Point-of-care diagnostics of childhood central nervous system infections, with a focus on usability in low-resource settings

Background: The inaccessibility of laboratory services sustains the high burden of paediatric infectious diseases, such as central nervous system (CNS) infections, in low-resource settings. New contextually fit and well-implemented point-of-care tests (POCTs) could relieve such a burden and narrow the diagnostic divide between rich and poor. Yet, current disengagement between product developers, end-users, and implementors of POCTs impedes their clinical use and utility in low-resource settings. Also, the lack of evidence gathered through field evaluations of many diagnostic instruments in low-resource settings raises questions of their clinical utility there. Objectives: The main aim of this thesis was to provide clinical and contextual guidance for developers of new POCTs for CNS infection diagnosis with high utility, especially in low-resource settings; and to implementors of POCT services towards their optimized clinical benefit. This was addressed through a multidisciplinary combination of qualitative, laboratory, and clinical studies. Methods: Qualitative focus group discussions were conducted with health care workers (HCW) in Mbarara, Uganda (Paper I), and in Stockholm, Sweden (Paper III). Discussions were audio recorded and transcribed verbatim. Qualitative content analysis with an inductive approach was pursued in for data analysis. Comparisons between the two settings were discussed. In Paper II, a vertical flow DNA microarray printed on paper was developed for the detection of Neisseria meningitidis – a major aetiology of paediatric bacterial CNS infection worldwide. The analytical performance of the microarray was laboratory evaluated on DNA extracted from the bacteria, through the detection of the ctrA gene sequence specific to N. meningitidis. In Paper IV, a commercially available polymerase chain reaction (PCR) instrument with the capability of multiplex single-sample cerebrospinal fluid (CSF) microbiology was prospectively field-evaluated for the diagnosis of paediatric CNS infection in Mbarara, Uganda. Clinical turnaround time (cTAT) was defined as time spent from lumbar puncture until reporting of microbiology analyses to clinicians. The PCR instrument’s influence on clinical and patient-centered outcomes (yield, cTAT, duration of hospitalization and antibiotic exposure, patient outcome) was compared to that of bacterial culture. Results: Fifty and 24 HCWs of different professions participated in the qualitative studies in Mbarara and Stockholm, respectively, expressing greater similarities than differences in perspectives of POCT use. POCTs were routinely used at both sites and credited for facilitating differential diagnostics and clinical decision-making. While the Ugandan setting with low laboratory accessibility was highly dependent on POCTs for sample analyses, the Swedish setting credited their use for having clinical and social value. Contrary to the described beneficial aspects, current POCTs were deemed contextually unfit in Mbarara, and their use to cause clinical distraction in Stockholm. Deficient implementation of POCT services was exposed in both places. Requests for ideal POCTs were aligned with those stipulated by the ‘ASSURED’ criteria of the World Health Organization. Specific POCTs for infectious diseases, including CNS infections, were requested. The laboratory study demonstrated an analytical sensitivity of 38 copies of ctrA per assay, with high specificity. The clinical study enrolled 212 children aged 0-12 years who were suspected of having CNS infection, with 193 of them being evaluated using the commercially available PCR instrument. A vast majority of children had been pre-administered antibiotics prior to lumbar puncture. Bacterial yield for the instrument was 12 % vs. 1.5 % for culture, with the addition of the instrument’s detection of viruses in 23 samples. Median cTAT for the instrument was 4.2 hours vs. 2 days for culture. Use of the instrument was associated with a statistically significant shorter antibiotic exposure of bacteria-negative vs. positive patients of five days, measured as from the time of reporting of laboratory results to the responsible clinicians. Similarly, its use was associated with a significantly shorter hospitalization for all-negative patients (five days) compared to those with any microorganism detected by it. No statistically significant differences in patient outcome were found due to its use, nor by its detection of any microorganisms. Conclusion: Point-of-care tests provide laboratory means to settings without laboratory capacity and to situations in need of timely results, and we could show how rapid molecular methods for CSF analysis could benefit paediatric children with suspected CNS infection. Yet, without any observed benefits in patient outcome, and at a cost not financially bearable in most lowresource settings. Contextually fit POCTs for paediatric CNS infections are needed in lowresource settings. Yet, there are design flaws in current POCTs and in implementations for their use, limiting their clinical benefits. Collaborative engagement of product developers, clinicians, laboratory professionals, and health policymakers would better serve low-resource settings with contextually fit POCTs and allow for their optimized implementation. The ‘POCTEST' framework for such an engagement is proposed in this thesis. Finally, as we provided proof of concept for a newly developed paper-printed molecular method, we will pursue its development towards contextual clinical utility in low-resource settings. Should we succeed, we hope to contribute to a decrease in preventable childhood mortality in such settings

Simulation of Socio-Economic Impacts due to Seismic Damage of Tehran Water Network

In recent years, the massive losses caused due to big earthquakes in urban areas. These cause significant casualties and losses. The economic losses exceed several billions dollars per year. The loss may be categorized in two types of direct and indirect loss. Direct economic losses occur just during the earthquakes or immediately after them. Indirect losses are resulted from direct losses. These losses are obtained in Tehran due to damage of Water Network. A scenario earthquake that would severely damage the city is assumed. The acceleration and velocities are determined in Tehran GIS map. The vulnerability coefficient for pipe via accelerations and velocities are given. There were less losses than other earthquakes in the world like Kobe or Los Angeles because the earthquake intensity was less, the soil was stronger and the manpower and maintenance value are much lower in Iran

Seismic Hazards for Lifelines

The response of lifelines against earthquakes and seismic hazard effects on them are studied in this paper. As lifelines pass through wide areas, it may be affected by many seismic hazards. These hazards are such as ground rupture, fault movement, landslides and large deformation due to liquefaction. Based on the experiences from past earthquakes, damages to the lifelines with attention to damaged parts are classified and illustrated. This classification is based on the damages of body, joints, facilities and serviceability. Since the buried lifelines are filled with some materials with almost same unit weight of soil, their seismic response characteristics are different from buildings or buried foundations. Surrounding soil affects its seismic behavior. These effective factors are ground characteristic, earthquake characteristic and structure condition

A Bargaining Game model for performance assessment in network DEA considering sub-networks:A real case study in Banking

Several network-data envelopment analysis (DEA) performance assessment models have been proposed in the literature; however, the conflicts between stages and insufficient number of decision-making units (DMUs) challenge the researchers. In this paper, a novel game-DEA model is proposed for efficiency assessment of network structure DMUs. We propose a two-stage modeling, where in the first stage network is divided into several sub-networks; we at the same time categorize input variables to measure efficiency of sub-networks within each input category. In the second stage, we calculate efficiency of the network by aggregating efficiency scores of sub-networks within each category. In this way, the issue of insufficient number of DMUs when there are many input/output variables can be handled as well. One of the main contributions of this paper is assuming each category and stage as a player in Nash bargaining game. Using the concept borrowed from Nash bargaining game model, the proposed game-DEA model tries to maximize distances of efficiency scores of each player form their corresponding breakdown points. The usefulness of the model is presented using a real case study to measure the efficiency of bank branches

STATISTIČKA ANALIZA UTJECAJA KONTROLIRANIH I NEKONTROLIRANIH PARAMETARA NA RAD DIJAMANTNOM ŽIČNOM PILOM, PRIKAZ SLUČAJA

Nowadays, most mining and quarrying industries utilize a diamond wire saw machine for bench cutting operations. This method uses a metal wire or cable assembled by diamond beads to cut the hard stone into large blocks. Many parameters classified into controllable and uncontrollable parameters affect the performance of the diamond wire saw cutting method. The uncontrollable parameters are related to rock engineering properties, and controllable parameters are related to operational aspects and machine performance. The diamond wire sawing process’s production rate is one of the most critical parameters influencing the design optimization and quarrying cost estimation. The cutting rate and wear rate of diamond beads are the most important factors to evaluate quarries’ production performance. This study aims to determine the effects of different controllable and uncontrollable parameters on different quarries’ production rates. Rock engineering properties like strength, hardness, and abrasivity, and operational aspects, such as cutting angle and drive wheel diameters, are considered as the main factors affecting the production performance of the diamond wire saw method. To discover the influence of these parameters, a detailed investigation in ten quarry operations was carried out. The relation between cutting rate and diamond bead wear with different parameters is estimated. It was observed that different controllable and uncontrollable parameters could increase or decrease the cutting rate and diamond bead wearing. Furthermore, using simple and multiple regression analysis, performance prediction of the cutting rate and wearing of diamond beads was developed, and the best equations were proposed.Danas se u najvećemu broju rudnika i kamenoloma upotrebljava dijamantna žična pila za razne operacije na čelima radilišta. Uporabom metalne žice (ili kabela) na koju su dodani dijamantni zupci mogu se rezati veliki blokovi arhitektonsko-građevnoga kamena. Pri tomu rezanje ovisi o nizu parametara od kojih se neki mogu, a neki ne mogu kontrolirati. Oni koji se ne mogu kontrolirati jesu inženjerska svojstva stijena, a oni koji se mogu kontrolirati jesu operativne varijable i svojstva stroja. Iznos rezanja/proizvodnje najkritičnija je varijabla prema utjecaju na iznos proizvodnje. Svojstva stijena kao čvrstoća, tvrdoća i abrazivnost te operativne vrijednosti poput kuta rezanja, promjera pogonskoga kotača najvažnije su varijable koje utječu na proizvodnju žičnih pila. Procijenjen je odnos između brzine rezanja i trošenja dijamantnih zubaca i opaženo je kako različite varijable utječu na povećanje ili smanjivanje iznosa proizvodnje. Analizirane su metodama jednostavne i višestruke regresije, uključivši sve spomenute varijable, te su predložene jednadžbe kojima se opisuju opažene pojave

RetiFluidNet: A Self-Adaptive and Multi-Attention Deep Convolutional Network for Retinal OCT Fluid Segmentation

Optical coherence tomography (OCT) helps ophthalmologists assess macular edema, accumulation of fluids, and lesions at microscopic resolution. Quantification of retinal fluids is necessary for OCT-guided treatment management, which relies on a precise image segmentation step. As manual analysis of retinal fluids is a time-consuming, subjective, and error-prone task, there is increasing demand for fast and robust automatic solutions. In this study, a new convolutional neural architecture named RetiFluidNet is proposed for multi-class retinal fluid segmentation. The model benefits from hierarchical representation learning of textural, contextual, and edge features using a new self-adaptive dual-attention (SDA) module, multiple self-adaptive attention-based skip connections (SASC), and a novel multi-scale deep self supervision learning (DSL) scheme. The attention mechanism in the proposed SDA module enables the model to automatically extract deformation-aware representations at different levels, and the introduced SASC paths further consider spatial-channel interdependencies for concatenation of counterpart encoder and decoder units, which improve representational capability. RetiFluidNet is also optimized using a joint loss function comprising a weighted version of dice overlap and edge-preserved connectivity-based losses, where several hierarchical stages of multi-scale local losses are integrated into the optimization process. The model is validated based on three publicly available datasets: RETOUCH, OPTIMA, and DUKE, with comparisons against several baselines. Experimental results on the datasets prove the effectiveness of the proposed model in retinal OCT fluid segmentation and reveal that the suggested method is more effective than existing state-of-the-art fluid segmentation algorithms in adapting to retinal OCT scans recorded by various image scanning instruments.Comment: 11 pages, Early Access Version, IEEE Transactions on Medical Imagin

Prevalence of vitamin D deficiency in healthy Iranian children : A systematic review and meta-analysis

Peer reviewedPublisher PD

In vitro effect of honey on Candida albicans and lactobacillus

زمینه و هدف: یکی از شایع ترین واژینیت ها در زنان واژینیت های کاندیدایی است که عامل آن قارچ کاندیدا آلبیکنس می باشد. لاکتوباسیلوس از شایع ترین فلورهای طبیعی واژن می باشد که در حفظ شرایط میکروبیولوژی واژن اهمیت زیادی دارد. این مطالعه با هدف بررسی آزمایشگاهی تاثیر عسل بر کاندیدا آلبیکنس و لاکتوباسیلوس انسانی انجام شده است. روش بررسی: در این مطالعه تجربی آزمایشگاهی غلظت های مختلف (وزنی حجمی) بین 20 تا 95 درصد عسل تهیه شد. پس از کشت کاندیدا در محیط کشت RPMI 1640 و عسل و لاکتوباسیلوس در محیط کشت تریپتی کیس سوی براث (TBS) و عسل و انکوباسیون، میزان رشد این میکروارگانسیم ها در ساعات مختلف مورد برسی قرار گرفت. یافته ها: ازغلظت های مورد بررسی، غلظت80 عسل به میزان زیادی از رشد کاندیدا جلوگیری نمود که بیشترین تاثیر مهار کنندگی عسل بر کاندیدا را نشان داد. در محیط های حاوی عسل با غلظت های کمتر و بیشتر از 80 میزان رشد کاندیدا متوسط یا شدید بود. در محیط کشت شاهد، قارچ به طور کامل رشد نمود. هیچکدام از غلظت های عسل نتوانست رشد لاکتوباسیلوس را مهار نماید. نتیجه گیری: با توجه به نتایج بدست آمده عسل می تواند به طور قابل توجهی از رشد کاندیدا جلوگیری کند بدون اینکه تاثیری بر روی لاکتوباسیلوس داشته باشد. با توجه به اینکه لاکتوباسیلوس یک فلور طبیعی واژن است، این مسئله حائز اهمیت است که عسل بدون تغییر فلور طبیعی واژن می تواند رشد کاندیدا را مهار نماید

Nanoliposomes and Tocosomes as Multifunctional Nanocarriers for the Encapsulation of Nutraceutical and Dietary Molecules

Nanoscale lipid bilayers, or nanoliposomes, are generally spherical vesicles formed by the dispersion of phospholipid molecules in a water-based medium by energy input. The other nanoscale object discussed in this entry, i.e., tocosome, is a recently introduced bioactive carrier made mainly from tocopheryl phosphates. Due to their bi-compartmental structure, which consists of lipidic and aqueous compartments, these nanocarriers are capable of carrying hydrophilic and hydrophobic material separately or simultaneously. Nanoliposomes and tocosomes are able to provide protection and release of sensitive food-grade bioactive materials in a sustained manner. They are being utilized for the encapsulation of different types of bioactive materials (such as drugs, vaccines, antimicrobials, antioxidants, minerals and preservatives), for the enrichment and fortification of different food and nutraceutical formulations and manufacturing of functional products. However, a number of issues unique to the nutraceutical and food industry must first be resolved before these applications can completely become a reality. Considering the potentials and promises of these colloidal carrier systems, the present article reviews various aspects of nanoliposomes, in comparison with tocosomes, including the ingredients used in their manufacture, formation mechanisms and issues pertaining to their application in the formulation of health promoting dietary supplements and functional food products

Detection of Helicobacter Pylori in Bronchoalveolar Lavage of Patients With Chronic Obstructive Pulmonary Disease by Real Time Polymerase Chain Reaction

Background: Chronic obstructive pulmonary disease (COPD) is one of the most important causes of disability and mortality in the world. Although cigarette smoking and environmental pollutants have been recognized as the major causes of COPD, the role of infection in the pathogenesis and progression of COPD has also been reported. Objectives: The aim of the present study was to find the relationship between Helicobacter Pylori infection and COPD through anti H. pylori IgG serology, real time PCR of bronchoalveolar lavage and trans bronchial biopsy urease tests. Patients and Methods: This descriptive cross-sectional study was carried out on 60 adults with COPD. After obtaining the patient’s history, physical examination, spirometry and confirmation of COPD diagnosis by pulmonologist, subjects were selected through convenience sampling. In order to determine the severity and prognosis of disease, the global initiative for chronic obstructive lung disease (GOLD) criteria and BODE index were used. Subjects underwent bronchoscopy for obtaining bronchoalveolar lavage (BAL) samples and biopsy was performed. Biopsy and BAL samples were investigated respectively by urease test and real time PCR. Moreover, patients’ serum samples were serologically studied for detection of anti H. pylori IgG. Results: Mean age of the participants was 60.65 ± 9.15 years, and 25% were female and 75% were male. The prevalence rate of H. pylori in COPD patients was 10% according to real time PCR, 88.3% according to the serology test and 0% based on the urease test. According to the results of PCR and considering the severity of disease based on the GOLD criteria, from those with a positive PCR, one patient (16.6%) had very severe obstruction, three (50%) had severe obstruction and two patients (33.3%) had moderate obstruction. The relationship between H. pylori presence (based on PCR) and disease severity and prognosis was not statistically significant. Conclusions: These findings can justify the hypothesis of direct injury and chronic inflammation via inhalation and aspiration resulting in H. pylori colonization. In fact, it is thought that H. Pylori infection, beside the host genetic vulnerability and other environmental risk factors might make the patient susceptible to COPD or lead to COPD worsening. Although we found H. pylori infection in some patients with COPD, the results of this study, could not explain the pathogenic mechanisms of COPD