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Parkinson’s disease (PD) is the most prevalent movement disorder known and predominantly affects the elderly. It is a progressive neurodegenerative disease wherein α-synuclein, a neuronal protein, aggregates to form toxic structures in nerve cells. The cause of Parkinson’s disease (PD) remains unknown. Intestinal dysfunction and changes in the gut microbiota, common symptoms of PD, are evidently linked to the pathogenesis of PD. Although a multitude of studies have investigated microbial etiologies of PD, the microbial role in disease progression remains unclear. Here, we show that Gram-negative sulfate-reducing bacteria of the genus Desulfovibrio may play a potential role in the development of PD. Conventional and quantitative real-time PCR analysis of feces from twenty PD patients and twenty healthy controls revealed that all PD patients harbored Desulfovibrio bacteria in their gut microbiota and these bacteria were present at higher levels in PD patients than in healthy controls. Additionally, the concentration of Desulfovibrio species correlated with the severity of PD. Desulfovibrio bacteria produce hydrogen sulfide and lipopolysaccharide, and several strains synthesize magnetite, all of which likely induce the oligomerization and aggregation of α-synuclein protein. The substances originating from Desulfovibrio bacteria likely take part in pathogenesis of PD. These findings may open new avenues for the treatment of PD and the identification of people at risk for developing PD.

Individuals acquire immunity to clinical malaria after repeated Plasmodium falciparum infections. Immunity to disease is thought to reflect the acquisition of a repertoire of responses to multiple alleles in diverse parasite antigens. In previous studies, we identified polymorphic sites within individual antigens that are associated with parasite immune evasion by examining antigen allele dynamics in individuals followed longitudinally. Here we expand this approach by analyzing genome-wide polymorphisms using whole genome sequence data from 140 parasite isolates representing malaria cases from a longitudinal study in Malawi and identify 25 genes that encode possible targets of naturally acquired immunity that should be validated immunologically and further characterized for their potential as vaccine candidates.

Currently the effect of urban discharges on water quantity and quality issues and additional recreational amenities perceived in the urban landscape have gained growing public interest for the provision of sustainable urban development. This is due to the fact that urbanization is converging to challenge city infrastructure due to their adverse impacts on precipitation extremes and the environment of urban areas at large. This study was aimed at identification of the treats of urban expansion and prediction of the environmental responses to urbanization of Jimma City. This is an important input for the decision of environmentalists, hydrologists, storm and waste water management for the better plan and sustainable development of the city. The study analysis of stream flow indicates, urbanization was found to be one of the responsible factors for changing the surface of the land disturbing the hydrological process of Jimma City by altering the magnitude of surface runoff, aquifer recharge and river flows. The expansion of Jimma city have intensified, surface water discharges from developed areas and uncontrolled waste release which have affected the social, environmental and economic state of the area. Increased flood peaks, water volume and pollutant loads, reduced ground water recharge were found to be the major sources water quantity and quality degradation. Degraded water quantity and quality in turn resulted in water crisis, ecological risk, reduced quality of life and reduced level of ecosystem service.

Abstract Metabolic alterations in the critically ill have been studied for more than a century, but the heterogeneity of the critically ill patient population, the varying duration and severity of the acute phase of illness, and the many confounding factors have hindered progress in the field. These factors may explain why management of metabolic alterations and related conditions in critically ill patients has for many years been guided by recommendations based essentially on expert opinion. Over the last decade, a number of randomized controlled trials have been conducted, providing us with important population-level evidence that refutes several longstanding paradigms. However, between-patient variation means there is still substantial uncertainty when translating population-level evidence to individuals. A cornerstone of metabolic care is nutrition, for which there is a multifold of published guidelines that agree on many issues but disagree on others. Using a series of nine questions, we provide a review of the latest data in this field and a background to promote efforts to address the need for international consistency in recommendations related to the metabolic care of the critically ill patient. Our purpose is not to replace existing guidelines, but to comment on differences and add perspective.

Abstract Background Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP1) antigens play a critical role in host immune evasion. Serologic responses to these antigens have been associated with protection from clinical malaria, suggesting that antibodies to PfEMP1 antigens may contribute to natural immunity. The first N-terminal constitutive domain in a PfEMP1 is the Duffy binding-like alpha (DBL-α) domain, which contains a 300 to 400 base pair region unique to each particular protein (the DBL-α “tag”). This DBL-α tag has been used as a marker of PfEMP1 diversity and serologic responses in malaria-exposed populations. In this study, using sera from a malaria-endemic region, responses to DBL-α tags were compared to responses to the corresponding entire DBL-α domain (or “parent” domain) coupled with the succeeding cysteine-rich interdomain region (CIDR). Methods A protein microarray populated with DBL-α tags, the parent DBL-CIDR head structures, and downstream PfEMP1 protein fragments was probed with sera from Malian children (aged 1 to 6 years) and adults from the control arms of apical membrane antigen 1 (AMA1) vaccine clinical trials before and during a malaria transmission season. Serological responses to the DBL-α tag and the DBL-CIDR head structure were measured and compared in children and adults, and throughout the season. Results Malian serologic responses to a PfEMP1’s DBL-α tag region did not correlate with seasonal malaria exposure, or with responses to the parent DBL-CIDR head structure in either children or adults. Parent DBL-CIDR head structures were better indicators of malaria exposure. Conclusions Larger PfEMP1 domains may be better indicators of malaria exposure than short, variable PfEMP1 fragments such as DBL-α tags. PfEMP1 head structures that include conserved sequences appear particularly well suited for study as serologic predictors of malaria exposure.

Understanding genomic variation in Plasmodium falciparum parasites and inferring migration patterns can guide malaria elimination strategies. Using genome-wide data for 1722 parasites collected from 54 districts, the authors use identity-by-descent approaches to estimate regional parasite migration and spread of artemisinin drug resistance.

Abstract Background Recent evidence suggests that acetate-buffered infusions result in better hemodynamic stabilization than 0.9% saline in patients undergoing major surgery. The choice of buffer in balanced crystalloid solutions may modify their hemodynamic effects. We therefore compared the inopressor requirements of Ringer’s acetate and lactate for perioperative fluid management in patients undergoing cardiac surgery. Methods Using a randomized controlled double-blind design, we compared Ringer’s acetate (RA) to Ringer’s lactate (RL) with respect to the average rate of inopressor administered until postoperative hemodynamic stabilization was achieved. Secondary outcomes were the cumulative dose of inopressors, the duration of inopressor administration, the total fluid volume administered, and the changes in acid-base homeostasis. Patients undergoing elective valvular cardiac surgery were included. Patients with severe cardiac, renal, or liver disease were excluded from the study. Results Seventy-five patients were randomly allocated to the RA arm, 73 to the RL. The hemodynamic profiles were comparable between the groups. The groups did not differ with respect to the average rate of inopressors (RA 2.1 mcg/kg/h, IQR 0.5–8.1 vs. RL 1.7 mcg/kg/h, IQR 0.7–8.2, p = 0.989). Cumulative doses of inopressors and time on individual and combined inopressors did not differ between the groups. No differences were found in acid-base parameters and their evolution over time. Conclusion In this study, hemodynamic profiles of patients receiving Ringer’s lactate and Ringer’s acetate were comparable, and the evolution of acid-base parameters was similar. These study findings should be evaluated in larger, multi-center studies. Trial registration Clinicaltrials.gov NCT02895659. Registered 16 September 2016.

Failure to account for genetic diversity of antigens during vaccine design may lead to vaccine escape. To evaluate the vaccine escape potential of antigens used in vaccines currently in development or clinical testing, we surveyed the genetic diversity, measured population differentiation, and performed in silico prediction and analysis of T-cell epitopes of ten such Plasmodium falciparum pre-erythrocytic-stage antigens using whole-genome sequence data from 1010 field isolates. Of these, 699 were collected in Africa (Burkina Faso, Cameroon, Guinea, Kenya, Malawi, Mali, and Tanzania), 69 in South America (Brazil, Colombia, French Guiana, and Peru), 59 in Oceania (Papua New Guinea), and 183 in Asia (Cambodia, Myanmar, and Thailand). Antigens surveyed include cell-traversal protein for ookinetes and sporozoites, circumsporozoite protein, liver-stage antigens 1 and 3, sporozoite surface proteins P36 and P52, sporozoite asparagine-rich protein-1, sporozoite microneme protein essential for cell traversal-2, and upregulated-in-infectious-sporozoite 3 and 4 proteins. The analyses showed that a limited number of these protein variants, when combined, would be representative of worldwide parasite populations. Moreover, predicted T-cell epitopes were identified that could be further explored for immunogenicity and protective efficacy. Findings can inform the rational design of a multivalent malaria vaccine.

Abstract Background In Pakistan, artesunate (AS) in combination with sulfadoxine–pyrimethamine (SP) is the recommended treatment for uncomplicated Plasmodium falciparum malaria. Monitoring molecular markers of anti-malarial drug resistance is crucial for early detection and containment of parasite resistance to treatment. Currently, no data are available on molecular markers of artemisinin resistance (K13 mutations) in P. falciparum isolates from Pakistan. In this study, the prevalence of mutations associated with SP and artemisinin resistance was estimated in different regions of Pakistan. Methods A total of 845 blood samples that were positive for malaria parasites by microscopy or rapid diagnostic test were collected from January 2016 to February 2017 from 16 different sites in Pakistan. Of these samples, 300 were positive for P. falciparum by PCR. Polymorphisms in the P. falciparum dihydrofolate reductase (pfdhfr) and dihydropteroate synthase (pfdhps) genes were identified by pyrosequencing while polymorphisms in the propeller domain of the pfk13 gene were identified by Sanger sequencing. Results The prevalence of the PfDHFR 108N and 59R mutations was 100% and 98.8%, respectively, while the prevalence of PfDHFR 50R and 51I mutations was 8.6%. No mutation was observed at PfDHFR position 164. In PfDHPS, the prevalence of mutations at positions 436, 437, and 613 was 9.9%, 45.2%, and 0.4%, respectively. No mutations were found at PfDHPS positions 540 and 581. The prevalence of double PfDHFR mutants (59R + 108N) ranged from 93.8% to 100%, while the prevalence of parasites having the PfDHFR 59R + 108N mutations in addition to the PfDHPS 437G mutation ranged from 9.5% to 83.3% across different regions of Pakistan. Nine non-synonymous and four synonymous mutations were observed in the PfK13 propeller domain, none of which correspond to mutations validated to contribute to artemisinin resistance. Conclusion The absence of the highly resistant PfDHFR/PfDHPS quintuple mutant parasites and the lack of PfK13 mutations associated with artemisinin resistance is consistent with AS + SP being effective in Pakistan.

MalariaGEN is a data-sharing network that enables groups around the world to work together on the genomic epidemiology of malaria. Here we describe a new release of curated genome variation data on 7,000 Plasmodium falciparum samples from MalariaGEN partner studies in 28 malaria-endemic countries. High-quality genotype calls on 3 million single nucleotide polymorphisms (SNPs) and short indels were produced using a standardised analysis pipeline. Copy number variants associated with drug resistance and structural variants that cause failure of rapid diagnostic tests were also analysed. Almost all samples showed genetic evidence of resistance to at least one antimalarial drug, and some samples from Southeast Asia carried markers of resistance to six commonly-used drugs. Genes expressed during the mosquito stage of the parasite life-cycle are prominent among loci that show strong geographic differentiation. By continuing to enlarge this open data resource we aim to facilitate research into the evolutionary processes affecting malaria control and to accelerate development of the surveillance toolkit required for malaria elimination.

This study introduces a fused filament fabrication (FFF) process for manufacturing complex-structured asteroid analogue objects to be applied in tomographic microwave radar measurements and inversion studies. We describe an approach to control the volume fraction of the plastic and, thereby, the effective relative permittivity within a tetrahedral wireframe which serves as metamaterial representing the actual asteroid composition. To determine the effective permittivity of the plastic–air mixture, we use an exponential model. In this study, two analogue objects based on the shape of the asteroids 1998 KY26 and (25143) Itokawa were 3D-printed in a scale suitable for microwave laboratory measurements using ABS filament with a controlled constant relative electric permittivity. The results obtained suggest that the permittivity of solid and powdery asteroid minerals can be modelled with the proposed technique and, in particular, that the numerical structural permittivity models of the earlier numerical studies can be approximated by 3D-printed analogues.

Emerging artemisinin resistance in Southeast Asia poses a significant risk to malaria control and eradication goals, including China’s plan to eliminate malaria nationwide by 2020. Plasmodium falciparum was endemic in China, especially in Southern China. Parasites from this region have shown decreased susceptibility to artemisinin and delayed parasite clearance after artemisinin treatment. Understanding the genetic basis of artemisinin resistance and identifying specific genetic loci associated with this phenotype is crucial for surveillance and containment of resistance. In this study, parasites were collected from clinical patients from Yunnan province and Hainan island. The parasites were genotyped using a P. falciparum-specific single nucleotide polymorphism (SNP) microarray. The SNP profiles examined included a total of 27 validated and candidate molecular markers of drug resistance. The structure of the parasite population was evaluated by principal component analysis by using the EIGENSOFT program, and ADMIXTURE was used to calculate maximum likelihood estimates for the substructure analysis. Parasites showed a high prevalence of resistance haplotypes of pfdhfr and pfdhps and moderate prevalence of pfcrt. There was no mutation identified on pfmdr1. Candidate SNPs on chromosomes 10, 13, and 14 that were associated with delayed parasite clearance showed a low prevalence of mutants. Parasites from Southern China were clustered and separated from those from Southeast Asia. Parasites from Yunnan province were substructured from parasites from Hainan island. This study provides evidence for a genomic population with drug resistance in Southern China and also illustrates the utility of SNP microarrays for large-scale parasite molecular epidemiology.

Background: Industrial and institutional activity, usage, and utilization of items or substances all contribute to waste creation. Solid waste is also thought to contain non-harmful trash from households, particularly while cooking, organizations, institutions, stores, other business segments, and manufacturing industries. In terms of international and environmental standard protocol, solid waste handling, sewage disposal, and correct disposal have been a major topic of discussion. Methods and Materials: A cross-sectional quantitative study design was incorporated to assess knowledge, attitudes, practice, and associated factors on the prevention of occupational risks and health hazards among sanitary workers. 321 solidwaste handlers found to be engaged in Bule Hora, Town presently. Results: The response rate of samples in the present study was found to be around 91.2% of which the majority were females, those accounted to be about 80%. The median age of the study samples was nearly 30 years. It was found that nearly three fourth of the study samples stated good knowledge on the prevention of occupational health risks. Most of the study participants had a good attitude and less the 10% showed good practice on the prevention of occupational health hazards. Job dissatisfaction was found to be a statistically significant factor along with the use of PPE’s in implementing good practices and work patterns among sanitary workers even after been provided with basic personal protective equipment. Conclusion: The research showed that preparations for implementing fundamental occupational health services, including mandating the use of personal protective equipment and regulating solid waste collectors, should be adopted.

Most people encounter art images as digital reproductions on a computer screen instead of as originals in a museum or gallery. With the development of digital technologies, high-resolution artworks can be accessed anywhere and anytime by a large number of viewers. Since these digital images depict the same content and are attributed to the same artist as the original, it is often implicitly assumed that their aesthetic evaluation will be similar. When it comes to the digital reproductions of art, however, it is also obvious that reproductions do differ from the originals in various aspects. Besides image quality, resolution, and format, the most obvious change is in the representation of color. The effects of subjectively varying surface-level image features on art evaluation have not been clearly assessed. To address this gap, we compare the evaluation of digital reproductions of 16 expressionist and impressionist paintings manipulated to have a high color saturation vs. a saturation similar to the original. We also investigate the impact of viewing time (100 ms vs. unrestricted viewing time) and expertise (art experts vs. laypersons), two other aspects that may impact the perception of art in online contexts. Moreover, we link these dimensions to a recent model of aesthetic experience [the Vienna Integrated Model of Top-Down and Bottom-Up Processes in Art Perception (VIMAP)]. Results suggest that color saturation does not exert a major influence on liking. Cognitive and emotional aspects (interest, confusion, surprise, and boredom), however, are affected – to different extents for experts and laypersons. For laypersons, the increase in color saturation led to more positive assessments of an artwork, whereas it resulted in increased confusion for art experts. This insight is particularly important when it comes to reproducing artworks digitally. Depending on the intended use, increasing or decreasing the color saturation of the digitally reproduced image might be most appropriate. We conclude with a discussion of these findings and address the question of why empirical aesthetics requires more precise dimensions to better understand the subtle processes that take place in the perception of today’s digitally reproduced art environment.

Abstract Objectives Presence of sleep‐disordered breathing (SDB) affects negatively recovery from stroke. The aim of this study is to evaluate the relationships between sleep‐disordered breathing (SDB) and outcome measures in Finnish stroke unit cohort: mRS, need of rehabilitation and hospitalization time. Material and Methods An observational longitudinal study consisted of 95 patients referred to the Stroke Unit of Satakunta Hospital District over a period of November 2013 to March 2016. Patients were tested for SDB within 72 hr from the hospital admission because of ischemic stroke or TIA. The patients underwent polysomnography with NOX T3 wireless recorder. Results There are 37% (n = 35) non‐OSA patients, 20% (n = 19) of patients have mild obstructive sleep apnea (OSA) and 39% (n = 37) have moderate/severe OSA and 4% (n = 4) have CSA. Patients with OSA have higher proportion of disability scores of mRS 3–5 (38%) compared to non‐OSA (11%) and mild OSA (5%) patients on registration day (mRS0), and the same trend is seen at hospital discharge 35% versus 9% and 5%. (p = .009). Proportion of patients with OSA who needed rehabilitation is 65% (n = 19) versus non‐OSA patients 17.5% (n = 4) and mild OSA patients 17.5% (n = 4; p = .039). We observed longer duration of hospitalization (5–15 days) in 29% of OSA patients compared to mild OSA patients 47% and OSA patients 54%. (p = .045). Conclusion Ischemic stroke patients with OSA have higher disability, higher need of rehabilitation, and longer hospitalization length. Prescreening tools for recognizing these stroke patients in acute phase could be valuable. That could result in earlier initiation of treatment and might prevent worse recovery from stroke.

Background: Blood biomarkers may enhance outcome prediction performance of head computed tomography scores in traumatic brain injury (TBI).Objective: To investigate whether admission levels of eight different protein biomarkers can improve the outcome prediction performance of the Helsinki computed tomography score (HCTS) without clinical covariates in TBI.Materials and methods: Eighty-two patients with computed tomography positive TBIs were included in this study. Plasma levels of β-amyloid isoforms 1–40 (Aβ40) and 1–42 (Aβ42), glial fibrillary acidic protein, heart fatty acid-binding protein, interleukin 10 (IL-10), neurofilament light, S100 calcium-binding protein B, and total tau were measured within 24 h from admission. The patients were divided into favorable (Glasgow Outcome Scale—Extended 5–8, n = 49) and unfavorable (Glasgow Outcome Scale—Extended 1–4, n = 33) groups. The outcome was assessed 6–12 months after injury. An optimal predictive panel was investigated with the sensitivity set at 90–100%.Results: The HCTS alone yielded a sensitivity of 97.0% (95% CI: 90.9–100) and specificity of 22.4% (95% CI: 10.2–32.7) and partial area under the curve of the receiver operating characteristic of 2.5% (95% CI: 1.1–4.7), in discriminating patients with favorable and unfavorable outcomes. The threshold to detect a patient with unfavorable outcome was an HCTS > 1. The three best individually performing biomarkers in outcome prediction were Aβ40, Aβ42, and neurofilament light. The optimal panel included IL-10, Aβ40, and the HCTS reaching a partial area under the curve of the receiver operating characteristic of 3.4% (95% CI: 1.7–6.2) with a sensitivity of 90.9% (95% CI: 81.8–100) and specificity of 59.2% (95% CI: 40.8–69.4).Conclusion: Admission plasma levels of IL-10 and Aβ40 significantly improve the prognostication ability of the HCTS after TBI.

Tässä tutkimuksessa perehdytään opettajan toimijuuteen tilanteessa, jossa useampi opettaja opettaa yhdessä. Yhteisopetuksella tarkoitetaan tilannetta, jossa ainakin kaksi opettajaa yhdessä suunnittelee, toteuttaa ja arvioi opetusta, joka toteutetaan pääasiassa samassa tilassa. Kun opetetaan yhdessä, saadaan luokkaan useamman opettajan osaaminen. Asiantuntijakeskustelujen kautta selvitetään, mitä pedagogit kertovat yhteisopetuksesta ja pohditaan, miten opettajan toimijuus toteutuu, kun opetetaan yhdessä. Tutkimuksemme tulosten mukaan yhteisopetus koetaan hyvänä, mutta sille löytyy selkeitä reunaehtoja. Eri ammattiryhmien (luokan-, aineen- ja erityisopettajien) kertomukset yhteisopettamisesta erosivat toisistaan. Koulutustaustasta riippumatta opettajat näkivät yhteisopetuksen yleensä omaa ammattitaitoa kehittävänä ja parhaassa tapauksessa opettajan perustyötä helpottavana tapana työskennellä. Osa opettajista koki sen lisäävän omaa toimijuutta, mutta osa taas kertoi yhteisopetuksen kapeuttavan toimijuutta. Yhteisopetuksen tekemisen tapaa venytettiin määritelmästä poiketen tarpeiden mukaan.

ABSTRACT Children are highly susceptible to clinical malaria, and in regions where malaria is endemic, their immune systems must face successive encounters with Plasmodium falciparum parasites before they develop immunity, first against severe disease and later against uncomplicated malaria. Understanding cellular and molecular interactions between host and parasites during an infection could provide insights into the processes underlying this gradual acquisition of immunity, as well as to how parasites adapt to infect hosts that are successively more malaria experienced. Here, we describe methods to analyze the host and parasite gene expression profiles generated simultaneously from blood samples collected from five consecutive symptomatic P. falciparum infections in three Malian children. We show that the data generated enable statistical assessment of the proportions of (i) each white blood cell subset and (ii) the parasite developmental stages, as well as investigations of host-parasite gene coexpression. We also use the sequences generated to analyze allelic variations in transcribed regions and determine the complexity of each infection. While limited by the modest sample size, our analyses suggest that host gene expression profiles primarily clustered by individual, while the parasite gene expression profiles seemed to differentiate early from late infections. Overall, this study provides a solid framework to examine the mechanisms underlying acquisition of immunity to malaria infections using whole-blood transcriptome sequencing (RNA-seq). IMPORTANCE We show that dual RNA-seq from patient blood samples allows characterization of host/parasite interactions during malaria infections and can provide a solid framework to study the acquisition of antimalarial immunity, as well as the adaptations of P. falciparum to malaria-experienced hosts.

The cholinergic nuclei in the basal forebrain innervate frontal cortical structures regulating attention. Our aim was to investigate if cognitive test results measuring attention relate to the longitudinal volume change of cholinergically innervated structures following traumatic brain injury (TBI). During the prospective, observational TBIcare project patients with all severities of TBI (n = 114) and controls with acute orthopedic injuries (n = 17) were recruited. Head MRI was obtained in both acute (mean 2 weeks post-injury) and late (mean 8 months) time points. T1-weighted 3D MR images were analyzed with an automatic segmentation method to evaluate longitudinal, structural brain volume change. The cognitive outcome was assessed with the Cambridge Neuropsychological Test Automated Battery (CANTAB). Analyses included 16 frontal cortical structures, of which four showed a significant correlation between post-traumatic volume change and the CANTAB test results. The strongest correlation was found between the volume loss of the supplementary motor cortex and motor screening task results (R-sq 0.16, p < 0.0001), where poorer test results correlated with greater atrophy. Of the measured sum structures, greater cortical gray matter atrophy rate showed a significant correlation with the poorer CANTAB test results. TBI caused volume loss of frontal cortical structures that are heavily innervated by cholinergic neurons is associated with neuropsychological test results measuring attention.

Background: Patients with traumatic brain injury (TBI) exhibit a variable and unpredictable outcome. The proteins interleukin 10 (IL-10) and heart fatty acid-binding protein (H-FABP) have shown predictive values for the presence of intracranial lesions.Aim: To evaluate the individual and combined outcome prediction ability of IL-10 and H-FABP, and to compare them to the more studied proteins S100β, glial fibrillary acidic protein (GFAP), and neurofilament light (NF-L), both with and without clinical predictors.Methods: Blood samples from patients with acute TBI (all severities) were collected 6 months post injury using the Glasgow Outcome Scale Extended (GOSE) score, dichotomizing patients into: (i) those with favorable (GOSE≥5)/unfavorable outcome (GOSE ≤ 4) and complete (GOSE = 8)/incomplete (GOSE ≤ 7) recovery, and (ii) patients with mild TBI (mTBI) and patients with TBIs of all severities.Results: When sensitivity was set at 95–100%, the proteins' individual specificities remained low. H-FABP showed the best specificity (%) and sensitivity (100%) in predicting complete recovery in patients with mTBI. IL-10 had the best specificity (50%) and sensitivity (96%) in identifying patients with favorable outcome in patients with TBIs of all severities. When individual proteins were combined with clinical parameters, a model including H-FABP, NF-L, and ISS yielded a specificity of 56% and a sensitivity of 96% in predicting complete recovery in patients with mTBI. In predicting favorable outcome, a model consisting IL-10, age, and TBI severity reached a specificity of 80% and a sensitivity of 96% in patients with TBIs of all severities.Conclusion: Combining novel TBI biomarkers H-FABP and IL-10 with GFAP, NF-L and S100β and clinical parameters improves outcome prediction models in TBI.

Background: The purpose of this study was to investigate if admission levels of total tau (T-tau) and β-amyloid isoforms 1-40 (Aβ40) and 1-42 (Aβ42) could predict clinical outcome in patients with mild traumatic brain injury (mTBI).Methods: A total of 105 patients with mTBI [Glasgow Coma Scale (GCS) ≥ 13] recruited in Turku University Hospital, Turku, Finland were included in this study. Blood samples were drawn within 24 h of admission for analysis of plasma T-tau, Aβ40, and Aβ42. Patients were divided into computed tomography (CT)-positive and CT-negative groups. The outcome was assessed 6–12 months after the injury using the Extended Glasgow Outcome Scale (GOSE). Outcomes were defined as complete (GOSE 8) or incomplete (GOSE < 8) recovery. The Rivermead Post Concussion Symptoms Questionnaire (RPCSQ) was also used to assess mTBI-related symptoms. Predictive values of the biomarkers were analyzed independently, in panels and together with clinical parameters.Results: The admission levels of plasma T-tau, Aβ40, and Aβ42 were not significantly different between patients with complete and incomplete recovery. The levels of T-tau, Aβ40, and Aβ42 could poorly predict complete recovery, with areas under the receiver operating characteristic curve 0.56, 0.52, and 0.54, respectively. For the whole cohort, there was a significant negative correlation between the levels of T-tau and ordinal GOSE score (Spearman ρ = −0.231, p = 0.018). In a multivariate logistic regression model including age, GCS, duration of posttraumatic amnesia, Injury Severity Score (ISS), time from injury to sampling, and CT findings, none of the biomarkers could predict complete recovery independently or together with the other two biomarkers. Plasma levels of T-tau, Aβ40, and Aβ42 did not significantly differ between the outcome groups either within the CT-positive or CT-negative subgroups. Levels of Aβ40 and Aβ42 did not significantly correlate with outcome, but in the CT-positive subgroup, the levels of T-tau significantly correlated with ordinal GOSE score (Spearman ρ = −0.288, p = 0.035). The levels of T-tau, Aβ40, and Aβ42 were not correlated with the RPCSQ scores.Conclusions: The early levels of T-tau are correlated with the outcome in patients with mTBI, but none of the biomarkers either alone or in any combinations could predict complete recovery in patients with mTBI.

Perinteinen opettajuuden malli on pitkälti perustunut opettajien autonomian kunnioitukseen ja samalla luonut kouluihin yksintekemisen kulttuuria. 2000-luvulla opettajan tehtäväkuvat ovat olleet murroksessa ja ammattiin kohdistuvat odotukset ristiriitaisia. Siirtyminen oppimisen kolmiportaiseen tukeen vuonna 2010 velvoitti kaikki opettajat tarjoamaan tukea sitä tarvitseville oppilaille. Myös vuonna 2016 käyttöön otetussa opetussuunnitelmassa perusopetusta on sitouduttu kehittämään inkluusioperiaatteen mukaisesti. Inkluusio voidaan nähdä jatkumona, jonka toisessa päässä on sujuva inkluusio ja toisessa päässä totaalinen ekskluusio. Toimivan inkluusion saavuttaminen heterogeenisissä ryhmissä voi olla haasteellista. Yksi keino vastata oppilaiden tuen tarpeisiin sekä kehittää opetusta inklusiivisempaan suuntaan on yhteisopettajuus. Yhteisopettajuudella tarkoitetaan useamman opettajan yhdessä suunnittelemaa, toteuttamaa ja arvioimaa opetusta. Yhteisopettajuudesta on paljon hyötyä, mutta sen toteuttamisessa on usein myös haasteita. Tässä tutkimuksessa keskitytään tutkimaan opettajien onnistuneita yhteisopetuskokemuksia ala- ja yläkoulussa. Onnistuneista yhteisopetuskokemuksista on sisällönanalyysin keinoin tiivistetty kolme ydinkertomusta, jotka kuvaavat erilaisia tapoja toteuttaa yhteisopettajuutta. Nämä yhteisopetuksen toteutustavat sijoittuvat eri kohtiin inkluusion jatkumolla. Yhteisopettajuus näyttäytyy kehittyvänä, mutta selkeästi inkluusiota tukevana opetuksen tapana.

Phytochrome proteins control the growth, reproduction, and photosynthesis of plants, fungi, and bacteria. Light is detected by a bilin cofactor, but it remains elusive how this leads to activation of the protein through structural changes. We present serial femtosecond X-ray crystallographic data of the chromophore-binding domains of a bacterial phytochrome at delay times of 1 ps and 10 ps after photoexcitation. The data reveal a twist of the D-ring, which leads to partial detachment of the chromophore from the protein. Unexpectedly, the conserved so-called pyrrole water is photodissociated from the chromophore, concomitant with movement of the A-ring and a key signaling aspartate. The changes are wired together by ultrafast backbone and water movements around the chromophore, channeling them into signal transduction towards the output domains. We suggest that the observed collective changes are important for the phytochrome photoresponse, explaining the earliest steps of how plants, fungi and bacteria sense red light.

Finite element analysis of transformers with stranded conductors can be computationally heavy due to the fine mesh required for winding domains. In this paper, a domain decomposition method with subdomain pre-processing is proposed to overcome with this problem. In order to solve the field-circuit problem with finite element analysis, the winding domain is modelled initially. Next, the reduced matrix system is obtained from the winding domain formulation. The solution of the entire problem is obtained by solving the winding domain formulation and the reduced matrix system separately. The method is tested on a transformer model in no load operation. Accurate solutions are obtained in both frequency and time domains 7-9 times faster than when using brute-force method.

A harmful impact of climate change and global warming has concerned various sectors of the international community. Numerous energy policies aiming at climate change mitigation have been implemented on a national and global scale. Renewable energy technologies (RETs) play a critical role in enhancing sustainable solutions that significantly limit greenhouse gas (GHG) emissions. Such innovative technologies can facilitate energy transition through providing, e.g., energy security, sustainable development, and effective usage of indigenous resources. However, the commercialization of RETs is extremely challenging. The barriers can be of a different nature, although this study focused on socioeconomic and regulatory issues. There is ample evidence that energy policies play a central role in supporting adoption of renewables. It is also claimed that RETs require the whole ecosystem to support their successful diffusion. In this study, we explored multifarious barriers for widespread RET diffusion in two European Union countries, Finland and Poland, indicating the most common barriers existing in the literature as well as analyzing major bottlenecks from the viewpoint of renewable energy companies’ executives. We also present statistics of the most commonly used RETs in these countries in order to express the diffusion issues more appropriately. The research shows that inflexible, ineffective, and excessive regulatory frameworks; limited financing options; as well as an insufficient level of societal awareness have been seen as the main bottlenecks for RET diffusion in both countries. The outcomes of this study provide useful insights for the researchers in the energy transition field as well as practical managerial and regulatory implications aimed at overcoming these challenges.

Phytochromes are red-light photoreceptors that were first characterized in plants, with homologs in photosynthetic and non-photosynthetic bacteria known as bacteriophytochromes (BphPs). Upon absorption of light, BphPs interconvert between two states denoted Pr and Pfr with distinct absorption spectra in the red and far-red. They have recently been engineered as enzymatic photoswitches for fluorescent-marker applications in non-invasive tissue imaging of mammals. This article presents cryo- and room-temperature crystal structures of the unusual phytochrome from the non-photosynthetic myxobacterium Stigmatella aurantiaca (SaBphP1) and reveals its role in the fruiting-body formation of this photomorphogenic bacterium. SaBphP1 lacks a conserved histidine (His) in the chromophore-binding domain that stabilizes the Pr state in the classical BphPs. Instead it contains a threonine (Thr), a feature that is restricted to several myxobacterial phytochromes and is not evolutionarily understood. SaBphP1 structures of the chromophore binding domain (CBD) and the complete photosensory core module (PCM) in wild-type and Thr-to-His mutant forms reveal details of the molecular mechanism of the Pr/Pfr transition associated with the physiological response of this myxobacterium to red light. Specifically, key structural differences in the CBD and PCM between the wild-type and the Thr-to-His mutant involve essential chromophore contacts with proximal amino acids, and point to how the photosignal is transduced through the rest of the protein, impacting the essential enzymatic activity in the photomorphogenic response of this myxobacterium.

As morphometric investigation is connected to prioritization of watershed, morphometric analysis has got a significance role in light of soil and water conservation. In this study, an endeavour for the examination of point by point morphometric analyses of sub-basins was accomplished through the measurement of linear and shape parameters by using ArcGIS-9.3 software. Specifically, linear and shape morphometric parameters like stream length, stream order, drainage density, stream frequency, bifurcation ratio, Length of overland flow, basin perimeter, form factor, compactness coefficient, elongation ratio has been considered. The SRTM DEM (30 x 30 m) is processed for the delineation resulting in 61 sub-basins. The morphometric parameters which affect the soil erodibility are considered to organize the sub-basins and relegate positions on the premise of their association with erodibility to get compound parameter (Cp) esteem. Based on the value of Cp the sub-basin with the lowest Cp value was given the highest priority and then categorized the sub-basins into three classes as high, medium and low in terms of priority. Accordingly, high priority zone comprises 11 sub-basins, medium 19 and low 31 sub-basins. The sub-basins which are falling under high priority were a great deal more defenceless to soil disintegration and ought to be given high need for land preservation measures.

Focusing on a rural municipality in northern Finland, the aim of this study is to investigate educators’ thoughts and experiences with co-teaching. The data from 40 teachers were collected via an electronic questionnaire, and a mixed-methods approach was used. In the quantitative responses, the teachers positioned themselves as spokespeople for co-teaching, even though they had little experience with this teaching method. The written responses were condensed into four main themes: requirements, interpretations, inclusion and joy. Various requirements, such as more time for planning, better facilities to teach in and more training, were required before co-teaching could be executed. However, those who had co-taught expressed joy and improved wellbeing at work compared with their time teaching alone. Finally, the various themes of teachers’ experiences in relation to co-teaching are discussed.

Increasing resistance of Plasmodium falciparum strains to piperaquine (PPQ) in Southeast Asia is of concern and resistance mechanisms are incompletely understood. Here, Ross et al. show that mutations in the P. falciparum chloroquine resistance transporter are rapidly increasing in prevalence in Cambodia and confer resistance to PPQ.

Abstract Background Hemodynamic instability is one of the leading causes of intensive care unit (ICU) admission. Early stabilization of hemodynamics is associated with improved outcome. The monitoring used to guide hemodynamic support may influence the time needed to achieve stable hemodynamics. Visualization of the heart using echocardiography offers the advantage of direct measurement of cardiac volumes and ventricular function. A miniaturized monoplane transesophageal echocardiography (TEE) probe was developed, allowing for almost continuous qualitative hemodynamic TEE assessment (hTEE) after brief bedside training. The primary objective of the study is to assess whether hemodynamic monitoring using the hTEE technology shortens time to resolution of shock in ICU patients in comparison to standard monitoring using a central venous catheter, pulmonary artery catheter, or conventional echocardiography. Methods Five hundred consecutive subjects with circulatory shock (low mean arterial blood pressure (MAP) and signs of organ hypoperfusion) at the time of ICU admission are included in the study. The subjects are randomly assigned to one of four groups using a 2 × 2 factorial design stratified by method of hemodynamic monitoring (hTEE vs standard hemodynamic monitoring) and frequency of hemodynamic assessments (minimum every 4 h vs standard of care). The primary study outcome is the time from study inclusion to resolution of circulatory shock, defined as MAP > 60 mmHg for ≥ 4 h after discontinuation of vasopressors and inotropes. The hTEE monitoring consists of the acquisition of three defined echocardiography views: Transgastric mid-esophageal short axis with measurement of fractional area change of left ventricle, mid-esophageal four-chamber view with measurement of the ratio of right to left ventricular area, and mid-esophageal ascending aortic short-axis view with measurement of the superior vena cava collapsibility index. In the control groups, monitoring modalities, including conventional TTE and TEE but not hTEE, are at the discretion of the treating physician. The interpretation of hemodynamic monitoring and the subsequent changes in patient management are recorded after each hemodynamic assessment. Differences in the primary and further secondary time-to-event outcomes will be assessed using a competing risk model accounting for the competing risk of death. Discussion The effect of using echocardiography as a monitoring modality on relevant patient outcomes has not been established so far. The study at hand may be one of the first trials to provide detailed data on effectiveness and safety of echocardiography to guide treatment in patients with circulatory shock. Trial registration ClinicalTrials.gov, ID: NCT02048566. Registered on January 29, 2014.

Among other purposes, companies and regulatory agencies from around the world often adopt International Standard Organization (ISO) standards to determine acceptable practices, equipment and criteria for preventing occupational injuries and illnesses. ISO standards are based on a consensus among individuals who participate in the process. This discussion paper examines the scientific process for the development of several ISO standards on biomechanical factors, comparing it with processes used by other professional organizations, including scientific committees working on the development of clinical guidelines. While the ISO process has value, it also has clear limitations when it comes to developing occupational health and safety standards that should be based on scientific principles.

Abstract Progressive rendering, for example Monte Carlo rendering of 360° content for virtual reality headsets, is a time-consuming task. If the 3D artist notices an error while previewing the rendering, they must return to editing mode, make the required changes, and restart rendering. We propose the use of eye-tracking-based optimization to significantly speed up previewing of the artist’s points of interest. The speed of the preview is further improved by sampling with a distribution that closely follows the experimentally measured visual acuity of the human eye, unlike the piecewise linear models used in previous work. In a comprehensive user study, the perceived convergence of our proposed method was 10 times faster than that of a conventional preview, and often appeared to be instantaneous. In addition, the participants rated the method to have only marginally more artifacts in areas where it had to start rendering from scratch, compared to conventional rendering methods that had already generated image content in those areas.

Janie Anne Zuber, Shannon Takala-Harrison Division of Malaria Research, Institute for Global Health, University of Maryland School of Medicine, Baltimore, MD, USA Abstract: Based on the emergence and spread throughout the Greater Mekong Subregion (GMS) of multiple artemisinin-resistant lineages, the prevalence of multidrug resistance leading to high rates of artemisinin-based combination treatment failure in parts of the GMS, and the declining malaria burden in the region, the World Health Organization has recommended complete elimination of falciparum malaria from the GMS. Mass drug administration (MDA) is being piloted as one elimination intervention to be employed as part of this effort. However, concerns remain as to whether MDA might exacerbate the already prevalent problem of multidrug resistance in the region. In this review, we briefly discuss challenges of MDA, the use of MDA in the context of multidrug-resistant malaria, and the potential of different drug combinations and drug-based elimination strategies for mitigating the emergence and spread of resistance. Keywords: malaria, drug resistance, mass drug administration

Linn Karlsson,1 Björn Gerdle,1 Esa-Pekka Takala,2 Gerhard Andersson,3,4 Britt Larsson1 1Pain and Rehabilitation Centre, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden; 2Work-related Diseases, Finnish Institute of Occupational Health, Helsinki, Finland; 3Department of Behavioural Sciences and Learning, Swedish Institute for Disability Research, Linköping University, Linköping, Sweden; 4Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institute, Stockholm, Sweden Purpose: The purpose of this study was to describe how patients with chronic pain experience physical activity and exercise (PA&E).Method: This qualitative interview study included 16 women and two men suffering from chronic pain and referred to a multimodal pain rehabilitation program. Semi-structured interviews were conducted and qualitative content analysis was used to analyze the interviews.Results: One main theme emerged: “To overcome obstacles and to seize opportunities to be physically active despite chronic pain.” This main theme was abstracted from five themes: “Valuing a life with physical activity,” “Physical activity and exercise – before and after pain,” “A struggle – difficulties and challenges,” “The enabling of physical activity,” and “In need of continuous and active support.” Conclusion: Although these participants valued PA&E, they seldom achieved desirable levels, and performance of PA&E was undermined by difficulties and failure. The discrepancy between the intention to perform physical activity and the physical activity accomplished could be related to motivation, self-efficacy, and action control. The participants desired high-quality interaction with healthcare providers. The findings can be applied to chronic pain rehabilitation that uses PA&E as treatment. Keywords: chronic pain, experiences, physical activity, rehabilitation, qualitative content analysis