. However, often the large quantities of data generated from such studies as well as from historical batch records are not fully harnessed for their potential insights. Multivariate data analysis (MVDA) is a well-known technique that can reduce the dimensionality of large data sets and help generate useful correlations of typical process behaviour and determine root causes of process deviations. This work focuses on the application of various MVDA techniques and data mining tools to investigate the impact of process variations on the critical quality attributes (CQAs) of mammalian cell processes. Three separate projects investigating the application of these techniques were explored. The first focuses on understanding the impact of cell culture operation, generation number and initial conditions on final titre and impurity levels. A systematic methodology was applied to analyse HT data generated in a Design of Experiment (DOE) study using the ambr® 48 (advanced micro-bioreactor) system. The project applied multiple MVDA techniques including Principle Component Analysis (PCA) and Partial Least Squares (PLS) to successfully identify the key critical process measurements impacting on the target antibody concentration and host cell protein (HCP) levels at harvest. A similar approach was adopted in the second project that investigated the influence of manufacturing beyond standard operating conditions on the product-related CQAs of a mammalian cell process. The insights from the MVDA allowed the modification of the control limits of key process parameters to be redefined with confidence. The final project focuses on the development of an advanced glucose control strategy for a high titre mammalian cell line. The project aims to predict the on-line glucose concentration through correlations developed between the available on-line process measurements and the off-line metabolic profiles. The predicted glucose concentration is then used to manipulate the substrate feed rate to control the glucose concentration at a desired set-point. Better control of the glucose concentration aims to further increase titre production as well as potentially reducing unwanted post-translation modifications (PTMs) in susceptible cell lines. These techniques can be combined with the application of Process Analytical Technologies (PAT) and Quality by Design (QbD) allowing for the development of more efficient and better controlled processes

Multivariate data analysis enabling improved clone selection

Selecting a single cell from a heterogeneous transfection pool that will scale-up appropriately from a micro-scale system to a commercial facility is a challenging and hugely important task. This clonal cell line needs to demonstrate the desired product quality attributes and ensure manufacturability throughout the entire drug manufacturing lifecycle. This process typically requires 6 to 12 months and is a time, capital and labour intensive process. High throughput (HT) methodologies are increasingly being adopted to speed up this cell line selection protocol. However, often the large quantities of data generated in combination with the increase in availability of analytics results in a daunting multivariate data analysis problem. Typically, the cell line selection strategy focuses on quality attributes recorded at point of harvest such as final concentrations of process parameters including titre and viable cell density, level of aggregates or addition product quality attributes. Time-series data such as dissolved oxygen, pH or gas flow rates are often overlooked due to challenges with visualization and interpretation of the large number of process variables recorded. This work describes a novel method that implements advanced multivariate tools including principal component analysis (PCA) to better leverage the available data to help guide this challenging decision making process. The inclusion of additional process variables was demonstrated to enhance the selection of a high-yielding mammalian cell line through inclusion of scale-up dependent process parameters related to high oxygen demands and varying nutrient uptake rates. Furthermore, this technique was demonstrated to highlight problematic product heterogeneities of parent clones that were not identified through univariate analysis of the multiple cell lines. The inclusion of this MVDA methodology demonstrated a more efficient and better decision-making protocol compared to conventional cell line selection processes

Effect of nano-size on magnetostriction of BiFeO3 and exceptional magnetoelectric coupling properties of BiFeO3_P(VDF-TrFE) polymer composite films for magnetic field sensor application

The existence of magnetostriction in bulk BiFeO3 is still a matter of investigation and it is also an issue to investigate the magnetostriction effect in nano BiFeO3. Present work demonstrates the existence of magnetostrictive strain in superparamagnetic BiFeO3 nanoparticles at room temperature and the magnetoelectric coupling properties in composite form with P(VDFTrFE). Despite few reports on the magnetostriction effect in bulk BiFeO3 evidenced by the indirect method, the direct method (strain gauge) was employed in this work to examine the magnetostriction of superparamagnetic BiFeO3. In addition, a high magnetoelectric coupling coefficient was observed by the lock-in technique for optimized BiFeO3_P(VDF-TrFE) nanocomposite film. These nanocomposite films also exhibit room-temperature multiferroic properties. These results provide aspects of material with immense potential for practical applications in spintronics and magneto-electronics applications. We report a magnetoelectric sensor using superparamagnetic BiFeO3_P(VDF-TrFE) nanocomposite film for detection of ac magnetic field

Enhancing the Functionality of a Microscale Bioreactor System as an Industrial Process Development Tool for Mammalian Perfusion Culture

Without a scale-down model for perfusion, high resource demand makes cell line screening or process development challenging; therefore potentially successful cell lines or perfusion processes are unrealised and their ability untapped. We present here the re-functioning of a high capacity microscale system that is typically employed in fed-batch process development to allow perfusion operation utilising in situ gravity settling and automated sampling. In this low resource setting, which involved routine perturbations in mixing, pH and dissolved oxygen concentrations, the specific productivity and the maximum cell concentration were higher than 3.0x106 mg/cell/day and 7x107 cells/ml, respectively, across replicate microscale perfusion runs conducted at one vessel volume exchange per day. A comparative analysis was conducted at bench scale with vessels operated in perfusion mode utilising a cell retention device. Neither specific productivity nor product quality indicated by product aggregation [6%] was significantly different across scales 19 days post inoculation, thus demonstrating this setup to be a suitable and reliable platform for evaluating the performance of cell lines and the effect of process parameters relevant to perfusion mode of culturing

Jais and Jais-chat: Arabic-Centric Foundation and Instruction-Tuned Open Generative Large Language Models

We introduce Jais and Jais-chat, new state-of-the-art Arabic-centric foundation and instruction-tuned open generative large language models (LLMs). The models are based on the GPT-3 decoder-only architecture and are pretrained on a mixture of Arabic and English texts, including source code in various programming languages. With 13 billion parameters, they demonstrate better knowledge and reasoning capabilities in Arabic than any existing open Arabic and multilingual models by a sizable margin, based on extensive evaluation. Moreover, the models are competitive in English compared to English-centric open models of similar size, despite being trained on much less English data. We provide a detailed description of the training, the tuning, the safety alignment, and the evaluation of the models. We release two open versions of the model -- the foundation Jais model, and an instruction-tuned Jais-chat variant -- with the aim of promoting research on Arabic LLMs. Available at https://huggingface.co/inception-mbzuai/jais-13b-chatComment: Arabic-centric, foundation model, large-language model, LLM, generative model, instruction-tuned, Jais, Jais-cha

Impact of district mental health care plans on symptom severity and functioning of patients with priority mental health conditions: the Programme for Improving Mental Health Care (PRIME) cohort protocol

Background: The Programme for Improving Mental Health Care (PRIME) sought to implement mental health care plans (MHCP) for four priority mental disorders (depression, alcohol use disorder, psychosis and epilepsy) into routine primary care in five low- and middle-income country districts. The impact of the MHCPs on disability was evaluated through establishment of priority disorder treatment cohorts. This paper describes the methodology of these PRIME cohorts. Methods: One cohort for each disorder was recruited across some or all five districts: Sodo (Ethiopia), Sehore (India) , Chitwan (Nepal), Dr. Kenneth Kaunda (South Africa) and Kamuli (Uganda), comprising 17 treatment cohorts in total (N = 2182). Participants were adults residing in the districts who were eligible to receive mental health treatment according to primary health care staff, trained by PRIME facilitators as per the district MHCP. Patients who screened positive for depression or AUD and who were not given a diagnosis by their clinicians (N = 709) were also recruited into comparison cohorts in Ethiopia, India, Nepal and South Africa. Caregivers of patients with epilepsy or psychosis were also recruited (N = 953), together with or on behalf of the person with a mental disorder, depending on the district. The target sample size was 200 (depression and AUD), or 150 (psychosis and epilepsy) patients initiating treatment in each recruiting district. Data collection activities were conducted by PRIME research teams. Participants completed follow-up assessments after 3 months (AUD and depression) or 6 months (psychosis and epilepsy), and after 12 months. Primary outcomes were impaired functioning, using the 12-item World Health Organization Disability Assessment Schedule 2.0 (WHODAS), and symptom severity, assessed using the Patient Health Questionnaire (depression), the Alcohol Use Disorder Identification Test (AUD), and number of seizures (epilepsy). Discussion: Cohort recruitment was a function of the clinical detection rate by primary health care staff, and did not meet all planned targets. The cross-country methodology reflected the pragmatic nature of the PRIME cohorts: while the heterogeneity in methods of recruitment was a consequence of differences in health systems and MHCPs, the use of the WHODAS as primary outcome measure will allow for comparison of functioning recovery across sites and disorders

Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950–2021, and the impact of the COVID-19 pandemic: a comprehensive demographic analysis for the Global Burden of Disease Study 2021

Background: Estimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides new demographic estimates for 204 countries and territories and 811 additional subnational locations from 1950 to 2021, with a particular emphasis on changes in mortality and life expectancy that occurred during the 2020–21 COVID-19 pandemic period. Methods: 22 223 data sources from vital registration, sample registration, surveys, censuses, and other sources were used to estimate mortality, with a subset of these sources used exclusively to estimate excess mortality due to the COVID-19 pandemic. 2026 data sources were used for population estimation. Additional sources were used to estimate migration; the effects of the HIV epidemic; and demographic discontinuities due to conflicts, famines, natural disasters, and pandemics, which are used as inputs for estimating mortality and population. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate under-5 mortality rates, which synthesised 30 763 location-years of vital registration and sample registration data, 1365 surveys and censuses, and 80 other sources. ST-GPR was also used to estimate adult mortality (between ages 15 and 59 years) based on information from 31 642 location-years of vital registration and sample registration data, 355 surveys and censuses, and 24 other sources. Estimates of child and adult mortality rates were then used to generate life tables with a relational model life table system. For countries with large HIV epidemics, life tables were adjusted using independent estimates of HIV-specific mortality generated via an epidemiological analysis of HIV prevalence surveys, antenatal clinic serosurveillance, and other data sources. Excess mortality due to the COVID-19 pandemic in 2020 and 2021 was determined by subtracting observed all-cause mortality (adjusted for late registration and mortality anomalies) from the mortality expected in the absence of the pandemic. Expected mortality was calculated based on historical trends using an ensemble of models. In location-years where all-cause mortality data were unavailable, we estimated excess mortality rates using a regression model with covariates pertaining to the pandemic. Population size was computed using a Bayesian hierarchical cohort component model. Life expectancy was calculated using age-specific mortality rates and standard demographic methods. Uncertainty intervals (UIs) were calculated for every metric using the 25th and 975th ordered values from a 1000-draw posterior distribution. Findings: Global all-cause mortality followed two distinct patterns over the study period: age-standardised mortality rates declined between 1950 and 2019 (a 62·8% [95% UI 60·5–65·1] decline), and increased during the COVID-19 pandemic period (2020–21; 5·1% [0·9–9·6] increase). In contrast with the overall reverse in mortality trends during the pandemic period, child mortality continued to decline, with 4·66 million (3·98–5·50) global deaths in children younger than 5 years in 2021 compared with 5·21 million (4·50–6·01) in 2019. An estimated 131 million (126–137) people died globally from all causes in 2020 and 2021 combined, of which 15·9 million (14·7–17·2) were due to the COVID-19 pandemic (measured by excess mortality, which includes deaths directly due to SARS-CoV-2 infection and those indirectly due to other social, economic, or behavioural changes associated with the pandemic). Excess mortality rates exceeded 150 deaths per 100 000 population during at least one year of the pandemic in 80 countries and territories, whereas 20 nations had a negative excess mortality rate in 2020 or 2021, indicating that all-cause mortality in these countries was lower during the pandemic than expected based on historical trends. Between 1950 and 2021, global life expectancy at birth increased by 22·7 years (20·8–24·8), from 49·0 years (46·7–51·3) to 71·7 years (70·9–72·5). Global life expectancy at birth declined by 1·6 years (1·0–2·2) between 2019 and 2021, reversing historical trends. An increase in life expectancy was only observed in 32 (15·7%) of 204 countries and territories between 2019 and 2021. The global population reached 7·89 billion (7·67–8·13) people in 2021, by which time 56 of 204 countries and territories had peaked and subsequently populations have declined. The largest proportion of population growth between 2020 and 2021 was in sub-Saharan Africa (39·5% [28·4–52·7]) and south Asia (26·3% [9·0–44·7]). From 2000 to 2021, the ratio of the population aged 65 years and older to the population aged younger than 15 years increased in 188 (92·2%) of 204 nations. Interpretation: Global adult mortality rates markedly increased during the COVID-19 pandemic in 2020 and 2021, reversing past decreasing trends, while child mortality rates continued to decline, albeit more slowly than in earlier years. Although COVID-19 had a substantial impact on many demographic indicators during the first 2 years of the pandemic, overall global health progress over the 72 years evaluated has been profound, with considerable improvements in mortality and life expectancy. Additionally, we observed a deceleration of global population growth since 2017, despite steady or increasing growth in lower-income countries, combined with a continued global shift of population age structures towards older ages. These demographic changes will likely present future challenges to health systems, economies, and societies. The comprehensive demographic estimates reported here will enable researchers, policy makers, health practitioners, and other key stakeholders to better understand and address the profound changes that have occurred in the global health landscape following the first 2 years of the COVID-19 pandemic, and longer-term trends beyond the pandemic