The state-of-the-art models for medical image segmentation are variants of U-Net and fully convolutional networks (FCN). Despite their success, these models have two limitations: (1) their optimal ...depth is apriori unknown, requiring extensive architecture search or inefficient ensemble of models of varying depths; and (2) their skip connections impose an unnecessarily restrictive fusion scheme, forcing aggregation only at the same-scale feature maps of the encoder and decoder sub-networks. To overcome these two limitations, we propose UNet++, a new neural architecture for semantic and instance segmentation, by (1) alleviating the unknown network depth with an efficient ensemble of U-Nets of varying depths, which partially share an encoder and co-learn simultaneously using deep supervision; (2) redesigning skip connections to aggregate features of varying semantic scales at the decoder sub-networks, leading to a highly flexible feature fusion scheme; and (3) devising a pruning scheme to accelerate the inference speed of UNet++. We have evaluated UNet++ using six different medical image segmentation datasets, covering multiple imaging modalities such as computed tomography (CT), magnetic resonance imaging (MRI), and electron microscopy (EM), and demonstrating that (1) UNet++ consistently outperforms the baseline models for the task of semantic segmentation across different datasets and backbone architectures; (2) UNet++ enhances segmentation quality of varying-size objects-an improvement over the fixed-depth U-Net; (3) Mask RCNN++ (Mask R-CNN with UNet++ design) outperforms the original Mask R-CNN for the task of instance segmentation; and (4) pruned UNet++ models achieve significant speedup while showing only modest performance degradation. Our implementation and pre-trained models are available at https://github.com/MrGiovanni/UNetPlusPlus.
Many species of microalgae have been used as source of nutrient rich food, feed, and health promoting compounds. Among the commercially important microalgae, Haematococcus pluvialis is the richest ...source of natural astaxanthin which is considered as "super anti-oxidant." Natural astaxanthin produced by H. pluvialis has significantly greater antioxidant capacity than the synthetic one. Astaxanthin has important applications in the nutraceuticals, cosmetics, food, and aquaculture industries. It is now evident that, astaxanthin can significantly reduce free radicals and oxidative stress and help human body maintain a healthy state. With extraordinary potency and increase in demand, astaxanthin is one of the high-value microalgal products of the future.This comprehensive review summarizes the most important aspects of the biology, biochemical composition, biosynthesis, and astaxanthin accumulation in the cells of H. pluvialis and its wide range of applications for humans and animals. In this paper, important and recent developments ranging from cultivation, harvest and postharvest bio-processing technologies to metabolic control and genetic engineering are reviewed in detail, focusing on biomass and astaxanthin production from this biotechnologically important microalga. Simultaneously, critical bottlenecks and major challenges in commercial scale production; current and prospective global market of H. pluvialis derived astaxanthin are also presented in a critical manner. A new biorefinery concept for H. pluvialis has been also suggested to guide toward economically sustainable approach for microalgae cultivation and processing. This report could serve as a useful guide to present current status of knowledge in the field and highlight key areas for future development of H. pluvialis astaxanthin technology and its large scale commercial implementation.
Because of the rapid increase of non-communicable diseases (NCDs) and high burden of healthcare-related financial issues in Bangladesh, there is a concern that out-of-pocket (OOP) payments related to ...illnesses may become a major burden on household. It is crucial to understand what are the major illnesses responsible for high OPP at the household level to help policymakers prioritize key areas of actions to protect the household from 100% financial hardship for seeking health care as part of universal health coverage.
We first estimated the costs of illnesses among a population in urban Bangladesh, and then assessed the household financial burden associated with these illnesses.
A cross-sectional survey of 1593 randomly selected households was carried out in Bangladesh (urban area of Rajshahi city), in 2011. Catastrophic expenditure was estimated at 40% threshold of household capacity to pay. We employed the Bayesian two-stage hurdle model and Bayesian logistic regression model to estimate age-adjusted average cost and the incidence of household financial catastrophe for each illness, respectively.
Overall, approximately 45% of the population of Bangladesh had at least one episode of illness. The age-sex-adjusted average medical expenses and catastrophic health care expenditure among the households were TK 621 and 8%, respectively. Households spent the highest amount of money 7676.9 on paralysis followed by liver disease (TK 2695.4), injury (TK 2440.0), mental disease (TK 2258.0), and tumor (TK 2231.2). These diseases were also responsible for higher incidence of financial catastrophe. Our study showed that 24% of individuals who suffered typhoid incurred catastrophic expenditure followed by liver disease (12.3%), tumor (12.1%), heart disease (8.4%), injury (7.9%), mental disease (7.9%), cataract (7.1%), and paralysis (6.5%).
The study findings suggest that chronic illnesses were responsible for high costs and high catastrophic expenditures in Bangladesh. Effective risk pooling mechanism might reduce household financial burden related to illnesses. Chronic illness related to NCDs is the major cause of OOP. It is also important to consider prioritizing vulnerable population by subsidizing the high health care cost for some of the chronic illnesses.
The nicotinic acetylcholine receptor, a pentameric ligand-gated ion channel, converts the free energy of binding of the neurotransmitter acetylcholine into opening of its central pore. Here we ...present the first high-resolution structure of the receptor type found in muscle-endplate membrane and in the muscle-derived electric tissues of fish. The native receptor was purified from Torpedo electric tissue and functionally reconstituted in lipids optimal for cryo-electron microscopy. The receptor was stabilized in a closed state by the binding of α-bungarotoxin. The structure reveals the binding of a toxin molecule at each of two subunit interfaces in a manner that would block the binding of acetylcholine. It also reveals a closed gate in the ion-conducting pore, formed by hydrophobic amino acid side chains, located ∼60 Å from the toxin binding sites. The structure provides a framework for understanding gating in ligand-gated channels and how mutations in the acetylcholine receptor cause congenital myasthenic syndromes.
•High-resolution structure of a native muscle-type nicotinic acetylcholine receptor•Previously unresolved structural elements contribute to neurotoxin binding•Channel is stabilized in a closed conformation by α-bungarotoxin from snake venom•Transduction mechanism and myasthenic disease mutations
Rahman et al. report the high-resolution single-particle cryo-EM structure of a native muscle-type nicotinic acetylcholine receptor from the Torpedo electric ray, in complex with α-bungarotoxin from the banded krait. The structure was obtained in a lipidic environment shown to support channel function and reveals a closed, hydrophobic ion channel gate.
Binding of the neurotransmitter acetylcholine to its receptors on muscle fibers depolarizes the membrane and thereby triggers muscle contraction. We sought to understand at the level of ...three-dimensional structure how agonists and antagonists alter nicotinic acetylcholine receptor conformation. We used the muscle-type receptor from the Torpedo ray to first define the structure of the receptor in a resting, activatable state. We then determined the receptor structure bound to the agonist carbachol, which stabilizes an asymmetric, closed channel desensitized state. We find conformational changes in a peripheral membrane helix are tied to recovery from desensitization. To probe mechanisms of antagonism, we obtained receptor structures with the active component of curare, a poison arrow toxin and precursor to modern muscle relaxants. d-Tubocurarine stabilizes the receptor in a desensitized-like state in the presence and absence of agonist. These findings define the transitions between resting and desensitized states and reveal divergent means by which antagonists block channel activity of the muscle-type nicotinic receptor.
Traditional solar–thermal receivers suffer from high surface temperatures, which increase heat losses to the surroundings. To improve performance, volumetric receivers based on nanoparticles ...suspended in liquid (nanofluids) have been studied as an approach to reduce surface losses by localizing high temperatures to the interior of the receiver. Here, we report measured vapor generation efficiencies of 69% at solar concentrations of 10sun using graphitized carbon black, carbon black, and graphene suspended in water, representing a significant improvement in both transient and steady-state performance over previously reported results. To elucidate the vapor generation mechanism and validate our experimental results, we develop numerical and analytical heat transfer models that suggest that nanofluid heating and vapor generation occur due to classical global heating of the suspension fluid. This work demonstrates high nanofluid-assisted vapor generation efficiencies with potential applications in power generation, distillation, and sterilization.
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•A nanofluid-based solar receiver for water vapor generation was designed and tested.•The steady state solar-vapor generation efficiency was found to be ∼69%.•The transient vapor generation was found to depend on nanoparticle surface chemistry.•Nanofluid thermal behavior can be modeled using Fourier law at the microscale.•Nanobubble formation at the particle scale is unlikely to occur.
ObjectivesThis study aimed at exploring the factors associated with the reduction in the proportion of women reporting unwanted births in Bangladesh between 2007 and 2017/2018.Design and settingA ...cross-sectional analysis of the data collected by the 2007 and 2017/2018 Bangladesh Demographic and Health Surveys by using a two-stage stratified sampling covering the entire population in Bangladesh.ParticipantsOur analysis included 4810 (2007) and 7403 (2017/2018) weighted ever-married women aged 15–49 years reporting at least one birth in the 5 years preceding each of the surveys.ResultsThe proportion of women reporting unwanted births declined by 26.2% between 2007 and 2017/2018. Overall changes in women’s behaviour and their proportions with distinct characteristics explained 66.2% (0.051 points decrease, 95% CI −0.071 to –0.031, p<0.001) and 45.5% (0.035 points decrease, 95% CI −0.051 to –0.019, p<0.001) of the overall reduction in the proportion reporting unwanted births, respectively. Behavioural changes among those being visited by family planning (FP) workers (0.004 points decrease, 95% CI −0.008 to –0.000, p=0.047), having complete secondary education or higher (0.009 points decrease, 95% CI −0.016 to –0.003, p=0.002), and earning in kind (0.002 points decrease, 95% CI −0.005 to –0.000, p=0.035) were associated with a reduction in unwanted childbearing. Increases in the proportions of women married at age 18 or older (0.008 points decrease, 95% CI −0.010 to –0.005, p<0.001), and having some secondary education (0.013 points decrease, 95% CI −0.019 to –0.008, p<0.001) were negatively associated with unwanted childbearing. Conversely, an increase in the proportion expressing preference for a balanced sex composition of the family was positively associated with unwanted childbearing (0.013 points increase, 95% CI 0.008 to 0.017, p<0.001).ConclusionsWomen’s behavioural changes driven by the FP programmes and other external factors, and changes in their characteristics, could reduce the incidence of unwanted childbearing in Bangladesh, and thereby contribute to improvements in maternal health.
In Bangladesh, about 80% of healthcare is provided by the private sector. Although free diagnosis and care is offered in the public sector, only half of the estimated number of people with ...tuberculosis are diagnosed, treated, and notified to the national program. Private sector engagement strategies often have been small scale and time limited. We evaluated a Social Enterprise Model combining external funding and income generation at three tuberculosis screening centres across the Dhaka Metropolitan Area for diagnosing and treating tuberculosis.
The model established three tuberculosis screening centres across Dhaka Metropolitan Area that carried the icddr,b brand and offered free Xpert MTB/RIF tests to patients visiting the screening centres for subsidized, digital chest radiographs from April 2014 to December 2017. A network of private and public health care providers, and community recommendation was formed for patient referral. No financial incentives were offered to physicians for referrals. Revenues from radiography were used to support screening centres' operation. Tuberculosis patients could choose to receive treatment from the private or public sector. Between 2014 and 2017, 1,032 private facilities networked with 8,466 private providers were mapped within the Dhaka Metropolitan Area. 64, 031 patients with TB symptoms were referred by the private providers, public sector and community residents to the three screening centres with 80% coming from private providers. 4,270 private providers made at least one referral. Overall, 10,288 pulmonary and extra-pulmonary tuberculosis cases were detected and 7,695 were bacteriologically positive by Xpert, corresponding to 28% of the total notifications in Dhaka Metropolitan Area.
The model established a network of private providers who referred individuals with presumptive tuberculosis without financial incentives to icddr,b's screening centres, facilitating a quarter of total tuberculosis notifications in Dhaka Metropolitan Area. Scaling up this approach may enhance national and international tuberculosis response.
Bacterial pathogens acquire heme from the host hemoglobin as an iron nutrient for their virulence and proliferation in blood. Concurrently, they encounter cytotoxic-free heme that escapes the ...heme-acquisition process. To overcome this toxicity, many gram-positive bacteria employ an ATP-binding cassette heme-dedicated efflux pump, HrtBA in the cytoplasmic membranes. Although genetic analyses have suggested that HrtBA expels heme from the bacterial membranes, the molecular mechanism of heme efflux remains elusive due to the lack of protein studies. Here, we show the biochemical properties and crystal structures of
HrtBA, alone and in complex with heme or an ATP analog, and we reveal how HrtBA extracts heme from the membrane and releases it. HrtBA consists of two cytoplasmic HrtA ATPase subunits and two transmembrane HrtB permease subunits. A heme-binding site is formed in the HrtB dimer and is laterally accessible to heme in the outer leaflet of the membrane. The heme-binding site captures heme from the membrane using a glutamate residue of either subunit as an axial ligand and sequesters the heme within the rearranged transmembrane helix bundle. By ATP-driven HrtA dimerization, the heme-binding site is squeezed to extrude the bound heme. The mechanism sheds light on the detoxification of membrane-bound heme in this bacterium.
Bangladesh has failed to meet the United Nations goal for reducing maternal mortality in the last decade. The high prevalence of unskilled birth attendant (UBA) delivery (47%) has resulted in ...negative consequences for the health of mothers and newborn babies in the country. Spatial variations in UBA delivery and its predictors are yet to be explored in Bangladesh, which could be very helpful in formulating cost-effective policies for reducing that. This study examines the spatial variations in UBA delivery and its predictors in Bangladesh. This study analyzed the characteristics of 672 clusters extracted from the 2017/18 Bangladesh Demographic and Health Survey, and healthcare facility data from the 2017 Bangladesh Health Facility Survey. These data were analyzed using descriptive and spatial analyses (hot spot analysis, Ordinary Least Squares Regression, and Geographically Weighted Regression) techniques. Statistically significant hot spots of UBA delivery were concentrated in parts of the Mymensingh, Sylhet, Barishal, and Rangpur regions, while Khulna was the safest region. Predictive strengths of the statistically significant predictors of spatial variation in UBA delivery were observed to vary considerably across the regions. Poorest household wealth status and less than four antenatal care contacts emerged as strong predictors of UBA delivery in all the aforementioned hot spot-stricken regions, except Barisal. Additionally, primiparity and all secondary education or higher were strong predictors of lower UBA delivery rates in Mymensingh and Sylhet, while poorer household wealth status was also a strong predictor of UBA delivery in Sylhet. Multiparity was an additional strong predictor of UBA delivery in Rangpur. In Barisal, only poorer household wealth status exerted a strong positive influence on UBA delivery. The remarkable spatial variations in UBA delivery and its predictors' strengths indicate that geographically-targeted interventions could be a cost-effective method for reducing the UBA delivery prevalence in Bangladesh, thereby improve maternal and child health.
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