The cross sectional optical coherence tomography images have an important role in evaluating retinal diseases. The reports generated by the Stratus fast macular thickness scan protocol are useful for both clinical and research purposes. The centerpoint thickness is an important outcome measure for many therapeutic trials related to macular disease. The data is susceptible to artifacts such as decentration and boundary line errors and could be potentially erroneous. An understanding of how the data is generated is essential before utilizing the data. This article describes the interpretation of the fast macular thickness map report, assessment of the quality of an optical coherence tomography image and identification of the artifacts that could influence the numeric data. The introduction of Stratus optical coherence tomogram (OCT)  has advanced the knowledge and understanding of retinal diseases. Apart fr246The Stratus OCT comes with various scanning programs; the most commonly used protocols for retinal pathologies are line scan, cross hair scan, the macular thickness map protocol (MTM) and the fast macular thickness map protocol (FMTM). Both MTMLongitudinal assessment of the foveal thickness on OCT is an important outcome measure for many therapeutic trials. The fundus photograph reading center (FPRC), Madison WI, USA, serves as a central laboratory to receive and analyze OCTs for multicenter clinical trials. The scans are taken by trained and certified operators and evaluated at the reading center by ocular disease evaluators (ODE). Quality of the OCT is one of the most important evaluation procedures used by the ODE since it determines if the software-generated numeric data is erroneous or not. An understanding of the software algorithms and how each of the elements of the report is generated is essential for interpreting the thickness measurements. The purpose of this article is to assist with interpretation of the reports generated by the FMTM protocol and understanding of the artifacts generated by the OCT.3. The six radial B-scans are comprised of 128 A-scans each and the centerpoint of each of these scans is represented by A-scan no. 64 [The combined data from the six radial scans of the FMTM scanning protocol is represented in the FMTM retinal map analysis report. The individual component B-scans are available on retinal thickness reports. The map report should always be analyzed in conjunction with the six individual thickness reports. The map report has six components to it . (1) Then no. 64 . The algThe quality of the OCT scan needs to be evaluated before interpreting any of the components. There are two boundary lines identified by the software in a cross-sectional retinal scan-the first hyper-reflective band is the internal limiting membrane (ILM) and the second hyper-reflective band is considered to be the retinal pigment epithelium (RPE). Studies have shown that the second narrow hyper-reflective band in normal eyes is the photoreceptor inner segment-outer segment (IS-OS) junction and that the true RPE is missed by the segmentation algorithm.16 ErrorsBoundary line errors can easily be identified using the six individual B-scans. Wedge or bowtie artifacts on the pseudocolor map and a high standard deviation of the CPT are additional clues to the presence of this artifact . On occaCPT is an important parameter for evaluation in macular disease because it represents foveal thickness. An important aspect to quality assessment is to confirm whether the CPT truly represents the foveal thickness. If the radial lines of the scan pattern have not been centered on the fovea, the scan is considered decentered and the CPT would not represent the foveal thickness. The center of the macula corresponds to A-scan 64 as shown in Decentration artifact can be assessed using a combination of clues . In scanDecentration is mostly an operator-dependent error. Poor patient fixation or inability to identify the fovea in a distorted retina could be contributory factors. However, if identified, rescanning could help avoid this artifact. In decentered scans, remeasurement of foveal thickness using the software calipers (Stratus review software) is a possibility. The retinal thickness report with an identifiable fovea is selected and the calipers are placed at the inner and outer boundary lines of the point identified as fovea. This gives the true foveal measurement. The remaining data in the subfields cannot be reclaimed.In summary, artifacts on OCTs performed using the FMTM scan protocol of the Stratus OCT are common. Identification of operator-dependent artifacts and retaking images if required reduces the frequency of poor quality OCTs in clinical trials. Simple measures such as centering the scan in a well-dilated pupil, focus and z offset adjustment, and having the patient close their eyes to wet the cornea before taking the image also improves image quality. Poor quality OCTs with erroneous numeric data may still be useful for qualitative analysis of morphological abnormalities.


This study describes the endoscopic findings about the size of the adenoid tissue and the conditionof the nasopharyngeal orifice of the eustachian tube. Results confirmed that only fiberscopic examinationallows a thorough inspection of the nasopharyngeal anatomy to make a correct diagnosis anddesign therapeutic planning. When the presence of adenoid hypertrophy resulting in nasal obstruction,snoring, and/or otitis media was confirmed endoscopically, adenoidectomy proved to be highlyefficacious in relieving these symptoms.


The implementation of whole-genome sequencing in food safety has revolutionized foodborne pathogen tracking and outbreak investigations. The vast amounts of genomic data that are being produced through ongoing surveillance efforts continue advancing our understanding of pathogen diversity and genome biology. The implementation of whole-genome sequencing in food safety has revolutionized foodborne pathogen tracking and outbreak investigations. The vast amounts of genomic data that are being produced through ongoing surveillance efforts continue advancing our understanding of pathogen diversity and genome biology. Produced genomic data are also supporting the use of metagenomics and metatranscriptomics for detection and functional characterization of microbiological hazards in foods and food processing environments. In addition to that, many studies have shown that metabolic and pathogenic potential, antimicrobial resistance, and other phenotypes relevant to food safety can be predicted from whole-genome sequences, omitting the need for multiple laboratory tests. Nevertheless, further work in the area of functional inference is necessary to enable accurate interpretation of functional information inferred from genomic and metagenomic data, as well as real-time detection and tracking of high-risk pathogen subtypes and microbiomes. Microbiological food safety has traditionally been monitored using culture-based phenotypic methods for detection, characterization, and identification of target foodborne pathogens. Pathogens have primarily been studied at a species level and out of the context of microbial communities in which they reside. The breakthrough in high-throughput sequencing in the 2000s enabled the development of precise subtyping methods for tracking of foodborne pathogens and microbial communities. The implementation of these methods is profoundly changing foodborne pathogen surveillance and is expected to increasingly inform the control of foodborne pathogens in the coming years.I discuss three areas of opportunities that have tremendous potential for a paradigm shift in the detection and control of foodborne pathogens. The primary area pertains to the definition of a foodborne pathogen and associated ramifications for public health and the food industries. The next area considers opportunities for surpassing whole-genome sequencing to detect unknown pathogens, and the third area highlights the opportunities for improved control of foodborne pathogens through informed manipulation of food processing environmental microbiomes.Salmonella are highly risky for humans, while others typically cause the disease in animals and are far less frequently reported to cause illness in humans . The positive impacts of the real-time WGS surveillance are evident from the outcomes of the Listeria monocytogenes surveillance program that resulted in more frequently detected but smaller outbreaks since the implementation of the WGS in routine pathogen surveillance  in foodborne pathogen surveillance in the United States resulted in a rapid increase in public availability of foodborne pathogen whole-genome sequences . By the eillance . The crihe radar . Apart fn my lab . Using woutbreak . Using tDespite outstanding successes of WGS in food safety, microbial isolation workflows coupled with WGS still overlook an estimated 38.4 million cases of domestically acquired foodborne illnesses in the United States that are caused by unspecified agents . UnidentEscherichia coli and Salmonella at a low contamination level and with a strain-level resolution directly in foods, without isolation , they should complement rather than replace chemical and physical cleaning and sanitation practices to ensure that hygienic conditions are maintained in the food processing environment.Successful implementation of whole-genome sequencing in food safety has driven remarkable advances in foodborne pathogen tracking and surveillance. The next step toward advancing food safety is utilizing the vast amounts of available foodborne pathogen genomic sequences to extract functional information and identify biomarkers predictive of isolates’ pathogenic potential and other phenotypes relevant to food safety. Functional prediction will be critical for the optimization of detection methods and food safety risk assessment on a subspecies level that can have positive impacts on public health and the economic viability of food industries. Furthermore, going forward, we need to take a step beyond whole-genome sequencing and test the performance of metagenomic sequencing of food and clinical samples to facilitate identification of unknown causative agents of the vast majority of foodborne illness cases. Lastly, it is becoming increasingly important to understand the entire microbial landscape found in food systems to pinpoint the interactions and metabolic roles of individuals comprising microbial communities. This knowledge is necessary for the development of informed and biological pathogen control strategies. I anticipate establishment of metagenomic sequencing approaches in the food safety space with significant impact in the years ahead.


There is a lack of information regarding the safety of flexible bronchoscopy (FB) in patients with severe acute respiratory distress syndrome (ARDS). We read with great interest the letter by Kalchiem-Dekel and colleagues  in whichThe insertion of the bronchoscope through the endotracheal tube (ETT) increases airway resistance by obstructing the ETT, thereby limiting respiratory flows and ultimately increasing inspiratory and expiratory pressures. If the peak inspiratory pressure is greater than the high-limit pressure set on the ventilator, the tidal volume is not fully delivered. This leads to alveolar derecruitment with well-known consequences in ARDS . If the  We thank Drs. Guillon, Nay, and Kamel for their interest in our Letter to the Editor  and theiOur data are limited by the retrospective nature of the study and the lack of intra-procedural pressure measurements. The primary objective of our case series was to highlight the feasibility and possible benefit of secretion clearance in ARDS patients while in the prone position. We point out that all patients who underwent bronchoscopy while in the prone position in our case series had mild to moderate ARDS by the Berlin definition , whereasFinally, data regarding optimal performance of bronchoscopy in patients with ARDS is scarce. We read with great interest the report by Nay et al. describing a novel flexible bronchoscope designed specifically for preservation of lung protective ventilation in mechanically ventilated patients . We hope


This session addresses approaches to strengthening the capacity of family caregivers in the context of intense and complex care. Recognizing the increasing role that families play in delivering complex care at home to individuals with multiple conditions, this symposium highlights approaches to enhancing support and increasing the power of family caregivers. In the first half of the symposium, the papers elucidate characteristics of the caregiving situation that put caregivers at risk and suggest potential areas for intervention by health systems. The second half explores system level approaches to enhancing capacity for family caregivers. On the demand side, the first paper will examine the social network of family caregivers, highlighting effects of social isolation on caregiver health. The second paper uses national data to understand the relationship between higher demand caregiving situations and the strain and challenges that caregivers experience. On the potential solutions side, the third paper addresses a collaborative design of an intervention to enhance supports for family caregivers of persons with dementia at a critical time, during hospitalization. The last paper provides an overview of evidence-based technological solutions to support family caregiving. Taken together, these papers establish some of the demand characteristics of the caregiving situation and provide potential health system solutions to improve capacity of family caregivers. In the final segment, three discussants will reflect on the implications of these papers for clinical practice, education, research and policy.


Changes in climate and environmental conditions could be the driving factors for the transmission of hantavirus. Thus, a thorough collection and analysis of data related to the epidemic status of hemorrhagic fever with renal syndrome (HFRS) and the association between HFRS incidence and meteorological factors, such as air temperature, is necessary for the disease control and prevention.Journal articles and theses in both English and Chinese from Jan 2014 to Feb 2019 were identified from PubMed, Web of Science, Chinese National Knowledge Infrastructure, Wanfang Data and VIP Info. All identified studies were subject to the six criteria established to ensure the consistency with research objectives, (i) they provided the data of the incidence of HFRS in mainland China; (ii) they provided the type of air temperature indexes; (iii) they indicated the underlying geographical scale information, temporal data aggregation unit, and the data sources; (iv) they provided the statistical analysis method that had been used; (v) from peer-reviewed journals or dissertation; (vi) the time range for the inclusion of data exceeded two consecutive calendar years.A total of 27 publications were included in the systematic review, among them, the correlation between HFRS activity and air temperature was explored in 12 provinces and autonomous regions and also at national level. The study period ranged from 3 years to 54 years with a median of 10 years, 70.4% of the studies were based on the monthly HFRS incidence data, 21 studies considered the lagged effect of air temperature factors on the HFRS activity and the longest lag period considered in the included studies was 34 weeks. The correlation between HFRS activity and air temperature varied widely, and the effect of temperature on the HFRS epidemic was seasonal.The present systematic review described the heterogeneity of geographical scale, data aggregation unit and study period chosen in the ecological studies that seeking the correlation between air temperature indexes and the incidence of HFRS in mainland China during the period from January 2014 to February 2019. The appropriate adoption of geographical scale, data aggregation unit, the length of lag period and the length of incidence collection period should be considered when exploring the relationship between HFRS incidence and meteorological factors such as air temperature. Further investigation is warranted to detect the thresholds of meteorological factors for the HFRS early warning purposes, to measure the duration of lagged effects and determine the timing of maximum effects for reducing the effects of meteorological factors on HFRS via continuous interventions and to identify the vulnerable populations for target protection. China has the largest number of hemorrhagic fever with renal syndrome (HFRS) cases in the world. With the acceleration of China’s urbanization process, especially in the process of rapid transition of China’s agriculture-related landscapes to urban landscapes, the dual role of climate change and environmental change has led to a leap in the epidemic area range of HFRS. Exploring or clarifying the relationship between HFRS epidemic and those environmental factors may help to grasp the spread and epidemic pattern of HFRS and then the pattern could serve as the partial basis of accurate HFRS incidence prediction and the corresponding allocation of public health resources. The present systematic review first described the heterogeneity of geographical scale, data aggregation unit and study period chosen in the ecological studies that seeking the correlation between air temperature indexes and incidence of HFRS in mainland China during the period from January 2014 to February 2019. Raising the awareness of the appropriate adoption of geographical scale, data aggregation unit, the length of lag period and the length of incidence collection period is of great importance when exploring the relationship between HFRS incidence and meteorological factors such as air temperature. Three duplicated articles were subsequently removed, after intensive reading the titles, abstracts and full-texts of these article, 81 publications were also excluded. Thus, 27 publications (18 in Chinese and nine in English) were finally included in the systematic review, and among them 21 studies were with low risk of study bias and six studies were with moderate risk of study bias. The literature selection process is shown in A total of 111 articles related to the topic that published between Jan 1Among the 27 publications included, there were 22 journal articles and five dissertations; Those 22 journal articles scattered over 17 kinds of journals, with the journal ‘PLoS Neglected Tropical Diseases’ was identified as the most active journal about the topic during the study period. These 17 journals could be grouped into two categories, public health , and natural sciences, including environmental sciences .Among the included 27 studies, one study analyzed the HFRS data at the national level which included the data from 31 provinces, autonomous regions and municipalities in mainland China, and the remaining 26 studies involved 12 provinces and autonomous regions. Studies from Shandong Province accounted for 37.0% of all the included studies. Five studies collected HFRS data at provincial level, 17 studies collected HFRS data at municipal level, and four studies collected HFRS data at county  level. The study period of the data nested in the included studies ranged from 3 years to 54 years with a median of 10 years, as shown in Regarding the temporal unit of data aggregation, in the included studies, fifteen studies were based on monthly HFRS incidence or the number of monthly incident HFRS cases, five studies were based on the number of daily reported HFRS cases, two studies based on annual HFRS incidence, four studies based on both monthly and annual HFRS incidence, and one study was based on the number of weekly reported HFRS cases. As for the corresponding air temperature indicators, seven studies adopted all the three indicators of average air temperature, average maximum air temperature and average minimum air temperature, and the rest of the studies were based on either average air temperature only or average maximum air temperature only. Twenty-one studies considered the lagged effect of air temperature factors on the HFRS activity and the longest lag period considered in the included studies was 34 weeks.With regards to the statistical methods adopted by the researchers to explore the correlation between air temperature and HFRS incidence, Spearman correlation analysis, Pearson correlation analysis, generalized additive model, seasonal differential autoregressive moving average model, negative binomial multivariate regression analysis, distributed lag nonlinear model conditions, conditional logistic regression analysis and wavelet analysis have been indicated in the included studies, as shown in The associations observed at one scale were not present at another one. Fifteen studies indicated the negative correlation between air temperature and HFRS activity, while seven studies found the positive correlation between air temperature and HFRS activity. There were also two studies that defined a certain temperature as the dividing point between HFRS activity and air temperature, the correlation curve was inverted ‘U-shaped’ ,29. AlsoBecause the current China’s National Notifiable Infectious Disease Reporting system (NIDR) is still unable to distinguish the type of hantaviruses infected by HFRS patients, the direction and magnitude of the effects of temperature on HFRS activity in different seasons were also inconsistent. The study based on the monthly temperature index at county scale in Shandong Province found that the increase of average air temperature in spring was the risk factor of SEOV-type HFRS outbreak, but similar results could not be found in other seasons and in the HTNV-type HFRS . The stuIn addition to collecting data on the incidence of HFRS in the whole population, a certain study also collected data on HFRS incidence  from different populations based on the national legal infectious disease surveillance system. The study in Huludao City, Liaoning province found that HFRS activity in the population aged 35–59 years was significantly affected by air temperature, but this phenomenon could not be found in the population of other age groups ; the autIt is clear from the major part of the included studies that air temperatures are indirectly associated with HFRS activity, however, the temperature-HFRS association findings were inconsistent and location-dependent. Our systematic review indicated that the ecological effects of air temperature on HFRS incidence could be affected by the spatial or temporal scale of the data and also the study period involved, which might help to partly understand the contradicting observations in the included studies. The researchers need to consider or identify which temperature indicator and data aggregation unit are more appropriate to explain the correlations between HFRS incidence and air temperature at different geographical scales .Seeing that the effect of air temperature on the HFRS activity varied among different populations , it is sThe ecological correlation analysis is not only data-driven, but also technology-concentrated, the integration of the collection of high-quality HFRS incidence data and the multi-discipline development can open vast vistas for the correlation analysis techniques’ application in the field of infectious diseases epidemiology . In the The present systematic review might be improved if the following information could be considered in the future HFRS-related ecological studies. All the included studies in the present systematic review are descriptive, further exploratory analysis, explanatory analysis and statistical inference are needed. The distribution of Hantaan and Seoul type of HFRS was not available in the China’s surveillance system of the legally mandated notifiable infectious diseases. The data of HFRS vaccine coverage could not be obtained in the included studies, and HFRS vaccine coverage did affect the magnitude of HFRS incidence. Only one single included study investigated the correlation between air temperatures and HFRS incidence stratified by age group, thus the characteristic of the HFRS vulnerable population that was most affected by air temperature could not be obtained. Besides the different data scale and the differences in the hantaviruses type of HFRS, the factors relating to the dynamics of the rodent hosts and human activities, such as urbanization indicators, should be considered when understanding the results from these ecological studies, given the fact that China is a topographically heterogeneous country. It should also be emphasized that air temperature as an isolated indicator that cannot explain the HFRS incidence fully, confounding factors should always be considered. Caution should be used when studying the associations between HFRS activity and the isolated or the combination of meteorological variables, because of the possible multicollinearity. Therefore, meteorological factors and the impact of climate changes on the pathogenesis of HFRS still need to be further deepened, especially in the process of rapid transition of China’s agriculture-related landscapes to urban landscapes .In summary, the present systematic review first described the heterogeneity of geographical scale, data aggregation unit and study period chosen in the ecological studies that seeking the correlation between air temperature indexes and the incidence of HFRS in mainland China during the period from January 2014 to February 2019. The appropriate adoption of geographical scale, data aggregation unit, the length of lag period and the length of incidence collection period should be considered when exploring the relationship between HFRS incidence and meteorological factors such as air temperature. Further investigation is warranted to detect the thresholds of meteorological factors for the HFRS early warning purposes, to measure the duration of lagged effects and determine the timing of maximum effects for reducing the effects of meteorological factors on HFRS via continuous interventions and to identify the vulnerable populations for target protection.S1 Table(DOC)Click here for additional data file.S2 Table(XLSX)Click here for additional data file.


This special issue focuses on the current approaches for diagnosis, evaluation, and management of autoimmune diseases of the anterior segment of the eye, which range from immune keratoconjunctivitis to anterior uveitis. Immune diseases of the anterior segment of the eye may be caused by several local or systemic conditions and may present in a wide range of diseases including dry eye syndrome, ocular cicatricial pemphigoid (OCP), graft versus host disease (GVHD), and some forms of anterior uveitis often associated with systemic autoimmune diseases such as ankylosing spondylitis. These conditions represent some of the most difficult conditions to diagnose and manage in ophthalmology and often require a multidisciplinary approach.Specifically, in this special issue, Tao and colleagues evaluated reliability and validity of the most commonly used quality of life questionnaires in Chinese patients with dry eye disease; Szepessy et al. evaluated the alterations of central retinal and choroidal thickness and the severity of anterior chamber inflammation in patients with acute anterior uveitis associated with seronegative spondyloarthropathy; Qui et al. described the characteristics of ocular manifestations of a large cohort of patients with a diagnosis of acute or chronic ocular GVHD; Nebbioso et al. evaluated the potential role of vascular endothelial growth factor (VEGF) and mucins in patients with vernal keratoconjunctivitis (VKC). In addition, Leuci et al. reported the long-term clinical outcome of 6 patients with OCP treated with intravenous immunoglobulin therapy (IVIg), which maintained remission of the disease and did not show progression, for a total follow-up period of 9 years after the end of IVIg treatment.The topics presented in this special issue evaluated few aspects of the large and heterogeneous group of disorders which may be included in the group of autoimmune diseases of the anterior segment of the eye. However, it is clear that these conditions require a multidisciplinary approach and often represent a challenge for clinicians due to the lack of specific diagnostic criteria and specific treatments. In fact, most immune diseases are currently treated with local or systemic corticosteroids or immunosuppressive drugs, which may be effective in controlling the inflammatory reaction but are commonly associated with important local and systemic side effects. By this point of view, the increasing understanding of novel pathogenic mechanisms of autoimmune diseases will lead to the development of novel, more specific drugs designed to target the molecules involved in the inflammatory reaction.In addition, autoimmune diseases of the anterior segment of the eye may have complications that extend beyond the anterior segment and can impair visual function. In fact, visual function may be directly impaired in dry eye disease or immune keratoconjuctivits due to corneal damage and scarring, or, alternatively, other autoimmune diseases such as anterior uveitis may induce glaucoma with damage to the optic nerve or macular changes, which cause decrease of visual acuity. Not only the diseases but also some of their treatments may induce long-term adverse effects impairing visual function; for example, chronic use of corticosteroid eye drops in patients with immune diseases of the eye is a well-known cause of cataract and glaucoma.Based on these considerations, it is clear that a further progress in understanding the pathogenesis of ocular immune reactions is highly sought after, together with more standardized diagnostic procedures and protocols for several autoimmune diseases of the anterior segment of the eye. Such progresses will hopefully also lead to the development of novel and more targeted therapeutic approaches that can improve clinical outcome and quality of life of patients with these diseases.


A model of analysis and environmental evaluation was applied to 11 stretches of the Adige River, where an innovative procedure was carried out to interpret ecological results. Within each stretch, the most suitable methods were used to assess the quality and processes of flood plains, banks, water column, bed, and interstitial environment. Indices were applied to evaluate the wild state and ecological quality of the banks  and the landscape quality of wide areas of the fluvial corridor . The biotic components  were analysed by both quantitative and functional methods . The results achieved were then translated into five classes of functional evaluation. These qualitative assessments have thus preserved a high level of precision and sensitivity in quantifying both the quality of the environmental conditions and the integrity of the ecosystem processes. Read together with urban planning data, they indicate what actions are needed to restore and rehabilitate the Adige River corridor.


Microelectromechanical systems (MEMS) have established themselves within various fields dominated by high-precision micromanipulation, with the most distinguished sectors being the microassembly, micromanufacturing and biomedical ones. This paper presents a horizontal electrothermally actuated ‘hot and cold arm’ microgripper design to be used for the deformability study of human red blood cells (RBCs). In this study, the width and layer composition of the cold arm are varied to investigate the effects of dimensional and material variation of the cold arm on the resulting temperature distribution, and ultimately on the achieved lateral displacement at the microgripper arm tips. The cold arm widths investigated are 14  Microgrippers are an example of microelectromechanical systems (MEMS) that are extensively applied in fields dealing with the handling, positioning and assembly of micromechanical parts ,2, as weThis paper focuses on a horizontal electrothermally actuated ‘hot and cold arm’ MEMS microgripper design developed for the manipulation and deformability study of human red blood cells (RBCs). Thermally activated beam flexure has been one of the leading actuation principles within the MEMS domain ,20, wither study , the autThe presented microgripper design is aimed to study the deformability characteristics of RBCs whose pathophysiological relevance allows them to serve as an important marker of the health status of patients ,23. RBCsocedures . The mai tissues . The expThis work presents a number of microgripper structures whose design is based on the U-shape ‘hot and cold arm’ electrothermal actuator configuration . Such a One of the main factors that affects the performance of the presented microgripper design is the resulting temperature difference between the hot and cold arms under an actuation voltage. The larger this temperature difference, the more efficient a horizontal microgripper is expected to be. A higher efficiency of a horizontal microgripper is defined by a larger in-plane displacement obtained at the microgripper arm tips for the same applied voltage. A number of studies ,29,30 haThe microgripper test structures presented in this work were fabricated by MEMSCAP, Inc. , using one of their standard and commercially available Multi-User MEMS Processes  was developed in CoventorWareA number of electrical, thermal and mechanical boundary conditions were implemented within the numerical model, as also shown in A critical aspect in the modelling of electrothermally actuated structures is accounting for the temperature dependency of certain material properties. For this reason, temperature-dependent material properties were used within the microgripper models in CoventorWarex-y-z positioning system. A power supply was used to apply a potential in increments of 0.5 V up to 12 V across the probe pads of each fabricated microgripper structure. The resulting gap opening between the microgripper arm tips was then characterised through the use of the optical microscope-based vision system embedded within the probe station.Experimental testing was performed on the ten microgripper design variants using the setup shown in The electrothermomechanical performance of the ten microgripper design variants has been studied both numerically and experimentally in this work. A lumped analytical model for the SOIMUMPs™ microgripper structure has already been developed and presented in the authors’ previous work  where thThe temperature distribution developed within a microgripper structure during actuation is an important design criterion as it significantly influences the microgripper’s performance. A larger temperature difference developed between the hot and cold arms is expected to result in an increase in the gap opening achieved between the microgripper arm tips due to a larger difference between the thermal expansion of the two arms. Another important aspect of an electrothermal microgripper designed for the handling of biological cells is the temperature developed at the cell gripping zone.Thermal characterisation of the microgripper as a function of the applied voltage has not been conducted experimentally in this study due to the absence of the necessary equipment to obtain such data. A micro radiometric thermal imaging microscope with adequate temperature and spatial resolutions would be able to measure and display the temperature distribution over the microgripper’s surface, enabling the quick detection of hot spots and thermal gradients, as well as the possibility of numerical benchmarking. In the absence of such experimental data, the current work presents and compares the numerical thermal characterisation of the different microgripper designs under electrothermal actuation. The predicted temperature distribution on an actuated SOIMUMPs™ microgripper structure, as obtained with CoventorWareIt can be noted that the value of the maximum temperature on the hot arm is the same for all the microgripper designs shown in cold arm b. It canThe process of adding a metal layer on the cold arm affects the temperature distribution on the hot arm as can be seen by comparing the design variants without and with metal deposition on the cold arm  in In the ‘hot and cold arm’ microgripper design, the lateral displacement achieved at the microgripper arm tips is influenced by the temperature difference developed between the hot and cold arms, with this displacement expected to increase as the stated temperature difference increases for the same applied voltage. Different ways to maximise this temperature difference include designing the hot arm with the smallest possible cross-sectional area as allowed by the capability of the fabrication process (the resulting effect is to maximise the temperature on the hot arm due to a higher current density within the hot arm), increasing the width of the cold arm (the resulting effect is to minimise the temperature on the cold arm due to a decrease in the resistance of the cold arm), and depositing a metal layer on the cold arm . The SOIMUMPs™ fabrication technology recommends a minimum feature width of 3  process , and thiThe resulting numerical temperature difference between the hot and cold arms is shown in cold arm b, conseqThe design of a horizontal MEMS microgripper should be such that it maximises the achieved lateral end-effector displacement as required for the application in consideration, while minimising the temperature developed at the arm tips in the case of biomedical applications. The predicted lateral displacement distribution of the designed microgripper structure is shown in The numerical models of the ten microgripper design variants were validated through experimental tests performed under atmospheric pressure using the setup described in As already highlighted in This paper has presented a number of design variants of a horizontal electrothermal MEMS microgripper that was developed for the micromanipulation and deformability study of RBCs. The different microgripper structures were achieved by varying the cold arm width (14 The electrothermomechanical performance, specifically the temperature distribution and the lateral deflection at the microgripper arm tips, were investigated and compared for the different microgripper designs. Steady-state numerical simulations were performed with the commercial software package CoventorWareIt could be observed that the increase in cold arm width in the case of the design variants of the SCS microgripper structure without metal deposition on the cold arm resulted in a larger temperature difference between the hot and cold arms and in an increase in the achieved gap opening at the microgripper arm tips. Moreover, for a certain cold arm width, metal deposition on the cold arm further increased the temperature difference between the hot and cold arms. It could, however, be noted that, in the case of the design variants with metal deposition on the cold arm, the benefit of depositing metal on the cold arm to maximise the resulting temperature difference decreased as the cold arm width increased, resulting in similar gap openings achieved for the different cold arm widths. This is due to the resulting reduction in both the hot arm and cold arm temperatures with increasing cold arm width in the case of the design variants with metal deposition on the cold arm, causing a much smaller effective temperature difference achieved between the hot and cold arms.All fabricated microgripper structures were actuated under atmospheric pressure and the achieved displacement at the arm tips was investigated via optical microscopy studies. Good agreement was achieved between the tip displacement results from the actuation testing and the numerical predictions. The temperature at the cell gripping zone was also studied numerically and compared with the gap opening for each design variant. It could be observed that the optimal combination of gap opening and temperature at the arm tips for RBC manipulation was obtained from a microgripper structure with a cold arm width of 70 Future work will thus focus on the enhancement of the presented microgripper design to include force feedback, on the modification of the microgripper arm geometry to limit the temperature developed at the cell gripping zone for biomedical applications as well as on the attainment of thermal experimental results via thermal microscopy studies. All these factors will build on the current work in order to futher optimise the SOIMUMPs™ microgripper structure for the successful deformability study of RBCs.


Agrochemicals are essential but hazardous inputs being utilized at different stages in cocoa production. Safeguarding the health of workers handling these chemicals is therefore of utmost importance. Although Ghanaian government implemented mass spraying of cocoa with every essential occupational safety being followed, non-workability of the programme in many parts of the cocoa producing areas necessitates supplementary application of agrochemicals by many farmers. Therefore, a survey was conducted in Ahafo Ano North district of the Ashanti region in 2015 to understand the compliance of farmers to safety guidelines in handling agrochemicals. The survey was conducted with structured questionnaires that were written in English language and translated into the local language in the course of the interviews. A total of 246 cocoa farmers were interviewed using stratified sampling procedures. The questionnaire, which was divided into four sections solicited information on farmers’ socioeconomic characteristics, safeguard measures being taken by the farmers in the course of handling agrochemicals, health complaints after handling agrochemicals and stress and occupational hazards. The dataset is herewith made available and it is considered of vital usefulness given some serious policy implications of occupational health hazards among cocoa farmers. The aim of the survey was to understand some safety precautions being taken by cocoa farmers in the course of handling agrochemicals and associated health complaints. The dataset provides researchers with some variables that can be used to explore research topics on issues of occupational hazards from mishandling of agrochemicals and health complaints among cocoa farmers. The subject of agrochemical usage in agricultural production is vital and for cocoa, it is of critical relevance given the spectrum of pests and diseases being associated with cocoa plant . The datThe data also contain information on the types of agrochemicals that were being used by cocoa farmers, awareness of precautionary measures to be taken in the course of handling agrochemicals, ownership and use of basic safety kits  while handling agrochemicals and understanding of the right way of agrochemical application and disposal of containers/leftovers. 2The survey that resulted into generation of this dataset was conducted in June 2015 at Ahafo Ano North district in Ashanti region of Ghana. The district was purposefully chosen because it is among the top cocoa growing areas in the region. With the assistance of residence extension officers, we employed stratified random sampling procedure with sample size selected in proportion to the estimated number of cocoa farmers in each stratum. The district was stratified into twenty main communities based on prominence of farming. Out of these twenty strata, eight were randomly selected and sample sizes were allocated based on estimated number of cocoa farmers as provided by the extension officers. The sampled communities were Akwasiase (125), Bonkrom (42), Tepa (37), Abonsuaso (14), Jacobu (9), Kwekwewere (9), Dwahoo (6) and Anyinasuso (4). The enumerators were largely farm extension officers who were working directly with cocoa farmers in the district. Prior to the commencement of the survey, the enumerators were properly trained on the requirements of the survey and a pre-testing of the questionnaire was undertaken among few farmers cocoa farmers. In each of the selected communities, the leaders of the cocoa farmers’ groups and/or the chiefs assisted the extension agents in informing cocoa farmers on the purpose of the survey. Although the questionnaire  was designed in English language, interviews were conducted for majority of the farmers in their local language (Akan-twi).North-West University Management Council.The funding for this dataset was obtained from the 2014 IREA of the researcher as approved by the


Microbubble is an emerging modality in the field of Medicine for treatment and imaging. Ultrasound-guided microbubble is an effective diagnosing and treatment technique as it can reduce the systemic toxicity of chemotherapeutic drugs. It is also used in targeted gene delivery in gene therapy. The objective of the review article is to formulate a narrative review on the emerging importance of microbubbles in the diagnosis and treatment of cancer and its future in cancer management. The article focuses on the effectiveness of ultrasound-targeted microbubble in the treatment of malignancy. Microbubble is useful for targeted drug delivery . MicrobuThe diameter of a microbubble, being less than 10 μm approximately, equals the size of a red blood cell and it exhibits a similar rheology in the blood vessels and capillaries in the body . Recent A case report published in China described the use of low-frequency ultrasound combined with microbubbles in the treatment of inoperable hepatic cancer . After tA clinical case study conducted on patients with pancreatic cancer demonstrated the effectiveness of the combination of ultrasound, microbubbles, and gemcitabine in decreasing the tumor size. Being a very aggressive tumor, it is very rare to see a decrease in the size of the tumor by cancer drugs. Surprisingly, combination therapy using ultrasound and microbubbles showed a decrease in tumor growth. The patients in the treatment group were able to undergo more cycles of treatment and the overall quality of life improved. Furthermore, the patients did not notice any discomforts during the treatment cycle .Many studies utilized the blood vessel destructing properties of microbubbles and ultrasound in the treatment of prostate cancer. One remarkable study explored the effect of low-frequency low-intensity ultrasound with microbubble on the hypoxia environment of prostate cancer . AnotherDifferent studies demonstrated the effectiveness of ultrasound targeted microbubbles in the treatment of ovarian cancer. One experiment demonstrated the effectiveness of paclitaxel-loaded microbubbles coated with Luteinizing hormone releasing hormone analogue and ultrasound-targeted microbubble destruction greatly enhanced the therapeutic effect of paclitaxel . AnotherUltrasound-targeted microbubble destruction can be used as a noninvasive way in the treatment of breast cancer. A study noted that there was tumor regression by using ultrasound targeted delivery of miR‐133a‐MB without significant side effects . US targStudies have shown that Doxorubicin, one of the widely used antineoplastic drug, can be delivered to the tumor site as Doxorubicin-liposome-containing microbubbles with the use of ultrasound . UltrasoMicrobubble-mediated ultrasound therapy with Cisplatin or Cetuximab has shown to decrease the tumor size significantly in head and neck squamous cell carcinoma .Microbubble is a treatment and diagnostic modality that is gaining popularity in the field of cancer treatment. The above-mentioned studies demonstrate the efficacy and scope of microbubbles in cancer detection and treatment. Microbubbles can greatly reduce the side effects of the highly toxic chemotherapeutic drugs as the drug is encapsulated inside the microbubble and will only be released at the desired site. To conclude, ultrasound-guided microbubble is a promising new technique for diagnosing and treating cancer. Further clinical studies and research should be needed to completely know the effectiveness and safety profile of the method. So far, the study results have been encouraging.


Manis crassicaudata) is the only pangolin species present in Sri Lanka. There is no comprehensive assessment of its ecology or conservation status carried out in the Sri Lankan context. The dataset described herein is a compilation of information on the distribution, habitats and conservation status of Indian pangolins in Sri Lanka which is collected from a variety of primary and secondary data sources. All information included in the dataset has been recorded between January 2000 and December 2018. The data on distribution, crimes and rescue activities involving Indian pangolins all over the country were collected from the registries maintained by the Department of Wildlife Conservation, Department of National Zoological Gardens and non governmental organizations committed to the conservation of wildlife in Sri Lanka. Verified records from mass media and reliable field data gathered by the authors and their contact networks were further included in the dataset. The data on the distribution can be analyzed to identify the different habitats of the Indian pangolins and their abundance in different climatic zones. The data on distribution include the recorded area, habitat and approximate GPS coordinates of the recorded locality. The data on crimes involving pangolins was extracted from the offices of the Department of Wildlife Conservation which record the crime, date of crime, approximate GPS coordinates of localities where crimes occurred, nature of the crime and fines/actions taken against the offenders. Data on the rescue events include approximate GPS coordinates of the places where the Indian pangolins were rescued, health conditions at the point of rescue and post rescue status [Indian pangolin ( Data on1.1Data on the distribution  include 1.2Data on crime records involving Indian pangolins  include 1.3Data on rescue records of Indian pangolins  include 2Manis crassicaudata in Sri Lanka. Indian pangolin is the only pangolin species in Sri Lanka [Collection of ecological data on nocturnal elusive mammals such as pangolin is difficult due to lower number of records per significant time period . Thus inri Lanka  and it hri Lanka . The datri Lanka . Thus, r


In the original article, there was an error. Near infrared spectroscopy (NIRS) is described under the heading Invasive Multimodality Monitoring of Comatose Patients After Cardiac Arrest and the subheading Use of Invasive Multimodality Monitors when it is a non-invasive modality of monitoring. A correction has been made to the heading, which now reads Other Multimodality Monitoring of Comatose Patients After Cardiac Arrest and the subheading which now reads Use of Invasive and Noninvasive Multimodality Monitors. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


This paper deals with the recent levels of this radionuclide in seawater and with the link between an Arctic fjord, Kongsfjorden, and the Western Spitsbergen Current (WSC), investigated using 99Tc results. By means of the WSC, the 99Tc radionuclides ultimately reach the eastern Fram Strait west of Spitsbergen . Results from oceanographic modelling and sea ice observations indicate a direct coupling between Kongsfjorden and the area west of it. The findings in connection with new radionuclide results presented in this paper concur with these assumptions. Furthermore they indicate that the inner part of Kongsfjorden is also well linked to the WSC. Surface seawater from the central part of the WSC, sampled during a cruise with RV Polarstern in the summer of 2000, shows a higher level of 99Tc than those measured in Kongsfjorden in spring 2000. However, all levels measured in surface water are of the same order of magnitude. Data from sampling of deeper water in the WSC area provide information pertaining to the lateral distribution of 99Tc. The results, along with additional data from spring 2001, indicate that Kongsfjorden is suitable for monitoring the levels of 99Tc arriving in the European Arctic and that the sheltered setting of this fjord does not necessarily provide protection against pollution from the open sea.Seawater from the western coast of Svalbard was sampled in the spring and summer of 2000 to determine levels of technetium-99 (


Recent advances in neural circuitry techniques, like optogenetics and chemogenetics, have allowed for a greater understanding of the periaqueductal gray (PAG) and its importance in predator and prey behaviors. These studies in rodents have highlighted the role of the rostrolateral PAG in hunting behaviors, and have demonstrated functional differences across the dorsal-ventral/rostral-caudal axes of the PAG associated with defensive behaviors. Human imaging studies have further demonstrated that the PAG is active during situations involving imminent threat suggesting that the function of the PAG is likely largely conserved across species. This mini-review article highlights some of the recent advancements towards our understanding of the functional neuroanatomy of the PAG and its importance in the predator and prey behaviors that are critical for survival. The periaqueductal gray (PAG) is essential for the expression of both the hunting behaviors performed by predators and the defensive behaviors performed by prey. Anatomically, it is largely bordered dorsally by the superior colliculus, and ventrally by the dorsal raphe (DR) and midbrain reticular nucleus. It can be further sub-divided into four columns arranged around the cerebral aqueduct . Environmental factors, like the presence of escape routes, and the proximity to the threat, contribute to the type of defensive behavior elicited. In the case of distal threats, rodents will engage in freezing behaviors, and will switch their defensive response to escape-related behaviors like flight and jumps as the likelihood of attack increases  identified distinct subsets of dorsal PAG neurons that are responsible for risk assessment, flight, and freezing with a very small percentage of cells firing in association with more than one of these behaviors  is a protein that regulates expression of many synaptic plasticity-related genes, and thus its expression can be used as a marker of neural plasticity. pCREB expression is increased transiently 20 min following predator exposure in the lateral PAG  activity in the PAG increases as innately threatening stimuli  becomes more imminent  technology, much of this research has not sub-divided the human PAG into its dorsal and ventral sub-areas (Linnman et al., TF is the sole author of this review article.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Air-sea flux exchanges influence the climate condition and the global carbon-moisture cycle. It is imperative to understand the fundamentals of the natural systems at the tropical coastal ocean and how the transformation takes place over the time. Hence, latent and sensible heat fluxes, microclimate variables, and surface water temperature data were collected using eddy covariance instruments mounted on a platform at a tropical coastal ocean station from November 2015 to October 2017. The research data is to gain the needful knowledge of the energy exchanges in the tropical climatic environment to further improve predictive algorithms or models. Therefore, it is intended that this data report will offer appropriate information for the Monsoonal, and diurnal patterns of latent (LE) and sensible (H) heats and hence, establish the relationship between microclimate variables on the energy fluxes at the peninsular Malaysian tropical coastal ocean. Specifications TableValue of the data•This data showed that the tropical coastal ocean energy exchanges between the atmosphere and the ocean biospheres is dynamic in nature and thus not easily predicted by the applications of the existing TOGA-COARE models.•Data of this nature are very important for researchers working on the relationship between microclimate variables and the energy budgets.•The research data is related to the government policy of improving the environmental and health conditions of the coastal and estuaries in any part of the world.1The tropical coastal ocean plays a significant role in the energy exchange between the air and sea compared to higher and lower latitude regions due to increased and persistent solar radiation and high and constant water surface temperature Therefore, the data has helped to determine the Monsoonal, and diurnal patterns of latent (LE), i.e., 2Air-sea flux exchanges drive the climate and the global carbon-moisture cycle. Climate models forecast an increase in sea-surface temperature because of global warming, that subsequently intensifies the oceans׳ capacity to deliver heat to the atmosphere in the form of fluxes Energy flux exchange in the tropical ocean requires further study as the magnitude of these fluxes have generally been estimated and seldom directly measured, except for a handful of studies for instance Planet-scale studies of air-sea interactions ubiquitously depend on indirect flux quantification methods such as the bulk flux algorithm


We present an unusual case of five months old neglected anterior dislocation of the right elbow joint in a 19-year old man. The patient had been initially treated by a traditional bone setter, but the elbow remained unreduced. He presented to us with pain, deformity and limited range of motion of his right elbow joint. Radiographs revealed an unreduced anterior dislocation of the right elbow joint. We describe the problems encountered during open reduction and rehabilitation and result one year after the operation with the patient having a stable elbow and a functional range of motion. Acute uncomplicated anterior dislocation of the elbow joint is rare compared to its posterior counterpart and good treatment outcomes have been reported4. Old unreduced anterior dislocation of the elbow joint has not been reported. Here we discuss the likely mechanism, clinical features, disability at presentation, challenges anticipated, problems encountered and result after open reduction in a five-month old unreduced anterior dislocation of the elbow joint in a 19-year old male patient.The elbow is the second most common joint that sustains dislocation in adults, and the treatment is simple. Old unreduced posterior dislocation of the elbow joint is common in developing countries. The reasons ascribed are the lack of awareness, inadequate access to health care facilities and easy access to traditional bone setters. Acute anterior dislocation of the elbow joint associated with fracture of olecranon have been reported in adults and childrenA 19-year old male presented to us in the outpatient department with complaints pain on lifting weight with the right arm, deformity and limited range of motion of the right elbow for five months. The patient had fallen down and sustained the injury to his right elbow while hanging from the rootlets of a Banyan tree, following which, he had pain, swelling, and deformity of the right elbow. He had sought treatment from a local bone setter for four weeks following which pain and swelling decreased, but the deformity and elbow stiffness had persisted, for which he attended our hospital.On examination, the Beighton hyperlaxity score of the patient was 5/9. There was flexion deformity of the elbow joint and wasting of muscles of the arm and forearm. The olecranon process was displaced from the olecranon fossa of the right humerus and an abnormal bone mass was palpable on the anterior aspect of the distal humerus. There was a flexion deformity of 40 degrees of the elbow joint with further flexion of 70 degrees. Pronation and supination were normal. There was a valgus laxity of the right elbow joint. The differential diagnoses were neglected dislocation of the elbow joint (posterior/anterior) and mal-united supracondylar fracture.Antero-posterior and lateral radiographs of right elbow demonstrated an anterior dislocation of the elbow joint with an anterior bone mass at the distal humerus. The bony anatomy of the elbow appeared unclear on radiography, and a Computed Tomogram (CT) with 3D reconstruction  confirmeWe performed an open reduction of the elbow by combined medial and lateral approach based on findings of the CT scan. We were successful in excising the bone mass but failed to reduce the elbow joint. There was some early degeneration of the articular cartilage of the distal humerus and olecranon. It was impossible to reduce the olecranon posteriorly. We extended the approach through the subcutaneous plane to the posterior aspect and performed an olecranon osteotomy. The humerus was reduced into the osteotomy, and it was fixed with tension-band wiring. Indomethacin was started at 25mg eight hourly after surgery for three weeks after the operation. We did not immobilise the elbow and started active assisted mobilisation of the elbow joint after surgery as tolerated by the patient. The patient was discharged after wound inspection on the 5th post-operative day and advised to attend the rehabilitation department for physiotherapy for six weeks.At review one year postoperative he had a painless range of motion of 30 degrees to 120 degrees at the elbow joint. He has excellent pronation and supination and could perform light activities. The olecranon osteotomy healed well  though t4. Venkatram et al have described the mechanism of anterior dislocation in a 1-year old child. They hypothesised that a sudden pull on the forearm in an attempt to stop the child from running and falling down on the floor might cause an anterior dislocation at the elbow joint2. We believe that a mechanism similar to the one described by them operated in our case. An association of fractures of the olecranon, medial epicondyle, lateral epicondyle and pulled elbow has been reported with anterior dislocation of the elbow joint5.Acute anterior dislocations of the elbow joint have been described in the literature5. The case described here presented with similar clinical and anatomical findings. The delay in seeking treatment and presence of bony mass anteriorly at the distal humerus posed a challenge in arriving at the diagnosis of elbow dislocation. Good outcome has been reported in neglected posterior elbow joint dislocations after open reduction utilising the posterior approach with or without V-Y plasty. We had several challenges in deciding the surgical approach, extent of soft tissue release and duration of postoperative immobilisation in our case. We planned open reduction of the elbow by utilising combined medial and lateral approaches because of the position of olecranon and radial head in an antero-medial location. A posterior approach in itself would have severely hampered the access anteriorly. We believe that antero-medial displacement of olecranon and radial head in relation to the distal humerus led to stretching of the triceps. A triceps split or a V-Y plasty of the triceps would have been probably insufficient and challenging to bring the trochlea into the olecranon. However, the inability to reduce the humero-ulnar articulation despite complete release made us apply the unconventional step of an olecranon osteotomy through the existing medial limb of the combined medial and lateral approach.Clinical features described for an acute anterior dislocation of the elbow joint are a flexed attitude, pain, swelling, deformity and painful restriction of range of motion. Anatomically there is disruption of the bony relationship between the olecranon, the lateral and the medial epicondylesTo summarise, anterior dislocation of the elbow joint is infrequently reported. Treatment of unreduced anterior dislocation of the elbow joint can be a challenging problem. A good outcome can be expected in adequately treated cases.The authors declare no conflicts of interest.


In this context, multiscale simulations can contribute to deciphering the intricacies of the splicing mechanism by assessing the chemical details of the pre-mRNA cleavage, and the role of the extraordinarily convoluted protein/RNA environment in creating the appropriate structural scaffold that finely modulates introns removal   complex , and electrostatic calculations disentangled the cooperative motions underlying the SPL functional dynamics, unraveling the role of electrostatics in modulating these movements (Casalino et al., A detailed comprehension of the molecular terms of eukaryotic splicing has entailed implications for revolutionary gene modulation therapies and drug discovery studies aimed at fighting the over 200 human diseases associated with splicing defects. Upon the deposition of the first SPL structure from yeast in 2015, many human cryo-EM maps have been solved, thus opening new opportunities to dissect detailed aspects of this machinery (Kastner et al., Although the reported results from all-atom simulations—and all the possible future applications—appear to be very encouraging (Casalino et al., In this scenario, we expect that new methodological advances in computer simulations, modeling and analysis techniques will foster atomic-level studies of the SPL, contributing to an utter comprehension of this fundamental step of gene expression. This will also be of service for a better understanding of the allosteric signaling between distal sites, which occurs via the entangled protein/RNA networks characterizing the SPL, and for the discovery of druggable allosteric sites (Palermo et al., LC and AM designed research and wrote the paper.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


We therefore conducted scaffold diversity and comparison analysis of natural products with in vitro antiplasmodial activities (NAA), currently registered antimalarial drugs (CRAD) and malaria screen data from Medicine for Malaria Ventures (MMV). The scaffold diversity analyses on the three datasets were performed using scaffold counts and cumulative scaffold frequency plots. Scaffolds from the NAA were compared to those from CRAD and MMV. A Scaffold Tree was also generated for each of the datasets and the scaffold diversity of NAA was found to be higher than that of MMV. Among the NAA compounds, we identified unique scaffolds that were not contained in any of the other compound datasets. These scaffolds from NAA also possess desirable drug-like properties making them ideal starting points for antimalarial drug design considerations. The Scaffold Tree showed the preponderance of ring systems in NAA and identified virtual scaffolds, which may be potential bioactive compounds.In light of current resistance to antimalarial drugs, there is a need to discover new classes of antimalarial agents with unique mechanisms of action. Identification of unique scaffolds from natural products with  Plasmodium  is highly desirable and needed. Since the molecular scaffolds as well as the pharmacophore features of a compound define the uniqueness of a compound, exploration of scaffolds of NAA may lead to identification of new antimalarial chemotypes. The term molecular scaffold is used to describe the core structure of a molecule and it determines the spatial orientation within the binding pocket of biological targets , a robust artificial neural network algorithm, was used to organize Murcko scaffolds of CRAD and bioactivity subgroups of NAA  based on scaffold structural similarity. Scaffold structural similarity was assessed with “Fragfp descriptors” from DataWarrior . Fragfp in vitro antiplasmodial activities (NAA); currently registered antimalarial drugs (CRAD) and malaria box from Medicine for Malaria ventures (MMV). The scaffold diversity of these antimalarial compound datasets were computed and compared. The scaffold count and cumulative scaffold frequency plots (CSFP) showed that CRAD is the most scaffold diverse dataset while NAA displayed more scaffold diversity than MMV. Amongst the bioactivity subgroups of NAA, the high active (HA) compound set had the highest scaffold diversity. The Scaffold count and Cumulative scaffold frequency plots (CSFP) were useful indicators of scaffold diversity of the antimalarial and antiplasmodial datasets studied.Murcko scaffolds and Scaffold Trees were generated from natural products with It was evident that many of the scaffolds from the NAA  were not similar to those from CRAD, thereby highlighting the novelty of these scaffolds in the antimalarial chemical space. Moreover, most of the scaffolds have desirable drug-like properties and these novel scaffolds may be used as frameworks to design new antimalarial focused compound libraries.Scaffold Tree was also used to explore the scaffolds present in CRAD and bioactivity subgroups of NAA . The presence of scaffolds at increasing levels of the Scaffold Tree for HA, A, MA and LA indicate the prevalence of ring systems and increasing molecular complexity of the compounds in these datasets. More importantly, virtual scaffolds present at different levels of the Scaffold Tree of the NAA compounds were identified, which are chemically significant, and may also provide starting points for new potential antimalarial compounds.Overall, the exploration and comparison of the scaffolds from CRAD, MMV and NAA  enabled us to find novel scaffolds and chemotypes that may result in progress towards design of new compound libraries and development drug candidates to combat malaria. This study also underscores the potentially significant contributions from nature to antimalarial drug development.


There are considerable individual differences in the rates of cognitive decline across later adulthood. Personality traits are one set of factors that may account for some of these differences. The current project explores whether personality traits are associated with trajectories of cognitive decline, and whether the associations are different before and after a diagnosis of dementia. The data will be analyzed using linear mixed effects regression. Across these goals is a focus on replicability and generalizability. Each of these questions will be addressed in four independent longitudinal studies of aging , then meta-analyzed, thus providing an estimate of the replicability of our results. This study is part of a registered report of existing data that is currently under stage 1 review.


The complete or the partial absence of pericardium is a rare congenitalmalformation for which the patients are commonly asymptomatic and the diagnosisis incidental. The absence of the left side of the pericardium is the mostcommon anomaly that is reported in the literature while the complete absence ofpericardium or the absence of the right side of the pericardium are uncommon andtheir criteria are still unrecognized given their rare occurrence in clinicalpractice. This paper aims to report a case of 19-year-old male with thecongenital partial absence of both sides of the pericardium and to highlight thesymptoms and the different cardiac imaging modalities used to confirm thediagnosis of this defect. A 19-year-old male patient was admitted to the radiology department of the MilitaryHospital of Tunis in July 2017 for a physical fitness test. His past medical historywas not remarkable. He had no chest pain, no dyspnea or other specific signs. Theelectrocardiogram (ECG) indicated a normal sinus rhythm with a heart rate of 65 bpmand diffuse T wave inversion in anteroseptal leads. The transthoracicechocardiography and the transesophageal echocardiography showed an enlarged rightventricular dimension with no evidence of atrial septal defect. The Chest X-rayrevealed a lucent area due to the interposition of lung tissue between the aorta andpulmonary artery . In addiFurthermore, the exam showed an interposition of lung tissue between the diaphragmand the base of the heart and between the aorta and the superior vena cava  and D wi2 and 58.6 % which is normal.All these findings revealed by cardiac imaging examinations confirmed a diagnosis ofpartial agenesis of right and left pericardium.Right end-diastolic volume index (RVEDi) and right ventricular ejection fractionobtained by MRI were respectively 87 ml/m. Among the different classes of CAP, the absence of theleft side of the pericardium is the most common defect with a prevalence of 70 %while the incidence of the total absence of pericardium or the absence of the rightside of the pericardium is still relatively uncommon.The absence of pericardium is a rare congenital malformation generally characterizedby non-specific symptoms. The majority of clinical cases reported in the literatureshowed that the congenital absence of pericardium (CAP) includes a total absence ofpericardium and complete or partial absence of the left or the right side of thepericardium. The possible embryological origins of this pericardial anomaly are notwell understood, but most studies demonstrated that it is due to defectivedevelopment of the pleuropericardial membranes. In themajority of reported cases of CAP, the clinical presentation is not specific.Patients are asymptomatic and the findings of this congenital disease are generallyoccurring incidentally. In this regard, the advent of different cardiac imagingmodalities has significantly improved the specificity of the diagnosis of CAP byproviding valuable information and indications that confirm the presence of thiscongenital heart disease.For this reason, the majority of literature reviews have focused on the possiblesymptoms, indications, and management algorithm that could be associated with theabsence of the left side of the pericardium. Among the typical clinical signs, wecould observe chest pain, dyspnea, the episode of acute respiratory distress leadingto syncope, palpitation.In the current paper, a case of partial absence of right and left sides of thepericardium is presented. The findings of our study showed that the present case wasasymptomatic without a remarkable medical history. In addition, the ECG showed aregular rhythm with diffuse T wave inversion in anteroseptal leads. While physicalexamination and ECG are not specific for the diagnosis of partial agenesis of thepericardium, the echocardiography contributes to the identification of severalfeatures related to this defect. The typical echocardiography findings of partialagenesis of left pericardium include cardiac levoposition, abnormal septal motionand increased mobility of the heartassociated with this type of defect, an enlarged right ventricle and hypertrophiedright atrium with severe tricuspid regurgitation could be observed.A few case reports in the literature have shown the findings of echocardiography inpatients with partial agenesis of the right pericardium. Among the echocardiographyfindings described by Shah et al2 which is normal. This finding indicated that echocardiographyshowed a what appears to be a dilated right ventricle due to its anterior location.This would tend to yield a larger measured right ventricular dimension. As a result,the patient might be falsely labeled as affected by arrhythmogenic right ventriculardysplasia.In the current case, the echocardiography showed an enlarged right ventriculardimension without an atrial septal defect. RVEDi obtained by MRI was 87ml/mIn addition to the echocardiography, chest X-ray and cardiac CT play an essentialrole in the confirmation of the diagnosis and to the exclusion of some complicationsassociated with partial agenesis of the pericardium. The chest X-ray showed that theinterposition of lung tissue causes a lucent area between the aorta and pulmonaryartery.While echocardiography and chest X-ray exams are helpful in the extraction of somepartial agenesis features as well as in the exclusion of other cardiac diseases,they are not able to confirm the diagnosis of partial absence of the pericardium.For this reason, a Chest CT or a Magnetic Resonance Imaging are always required inorder to provide a definitive diagnosis and to assess the extent of theabnormality.. All These CTfindings were shown in our case with a non-visualization of the superior portion ofthe right pericardium. Furthermore, the outcome of the cardiac CT showed aninterposition of lung tissue between the aorta and the superior vena cava, whichstrongly confirms a diagnosis of partial agenesis of right and left pericardium.The chest CT features of the absence of right pericardium include visualizingherniation of right structure while the partial agenesis of the left pericardium iscommonly revealed by the interposition of lung tissue between the aorta andpulmonary arteryThe management of partial agenesis of right and left pericardium depends on the typeand the extent of the pericardial defect. Usually, an intervention is not needed incase of patients with a complete absence of the pericardium. Complications are moreoccurring for patients with partial agenesis. Among the major complications thatrequired a surgical intervention, we can note necrosis due to the herniation of theleft atrial appendage, myocardial strangulation and incarceration of cardiacstructures. In our case, the patient does not have these complications. Therefore,an intervention is not needed unless significant complications occur.In the current paper, we presented a case with the congenital partial absence of bothsides of the pericardium. The outcomes of this study showed that this defect isusually asymptomatic. For this reason, a combination of several cardiac imagingmodalities is needed to establish an accurate diagnosis of partial agenesis of rightand left sides of the pericardium.


The role of entropy in materials science is demonstrated in this report in order to establish its importance for the example of solute segregation at the grain boundaries of bcc iron. We show that substantial differences in grain boundary chemistry arise if their composition is calculated with or without consideration of the entropic term. Another example which clearly documents the necessity of implementing the entropic term in materials science is the enthalpy-entropy compensation effect. Entropy also plays a decisive role in the anisotropy of grain boundary segregation and in interface characterization. The consequences of the ambiguous determination of grain boundary segregation on the prediction of materials behavior are also briefly discussed. All the mentioned examples prove the importance of entropy in the quantification of grain boundary segregation and consequently of other materials properties. Grain boundary segregation is a phenomenon that influences the behavior of the whole material under external conditions . By affeExperimental data on grain boundary segregation have been most frequently obtained from measurements by Auger electron spectroscopy (AES) but recently also from analytical transmission electron microscopy or 3D atom probe tomography . The temThermodynamic quantities have been calculated by theoretical models such as density functional theory (DFT), molecular statics and dynamics, and the Monte Carlo methods . HoweveIn the present paper, it is discussed whether the differences caused by neglecting the entropic contribution are important for the determination of the grain boundary solute concentration or not. Other aspects of the entropic term, such as the enthalpy-entropy compensation effect and the reversed anisotropy of grain boundary segregation, are discussed. The effects of an incorrect determination of the grain boundary segregation on related materials properties are also briefly listed. Based on all findings, it is shown that the entropy of grain boundary segregation is an important parameter that cannot be neglected.I at the grain boundary and in the volume of the host material, M, respectively. I-I interaction in the host material M. The standard term is constructed by the enthalpy (H) and entropy (S) terms,As mentioned above, the most popular expression for the description of solute concentration at the grain boundary is the Langmuir–McLean segregation isotherm,XIGBX0−XIXIGBX0−XIFrom the experimentally measured temperature dependence of the chemical composition of the grain boundaries, the values of all three parameters required for a complete description of grain boundary segregation, i.e., IF. There is a simple thermodynamic relationship between P is pressure and Theoretical calculations result in the values of the Helmholtz energy of solute segregation, Δpressure ,(6)ΔGI≅T = 0 K, the entropic term is zero and I in M. Equation (7) represents the basis for comparison of the theoretical data with the experimental results [At  results . A considerable number of published values of segregation energy and enthalpy exist. These values have been obtained either theoretically or experimentally, and much of the available data for selected host materials has been summarized in References ,5, whereA comparison of experimental results and theoretical calculations on the values of the enthalpy and/or energy of grain boundary segregation found in the literature shows excellent agreement between cases where all physical prerequisites are fulfilled ,13,14. LIt is obvious from The importance of entropy in grain boundary segregation was already demonstrated in the case of the enthalpy-entropy compensation effect in Reference . In factCET is the compensation temperature and In Equations (8) and (9), The existence of the enthalpy-entropy compensation effect has another very important consequence. The combination of Equations (4) and (8) gives: CET. This means that the grain boundary concentration is the same for all grain boundaries at CET. This can be documented by the reversed character of phosphorus segregation at {013} and {058} grain boundaries, as shown in As a consequence, the sign of the differences in chemical composition which occur at temperatures lower than In the above analysis, we saw that the consideration or negligence of entropy in the quantification of grain boundary segregation as a representative for intergranular properties gives very different results. Large differences are apparent between the grain boundary concentrations determined in these two ways, and the enthalpy-entropy compensation effect cannot be considered if entropy is neglected. These differences led us to conclude that calculations of the grain boundary composition that neglect the entropy term are incorrect.An incorrect determination of the grain boundary segregation can have important consequences for practical applications. It is known, for example, that phosphorus segregation at grain boundaries induces the temper embrittlement of ferritic steels, which can result in brittle fracture ,19. If tGrain boundary segregation of impurities in steels also affects other materials properties controlled by interfaces . PhosphoAs mentioned in the introduction, grain boundary segregation can also have an important effect on the reduction of grain boundary mobility  and, conTo assess the segregation effect on material behavior correctly, we must know the precise value of the grain boundary concentration of an impurity. An incorrect determination of the grain boundary concentration can thus result in misleading practical conclusions. For example, the systematically lower values of grain boundary concentrations of phosphorus as determined in Both model calculations, as well as phenomena such as the temperature and concentration dependences of grain boundary segregation, clearly prove that the entropy term is irreplaceable in all considerations of grain boundary segregation. This conclusion is supported by several examples: (1) the comparison of the temperature dependence of phosphorus and silicon segregation at two differently oriented grain boundaries, calculated with and without the entropic term; and (2) the enthalpy-entropy compensation effect and its consequence in changing the character of grain boundary segregation as compared with the two defined grain boundaries. These examples clearly illustrate that the entropy of grain boundary segregation cannot be neglected in any treatment that deals with this phenomenon. As the entropy of segregation can be obtained from experimental studies on the temperature dependence of grain boundary chemistry at present, it is a great challenge to find new approaches for theoretical calculations of this parameter in order to make significant progress in understanding the phenomenon of grain boundary segregation.


Foot-and-mouth disease (FMD) is a highly infectious transboundary disease that affects domestic and wild cloven-hoofed animal species. The aim of this review was to identify and critically assess some modelling techniques for FMD that are well supported by scientific evidence from the literature with a focus on their use in African countries where the disease remains enzootic. In particular, this study attempted to provide a synopsis of the relative strengths and weaknesses of these models and their relevance to FMD prevention policies. A literature search was conducted to identify quantitative and qualitative risk assessments for FMD, including studies that describe FMD risk factor modelling and spatiotemporal analysis. A description of retrieved papers and a critical assessment of the modelling methods, main findings and their limitations were performed. Different types of models have been used depending on the purpose of the study and the nature of available data. The most frequently identified factors associated with the risk of FMD occurrence were the movement  and the mixing of animals around water and grazing points. Based on the qualitative and quantitative risk assessment studies, the critical pathway analysis showed that the overall risk of FMDV entering a given country is low. However, in some cases, this risk can be elevated, especially when illegal importation of meat and the movement of terrestrial livestock are involved. Depending on the approach used, these studies highlight shortcomings associated with the application of models and the lack of reliable data from endemic settings. Therefore, the development and application of specific models for use in FMD endemic countries including Africa is encouraged. Aphthovirus of the family Picornaviridae called foot-and-mouth disease virus (FMDV). The primary mode of transmission of FMDV is via direct contact from infected to susceptible animals 87] relat(DOCX)Click here for additional data file.


Li J et al. conduct a sufficiently large cohort study and show that the risk of gestational diabetes mellitus (GDM) is inversely correlated with the height of the pregnant women . This asFirst, short stature can be associated principally through the mechanism of greater risk of obesity/fat mass . Co-presGDM, as a form of diabetes is multifactorial disease in origin. Several factors such as greater prepregnancy BMI, age, weight gain and a parental history of diabetes mellitus are independently associated with the GDM . The epiGB wrote the first draft and reviewed all drafts of the commentary. AN reviewed and provided inputs for finalization of the commentary. DJ reviewed and provided inputs for finalization of the commentary through all stages.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


It is increasingly clear that the intestinal microbiota plays key roles in the pathogenesis of the conditions known as Crohn disease and ulcerative colitis (jointly known as the inflammatory bowel diseases). Perturbations of the microbiota, termed dysbiosis, are present at diagnosis and likely reflect earlier environmental influences along with interactions with intestinal immune responses. Over the last two decades, there has been increasing interest in the use of a nutritional therapy to induce remission of active Crohn disease. Amongst a number of recent studies focusing on the putative mechanisms of action of enteral nutrition in Crohn disease, there have been several reports illustrating profound interactions between this nutritional therapy and the intestinal microbiota. Although at present it is still not clear how these changes relate to concurrent improvements in inflammation, it has become an area of increasing interest. This review article focuses on the impacts of nutritional therapy in individuals with active Crohn disease and overviews the most recent data arising from international studies. Although the two main subtypes of IBD, Crohn disease (CD) and ulcerative colitis (UC), share similar features, CD is differentiated from UC by disease location, histological changes and disease behaviour The pathogenesis of IBD is still not completely understood. At present, the best accepted hypothesis is that environmental factors lead to key changes in the intestinal microbiota that then trigger dysregulated innate and acquired immune responses in individuals with genetic risk factors At present IBD is incurable: management involves induction of remission followed by maintenance of remission 2.EEN involves the exclusive use of a liquid diet for a period of time , with exclusion of normal diet over this time Although the main role of EEN is the induction of remission, this intervention also has various other benefits. These include enhancing nutritional status and improving bone health Following a period of EEN, many units recommend ongoing maintenance enteral nutrition (MEN), involving supplementary enteral formulae intake supplied in addition to standard or habitual diet. This intervention is associated with maintenance of remission, with reduction in relapse 3.Campylobacter species, Mycobacterium paratuberculosis (MAP) and Escherichia coli (e.g. adherent invasive E. coli). As one example, a number of studies illustrate higher rates of CD developing after Campylobacter infections. In addition, data shows a significantly greater prevalence of specific Campylobacter species (C. concisus) in children with CD compared to well control children Many studies have focused on looking at a single organism as the causative factor for the development of IBD Faecalibacterium prausnitzii is paramount Most recent data illustrate that the presence of distinct changes in the patterns of the flora, so called dysbiosis, are more important in the development of IBD. This dysbiosis is considered to be present prior to and at the onset of IBD and is characterised by variations in the balance between bacterial groups (e.g. Firmicutes and Bacteroidetes). Some recent data also indicate that a reduction in one particular group of bacteria, Several animal and human observations confer a critical role for the intestinal microbiota in the development of IBD. Firstly, the presence of microbiota is required to promote the development of inflammation in various animal models of IBD. An example is the interleukin (IL)-10 knock out mouse model In the setting of individuals with CD, a defunctioning surgical procedure  is typically followed by resolution of inflammation in the bypassed section of gut 4.Although EEN has been utilised to induce remission in individuals with active CD for many years, it has only been in the last few years that investigators have worked to elucidate the mechanisms by which this intervention leads to reduced inflammation. Several mechanisms have been demonstrated and proposed. These include enhanced barrier function with increased tight junction performance and direct anti-inflammatory effects during EEN therapy Clostridium leptum group was associated with change in disease activity and change in levels of S100A12 .The first reports that considered the direct effects of EEN on the intestinal microbiota utilised temperature temporal or density gradient gel electrophoresis (TTGE or DGGE respectively) methods. These reports demonstrated significant alterations consequent to the nutritional intervention F. prausnitzii species, contrary to the authors' hypothesis and contrary to expectations arising from the earlier observations made in adult patients with CD In a more recent report that also utilised TTGE (augmented with quantitative PCR), Gerasimidis et al. As well as assessing the impact of EEN on the structure of the intestinal microbiota, these authors also characterised functional aspects subsequent to the period of nutritional intervention A number of subsequent studies have employed 16S rRNA high throughput sequencing and some reports have also employed whole genome or shot-gun sequencing techniques. Some additional reports have also utilised methods to further describe the functional implications of the changes in the microbiota.One of the first studies to utilise 16S rRNA sequencing showed dysbiosis at the time of diagnosis of the five subjects with CD, which was not apparent in control children Quince et al. Lewis and colleagues This study also delineated the patterns of the intestinal microbiota after 8 weeks of therapy and stratified according to response  or non-response. Response in the groups treated with EEN or a biologic therapy was associated with the microbiota reverting closer to the patterns seen in the control children.Bacteroidetes phylum, and with increases in bacteria in the Firmicutes phylum. These changes were evident after just two weeks of EEN. Interestingly the changes in the children who were recently diagnosed differed from those with longstanding disease. In contrast to the findings described by Kaakoush et al. More recently, Schwert and colleagues This study also characterised specific and detailed changes in innate and acquired immune status Dunn et al. F. prausnitzii alone. EEN was noted to reduce several types of this bacterium, similar to and supporting the changes described in the afore-mentioned paediatric study Each of the studies reported above were conducted in children. To add to this pattern, two studies have been reported to date that included adult subjects. Jia et al. Bacteroides fragilis group reduced by one tenth: there were no significant changes in the other bacterial groups assessed.Shiga and co-authors The focus of the work reviewed above was on the impact of the EEN on the intestinal microbiota in the context of CD. Interestingly, there have been a series of reports demonstrating that this nutritional intervention is also efficacious and also leads to alteration of the structure and function of the intestinal microbiota in rheumatological disease. Swedish authors reported that a course of EEN given over 3 to 8 weeks in 13 children with juvenile idiopathic arthritis (JIA) promptly resulted in marked reduction of joint inflammatory scores and decreased levels of key pro-inflammatory cytokines implicated in joint inflammation 5.There are now a number of reports that have utilised various techniques to elucidate the specific changes in the intestinal microbiota following the intervention of EEN in the setting of CD. Additional reports have also characterised some functional implications of the changes in the microbiota.F. prausnitzii, which has been characterised as a defensive bacterium in adults with CD. Whilst this reduction may just reflect the change in nutrient intake for this organism, it is intriguing that this reduction is concurrent with improved inflammation and disease activity, which is contrary to the previously-reported activity of this bacterium.Overall, these reports have all shown that EEN leads to profound alterations in the intestinal microbiota, with these changes being rapid (within one week) and generally maintained throughout the dietary intervention. The reports have also emphasised significant interindividual variations. Interestingly, at least two reports have specifically demonstrated changes in F. prausnitzii, as noted in several reports, may reflect the change in nutrient supply for this bacterium. None of the enteral nutrition formulae utilised in the recent EEN studies contain dietary fibre. The lack of this may contribute to the consequent reduction in abundance of organisms that have fermentative activities. Consistent with this are the studies that have measured specific short chain fatty acids: each of these reports have indicated a reduction in levels of faecal butyrate, a product of fermentation of dietary fibre. This feature was also shown in the studies involving children with joint disease (without known gut inflammation) reflecting that the response is more likely secondary to the nutritional change.The changes in the abundance of Several reports have also demonstrated that the changes in the structure in the intestinal microbiota may be reflective of the duration of disease (newly-diagnosed versus long-standing disease) and also provide predictive pointers to the response to EEN itself. Other reports have demonstrated that the changes seen in response to EEN are subsequently reversed in those who have an exacerbation of their disease. Together these findings indicate that characterisation of the structure of the intestinal microbiota may have significant prognostic relevance in children with CD. Prompt assessments of key aspects of the intestinal microbiota may be able to be utilised to predict the response to EEN, and also to predict the risk of subsequent relapse of disease. Inclusion of these bio-indicators in a panel with other specific bio-markers  may be even more advantageous.At present the reports of the impact of EEN on the intestinal microbiota do not fully illuminate the mode of action of this intervention in the context of active CD. The network modelling of Schwert et al. Although the data outlined in this report have focused on individuals with CD, it is intriguing to note that EEN has also been demonstrated to have benefits in other inflammatory conditions, such as joint disease. Combined studies of dietary interventions in various inflammatory conditions may also help to further advance the roles and mechanisms of EEN.In conclusion, there is no doubt of the role of the intestinal microbiota in the development and pathogenesis of IBD, especially CD. These data demonstrate that nutritional intervention in individuals with CD is associated with wide and profound changes in the patterns of the microbiota. These data give strong indications that these changes may be employed in prognostic or predictive models to enhance the outcomes of individuals with CD.