This commentary presents a summarized discussion of key findings and relevant ideas from previously published study, index analysis, and human health risk model application for evaluating ambient air-heavy metal contamination in Chemical Valley Sarnia (CVS). The CVS study provides previously unavailable data in the CVS area which evaluates the adverse effects on air quality due to nearby anthropogenic activities. The study provided an assessment of environmental pollutants, finding that carcinogenic and non-carcinogenic substances are present in trace quantities. The main findings of the study suggest that chronic exposure of humans to several contaminants identified in the area studied may lead to carcinogenic health effects, including cancer (such as nephroblastomatosis) as well as non-carcinogenic health effects, such as damage to the tracheobronchial tree. Children were found to have a significantly higher risk, that is, a higher hazard index: a value used to measure non-carcinogenic health risk from heavy metals identified in air samples collected during the research period from 2014 to 2017. This study quantified the influence of environmental contaminants, relative to human exposures and the consequence of developing nephroblastomatosis in the human population. Comment on: Olawoyin R, Schweitzer L, Zhang K, Okareh O, Slates K. Index analysis and human health risk model application for evaluating ambient air-heavy metal contamination in Chemical Valley Sarnia. Ecotoxicol Environ Saf. 2018;148:72-81. doi:10.1016/j.ecoenv.2017.09.069.The advent of technological advancement and innovation has yielded enormous benefits supporting industrialized economies and the development of the new industry known as “Industry 5.0”—the industry of the future with focus on personalization and customization of products and services for all. Industry 5.0 also increases the collaboration between machines and humans working side by side for optimal productivity.1 the vulnerability of children and families, and communities, to the psychological, social, economic, and ecological consequences of environmental degradation from anthropogenic activities was found to extend beyond the initial periods of the disasters. The strongest predictors of stress were family health concerns, commercial ties to renewable resources, and concern about economic future, economic loss, and exposure to the contaminants. Upsurge in the levels of contaminants generated and released into the environment from anthropogenic activities such as industrial or manufacturing processes is problematic and will continue to arouse public attention.The expansion in human activities has been the dominant influence on the environment, including the human environment, in a period known as the Anthropocene. Environmental pollutions affecting the ecosystems and human health indicate an increase in stress response among the individuals impacted. In an extant study,Environmental pollution in the Anthropocene has adverse toxic effects on human health depending on the concentration and dose of the chemicals of exposure relative to the location of the receptor. A conventional deterministic risk assessment method can be used to estimate the potential carcinogenic and non-carcinogenic risks from worst-case inhalation, ingestion, and dermal contact exposures to chemicals of potential concern (CoPC), in the air, food, water, and soil for susceptible population in polluted areas such as the Chemical Valley Sarnia (CVS).The route of entry of toxic pollutants into the human body can be through 3 main exposure pathways: (1) inhalation of particles present in the air, (2) ingestion, and (3) dermal absorption as shown in 2 Environmental research is effective in providing appropriate identification, assessment, and characterization of pollutants, which will in turn help protect the public from environmental pollution hazards, especially in the Anthropocene.Inhalation is a major exposure pathway for volatile organic compounds (VOCs) and particulate matters with impregnated toxic heavy metals. The presence of such pollutions near human habitation agitates the public due to the potentially hazardous nature of the pollutants. Both acute and chronic exposures to CoPC are critically important for the assessment of the potential impacts to human health. Unfortunately, public attention is often not garnered and maintained because of the intricacy of incremental degradation of human health from long-term chronic exposures. This subtle and potential source of exposures to familiar substances such as trace amounts of metals may pose significant public health hazards but too often remain largely unidentified.The CVS impact assessment provides benefits to the community by presenting the findings of the study to the public and provided significant conclusions that can help promote human health protection for the residents of the area. The study considered the following:Environmental pollution effects on human health from air quality degradation in the region;Assessment of human exposure (chronic and acute) to hazardous contaminants based on comprehensive assessment of exposure for both adults and children;Risk level assessment and characterization of the prevalence of nephroblastomatosis (Wilms kidney cancer) in the area;Risk assessment and determination of other carcinogenic and non-carcinogenic health effects based on the impacts of human exposure to the pollutants based on the quantities identified during the study.3Considering the significance of the area of research selected for the CVS study, it is also important to evaluate the heavy industrial activities on the waterfront of the Sarnia. Located at the mouth of Lake Huron, which provides significant coastlines of Michigan and the Ontario Province, Sarnia Canada also sits along the St Clair River which borders between Ontario and Michigan and flows into the nearby Lake St Clair.The river continues its flow out as the source of the Detroit River, feeding directly into Lake Erie which provides coastlines for Ohio, Pennsylvania, and New York. The CVS study provides Sarnia with important data to better understand anthropogenic sources of atmospheric pollutants generating hazardous air quality conditions which are certain to be a source of atmospheric deposition of these contaminants to surrounding populations.Sarnia is located at the top center position (upwind), with potential of generated pollutants reaching sufficiently high altitudes and dispersed downwind toward the Detroit Metropolitan Area see . When co4 This single chemical spill affected more than a dozen water plants, shown in 4The surrounding environment and populations sharing local waterways and proximity with Sarnia are where contaminants mostly accumulate with potentially adverse effects within aquatic biomes, including the ocean as the water of the Great Lakes terminates in the Atlantic. Direct contamination of waterways from industrial activities in Sarnia is a recurrent event. An example is the 2004 river contamination, when an estimated 39 000 gallons of methyl ethyl ketone and methyl isobutyl ketone were discharged into the St Clair River.5 In effect, anthropogenic pollutants released into the atmosphere in Sarnia only need to be transported short distances before they are compounded as they become available for deposit in Cleveland, Toledo, or at other surrounding suburbs.The CVS study is quintessential due to the proximity of the heavy industrial activities along Sarnia to multiple densely populated urban locations. Potential exposures to hazardous air conditions of suburban areas were considered in the study and the diminished air quality around these locations. Urban centers continually generate their own ongoing source of airborne contaminants including lead from sources such as leaded fuel and leaded paints or incinerated refuse.The travel time by which environmental airborne pollutants can be transferred across locations such as from Sarnia to Detroit is illustrated in A comparison of the wind and travel time is shown in 3 Thus, it is a noteworthy idea as a location of research, given the potential benefit to improve human health of the at-risk population in the CVS area. The research study provides crucial information from which to determine the sufficiency of air quality according to standards for harmful pollutants set by the US National Ambient Air Quality Standards (NAAQS) of the United States Environmental Protection Agency (US EPA).3 Based on the level of air quality as assessed during the air quality analysis study in the CVS area, the populations represented within the studied area and their municipalities can, for the first time, accurately begin to understand the human health risks posed by anthropogenic environmental contaminants, primarily from activities of the significant presence of the petrochemical industries located in Sarnia.An air quality study quantifying the concentration of anthropogenic pollutants in the region had not been provided until the CVS study.Time-weighted average dose was linked to the exposure simulation concentrations for heavy metals and this was used for the exposure analysis for the inhalable particulates. The assessment of the chronic and acute inhalation exposure risks considered the dose-response criteria of the US EPA and the carcinogenic and non-carcinogenic risks for all risk-posing CoPC were estimated for the different population groups. These activities included collecting and analyzing air samples from multiple locations during a 3-year span of the CVS study, and the resulting data that were analyzed offer further benefits as a guide to organizing efforts tasked with mitigating hazardous exposure to environmental contaminants. By providing data on the distribution of contaminants at sampled locations, the CVS study contributes to the body of knowledge necessary for identifying and mitigating the pollution debacle in the region. Cleanup efforts which strategize hazard mitigation according to the available data maximize the health improvements which can be made on behalf of the at-risk population. In addition, the CVS study can be used as a tool for understanding the fate and transport of hazardous materials in the region and evaluate the rate of human exposures to the pollutants of concern.To achieve the study objectives, an ecological risk index assessment was conducted on the collected air samples to estimate the deposition fractions and deposition fluxes in the human respiratory system. The study assessed the effects of the trace-metal-bound particles and the penetration potentials through the head airways and possible damages to the tracheobronchial tree and the alveolar region, thus leading to the development of nephroblastomatosis, especially among children.The CVS study also calculated the contamination factors, enrichment factors, pollution load index, and contamination indices. Hazard quotient (HQ) is the ratio of exposure to the estimated daily exposure level at which no adverse health effects are likely to occur. Non-carcinogenic risk assessment of the CoPC was conducted and the HQs of the individual exposure from the heavy metals were determined. If HQ > 1, the receptor is at risk of non-carcinogenic effects. When HQ > 1, the risk of non-carcinogenic can result in adverse health damages to the human body. The HQs were calculated for non-carcinogenic parameters for inhalation pathways.−4, it is considered as “definite risk,” and the other risk levels are described in Incremental lifetime carcinogenic risks (ILCRs) from the heavy metals were also investigated. If the ILCR of the CoPC is more than 1×105 To establish an ecological risk index, the CVS study provided the following assessments:The study determined that the main route of entry of contaminants into the human body is through inhalation of respirable fractions of the contaminated-particulate-matter-bound heavy metals. These inhalable fractions of airborne particles are deposited in the respiratory tract along the airways during a single regular breath.Assessment of contamination factors to determine the extent of environmental pollution from industrial activities and the contamination of air quality in the CVS;Assessment of the pollution load index to estimate the contamination of the ambient environment for the use of comparing the assessed pollution levels between sample locations;Assessment of the enrichment factor to determine if the concentration of the enriched sample is from natural deposits by geogenic  or anthropogenic (man-made) sources;Assessment of human health risk to determine exposure via inhalation of atmospheric particulate matter bound with heavy metals;Assessment of the ILCR to determine the incremental probability of an exposed person to carcinogenic substances developing cancer in his or her lifetime;3Assessment of non-carcinogenic health risks provided with use of the target HQ and hazard index used to measure health risks of heavy metals found in airborne particles.3The negative human health effects that may result from chronic exposures to the toxic metals selected for chemical and statistical analyses do include health risks which are important to consider. Through the application of the briefly described statistical methods, the CVS study concludes that anthropogenic heavy metals within sample particulate matter may be a potential source of the adverse effects leading to the concentration of the nephroblastoma disease in the area.3 From 2000 to 2009, approximately 72% of these nephroblastoma cases occurred in Marine City, MI. This community located within 20 miles down the St Clair River from Sarnia, which was defined as a cancer cluster because of the high prevalence of cancer over time.6 The CVS study provides a characterization of nephroblastoma as a solid tumor of epithelial tissue formed from immature kidney cells which grows quickly on the exterior of the human kidney resulting in nephroblastomatosis.3Between 1990 and 2009, 63% of occurrences of nephroblastoma occurred among children under 5 years of age.7 The prognosis of nephroblastoma is highly variable depending on its stage of development and has 2 histopathologic types, favorable and unfavorable, each having outcomes across the spectrum for each of these 2 categories.7 The cancer tumors are usually found in the adrenal gland, resulting in abdominal pain and distention. The tumors are mostly large in size. Ultrasound imaging procedures are an effective means of assessing internal tumors without subjecting children to harmful sources of radiation allowing medical staff to rule out occurrences of capsular or vascular invasion occurring in 4% to 10% of all patients.8Nephroblastoma or Wilms tumor is the most common renal tumor in children with peak instances occurring at the age of 3 to 4 years.9 Other determinates for course of treatment include factors such as age, overall health, medical history, the extent of the disease, and tolerance to specific therapies. Common treatment also includes the surgical procedure of a radical nephrectomy which removes the kidney in its entirety, the surrounding tissues of the kidney, the ureter which drains urine from the kidney to the bladder, and the kidneys’ corresponding adrenal gland which is located on the top of the kidney.9 When the tumor presents on both kidneys, surgical treatment consisting of a partial nephrectomy is recommended. This surgery is intended to remove the entirety of the tumor, leaving behind the maximum amount of kidney tissue unaltered by the tumor in an effort to spare as much of the kidney as possible. Approximately 5% to 8% of children diagnosed with capital nephroblastoma developed tumors in both kidneys.10 In cases where treatments are difficult or impossible, to remove tumors affecting both kidneys, which are too large to perform a partial nephrectomy, patients will be subjected to radiation therapy in an attempt to shrink the tumors prior to surgical removal.8Treatment of the condition varies depending on the size of the tumor developed at the time of treatment as well as other considerations such as the bilateral presence of tumors on both kidneys.9 Over time, the overall success rate of medical treatment and the patient experience of treatment side effects have both improved significantly. For the past 20 years, the 5-year survival rate among children diagnosed and living with nephroblastoma is approximately 86% and the overall longter survival rate is even higher (up to 90%).11In children, the prognosis for long-term viability of nephroblastoma survivors depends on many factors including the stage of the disease as well as the characteristics of the tumor cells, which may be assessed under the magnification microscope, the promptness of nephroblastoma identification and treatment, and the continued follow-up of medical care provided to the patient including ongoing adjustments to the course of treatment and continued nephroblastoma screenings.3Whereas the treatability and long-term survivability of the cancer may be a source of hope to patients and their health care providers, the dramatic courses of treatment required for nephroblastoma survivors merit a closer look into causative forces. The CVS study offers the populations affected and at risk of adverse health effects a clearer understanding of a potential source of pollutants resulting in the cancers prevalent around their communities. Among the results from the CVS study were the confirmation of the findings: (1) concentrations of airborne lead are present in air samples in excess of 350% above NAAQS air quality standards; (2) concentrations of chromium (VI), lead, and nickel are partly the result of anthropogenic activity; (3) ambient air is polluted in the study area with particle material with bound metals which may increase the human health risk of nephroblastoma, especially in children; (4) high risk of potential cancer affects children and adults in the area studied; (5) children are more likely to develop carcinogenic and non-carcinogenic health effects from exposures to elemental concentrations of airborne particulate matter.The public health benefits of the CVS study are quintessential to the proper identification of anthropogenic pollutant sources, the concentration in the environment, and the potential effects on receptors exposed to the contaminants. Ideally, the prevalence of childhood nephroblastomatosis combined with the results of this study will help decision-makers provide adequate care for the residents of the CVS area and other adjoining areas.


Data on the micrometeorological parameters and Energy Fluxes at an intertidal zone of a Tropical Coastal Ocean was carried out on an installed eddy covariance instruments at a Muka head station in the north-western end of the Pinang Island , Peninsula Malaysia. The vast source of the supply of energy and heat to the hydrologic and earth׳s energy cycles principally come from the oceans. The exchange of energies via air-sea interactions is crucial to the understanding of climate variability, energy, and water budget. The turbulent energy fluxes are primary mechanisms through which the ocean releases the heat absorbed from the solar radiations to the environment. The eddy covariance (EC) system is the direct technique of measuring the micrometeorological parameters which allow the measurement of these turbulent fluxes in the time scale of half-hourly basis at 20 Hz over a long period. The data being presented is the comparison of the two-year seasonality patterns of monsoons variability on the measured microclimate variables in the southern South China Sea coastal area. The data acquisition processes and instrumentations is reproduceable in any region of the world.1The data for the monsoonal variability in the tropical coast of Peninsula Malaysia on the micrometeorological parameters and Energy budget was observed based on the 2 years . The data recorded cut across two annual cycles of the Southeast Asia monsoon seasons. The data was collected to appreciate the climate variability on the overall variations of the meteorological parameters measured occasion by precipitation and temperature anomalies a broughtThe patterns of the micrometeorological data and other parameters were examined to understand the monsoon seasons on their distributions and variability . Tempera2The EC method used offers measurements of gas emission and ingestion that also allow measurements of energy exchanges in an area. The data collected is globally used in micrometeorological measurements in more than 3 decades. This has allowed it to grow into more advanced instrumentation and stronger practice that caused its usage across diverse disciplines and industries for environmental monitoring and inventory Eddy Covariance (EC) is a statistical tool to compute micrometeorological parameters, turbulent fluxes, and other useful parameters to define climate variability for environmental impact purposes


Moreover, in favorable (won) matches the higher values of degree centrality of central defenders  and defensive midfielders  were also found in unbalanced scores. The comparisons between positions revealed that the highest and significant degree prestige levels were found in defensive midfielders in both close (12.10%) and unbalanced scores (10.95%). In conclusion, it is possible to observe that winning by an unbalanced score significantly increased the centrality levels of the wingers and forwards in comparison to close scores. Moreover, it was also found that independent of the final score or the unbalanced score level, the defensive midfielders were the most prominent or recruited players during the passing sequences.The purpose of this study is twofold: (i) analyze the variations of network centralities between close  and unbalanced  scores; and (ii) compare the centrality levels between playing positions. The passing sequences that occurred during the 64 matches played by the 32 national teams that participated in the 2018 FIFA World Cup were analyzed and coded. The network centralities of degree prestige and degree centrality were calculated based on the weighted adjacency matrices built from the passing sequences. The results reveal that higher degree centralities of midfielders occurred in unfavorable (lost) unbalanced scores ( The game of soccer allows the observation of two main types of relationships: (i) a network process between teammates aiming to synchronize the different individual behaviors and optimize the collective organization of the team; and (ii) a rapport of strength, that results from the interactions between two teams to beat each other in a dynamic system . Both reUsually in match analyses conducted on soccer, there is a strong tendency to code, collect and report evidence about the variation of different performance indicators  between different contextual factors  . HoweverIn a mixed approach, the social network analysis (SNA) applied to team sports has proposed a new way to interpret the outcomes of the match . The proUsing the pass as the linkage indicator in the network  it has been possible to identify some evidence about the centrality levels of players during soccer matches . In the Considering the type of analysis, there is a lack of evidence about the influence of specific contextual factors in the studies that compared the network centrality levels of playing positions, namely considering the winning/losing factor and, most of all, the balance levels of the final scores. As one of the well-known contextual factors that may lead to different tactical behaviors and interactional processes between teammates, we hypothesize that network centralities may be different based on distinct contextual factors. Taking this rationale in mind, the unique study that tested the network levels between close scores  and unbalanced scores  revealed that the dyadic reciprocity levels of the players increased in winners during unbalanced matches and that total arcs and density were slightly greater in winners of close matches . Those mThis study coded the passing sequences of the 64 matches of the 2018 FIFA World Cup. Therefore, all the 32 national teams were observed and included in the analysis process. The passing sequences were coded and included in the analysis after testing the intra- and inter-reliability level of the expert observers. The weighted adjacency matrices built based on the passing sequences were then treated for the subsequent network analysis.The study was approved by the local ethical committee  with the code IPVC-ESDL09052018. There is no contact or intervention with the players and the process was exclusively made based on observation.This study followed a cross-sectional observational design. All the passing sequences made by each team during each entire match of the 2018 FIFA World Cup were observed, coded and transformed in weighted adjacency matrices. Those matrices were then treated and the degree prestige and degree centrality (network measures) were calculated considering the playing positions of the players: (i) goalkeeper (GK); (ii) external defenders (ED), players that act as defenders in the side of the field; (iii) central defenders (CD), players that acts as defenders in the central region of the field; (iv) defensive midfielders (DMF), players that acts as midfielders in a region closer to the central defenders; (v) midfielders (MF), players that acts in the middle of the field linking the defensive and attacking players; (vi) wingers (W), players that act in forward and side regions; and (vii) forwards (FW), players that acts in the middle of attacking regions. The variations of degree prestige and centrality between playing positions were tested considering the unbalance level of the final score. Based on such options, we have excluded the draw situations that did not provide the same score (losing or winning) that can be comparable between unbalanced and balanced games. The matches with a final score difference of one goal were considered close scores and those with two goals or more of difference as unbalanced scores. The classification of balanced vs. unbalanced score was exclusively made considering the final score (end of the match). This definition of balanced vs. unbalanced score was used in a previous study on soccer .Two expert observers (sport scientists with more than 5 years of experience on soccer) were recruited to observe and code the passing sequences of all matches of the 2018 FIFA World Cup. All the successful passes between two teammates were considered to include in the sample. Those observers were tested for their reliability levels following a pre-post pilot study design using a total of seven matches of the competition . The pre-post analysis was interspaced by a 20-day interval period aiming to test the reliability level of the observers. The process was made before the full-data being collected, aiming to ensure the desirable level of reliability. The results obtained from the pilot study revealed an average of intra-class correlation level of 0.97 (excellent reliability) for the case of intra-observer analysis and an average of 0.91 (excellent reliability) for the case of inter-observer analysis. The values obtained revealed that the reliability level of the observers was enough to follow through with the data collection .After confirmation of the reliability level of the observers to code the passes between teammates, all the matches were observed, coded and treated following a network analysis process. The players were first coded by the playing position in the pitch and even in the case of replacements or changes during the match, the aim was to analyze the centrality levels of positions and not the specific players .Each passing sequence was converted in a weighted adjacency matrix . The pasThe weighted adjacency matrices of all matches were imported into Social Network Visualizer software . This free software allows converting weighted adjacency matrices into networks and calculating the centrality levels of the nodes (players). For this study, the calculation of the standardized degree prestige and degree centrality was made.This network measure quantifies the inbound links that a specific player received from his teammates  and, foraji can be considered the elements of the weighted adjacency matrix of a G with a ni as vertex.in which The network measure of degree centrality represents the overall level of connection of a player with the teammates, considering the number of outbounds, thus a higher level of degree centrality suggests that the player contributed more often to the passing sequence by executing more passes . The staaji can be considered the elements of the weighted adjacency matrix of a G with a ni as vertexin which post hoc test after confirmation of the normality and homogeneity assumptions of the sample. The partial eta squared tested the effect size (ES) of the univariate MANOVA. The statistical procedures were executed in the SPSS  for a p-value < 0.05. Moreover, the Cohen d tested the ES of the pairwise comparisons between playing positions. The following scale was used to determine the magnitude of ES for the case of Cohen d . The variations of centralities between playing positions  and type of final score  were tested with a univariate MANOVA and one-way ANOVA with Tukey HSD  Cohen d : 0.0−0.2∗playing position  and final score∗playing position  for the case of degree prestige, however, no significant interaction were found in the pair difference of goals∗ final score . In the case of degree centrality were found significant interactions in the pairs difference of goals∗playing position  and final score∗playing position , however, no significant interactions were found in the pair differences of goals∗final score .The univariate MANOVA tested the interactions between factors revealing significant interactions in the pair difference of goalsp = 0.046; ES = 0.472, small effect). In won matches it was observed that the degree centralities were higher in close scores for the cases of central defenders  and defensive midfielders . Similar evidence was found for the case of degree prestige in central defenders  and defensive midfielders . On the other hand, a significant increase of degree centralities in unbalanced scores among wingers  and forwards  was also observed in won matches. The degree prestige also increased in midfielders in the case unbalanced scores .Comparisons of network centralities within playing positions and between close and unbalanced scores can be observed in Descriptive statistics of network measures between playing positions in the case of close and unbalanced scores were tested .Comparisons between positions revealed that the highest degree prestige levels were found in defensive midfielders in both close (12.10%) and unbalanced scores (10.95%). On the other hand, the forwards presented the lowest degree prestige in both close (6.41%) and unbalanced scores (7.06%). However, as can be observed in The greatest degree of centrality levels were verified in defensive midfielders in both close (13.45%) and unbalanced matches (12.08%). On the other hand, the lowest degree centralities were observed in forwards in both close (4.60%) and unbalanced matches (5.12%). However, similarly to the case of degree prestige, the magnitude of changes between playing positions decreased from close to unbalanced matches .The network centralities allows to better identify the prominence of each player in the passing sequences of a team, namely considering the direction and weight of the passes . In the The first purpose of the study was to analyze the variations of centrality levels between favorable and unfavorable close and unbalanced scores within playing positions. The results revealed that in unfavorable results (lost) only the external defenders and defensive midfielders presented meaningful small increases of prominence levels in unbalanced matches, however, the remaining playing positions did not meaningfully change the prominence levels. In the other hand, in favorable (won) results there was two main type of evidence: (a) central defenders and defensive midfielders had meaningful greater values of degree prestige and degree centrality in close scores; (b) midfielders, wingers and forwards had meaningful greater values of degree centrality and degree prestige in unbalanced scores. Therefore, two main conclusions could be extracted from the results: (i) generally, independent from the differences of goals in unfavorable results, there are no meaningful differences in the degrees of centrality and prestige of the great majority of the playing positions; and (ii) won by one goal requires a meaningful greater participation of central defenders and defensive midfielders, however, won by an unbalanced score requires a meaningful increase in the centralities of the positions that occupy forward lines, namely midfielders, wingers and forwards.The fact of central defenders and defensive midfielders increasing their participation in favorable close scores may result from the team strategy to keep the ball in zones of low pressure and more security than in forward regions may be what increases the possibility of non-success . The styThe present study also tested the variations of network centralities between playing positions. In terms of close scores, it was found that the degree prestige (inbound) was largely greater for central defenders and defensive midfielders than for wingers and forwards. Interestingly, the magnitude of the differences decreased in the case of unbalanced scores, despite revealing the same tendencies. The degree prestige can be considered an indicator of the overall prominence level of a player to be recruited by his teammates . The resIn the case of degree centrality (outbound), larger differences were observed between playing positions than in the case of degree prestige, namely considering the comparisons of more defensive positions  with forward players (wingers and the forwards). Forwards and wingers were clearly and meaningfully- less prominent than the remaining playing positions in both close and unbalanced scores. This suggests that the overall participation of these two positions in constructing the passing sequences and establishing relationships with their teammates is significantly smaller; however, this depends on the type of analysis. Naturally, in the case of counter-attacks or passing sequences that result in shots or goals, the rate of prominence may increase in forward players, based on previous research . HoweverThis study had some limitations. The passing sequences were not split by type of attack or final outcome and for that reason the results about the prominence level should be carefully interpreted. Moreover, the analysis of different team’s formations was not considered. Also, there is no information about the tactical behavior that explains the prominence levels observed. Based on those limitations, it is important for future studies to split the passing sequences by type  and final outcome  and also add information about the pitch regions in which the passes occurred. The analysis of the formations and tactical behavior of the players should also be considered to provide a qualitative interpretation and to increase the holistic view about the dynamics that contribute to the final outcomes. Future studies should also consider other technical actions that may provide information about the interactions between team players. Moreover, an analysis that considers the spatio-temporal dimension should be considered to improve the understanding about the dynamics of the match. To do that, it may be important to add an analysis per period of time  or per changes in specific moments .Despite the study limitations, this study is, in the best of our knowledge, the first that compared the prominence level of different playing positions in favorable and unfavorable close and unbalanced scores. The results of this study allow coaches to identify that favorable unbalanced scores increases the overall centrality levels of wingers and forwards and this may represent a transfer for training scenarios or even to options to make during the matches. Moreover, the evidence that defensive players are more prominent in building the attack in the generality of the passing sequences should encourage adopting strategies to reduce the success of the opponent’s teams in their zone of comfort.Considering the comparisons of network centralities between close and unbalanced scores, the main evidence revealed that defensive midfielders and central defenders presented meaningful greater levels of centrality (inbound and outbound) in won close scores than in unbalanced. On the other hand, won unbalanced matches meaningfully increased the centrality levels of wingers and forwards. Regarding the second purpose of this study – to compare the variations of network centralities between playing positions – it was possible to observe that defensive midfielders were the most recruited and also the most contributing to the passing sequences and that the forwards and wingers presented the lowest values of participation in both close and unbalanced matches. As a conclusion, this study suggests that independent of the magnitude of difference in the final score, there are playing positions (the midfielders) that are relatively stable in the participation during passing sequences and other positions (the forward players) that increase in participation in favorable unbalanced scores.filipe.clemente5@gmail.com.The datasets for this manuscript are not publicly available because data are available upon request from the first author FC: filipe.clemente5@gmail.com. Requests to access the datasets should be directed to FC: The study was approved by the local ethical committee  with the code IPVC-ESDL09052018. There is not contact or intervention with the players and the process was exclusively made based on the observation.FC conceived the study. FC, HS, and GP designed the study. FC collected, analyzed, and interpreted the data. FC, HS, GP, PN, TR, and BK drafted, revised and approved the final version.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.


The complexity of developing and applying increasingly sophisticated new medicinal products has led to the participation of many non-medically qualified scientists in multi-disciplinary non-clinical and clinical drug development teams world-wide. In this introductory paper to the “IFAPP International Ethics Framework for Pharmaceutical Physicians and Medicines Development Scientists” it is argued that all members of such multidisciplinary teams must share the scientific and ethical responsibilities since they all influence directly or indirectly both the outcome of the various phases of the medicines development projects and the safety of the research subjects involved. The participating medical practitioner retains the overriding responsibility and the final decision to stop a trial if the well-being of the research subjects is seriously endangered. All the team members should follow the main ethical principles governing human research, the respect for autonomy, justice, beneficence and non-maleficence. Nevertheless, the weighing of these principles might be different under various conditions according to the specialty of the members. For hundreds of years, treatments based on experience formed a continuum with uncontrolled individual therapeutic trials performed by the treating physicians in the hope of helping their patients. The deep ethical concern of the practicing physicians is expressed with great clarity by William Withering who introduced digitalis into medical practice in the 18th century: “After all, in spite of opinion, prejudice or error, Time will fix the real value upon this discovery, and determine whether I have imposed upon myself and others, or contributed to the benefit of science and mankind.” , Reason, , and by Multidisciplinary teams gained broad acceptance in drug development when, beside the determination of clinical efficacy and safety, the correlations between the plasma level of the drugs and their pharmacodynamic effects also became the additional focus of clinical pharmacological investigations. Such cooperation is primarily characterized by the parallel work of the clinical and various non-medical experts who perform pharmacokinetic, biochemical, immunological and other investigations on human samples. The ethical problems of such cooperation are usually limited to the amount and frequency of the sampling of human materials needed for conducting the studies. The situations can be handled by finding a scientifically acceptable compromise which does not cause additional harm for the human subjects. A conceptually entirely different and much more sophisticated cooperation becomes necessary for investigating and applying advanced therapeutic products in patients.in vitro before re-transfusion for reaching the required number of modified T-cells for effective tumor kill. The production of the individually prepared targeted medicinal product is carried out under Good Manufacturing Practice (GMP) conditions by a multidisciplinary expert team specialized in immunology, cell and molecular biology  cancer therapy. For this treatment the genes coding for the specific CAR-T receptor recognizing the cancer surface antigen(s) of the individual patients must be transferred into the harvested T-cells of the patients. The modified T-cells are then further incubated In such multidisciplinary teams the physician is only one member with a specific right to stop the intervention if the safety of the patient is endangered and the interruption of the therapy does not cause additional harm. It is not surprising that the FDA requires that the entire staff involved in this complex therapy should be specifically trained and certified (FDA News Release, The rapid progress of advanced therapies will further increase the need for including many different professionals into clinical teams. In addition, new scientific knowledge continuously generates unforeseen ethical problems. For successfully managing increasingly sophisticated ethical challenges IFAPP recommends and plans to contribute to the strengthening education of ethics at the under-graduate and post-graduate levels both for medical and other biomedical professionals.The aim of the linked IFAPP International Ethics Framework is to highlight the ethical issues relevant to the increasingly close cooperation of physicians and non-medically qualified experts in human drug development and application. All authors contributed both to the development of the ideas as well as to the writing of the paper and the linked 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.


Anterior tibial artery is a nonvital artery which is one of the three arteries of the leg. This artery has a short proximal l segment in the popliteal region and a long segment in the anterior compartment of the leg designated as distal segment. With consideration of the deep location of the proximal segment in the popliteal fossa, it is less susceptible to trauma and subsequent formation of an aneurysm. On the contrary, the superficial long distal segment is more susceptible to trauma with high chance of pseudoaneurysm formation at the site of unrecognized injury. In this article, a 38-year-old military man being manifested about a decade after a trivial missile fragment injury with progressive posterior tibial neuropathy is presented. A giant pseudoaneurysm arising from the proximal segment of the anterior tibial artery was confirmed with angiography and the exact size of this pathology was documented with contrasted computed tomographic scan. The aneurysmal sac removal was accomplished after ligation of the corresponding artery proximal and distal to the sac followed by tibial nerve neurolysis which result in full recovery. In careful review we found that neither pseudoaneurysm arising from the proximal tibial artery nor posterior tibial neuropathy due to the compressive effect of the aneurysmal sac of this segment has been reported previously. Our primary purpose for reporting this case is not to describe the rarity of pseudoaneurysm formation at proximal segment of this artery but rather to describe delayed-onset posterior tibial vascular compressive neuropathy due to such an aneurysm. Eventually due to the potential sequel of a pseudoaneurysm, it is important for the surgeons to have high index of suspicion to prevent a missed or delayed diagnosis. Arterial injuries are common event in military and civilian practice with iatrogenic one occurring in increasing frequency.If the initial injury, in particular in noncritical arteries, is left unrecognized or is regarded insignificant to seek medical advice, a traumatic aneurysm might develop.Traumatic aneurysms are true when the arterial wall injury occurs in intimal and medial layers of the artery with intact adventitia, and hence tend to be fusiform and their expansion is limited. A pseudoaneurysm or false aneurysm develops when all three layers of the artery are affected. In such circumstances, low-flow bleeding continues at the site of injury and this will gradually result in the reaction of the surrounding tissues with formation of a fibrous capsule around the hematoma.The leg arterial network is composed of three arteries: posterior tibial, peroneal, and anterior tibial. Anterior tibial artery is a nonvital artery of the leg with a short, but deeply located proximal and a long superficially located distal segment. Anterior tibial artery injury is one of the least among the arterial injuries of the extremities and account for approximately 2%, both in civilian and military experience.On the contrary, formation of an arterial pseudoaneurysm due to missile fragment in the lower extremities and in particular in the leg is a well-known pathology in military practice. Reviewing the military experience since World War II, we found that traumatic aneurysms of anterior tibial artery account from 0 to approximately 2% of all traumatic aneurysms of the extremities with antipersonnel mines standing at the top.Survey of civilian experience yielded the same result regarding the incidence.Recently, iatrogenic pseudoaneurysms of this artery due to orthopedic procedures are reported in increasing frequency.In careful review of the literature, we found that the injury of the proximal segment of the anterior tibial artery has been reported only in one rare occasion, where not a single case of pseudoaneurysm originating from this segment has been reported.In this article, we present the first example of a pseudoaneurysm of the proximal segment of the anterior tibial artery with compressive posterior tibial neuropathy which was diagnosed 12 years after being injured by a small missile fragment. This pathology was managed by exclusion of the pseudoaneurysm after ligation of the artery proximal and distal to the aneurysmal sac and subsequent neurolysis of the posterior tibial nerve.Furthermore, where the usual delay in the diagnosis of the posttraumatic pseudoaneurysms of the extremities may range from a few days to several weeks with a mean of 45 days, onset of the pathology after such a long delay following a penetrating injury makes this case more interesting.This 38-year-old military man was referred for the evaluation of radicular pain over the posterior aspect of his right leg and numbness at the planter aspect of his right foot for 3 weeks of duration. The patient had a history of being injured by several missile fragments 11 years before admission. With probable diagnosis of S1 root radiculopathy from L5–S1 disc herniation, lumbar myelography in another institution was normal. With continuing discomfort, he was referred to our institution.His neurological exam revealed distal sciatica at the course of S1 root, with hypoesthesia of the right sole. Further examination and palpation revealed a painful and pulsatile mass in the popliteal region. A bruit was heard in auscultation. With the diagnosis of a pseudoaneurysm, selective angiography was done and this revealed a pseudoaneurysm arising from the proximal segment of the anterior tibial artery. The artery bowed because of the compressive effect of the pseudoaneurysms . With cS-shape posterolateral incision. The popliteal, tibiofibular trunk and the proximal part of anterior tibial artery were identified and exposed. The proximal anterior tibial artery was ligated. Then the aneurysmal sac with dense fibrous wall was incised. Large quantities of old and fresh bloods were evacuated. Then, the orifice of the artery distal to the aneurysm was identified through its faint retrograde bleeding and this was sutured and occluded. Subsequently, the aneurysmal sac was dissected from surrounding structures including the flattened discolored posterior tibial nerve and was totally removed, and the affected nerve was released separately from the adhesions using magnification. Postoperative course was uneventful. At 2-month follow-up, he was neurologically normal.The popliteal fossa was approached through a looseAnterior tibial artery injury is one of the three arteries of the leg which has a deep proximal segment and superficial distal segment. Vulnerability of this artery to trauma differs in these two segments. For better understanding of this difference, review of its anatomy is necessary. This artery is the first branch of the popliteal artery which after traversing a few centimeters in the popliteal fossa pierces the interosseous membrane and descends into the anterior compartment of the leg along the shin in close proximity to peroneal nerve. The popliteal artery, currently being called tibiofibular trunk, divides into two branches, posterior tibial and peroneal arteries. Expectedly, the superficial and unprotected distal segment of the anterior tibial artery allows access for wounds not strong enough to be able to traumatize the short proximal segment embedded deeply in a rather more protected location. Even among the arteries of the popliteal region, the distal anterior tibial artery is the least susceptible.With arterial injury left unrecognized, a pseudoaneurysm might develop. Especially if the initial trauma is regarded too insignificant to seek medical advice.With more susceptibility of the distal segment of this artery, the pseudoaneurysms of this part of anterior tibial artery are reported in increasing frequency. In the past only missile wounds, low-velocity bullet injuries, penetrating injuries such as stab wounds, and tibia-fibula closed fractures had been the major causes of the pseudoaneurysms formation.Before surveying the literature, with respect to the rarity of the distal segment arterial injury, a traumatic pseudoaneurysm developing at this site was expected to be an extremely rare event. Therefore, we were not surprised that not a single case of such pathology could be found in careful review.The timeframe for the development or detection of a pseudoaneurysm after a trauma is quite variable and ranges from a few days to a few months or even years. In our case, the depth of the affected artery and the size of the missile fragment may explain the rather slow process and the unusual delay in diagnosis.Pseudoaneurysm detection several years after injury has been reported only in six occasions including our case.Usually, a peripheral nerve accompanies the arteries of the extremities and with formation of an aneurysm, vascular compressive neuropathy might appear.However, compressive neuropathy due to a pseudoaneurysm of proximal segment is unlikely because of its far distance from the nearest nerve, which is posterior tibial nerve. Reasonably, if posterior tibial compressive neuropathy coinciding a traumatic aneurysm of the proximal anterior tibial artery occurs, it should be an exception and only occur when the corresponding pseudoaneurysm reach to a giant size.Historically, surgical strategy for pseudoaneurysm of less vital arteries had been ligation of the artery proximal and distal to the aneurysm followed by aneurysmal sac excision.With improvements in medical technology, treatment options for pseudoaneurysms of the peripheral arteries have evolved to less invasive methods.These new therapeutic techniques were started with ultrasonic-guided manual compression of the neck of the aneurysm. Later, echo-guided thrombin injection was introduced which has been tried successfully in a patient with anterior tibial artery pseudoaneurysms.Transcatheter coil embolization is another accepted treatment modality which offers many advantages including rapid safe occlusion and this had been successfully accomplished in the pseudoaneurysms of the anterior tibial artery as well.Recently, endovascular anatomic reconstruction of the arterial wall with covered stent has been developed.Obviously, none of these noninvasive options are recommended in the patients with aneurysmal compressive neuropathy where excision of the aneurysm and subsequent neurolysis of the affected nerve are the mainstay of surgery. In our patient, because of posterior tibial neuropathy, open surgical intervention was preferred. Furthermore, reconstruction of the artery was not indicated because of the integrity of tibioperoneal trunk and its two major branches.Duration and extent of compression have prognostic influence on associated neural recovery.In conclusion, we believe that this presentation can serve as a good reminder of another uncommon possible cause of posterior tibial neuropathy diagnosed with high index of suspicion. This report also emphasizes on the importance of taking into account the possibility of a pseudoaneurysm in differential diagnosis and a compressive neuropathy even years after trivial missile injuries.


This Special Issue of Frontiers in Biomolecular Sciences contains several articles in which different elements of environmental complexity are explored and discussed from theoretical and/or experimental points of view.Biochemical reactions have historically been studied in purified solutions that that are dilute in macromolecules and contained in large vessels. During the last several decades it has become increasingly clear that physiological media differ substantially from the solutions in which such studies are carried out. The fluid component of cells is distributed among numerous microenvironments that are highly heterogeneous in both composition and spatial organization. These factors have been shown to significantly influence the rates and equilibria governing many biochemical reactions. The results of recent efforts to characterize the behavior of individual proteins and other macromolecules within living cells are difficult to interpret unambiguously due to the complexity of the system. The study of biochemical kinetics and equilibria in well-characterized media designed to incorporate one or more  elements of the complexity of living cells, termed cytomimetic media, has been advocated as a means for bridging the gap between traditional Nguemaha et al. have utilized atomically detailed computer simulations to estimate the concentration-dependent free energy of transferring each of eight dilute “test” proteins from dilute solution to concentrated solutions of one of two concentrated “crowder” proteins. The simulation allows decomposition of the total transfer free energy into contributions from “hard” or steric repulsive interactions and “soft” or longer-ranged electrostatic or solvent-mediated interactions. Hoppe and Minton utilize an approximate analytical solution for the concentration-dependent transfer free energy of macromolecules interacting via a model square well-potential in order to calculate the effect of non-specific interactions on the concentration dependence of light scattering, sedimentation equilibrium, osmotic pressure, and liquid-liquid phase transitions of concentrated protein solutions. Their results show that this highly simplified interaction potential can recapitulate many experimentally observed phenomena as well as some key results of the atomistic simulations.One of the elements of complexity is the presence of locally high concentrations of multiple species of macromolecules, which may interact with each other both specifically and non-specifically. Such interactions affect both the state of association and the chemical potential, or reactivity, of individual macromolecular species. Nakashima et al. review theoretical models for the formation of incompatible phases and factors affecting their compositions, including salt concentration, pH, temperature, and the strength of intermolecular interactions. They further discuss factors regulating the partitioning of biomolecular reactants between the two phases, and the consequences of partitioning for reaction rates and equilibria in each of the phases.A second element of intracellular complexity is the presence of multiple microenvironments in which reactions may take place. Membraneless organelles, representing one class of these microenvironments, are thought to arise through liquid-liquid phase transitions. Gnutt et al. review the effects of induced differentiation of neuronal cells and induced proteostasis of HeLa cells on the thermal stabilities of a synthetic folding sensor and a labeled mutant of superoxide dismutase. They report that these changes result in destabilization of the labeled sensor species. Because the analysis of the data is based upon signals averaged over the whole cell, the authors recommend development of cytomimetic media for a more detailed analysis.A third element of complexity in the cellular environment is the dynamic nature of this environment, which is subject to changes with experimental conditions. Schavemaker et al. review a number of factors affecting the rate of diffusional transport of macromolecules, which include transient binding to other species as well as the necessity of tortuous trajectories to bypass obstacles. The authors present examples of diffusion-limited reactions in small prokaryotic cells and point out that the functioning of certain intracellular oscillatory dynamic systems depends crucially upon the maintenance of diffusional rates.A fourth element of complexity in the cellular interior is the presence of mobile and stationary obstacles to the free diffusion of macromolecular reactants. GR and AM wrote the manuscript.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.


The network engages in empirical clarifications on both the distinctness and validity of the construct  as well as in critically reviewing terminology and measures of views on aging . The network aims to help clarifying the dynamic interplay of determinants and outcomes in the context of health  as well as disentangling intra- and intergenerational stereotypic perceptions . Both of these are understudied issues with highly practical implications for two of the largest demographic challenges: shaping the coexistence of generations as well as providing adequate health care supply. Integrating both pertinent theoretical approaches and empirical findings the network regards views on aging under a lifespan perspective. Recently, it suggested three core principles of views on aging regarding lifelong bio-psycho-social development, their multidimensional nature, and their impact across life. These considerations provide a background for an integrative discussion of the symposium’s contributions.Over the past 20 years, research on views on aging has substantiated their importance for successful development and sustained quality of life over the full length of the life span. However, a deep understanding of the origins of views on aging and the underlying processes of their lifespan development and manifestation is lacking. Since 2017, the scientific network “Images of Aging” funded by the German Research Foundation (


It is my pleasure to announce that two distinguished internationalscientists have joined the editorship of the FreshwaterSystems domain of TheScientificWorldJOURNAL — Professor BrijGopal of Jawaharlal Nehru University (India) and Dr. Manual Graça of the Universityof Coimbra . Professor Gopal is the Secretary General of the NationalInstitute of Ecology, Editor of the InternationalJournal of Ecology & Environmental Science,and Chairman of the SIL  Committee on Limnology in Developing Countries. His research interestsinclude the ecology, biogeochemistry and biodiversity of wetland ecosystems,the management of wetlands as an integral part of the watershed, and wetlandwater policy–related issues. Dr. Graça is a stream ecologist whose researchinterests include the two general areas of organic matter decomposition andbiological monitoring. His specific areas of research focus include quantificationof organic matter and other chemical changes in decomposing leaves, the ecologyof aquatic hyphomycetes, and the ecology of animals feeding on detritus. Hisresearch dealing with biological monitoring is carried out in close cooperationwith the paper and mining industries, facilitating the practical applicationof his work.


The assay of parathyroid hormone continues to remain problematic as a result of the presence in the circulation of a variety of parathyroid hormone (PTH) peptides derived from secretion and from peripheral metabolism. The detection of these PTH fragments to varying degrees leads to widely differing results in the various assays used, particularly in the setting of chronic kidney disease, where PTH fragments accumulate as glomerular filtration rate (GFR) falls. The differing results not only lead to problems in comparing values from various laboratories but also limit efforts to develop useful clinical practice guidelines. At the same time, research into the precise identification of the PTH fragments which contribute to the assay problems has uncovered a relatively new area of parathyroid research that has pointed to potential biologic activity of PTH peptides previously thought to be biologically inactive and which may act on a novel PTH receptor. These issues have brought new focus to the difficulties in standardization of PTH assays and have provoked efforts to provide standards to help in the characterization of PTH assays and to facilitate the development of clinical practice guidelines. Assay of parathyroid hormone is extremely important in clinical medicine because of the major role of parathyroid hormone in the regulation of mineral metabolism and skeletal physiology. Since the introduction of radioimmunoassay for parathyroid hormone (PTH) in 1963 by Berson et al., the assay of parathyroid hormone has been problematic and remains so to the present day . Thus, iA major breakthrough in PTH assay occurred with the application of immunometric assay technology to the measurement of PTH , 9. WithFurther refinements in assay technique, by utilizing detection antibodies that had specificity for the first four amino-acids of PTH, allowed the measurement of true PTH (1–84) and facilitated detailed investigations of parathyroid hormone assay and parathyroid hormone physiology . AlthougThese observations have expanded our knowledge of parathyroid physiology, but, at the same time, they have focused attention on some significant clinical problems. One such problem is that even with current immunometric assay techniques, there is considerable heterogeneity in results obtained using different assays from different manufacturers . The widOn the other hand, these apparent problems in PTH assay also lead to a number of opportunities that may help the field move forward. First, the recognition of potential biologic activity for N-terminally truncated PTH fragments provides a stimulus to try and uncover and define the physiological importance of the biological role for such PTH fragments in humans. Some evidence in vitro and in animal experiments has been developed to indicate the likely presence of a specific receptor for such PTH fragments (C-PTH-R), and preliminary data have suggested that such receptors might exist particularly in cells of the osteocyte lineage, thereby opening a new field of parathyroid biology –19. ThesAn additional problem raised by these observations is the difficulty in trying to standardize PTH assay results from different laboratories or reagent suppliers using the various techniques and to achieve precise characterization of antisera used. This issue is not unique to the assay of PTH but is also relevant to other peptide hormone assays, such as the assay of growth hormone . The proIn summary, problems with the assay of parathyroid hormone continue but have uncovered new areas of parathyroid hormone physiology and opened a new area of investigation into potential biologic activity of PTH fragments. As these assay problems are solved, and efforts at standardization of PTH assays continue, it is likely that we will be able to understand the total spectrum of biologic activity of PTH and PTH fragments and incorporate the information into clinical practice to improve the assessment and management of abnormalities of mineral metabolism in a variety of clinical circumstances.


Posteromedial elbow instability has been described as an injury to the lateral ulnar collateral ligament (LUCL) and an anteromedial coronoid fracture, typically with absence of a radial head injury and mild incongruity of the elbow that can lead to a rapid onset of degenerative joint changes When assessing an elbow injury, we naturally interpret the available data to try to understand the mechanism of injury and it follows to assess the integrity of the typically associated injuries. However, the observation of a posterolateral elbow dislocation with absence of injury to the radial head may be interpreted as a simple elbow dislocation. The finding of a coronoid tip fracture may indicate a complex pattern of instability. The failure to adequately recognise the severity of coronoid fractures may lead to inadequate treatment.We present a case that presented in the emergency room (ER) with a radiographic posterolateral elbow dislocation and absence of radial head injury with an unrecognised fracture of the anteromedial coronoid, typically associated with a posteromedial pattern of instability treated like a posterolateral simple elbow dislocation and a similar case with adequate recognition of the pattern and severity of the coronoid fracture.Case 1A 60-year-old bricklayer presented in the ER with a radiographic posterolateral dislocation after a fall on the outstretched hand from his own height. After an initial x-ray exam, his elbow was reduced and placed in a splint at 90° of flexion after testing for stability in flexion and extension .. He wasCase 2A 30-year-old man presented in the ER referring a fall on his outstretched hand and exhibiting pain and clinical signs of elbow dislocation. On his x-ray examination, a posterolateral elbow dislocation with a readily recognisable fracture of the anteromedial coronoid is apparent . The patAt 2-month follow-up, the patient showed the decrease of the ulnohumeral joint with full range of motion and slight pain when loading the elbow  that madThe observation of a posterolateral elbow dislocation on a roentgenographic exam may lead the treating physician to consider the existence of a posterolateral mechanism of injury with injury to the lateral ligamentous complex of the elbow and may direct the attention for associated injuries including radial head fractures and fractures of the tip of the coronoid O'Driscoll described the pathomechanics of posteromedial and posterolateral dislocation and it is believed that the injuries to the different ligamentous structures are sequential The detection of associated injuries is critical to identify the type of elbow instability and to apply the correct treatment. The majority of posterolateral elbow dislocations presenting in the ER are due to a posterolateral pattern of injury, but these cases show that some of these may be produced following a posteromedial pattern of instability. Obviously, the detection of the anteromedial fragment is obvious in Simple elbow dislocations typically obtain good outcomes after reduction and a short period of immobilisation Evidence of a posterolateral elbow dislocation on a presenting x-ray exam in the ER does not equate to the assumption of a posterolateral elbow mechanism. In posterolateral elbow dislocations, the search for associated injuries should include the anteromedial coronoid fractures, specifically in cases with absence of fracture of the radial head or with an associated tip fracture of the coronoid and appropriate management should be instituted to avoid early degenerative changes of the joint.Posterolateral elbow dislocations are the most frequent type of elbow dislocation but may follow a posteromedial instability pattern. The failure to detect and treat correctly an associated anteromedial coronoid fracture may compromise the outcome. A high index of suspicion for the presence of an associated anteromedial coronoid fracture may be established when a posterolateral elbow dislocation presents with absence of a radial head fracture and appropriate imaging techniques utilised for its detection.


Hirschsprung's disease is characterized by the absence of ganglia in the distal colon, resulting in a functional obstruction. It is managed by excision of the aganglionic segment and anastomosis of the ganglionated bowel just above the dentate line. The level of aganglionosis is determined by performing multiple seromuscular biopsies and/or full thickness biopsy on the antimesenteric border of the bowel to determine the level of pullthrough. The transition zone is described as being irregular, and hence a doughnut biopsy is recommended so that the complete circumference can be assessed. Herein, we described a child in whom there was a selective absence of ganglion cells in 30% of the circumference of the bowel along the mesenteric border for most of the transverse colon. This case defies the known concept of neural migration in an intramural and transmesenteric fashion and emphasizes the importance of a doughnut biopsy of the pulled-down segment. Hirschsprung's disease (HSCR) is a disorder of migration of neural crest cells during embryonic development characterized by the absence of ganglia in the distal colon, resulting in a functional obstruction. The principles of management involve excision of the aganglionic segment and anastomosis of the ganglionated bowel above the dentate line. The level of aganglionosis is determined by performing multiple seromuscular biopsies on the antimesenteric border of the bowel. This practice is substantiated by Coventry's theory that vagal neural crest cells colonize the gut by intra- and extramural migration.A boy baby born at 37 weeks of gestation was transferred for specialist care for abdominal distension and delayed passage of meconium at 36 hours of life with a significant maternal family history of HSCR. Plain abdominal X-ray showed free air . He undHSCR is thought to be the result of arrested enteric neural crest cell (ENCC) migration, which occurs rostrocaudally. The level of arrest determines the length of the aganglionic segment. Rare variations in the pattern of aganglionosis are well described and are categorized into “skip” lesions, in which there is a segment of ganglionated bowel surrounded proximally and distally by aganglionosis, occurring most commonly with total colonic aganglionosis.ENCC precursors originate in the vagal region (somites 1–7) and to a lesser extent from the thoracic and sacral regions of the neural tube.Failure of transmesenteric migration: in a mouse model, Druckenbrod and Epstein studied the transmesenteric migration of ENCCs from the midgut to the hindgut during the time these organs are transiently juxtaposed.Delayed migration: ENCC colonization has been shown to be a timed process.Genetic factors provide the framework for patterning and morphogenesis. However, it is now known that maternal and placental factors such as hypoxia, inflammation, drug intake, and nutrition can affect the survival of ENCC.The pattern of aganglionosis in the transition zone is unusual, and a proper doughnut biopsy will avoid a transition zone pullthrough.


Raman spectroscopy is a novel tool used in the on-line monitoring and control of bioprocesses, offering both quantitative and qualitative determination of key process variables through spectroscopic analysis. However, the wide-spread application of Raman spectroscopy analysers to industrial fermentation processes has been hindered by problems related to the high background fluorescence signal associated with the analysis of biological samples. To address this issue, we investigated the influence of fluorescence on the spectra collected from two Raman spectroscopic devices with different wavelengths and detectors in the analysis of the critical process parameters (CPPs) and critical quality attributes (CQAs) of a fungal fermentation process. The spectra collected using a Raman analyser with the shorter wavelength (903 nm) and a charged coupled device detector (CCD) was corrupted by high fluorescence and was therefore unusable in the prediction of these CPPs and CQAs. In contrast, the spectra collected using a Raman analyser with the longer wavelength (993 nm) and an indium gallium arsenide (InGaAs) detector was only moderately affected by fluorescence and enabled the generation of accurate estimates of the fermentation’s critical variables. This novel work is the first direct comparison of two different Raman spectroscopy probes on the same process highlighting the significant detrimental effect caused by high fluorescence on spectra recorded throughout fermentation runs. Furthermore, this paper demonstrates the importance of correctly selecting both the incident wavelength and detector material type of the Raman spectroscopy devices to ensure corrupting fluorescence is minimised during bioprocess monitoring applications. Saccharomyces cerevisiae fermentations [Escherichia coli fermentation [Raman spectroscopy is a non-invasive, non-destructive spectroscopic technique that exploits molecular vibrations for the qualitative and quantitative analysis of molecules . It has ntations ,10 and nentation . More adentation , in addientation  in the rIt is clear that Raman spectroscopy will play a pivotal role in the real-time monitoring and control of bioprocesses. However, a major hurdle hindering the wide-spread adoption of these process analysers relates to the high fluorescence observed during the analysis of biological molecules which often overlay the important Raman scattering bonds, diminishing the ability to estimate the material of interest ,15. TherTo address this issue and advance the use of this technology in fermentation applications, two Raman spectroscopic analysers were implemented on a highly fluorescence fungal fermentation process. One Raman analyser had an incident wavelength of 903 nm and used a silicon-based charged couple device (CCD) detector and the second device had a 993 nm wavelength with an indium gallium arsenide (InGaAs) array detector. Both analysers were implemented on a similar small-scale fungal fermentation process with the objective of estimating the critical process parameters (CPPs) and critical quality attributes (CQAs) of the fermentation. These have been previously identified for this process as the glucose and active pharmaceutical ingredient (API) concentration, respectively. The spectral data collected using the Raman device with the shorter wavelength and CCD detector was found to be significantly corrupted by a high background fluorescence signal in contrast to the 993 nm Raman device with the InGaAs detector which was only moderately affected by fluorescence. The spectra collected from both analysers was correlated with the off-line concentrations of both variables using partial least squares (PLS) modelling. Only the regression models generated using the spectra recorded on the 993 nm device enabled accurate predictions of both the glucose and API concentration. To the best of the authors’ knowledge, this is the first direct comparison of two Raman spectroscopy devices with different incident wavelengths and detector material to monitor the same fermentation process. This work highlights the need to better understand the fundamental principles of fluorescence on recorded Raman spectra and demonstrates the importance of correct probe selection in future applications of this novel technology to the biotechnology sector.A proprietary fungus supplied by Pfizer was used to inoculate both fermentations that was propagated from the same thawed culture stock supplemented with a proprietary nutrient feed. The fungus produces a high concentration of a commercially available antibiotic, referenced as the active pharmaceutical ingredient (API) concentration.Two fed-batch fungal fermentations (referred to as Fermentation A and Fermentation B) were performed in a 5 L bioreactor with a working volume of approximately 3.6 L. Each bioreactor was set to have identical operating conditions, both equipped with thermometers, dissolved oxygen and pH probes. The temperatures of the reactors were kept at 28 In Fermentation A, a 993 nm Raman spectroscopy device with an indium gallium arsenide (InGaAs) detector array with a spectral range of 200–2400 cmYYThe spectra collected by each device was combined with the off-line glucose and API measurements and was used to generate two PLS models. In Fermentation A, ten off-line glucose samples were recorded and 18 off-line samples for Fermentation B. For each fermentation eight off-line samples of the API concentration were recorded. The off-line glucose samples were interpolated using a cubic spline approximation and a 30-min sampling rate resulting in 522 and 475 sample points for Fermentation A and B, respectively. The off-line API concentrations were interpolated in a similar fashion resulting in approximately 360 sample points. The 30-min sampling rate was chosen to match the sampling frequency of each Raman device that was set up to produce a single spectra every 30 min through adjustment of the number of averages and integration times. The preprocessing of the spectra utilised the de-spiking algorithm outlined in Mori et al.  and was The wavelengths associated with the glucose were identified through the analysis of the aqueous calibration samples spiked with high concentrations of glucose  algorithm as outlined in detail by Wold et al. . The preB is generated that relates scores of the X block to the Y block as:A vector of inner-relationships The PLS model works iteratively for each latent variable and upon convergence a matrix of regression coefficients X block taking R latent variables:The cumulative sum of the regression coefficients predicts the response variable  and for the validation data set the root mean square error of prediction (RMSEP) was used. These functions were calculated as described in :(6)RMSEChThe fundamental principles of Raman spectroscopy are outlined in hhhhhhhRayleigh scattering occurs when the light interacts with the molecules of the sample and the net exchange of energy is zero i.e., energy of the incident light . The net energy deviation results in characteristic peaks in the resultant spectra. The positions of these peaks are defined by the molecular structure of the sample and its chemical environment, allowing Raman spectroscopy to be used for chemical identification and classification. Furthermore, the peak heights (or areas) of the spectrum are assumed linearly proportional to the molecular concentration and consequently can be used to monitor the CPPs or CQAs of bioprocesses, provided the Raman analyser can detect the material of interest .The intensity of Raman scattering (fined by  to be inIt is therefore necessary to filter out the Rayleigh scattered light in order to detect the weak Raman scattering effect .In competition with the weak Raman scattering is fluorescence which is a non-scattering process that occurs when the incident beam absorbs some energy from the light source and temporarily excites the electrons with enough energy to be transferred up to a higher quantum state (E’). There are multiple higher quantum states that the exited electrons can obtain and this is dependent on the energy and wavelength of the external light source. The electrons in their excited state are unstable and as they return to their respective ground state they release light with energy equal to 10−12 s) .Molecules that are susceptible to this fluorescence process when excited by visible, ultra-violet or near-infrared light are known as fluorophores or fluorescence molecules, these are typically polyaromatic hydrocarbons or heterocycle molecules with several property , howeverproperty . UnfortuPhaffia rhodozyma. However, some of the important Raman peaks observed in The spectra collected from two Raman spectroscopic devices were analysed to estimate the glucose and API concentration, previously identified as the primary CPP and CQA on this small-scale fungal fermentation. The spectra collected on the 993 nm Raman device was moderately influenced by fluorescence in comparison to the spectra recorded by the 903 nm Raman device which was significantly effected by fluorescence. o et al.  observedThe spectral data of each device and the corresponding off-line glucose measurements were used to generate two separate PLS models as previously discussed. The number of components of each model were chosen based on the RMSEC and RMSEP of both PLS models as defined by Equation . Figure The PLS model predictions of the glucose concentration in Fermentation B using the spectra collected using the 903 nm Raman device were very poor when compared to the off-line values as shown in Intensity of Raman scattered lightFrequency of light sourceWavelength of light sourceThe two main factors contributing to the large difference observed in the intensity of fluorescence effecting the spectra collected by both Raman analysers is related to the incident wavelength of each device and the detector material used. The choice of the excitation wavelength can significantly impact the level of observed fluorescence. In Raman spectroscopy the scattered energy of the light source is inversely proportional to the fourth power of the excitation wavelength defined as:Therefore the longer wavelength of 993 nm Raman device results in a decrease in energy of the light source compared to the 903 nm, hence reducing the probability of fluorescence by lowering the energy available to excite the electrons of the sample up to their quantum states. Frank et al.  also higFurthermore, the 903 nm Raman device uses a CCD detector which was highlighted to have low quantum efficiency above wavelengths greater than 800 nm ,36. Li eP. rhodozyma fermentation in addition to the prediction of antibody product concentrations in mammalian cell cultures [The on-line prediction of the API concentration of this fermentation was also investigated. The PLS predictions of the API concentration in comparison to the off-line values using the spectra collected from the 993 nm Raman device is shown in cultures ,38. The Fluorescence is a major problem experienced by many scientists and engineers implementing Raman spectroscopy to monitor and control biopharmaceutical processes. This paper is the first direct comparison of two different Raman spectroscopy devices on the same fermentation highlighting the significant influence of incident wavelength and detector material on fluorescence levels detected by each device. The spectra recorded by the Raman spectroscopy device with the 903 nm incident wavelength and a CCD detector was corrupted by high fluorescence and rendered the recorded spectra unusable for regression analysis. However, the spectra recorded by the Raman spectroscopy device with the 993 incident wavelength and an indium gallium arsenide (InGaAs) detector generated spectra with only moderate levels of fluorescence. The spectra recorded by this device enabled accurate estimations of both glucose and API concentrations through the generation of a PLS regression model. Therefore this work demonstrates that although a lower incident wavelength increases the Raman scattering effect it can also increase the level of fluorescence rendering the recorded spectra obsolete. However, at elevated incident wavelengths the probability of fluorescence is significantly reduced in addition to the Raman scattering effect which can be compensated for by a more sensitive detector material as demonstrated by the 993 nm Raman probe with the InGaAs detector. Thus Raman spectroscopy is a highly suitable tool for the quantification of the key process parameters in biopharmaceutical processing. However, caution is advised in implementing this novel tool particularly in the choice of the appropriate incident wavelength of the analyser and the sensor detector material to ensure problems relating to high fluorescence do not impact on the quality of the recorded spectra.


Lumbricus terrestris. Body burden analysis was used to analyze the intrinsic toxicity of the six hydrocarbon mixtures. The major fractions of the whole mixtures, the saturate, and aromatic fractions had different intrinsic toxicities; the aromatics were more toxic than the saturates. The toxicity of the saturate and aromatic fractions also differed between the mixtures. The flare saturate mixture was more toxic than the crude saturate mixture, while the crude aromatic mixture was more toxic than the flare aromatic mixture. The most dramatic difference in toxicity of the two sources was between the flare whole and crude whole mixtures. The crude whole mixture was very toxic; the toxicity of this mixture reflected the toxicity of the crude aromatic fraction. However, the flare whole mixture was not toxic, due to a lack of partitioning from the whole mixture into the lipid membrane of the exposed worms. This lack of partitioning appears to be related to the relatively high concentrations of asphaltenes and polar compounds in the flare pit whole mixture.The toxicity of whole, saturate, and aromatic hydrocarbon mixtures from flare pit and crude oil sources were evaluated using


Alec Coppen, a Honorary Fellow of the Royal College of Psychiatrists has acted as director of the Medical Research Council Unit for Neuropsychiatric Research in Epsom England until 1988. Among his international colleagues he was always highly respected as a pioneering psychiatrist and psychopharmacologist credited with the discovery of the role of serotonin in the pathogenesis of depression. His seminal paper in the Lancet 1963 showed that tryptophan markedly potentiated the antidepressant action of MAOIs. He pursued the serotonin theory conducting numerous studies including studies of serotonin metabolites in post-mortem brains of depressed suicides that culminated in his 1967 paper in the British Journal of Psychiatry on the biochemistry of affective disorders that became a citation classic and made him a much honoured member of the international group of psychopharmacologists and biological psychiatrists, the CINP . He acted as its president for the 17th annual CINP meeting in Kyoto in the year 1990. It is fair to state that the development of SSRI antidepressants have one origin in his work. He has published more than 500 papers and seven books on various studies of the biology of affective disorders. His other major contribution to the psychopharmacology of mood disorders was the establishment of the Lithium Clinic at West Park Hospital (in a chapter for a volume on the history of CINP he wrote: “One lesson we learned is that simply prescribing treatment is not effective”). He conducted the first placebo controlled trial of the effectiveness of lithium salts in the prophylaxis of recurrent mood disorders culminating in the discovery of lithium’s unique anti-suicidal effects concurrently with two German research groups in Berlin and Dresden. He conducted a trial of the optimum dosage of lithium establishing its minimum effective dose for prophylaxis. He studied its adverse effects on renal and thyroid functions to establish standards for safe medical practice. His last paper was a review of the effectiveness of lithium in the long-term treatment of unipolar (recurrent) depression in 2017. Alec often talked about the many letters he received from patients and their families thanking him for his good care years after he retired.Alec had been trained in psychiatry at the Maudsley Hospital where he started his research work in biological psychiatry and attained the MD in 1958. He established the MRC Neuropsychiatry Unit at West Park Hospital in 1959 which he directed until he retired in 1988.Alec Coppen received many honours such as the prestigious Anna Monica Prize in Biological Psychiatry Research in 1969. He was founding member of the British Association for Psychopharmacology (BAP) and was elected President 1976–1978. He was President of the Collegium Internationale Neuro-Psychopharmacologicum (CINP) 1988–1990 and was awarded the Honorary Fellowship of the Royal College of Psychiatrists in 1995. The BAP awarded him the first Gold Medal for lifetime achievement in psychopharmacology in 1998 and he was given the Pioneer of Psychopharmacology Award by the CINP in year 2000.Alec was well read, highly cultured and enjoyed opera and theatre. In the retirement he achieved his aim of seeing all 37 Shakespeare plays performed.He leaves his son, Michael and his grandchildren Daniel and Victoria.


We evaluated the impacts of entrainment and impingement at the Salem Generating Station on fish populations and communities in the Delaware Estuary. In the absence of an agreed-upon regulatory definition of “adverse environmental impact” (AEI), we developed three independent benchmarks of AEI based on observed or predicted changes that could threaten the sustainability of a population or the integrity of a community.Our benchmarks of AEI included: (1) disruption of the balanced indigenous community of fish in the vicinity of Salem ; (2) a continued downward trend in the abundance of one or more susceptible fish species ; and (3) occurrence of entrainment/impingement mortality sufficient, in combination with fishing mortality, to jeopardize the future sustainability of one or more populations .The BIC analysis utilized nearly 30 years of species presence/absence data collected in the immediate vicinity of Salem. The Trends analysis examined three independent data sets that document trends in the abundance of juvenile fish throughout the estuary over the past 20 years. The Stock Jeopardy analysis used two different assessment models to quantify potential long-term impacts of entrainment and impingement on susceptible fish populations. For one of these models, the compensatory capacities of the modeled species were quantified through meta-analysis of spawner-recruit data available for several hundred fish stocks.All three analyses indicated that the fish populations and communities of the Delaware Estuary are healthy and show no evidence of an adverse impact due to Salem. Although the specific models and analyses used at Salem are not applicable to every facility, we believe that a weight of evidence approach that evaluates multiple benchmarks of AEI using both retrospective and predictive methods is the best approach for assessing entrainment and impingement impacts at existing facilities.


Suspended particulate matter of samples of river water and waste water treatment plants was tested for genotoxicity and mutagenicity using the standardized umu assay and two versions of the Ames microsuspension assay. The study tries to determine the entire DNA-damaging potential of the water samples and the distribution of DNA-damaging substances among the liquid phase and solid phase. Responsiveness and sensitivity of the bioassays are compared.