Introduction: It is well-known in the field of endodontics that the presence of a smear layer in the root canals can harbor bacteria and limit the penetration of irrigating solutions and intracanal medications into the dentinal tubules which, in turn, causes the failure of endodontic treatment. Removing the entire smear layer throughout the root canal is essential for the success of endodontic treatment and these chemical agents that facilitate the removal of the smear layer are called chelating agents. Ethylenediaminetetraacetic acid (EDTA), being the most widely used chelating agent, brings about increased reduction in the microhardness of the root dentin, thereby making it friable.N-acetyl cysteine (NAC) is naturally occurring antioxidant that has various beneficial properties for the human being. Several studies have been done in determining the antimicrobial efficacy of NAC against various endodontic pathogens and concluded NAC to be advantageous. The chelating property of NAC has been utilized in heavy metal detoxification, where it binds to the metal ion and removes them from the human system. However, this chelating property has not been explored in the field of endodontics.Aim: This study was aimed to compare the ability of N-acetyl cysteine with the conventional chelating agent in the removal of the smear layer and in altering the microhardness of root dentin.Materials and Methodology: A total of 84 single-rooted human mandibular premolars with relatively similar dimension and morphology, freshly extracted with closed apices, were collected from adult patients. The crowns of all specimens were cut transversally at the cementoenamel junction (CEJ) with the double-faced diamond disc at low speed, with water coolant, to obtain a 12 mm root length. The root canals were randomly divided into three equal groups according to the final irrigation solutions: Group I: 17% EDTA, Group II: 20% NAC, and Group III: distilled water (control). They were then randomly divided into two parts: scanning electron microscope (SEM) analysis for the extent of smear layer removal and microhardness evaluation using the Vicker’s hardness test.Results: The smear layer removal ability of EDTA and NAC were more effective in the coronal and middle thirds of the root canal. However, both groups showed less smear layer removal in the apical region. Specimens treated with distilled water showed the least reduction in the smear layer throughout the length of the root canals. Regarding the evaluation of microhardness, both EDTA and NAC had a significant reduction in root dentin microhardness. However, the percentage of dentin microhardness reduction was significantly more in the EDTA group (p < 0.05) than N-acetyl cysteine in the coronal, middle, and apical third of the root canals.Conclusion: The chelating property of NAC is equally effective to that of EDTA in the smear layer from the root canal, and it induced a significantly lesser reduction in microhardness of root dentin than EDTA. Root canal morphology is complex by nature and dealing with such complexity is challenging as it hampers the ability to achieve thorough disinfection of the pulp cavity. Chemo-mechanical debridement of the pulp space with the aid of instruments and irrigating solutions determines the outcome of endodontic therapy. Root canal instrumentation produces a layer of organic and inorganic material called the smear layer that may also contain bacteria and their by-products . It is eChelators are stable complexes of metal ions with organic substances as a result of ring-shaped bonds . ChelatiEDTA is generally accepted as the most effective chelating agent in endodontic therapy. It is used to remove the smear layer and to prepare the dentinal walls for better adhesion of filling materials. The disodium salt of EDTA at a 17% concentration and neutral pH is widely preferred for root canal treatment. The recommended protocol for effective removal of both organic and inorganic components of the smear layer is sodium hypochlorite, followed by EDTA or citric acid. However, EDTA also has the potential for causing excessive dentinal erosion and can cause a moderate degree of irritation .N-acetyl cysteine (NAC) is a naturally occurring antioxidant, which is the acetylated form of the amino acid cysteine . In clinHence, the aim of this study was to compare the ability of NAC with a conventional chelating agent in the removal of the smear layer and in altering the microhardness of the root dentin.A total of 84 freshly extracted, single-rooted human mandibular premolars, with relatively similar dimension and morphology, were collected from adult patients. Each tooth was radiographed to confirm the presence of a single canal. Teeth with previous root caries, cracks, curved canals, endodontic treatment, internal resorption, or calcification were excluded. The selected teeth were cleaned and decontaminated by immersion in a 5.25% sodium hypochlorite solution for 30 minutes and stored in a sterile saline solution at room temperature [The root canals were randomly divided into three equal groups according to the final irrigation solutions. Access to the root canals were obtained using a round burr. The root canals of the teeth in all the three groups were irrigated with distilled water and shaping was done using Protaper Next® rotary files  till size X2. After instrumentation, final irrigation was done with one of the experimental solutions. A 30-gauge needle was used for irrigation and was inserted within 1 - 2 mm from the root apex. The experimental solutions used in each group were as follows: Group I: 17% EDTA, Group II: 20% NAC, Group III: distilled water (control).The specimens were randomly allocated for scanning electron microscope (SEM) analysis and microhardness evaluation.Preparation of NAC experimental solutionNAC solution , at a concentration of 200 mg/ml, was freshly prepared by dissolving 0.2 gm in 1 ml of sterile distilled water according to Quah et al. .Evaluation of smear layer removalA total of 48 roots were subjected for evaluation of the smear layer removal potential of the chelating agents. Each specimen was flushed with a volume of 5 ml of experimental irrigant solution for a period of one minute. After final irrigation, each root canal was flushed and copiously irrigated with 10 ml distilled water and dried with absorbent paper points . Two longitudinal grooves were prepared on the buccal and lingual surfaces of each root using a diamond disc and each root was then split longitudinally into two halves using a mallet and a stainless-steel chisel.The roots sections were coded and mounted on metallic stubs. Specimens were sputter-coated with gold to render the surface electrically conductive and observed with SEM . SEM photomicrographs of the specimens were taken at a 1000x magnification at the coronal third, middle third, and apical third of the root canals .The photomicrographs were saved and analyzed for the presence or absence of the smear layer by means of the scoring system proposed by Hulsmann et al. . The scoThe final result for each section of the canals was obtained by calculating the mean of the scores of each of the photographs. The data were tabulated for statistical analysis using the Statistical Package for Social Sciences (SPSS)  computer software. A descriptive analysis was computed as the frequency of each score for each tested group.Evaluation of microhardnessA total of 36 roots were subjected for evaluation of microhardness. For longitudinal sectioning of the root, longitudinal grooves were made on the buccal and lingual external root surface. These grooves were made using a double-faced diamond disc at low speed with care not to penetrate the root canals. Roots were then split into two halves which resulted in 72 specimens. Each prepared root half was horizontally embedded in an acrylic block, such that their dentin was exposed. Each root half was labeled on the acrylic block for indentation. The test surface was grounded with 400, 500, and 600 grit silicon carbide paper in a polishing machine  followed by hand polishing with a felt disc embedded with aluminum oxide paste.For testing the microhardness of the dentin surface, the specimens were randomly divided into the three experimental groups (n = 24) and specimens were treated with an experimental irrigation solution for five minutes.Microhardness was measured for each sample before and after application of different irrigating solutions. Microhardness testing was carried out using the Vickers microhardness tester  with a Vickers diamond indenter and a 40x objective lens to obtain a pre-treatment record for each individual half. Mean baseline Vickers hardness number (VHN) was calculated for each specimen at the cervical, middle, and apical third. The indentation was made on the dentin surface approximately 0.5 mm from the root canal space. Each measurement was carried out using a 200 gm load for 10 seconds, oriented perpendicularly to the root surface. The diagonal lengths of indentations were measured by a built-in scaled micrometer and measurements were converted into Vickers numbers.In order to prevent the dilution of the irrigants before the experiment, excess fluid was removed from the canal surface with sterile paper points. All experimental specimens were then flushed with 30 ml of sterile saline . SpecimeThe data were collected and tabulated for statistical analysis using the SPSS computer software. Inferential statistical analysis was done using one-way analysis of variance (ANOVA) to detect the difference between tested groups.Evaluation of smear layer removalThe smear layer removal ability of Groups I and II were more effective in the coronal and middle third of the root canal. However, both groups showed less smear layer removal in the apical region. Specimens treated with saline showed the least reduction in the smear layer in the coronal, middle, and apical thirds of the root canals. In Group I, the coronal third showed a Score 3 in all the specimens Figure , while fEvaluation of microhardnessAll irrigating solutions decreased the microhardness of the root canal dentin surface compared to the baseline measurements. Group I exhibited the highest reduction in root canal dentin microhardness, followed by Group II. Group III showed the least reduction in root dentin microhardness. The baseline measurements of microhardness of the root canal dentin surface showed no significant difference between the tested groups. The baseline microhardness value for each individual root sample was compared with its post-treatment. The hardness of radicular dentin varied at the cervical, middle, and apical levels, as shown in Table Statistical analysis using ANOVA showed that Groups I and II had a significant reduction in root dentin microhardness (p < 0.05) in the coronal, middle, and apical third of the root canal, as shown in Table During root canal instrumentation, there can be the formation of a smear layer, which can limit the penetration of the irrigating solution and inter-appointment medications into dentinal tubules . ChemicaThe most widely used chelating solution is EDTA, which acts by forming stable complexes with calcium present on the smear layer and removes it . EDTA haNAC is a thiol-containing antioxidant that possesses an antibacterial property against endodontic pathogens, such as Enterococcus faecalis , 16-17, Most irrigation materials come up short in removing the smear layer, particularly in the apical third of the canals . The entThe microhardness of dentin may vary considerably between teeth; thus, in the present study, the microhardness measurement was performed for each sample at baseline and after treatment with the irrigation solutions to establish a reasonable evaluation for the effect of the irrigant solutions on the dentin surface. Post-treatment indentations were performed on each sample at the same areas that were at symmetrical constant points of the baseline for both sides of the root canal to make an evaluation of the tested irrigant . The micA possible limitation of the current study was that the experiments were performed at room temperature and not body temperature. Additionally, the volume of the irrigant in a root canal clinically was small compared with the immersing root dentin in irrigating solutions. However, standardized circumstances for all study groups allowed for comparable results. The present study revealed that both irrigation solutions decreased dentin microhardness with the exception of the distilled water. This finding is in accordance with Sayin et al. , who conThe chelating action of the EDTA solution induces an adverse softening potential on the calcified components of the dentin, and subsequently, a reduction in the microhardness was expected. Studies have shown that EDTA facilitates chelation of the inorganic portion of dentin and, consequently, makes it much weaker than normal -27. In tThe results of the current study substantiated the chelating property of NAC to be equally effective to that of EDTA in passively removing the smear layer from the root canal and it induced a significantly lesser reduction in the microhardness of the root dentin than EDTA. Hence, with further studies, NAC can be explored to serve the triple purpose of an active irrigant, a potent intracanal medicament, and a chelating agent in root canal therapy.


The association between caregiver burden, quality of life and depression in patients with mental illness in a resource-limited setting is underresearched. Factors associated with caregiver burden may be amenable to intervention.To describe the level of caregiver burden and its association with quality of life and depression.The cross-sectional study was carried out in a psychiatric hospital in the Cape Flats, which is an urban area on the periphery of Cape Town. Data were collected from 104 caregivers of patients attending the outpatients service. Caregiver burden was measured using the Zarit Burden Interview questionnaire. The PHQ-9 questionnaire was to screen and measure severity of symptoms of depression. The WHOQOL-BREF was used to measure the subjective evaluation of the quality of life.Most caregivers were female (76.92%), and caregivers were mild to moderately stressed (mean ZBS score 33.38 ± 21.59) and experienced moderate depression (mean PHQ-9 score). These effects were significantly associated with quality of life in psychological and social domains.Caring for patients with mental illness can lead to immense physical and psychological distress, leading to poor quality of life. Strategies that may reduce the burden of care may include improving the patients’ quality of life and addressing psychosocial support, and clinicians should consider screening for symptoms of depression in caregivers.


Fetal growth restriction (FGR) is a complication of pregnancy associated with major neonatal morbidity and commonly diagnosed at birth based on birth weight below the 5th or the 10th centile. There is no consensus on the use of routine third-trimester ultrasound for the detection of FGR in a general population. This systematic review aims to estimate the performance of third-trimester ultrasound markers in the screening for babies who are small for gestational age in low-risk or general population.Quality Assessment of Diagnostic Accuracy Study 2 (QUADAS-2) tool will be used to assess the methodological quality and validity of individual studies. The hierarchal summary receiver operating characteristic and random effects hierarchal bivariate models (Bivariate) will be used to estimate the pooled sensitivity and specificity of each ultrasound marker and to compare the discriminative ability of the different ultrasound markers. Subgroup and sensitivity analyses will be performed to explore the heterogeneity between studies and to assess the effect of screening tests’ characteristics  on their discriminative ability.A systematic review of screening test accuracy will be conducted. The databases MEDLINE, Embase, Cochrane Library, and Web of Science will be searched from their inception until December 2017, as well as reference lists of included studies and previous related review articles. Studies screening for FGR in a low-risk or general population using third-trimester ultrasound markers and reporting low birth weight for gestational age  as a reference will be eligible. Two reviewers will independently screen references for inclusion, assess the risk of bias, and extract data. The This systematic review will determine the relevance of routine third-trimester ultrasound markers in the screening for FGR in low-risk or general population and their usefulness in standard pregnancy care. Additionally, this knowledge synthesis represents a step in the optimization of the discriminative ability of third-trimester ultrasound and predictive tools, allowing for targeted interventions aiming at the reduction of FGR complications and ultimately improving infants’ health.CRD42018085564.This protocol has been registered at PROSPERO: international prospective register of systematic reviews. The register number is The online version of this article (10.1186/s13643-018-0885-4) contains supplementary material, which is available to authorized users. It can arise from several maternal, fetal, and/or placental origins, including placental insufficiency or placental abnormality, a genetic abnormality, or an infection during pregnancy  will be excluded.Published clinical trials and cohort studies (prospective and retrospective) which estimated the predictive performance of any third-trimester ultrasound markers will be eligible. There will be no language or publication date restriction. If data from the same sample have been reported in different publications, only the report with the largest study group will be used in the quantitative analyses.MEDLINE (via PubMed), Embase, Cochrane Library, and Web of Science will be searched from their inception until December 2018 for the identification of eligible studies. Clinical registries  and the grey literature  will be searched for potentially eligible reports. References of selected articles and previous related review articles will also be screened to identify additional potentially eligible references. Co-authors who are experts in the field will be consulted to review the list of included articles and identify any studies unretrieved by our search of the literature.Our search strategies are presented in Table The EndNote X8 software  will be used to manage all the references retrieved from the electronic databases and to remove duplicates. The remaining references will be exported to Excel  to conduct the selection process. Two independent reviewers  will screen the titles and abstracts to assess the eligibility of studies, followed by a full-text evaluation of the remaining articles’ eligibility. If no consensus is reached between the two reviewers regarding the eligibility of a study, a third independent reviewer with expertise in perinatal epidemiology will be consulted (EB).Two reviewers  will independently extract data from the selected articles using a standardized data collection form and an Excel sheet. The data collection form will be piloted using three randomly selected articles and will be corrected to improve completeness, clarity, and usability, as needed. Any discordance between the two data collections will be resolved by consensus. A third independent reviewer (EB) will be consulted in case of persistent disagreement. Authors will be contacted if some data are missing and needed to conduct the analyses.Extracted data will include (1) study characteristics , (2) characteristics of participants , (3) characteristics of the screening tools , (4) characteristics of the reference , (5) performance data ]), and (6) other variables .Using the Quality Assessment of Diagnostic Accuracy Study 2 (QUADAS-2) tool , the risThe TP, FP, TN, and FN will be used to compute the sensitivity and specificity of each marker in all studies. The corresponding sensitivity and specificity will be presented in a coupled forest plot.hierarchal summary receiver operating characteristic (HSROC) [Bivariate) [Bivariate model will estimate the mean sensitivity and specificity for the specific thresholds with their 95% confidence region and 95% prediction region.As recommended by the Cochrane Collaboration , hierarc (HSROC) , 35 and variate)  will be HSROC meta-regression model including the different markers as a covariate to compare their screening test accuracy for SGA.Indirect comparison of each marker will be done using a Cochrane Review Manager  and the statistical software packages SAS  will be used to complete the analyses.Subgroup and sensitivity analyses will be conducted to explore the possible heterogeneity between studies. Subgroup analyses will be performed to observe the effect of the screening test characteristics  on the discriminative ability of third-trimester ultrasound markers. Also, sensitivity analyses by study design and restricted to studies at low risk of bias will be done.Grading of Recommendations, Assessment, Development and Evaluation (GRADE) domains .The quality and evidence of this review will be assessed using the There is no consensus on the recommendation of a third-trimester ultrasound for the assessment of fetal growth in a general population. This systematic review will synthesize the published evidence on the performance of third-trimester ultrasound markers in the screening for FGR in low-risk or general populations. The gathered knowledge will participate in the evaluation of the usefulness of a routine third-trimester ultrasound examination as part of standard antenatal visits schedule, and if any marker is deemed useful, the review will allow for the optimization of the third-trimester ultrasound screening process. Thus, this study will help to determine the tools allowing for the identification of pregnancies at higher risk of SGA which could benefit from closer monitoring and targeted interventions. Considering the frequency and potentially serious complications of FGR, this knowledge synthesis can significantly contribute to the improvement of the health of fetuses and infants.Additional file 1:PRISMA-P. (PDF 100 kb)


Large variation in measures of diagnostic activity has been described previously between English general practices, but related predictors remain understudied.To examine associations between general practice population and characteristics, with the use of urgent referrals for suspected cancer, and use of endoscopy.Cross-sectional observational study of English general practices. We examined practice-level use (/1000 patients/year) of urgent referrals for suspected cancer, gastroscopy, flexible sigmoidoscopy and colonoscopy. We used mixed-effects Poisson regression to examine associations with the sociodemographic profile of practice populations and other practice attributes, including the average age, sex and country of qualification of practice doctors.P < 0.001.The sociodemographic characteristics of registered patients explained much of the between-practice variance in use of urgent referrals (32%) and endoscopic investigations (18–25%), all being higher in practices with older and more socioeconomically deprived patients. Practice-level attributes explained a substantial amount of between-practice variance in urgent referral (19%) but little of the variance in endoscopy (3%-4%). Adjusted urgent referral rates were higher in training practices and those with younger GPs. Practices with mean doctor ages of 41 and 57 years  would have urgent referral rates of 24.1 and 19.1/1000 registered patients, Most between-practice variation in use of urgent referrals and endoscopies seems to reflect health need. Some practice characteristics, such as the mean age of GPs, are associated with appreciable variation in use of urgent referrals, though these associations do not seem strong enough to justify targeted interventions. Most studies of care quality examine variations in disease management, but the importance of studying variation in the diagnostic process is increasingly recognized . PrimaryCancer provides a useful disease model for examining the role of primary care in the diagnostic process ,3. In EnIn the present study, which forms part of a broader project that explores potential associations of a range of practice-based attributes with variation in measures of diagnostic activity, we examine whether the characteristics of GPs in a practice  and practice type  are associated with the use of urgent referrals for suspected cancer or the use of endoscopic investigations, independently of the characteristics of the practice population. Therefore, our objective was to examine whether and how such variables are associated with the use of urgent referrals for suspected cancer or endoscopies, in order to acquire insights about potential mechanisms responsible for variation in diagnostic care.n > 7000—see also Results and n/1000 registered patients/year) of urgent referrals for suspected cancer, gastroscopy, flexible sigmoidoscopy and colonosocopy. We examined whether and how the sociodemographic characteristics of registered patients and other practice-level attributes were associated with each of these four outcomes. The study year was 2013.In brief, we studied all English general practices with relevant data (sample size n/1000 registered patients/year)  data on the number of urgent referrals for suspected cancer and the number of gastrointestinal endoscopies  to model their practice rates (ts/year)  8,9). W,9. Wn/10ts/year) ,6.In order to examine the potential influence of the characteristics of practice population on the diagnostic activity measure of interest, we used data on the sociodemographic  profile of practice populations. In order to examine the potential influence of practice characteristics, we used data on eight practice-level attributes, comprising training status (yes/no); single-handed status (yes/no); rural/urban practice location (yes/no); mean GP age; the percentage of practice GPs who are male; the percentage of practice GPs who are UK-qualified; the number of registered patients and the number of patients per Full-Time-Equivalent GP, as a proxy measure of GP workload. For these variables, information was derived from the 2013 General and Personal Medical Services dataset, the 2012/2013 General Practice Patient Survey (GPPS), the practice index of multiple deprivation 2011  and the To appreciate the relative importance of the practice population compared with practice characteristics, we first compared the between-practice variance explained by each of the two families of relevant variables. To do this, for each of the four rate indicators, we used mixed-effects Poisson regression models, initially only including a random effect for general practice. These models capture the overall underlying variation between practices after removing the role of chance due to small numbers . SubsequWe used the final set of models  to obtain adjusted estimates of associations. Unadjusted associations were also derived from mixed-effects Poisson models including only a single exposure variable (and random effect for practice). Because continuous exposure variables have different distributions across practices, and to facilitate comparisons of their effect sizes, we standardized their practice values, such that the rate ratios derived from the regression models correspond to 1 SD change in the exposure variable see .a priori on associations with rate ratio values equal or greater to a 4% difference from parity  and with P < 0.01  scale, we used the regression models to predict how higher/lower centile attainment of practice characteristics translates to practice differences in use of urgent referrals for suspected cancer or endoscopies. We considered hypothetical scenarios that assumed all practices in England attained the 10th and the 90th centiles of the observed distribution of the studied exposure and subsequently predicted the nationwide rates of endoscopy of urgent referrals corresponding to those centiles. We additionally illustrate the corresponding changes that could be expected for a typical English general practice with an average practice population of 8000 cases if it attained values corresponding to these (10th centile/90th centile) scenarios.Additionally to the four main outcomes , we also considered three other diagnostic activity indicators: the proportion of urgent referrals for suspected cancer resulting in cancer diagnosis ; the proportion of all treated cancer patients in a practice which were diagnosed after an urgent referral for suspected cancer  and the proportion of cancer patients in a practice who were diagnosed through an emergency presentation to hospital services. For these three variables, our analytical approach was identical to that used for the rate variables, but, as they represent proportions, logistic models were used. Our interest in these indicators is supplementary  as it is not possible to change those indicators without changing the diagnostic processes that influence them.The analysis sample comprised 7064 to 7204 practices, depending on the outcome . There wBoth population and practice characteristics explained appreciable proportions of the between-practice variance in rates of urgent referrals for suspected cancer .Practices with averagely older and more deprived patients had higher rates of urgent referrals for suspected cancer [Relative Risk (RR) for a SD change in the proportion of patients aged ≥65 = 1.17; RR for deprivation quintile 5 versus 1 = 1.14; P < 0.001). Training practices had higher rates of urgent referrals , whereas single-handed practices had lower rates compared with non-single-handed practices . There was evidence (P < 0.001) for associations with the percentage of male GPs and the percentage of UK-qualified GPs, but effect sizes were smaller than our criterion of practical significance . There was no evidence of associations with practice rural/urban location, list size or the number of patients per full-time equivalent GP.Practices with older doctors had lower urgent referral rates , practice characteristics explained much smaller proportions .Practices with more deprived patients had higher rates of endoscopy use , without consistent patterns across the three types of gastrointestinal endoscopy.The observed differences translate to small absolute differences in referral rates but appreciable relative differences between practices . For exaPractice team characteristics associated with higher rates of urgent referral for suspected cancer were generally also associated with lower proportions of urgently referred patients, who were found to have cancer (lower ‘conversion rates’), and higher proportions of all cancer patients detected after urgent referral , without appreciable associations for any of the other (seven) practice characteristics studied, including the proportion of registered patients who belong to ethnic minorities.The practice’s deprivation quintile was strongly associated with the proportion of patients diagnosed through emergency presentation , though there was statistical evidence for weak associations for the latter two.Three recent US studies have examined the influence of doctors’ age, sex and country of qualification on patient outcomes, but the setting of care , methodology and outcome measures were markedly different; therefore, they are only tangentially relevant to our study . Higher The strengths of our study include the use of objectively defined outcomes and practice population and team characteristics in a large nationwide sample of practices. We had no access to patient-level data, so we could not adjust for the characteristics of patients that were investigated or referred at the individual level, although we used practice-level measures of age, gender and ethnic and deprivation groups. The studied associations may differ in the small number of practices that were not included in our analyses, though this does not undermine the validity of the findings regarding the great majority of English practices that were included. Ecological studies are often under-powered, but our study includes a large number of practices, increasing the power to detect associations if those are present . By the It is important to appreciate that, because both urgent referrals and endoscopies are relatively infrequent, the size of the associations we describe is small in terms of absolute differences but substantive in relative terms . It appears that decision-making by GPs about the use of urgent referrals and endoscopies is generally well-calibrated to the sociodemographic profile of their patients. This is evident given that although practices serving more deprived populations tend to refer patients urgently for suspected cancer at greater rate than practices serving relatively affluent patients, this is not associated with lower proportion of cancer diagnosis among referred patients  and 4. TAlthough distance to hospital may limit the use of hospital services in rural populations, we did not observe differences in the rate of urgent referrals for suspected cancer between rural and urban practices. Training practices had higher use of urgent referral rates for suspected cancer, which may reflect greater degree of compliance of referral guidelines for suspected cancer, or their more avid interpretation. Differences in urgent referral rates for suspected cancer between practices whose doctors vary by age may reflect that GPs of different seniority have different levels of professional experience or their era of medical training. The findings suggest that older doctors may be more comfortable in dealing with uncertainty in the diagnostic process , as theyThe optimal level of use of urgent referrals and endoscopies cannot be determined by our study, although it reveals likely mechanisms responsible for related variation. Nonetheless, the 2015 NICE guidelines for suspected cancer in primary care implicitly suggest that in England, greater use of urgent referrals than in the past would be desirable .We conclude that much of between-practice variation in use of urgent referrals and endoscopies reflects sociodemographic variation in patient populations. Interventions aimed at increasing the rates of referrals for suspected cancer in low referring practices seem justified given prior evidence indicating associations with clinical outcomes in cancer patients. However, only a few practice characteristics, such as the mean age of GPs, are associated with appreciable variation in use of urgent referrals. The number and strength of such associations seem inadequate to justify targeting of practice-level interventions.cmy118_suppl_Supplementary_data_tableClick here for additional data file.


Although the draft human genome was completed in 2001  did we cGenome Biology and BMC Biology, is a timely exploration and expansion both of our knowledge of microbiomes in different systems and of ways to study microbiomes more effectively. It builds on Genome Biology’s nearly decade-long tradition of publishing cutting-edge microbiome research and techniques, and on the journal’s 20-year tradition of publishing sweeping analyses of genomic features across broad swathes of the tree of life.This Special Issue, published jointly by Many of the articles in this Special Issue focus on new ways to acquire information from DNA sequences obtained using high-throughput sequencing approaches. For example, Fukuyama  introducBifidobacteria in the gut [Several articles in the Special Issue go beyond short-read sequencing. The combination of long-read sequencing and proximity ligation allows the identification of antimicrobial genes and the detection of the plasmids and chromosomes that they are associated with . This ap the gut , substanMany important questions about the human microbiome remain unaddressed, especially those relating to the dynamics of the microbiome. The field as a whole is moving from observational studies towards intervention studies, in which temporally resolved study designs offer considerably more power to detect and understand changes . BouslimMoving beyond a parochial view of our own species, Rhoades et al.  provide Complex microbial communities are by no means limited to those associated with hosts. This Special Issue also contains papers addressing important questions in the soil microbiome, including the distribution of arsenic resistance genes . These sTaken together, several themes emerge. First, even taking into account the advances in this Special Issue, there is still a critical need for the development of new tools. Second, studies that integrate many individual datasets are increasingly important for progress, and tools and resources that enable such meta-analyses will see increasing use , 17. Thi


This paper reviews the recent literature on numerical modelling of the dynamics of the Greenland ice sheet with the goal of providing an overview of advancements and to highlight important directions of future research. In particular, the review is focused on large-scale modelling of the ice sheet, including future projections, model parameterisations, paleo applications and coupling with models of other components of the Earth system.Data assimilation techniques have been used to improve the reliability of model simulations of the Greenland ice sheet dynamics, including more accurate initial states, more comprehensive use of remote sensing as well as paleo observations and inclusion of additional physical processes.Modellers now leverage the increasing number of high-resolution satellite and air-borne data products to initialise ice sheet models for centennial time-scale simulations, needed for policy relevant sea-level projections. Modelling long-term past and future ice sheet evolution, which requires simplified but adequate representations of the interactions with the other components of the Earth system, has seen a steady improvement. Important developments are underway to include ice sheets in climate models that may lead to routine simulation of the fully coupled Greenland ice sheet–climate system in the coming years. The Greenland ice sheet (GrIS) is the second largest ice body on Earth and is expected to be a major contributor to future sea-level rise . PotentiProjecting future changes and studying the past behaviour of the GrIS and its interactions with other components of the Earth system requires numerical ice sheet models built around a physical description of ice sheet flow Fig. . In its The rate of ice deformation is strongly dependent on ice thickness, surface slope and rheological properties of the ice and the underlying substrate, which change considerably with changing temperature, impurity concentration and water content of the ice. Thermodynamic coupling is needed to model the long-term  evolution as the ice sheet responds to climate changes and might only be neglected for short-term  simulations. Another long-term interaction mechanism of the ice sheet concerns isostatic bedrock adjustment under the varying load of the ice. The millennial to multi-millennial response time scales associated with bedrock changes and thermodynamics have led to the use of spin-up techniques that consist of running ice sheet models with boundary conditions of simulated or reconstructed past climate changes to capture the long-term memory of these processes , 6.However, the present-day configuration of the ice sheet simulated with such long-term reconstructions shows a rather large discrepancy when compared with available satellite and airborne observations , 8. StudGrIS numerical models vary largely in terms of the processes they include, the spatial resolution of their underlying grids and the forcings they apply  dependinAcknowledging considerable overlap between them, we discuss three different approaches to GrIS modelling in this paper: (1) The long-term modelling approach with thermodynamic coupling and isostatic bedrock adjustment, requiring spin-up techniques, (2) data assimilation techniques, typically applied to model initialisation for centennial time-scale projections, making extensive use of high-resolution observations of the present-day ice sheet with inversion techniques, (3) fully coupled ice sheet–climate modelling of different levels of complexity to physically represent feedbacks between the ice sheet, atmosphere and ocean. All three modelling approaches, for example, are represented in the GrIS model initialisation experiments (initMIP-Greenland)  performeDistinguishing between the different approaches is somewhat arbitrary but, in many cases, derives from the specific goals of individual research groups. In fact, closer collaboration across these boundaries could further advance the ice sheet modelling community and should be encouraged. None of the modelling approaches can be completely separated from the others. Aside from appreciating the strengths and limitations of the different approaches for specific model applications, the aim of this review paper is therefore also to stimulate possible directions of future research and cross-fertilisation between different groups. It is in this spirit that we have decided to discuss the different research priorities in one review paper.In this section, we review recent developments concerning specific aspects of large-scale GrIS modelling.Domain discretisation is central to any numerical problem. Models used for long-term simulations nowadays typically apply regular equidistant grids at a horizontal resolution of 5–20 km –17, but As ice is a viscous incompressible fluid, it is best modelled using full-Stokes equations. Due to the intensive computational resources needed to solve these equations and the thin aspect ratio of ice sheets, several approximations based on asymptotic developments of these equations have been derived . These cWhile a Stokes model without any approximation remains the best description of ice sheet flow and has been successfully applied for the GrIS on a century time scale , 32, it Ice sheet thermodynamics are an important element of long-term ice sheet modelling, since ice deformation is non-linearly dependent on ice temperature. In addition, large parts of the GrIS are at the pressure melting point, implying an active role for basal sliding as well. In order to compute both cold and temperate ice properties with a single energy-conserving framework, many models now included an enthalpy framework  and a rhTo aid understanding the evolution of the ice sheet interior, thermodynamic modelling has been used to explain the reconstructed temperature recovered from a Greenland deep ice core . The resAnisotropy is another potential source of discrepancies between observed and modelled ice properties, as rheological laws used in most ice sheet models rely on the isotropic Glen’s flow law . Deep icAn evaluation of the impact of observationally constrained thermal boundary conditions on the modelled thermomechanical state in western Greenland has shown that there is a strong influence of the surface thermal boundary .A study of the geothermal heat flux distribution beneath the GrIS  concludeThe thermal condition at the base of the ice sheet is known to have important consequences for basal meltwater production and hence for the basal friction and sliding velocity . This viAs the GrIS mass loss continues to accelerate , most dyIn addition, the interaction of marine-terminating glaciers with ocean water is recognised as an important forcing mechanism, as oceanic conditions impact both submarine melting and calving. However, modelling such interaction remains a challenging problem, mainly due to the large number of poorly mapped fjord geometries, properties of ocean circulation in the fjords and limited observations of melting along ice fronts. In the absence of detailed physically based methods to estimate interactions between outlet glaciers and the ocean explicitly, parameterisations of the bulk effect of the ice-ocean interaction in Greenland fjords have been developed , 63. TheAn important driver for recent development in the field of GrIS modelling is improving physically based projections of the ice sheet’s contribution to future sea-level change. Many ice sheet modelling studies build further on the legacy of the SeaRISE , 11 and Traditionally, long-term modelling approaches including thermodynamic coupling and isostatic bedrock adjustment were used to provide reconstructions of the present-day ice sheet. Using such a spin-up method, an attempt has been recently made to re-examine the SeaRISE experiments (that were difficult to interpret) with one specific model that is systematically perturbed . ResultsA relatively good match with the observed velocity structure , 73 and In principle, an almost perfect match with the observed geometry can be achieved with nudging techniques , 70, 71 A different approach to improve the match with the observed velocity and geometry consists of allowing for spatially explicit adjustment of model parameters , here stA second category of techniques relies entirely on observations of the ice sheet. Using observations of ice sheet geometry and assuming the ice rheology  is known, basal friction can be treated as the only unknown parameter. In that case, ice sheet initialisation becomes a time-independent data assimilation problem, with the goal of finding optimal model parameters that minimise the misfit with observations, usually surface velocities , 77–79. A new technique to improve basal topography between observations acquired along flight lines was designed, based on the continuity equation and taking advantage of the global coverage in surface velocities . In the The optimisation of the basal topography can also be directly integrated into the data assimilation procedure, either by applying the shallow shelf approximation  or a higInstead of only relying on a modelled ice temperature distribution to define the viscosity, one can complement inversion of the basal drag coefficient with an additional optimisation of the stiffness factor . This fatime-dependent observational data sets for data assimilation [As time series of surface elevation and velocity observations become available, a recent development in centennial scale ice sheet modelling concerns techniques that leverage milation , 82. Themilation , 84, whimilation , where SAnother opportunity to improve estimates of ice sheet configuration lies in the recent radar observation of ice isochrones  that havIn order to validate models and assess their reliability, attempts have been made to compare present-day GrIS simulations to remote sensing observations. Comparison with Gravity Recovery and Climate Experiment (GRACE) data  for the Coupling with the atmosphere in terms of prescribing SMB and temperature boundary conditions in an ice sheet model is common practice and is not further discussed here. Instead, we refer the reader to a review paper on SMB . HoweverWith ISMIP6 , fully cReconstructing the past evolution of the GrIS may have important implications for our understanding of its present and future behaviour, may provide analogues to the present-day climate and is a challenging scientific endeavour in itself. This is usually done with models representing not only the ice flow itself but also other components of the Earth system , often in parameterised or simplified form. While the spin-up of paleo-class ice sheet models to incorporate the long-term thermal memory typically covers the last or several glacial–interglacial cycles , 16, stuSensitivity experiments with different topographic reconstructions were performed to study the conditions during the first inception of the GrIS . The stuAn intercomparison of ice sheet models forced with simulated climate conditions of the mid-Pliocene warm period  indicateSimulations of the GrIS evolution during the LIG were performed with an ice sheet model asynchronously two-way coupled to a Regional Climate Model  to repreThe retreat history of the GrIS during the last deglaciation was reconstructed using an ice sheet model constrained with evidence of past margin positions and relative sea-level indicators , 112. ThGiven the long-term experiments needed in paleo simulations, ice sheet and climate models and their coupling, are typically treated with reduced resolution and/or reduced complexity for synchronously coupled experiments –109, 113We have discussed the literature of recent studies covering overlapping approaches to numerical modelling of the GrIS from paleo applications to future projections. The last few years have seen an important improvement in simulating the present-day dynamic state of the ice sheet, needed as an initial condition for projections of future ice sheet changes. Advances in data assimilation techniques that leverage the growing number of satellite and airborne observations of the ice sheets are at the core of these improvements and have led to modelled ice sheets that reproduce the observed velocity field much better. This is indicative of a growing link between the ice sheet modelling and observational communities, which will also pave the way towards better evaluation and validation mechanisms, which are needed to attach meaningful uncertainty estimates to the projections. However, the relatively short time coverage of satellite data is so far one of the biggest limitations to this effort and further progress is fundamentally dependent on a continuation of high-quality ice sheet observations over time, in order to allow for data assimilation techniques that take advantage of the temporal evolution. A limitation of the current generation of data-assimilated ice sheet models used for short-term projections is the missing representation of long-term processes of the bed response, thermodynamics and a prognostic evolution of the basal conditions. This is complemented by process-based models of long-term ice sheet evolution that typically include these physically based descriptions but often at lower spatial resolution and that exhibit considerable mismatch to the observed geometry and velocity at the present day. Recent development from this side of the modelling spectrum is therefore achieved by a continuous increase in model resolution and simulated detail and by an increasing size of model ensembles used for sensitivity studies and exploring various types of uncertainty.Two-way coupling between ice sheet models and AOGCMs has seen significant improvements and is on the way to parity in performance with standalone ice sheet models for the goal of performing future projections on multi-centennial time scales. Aside from the intricate complications that arise from coupling two models with dynamic feedbacks between them, one of the main challenges and limitations has long been to produce realistic enough SMB boundary conditions for the ice sheet. Recent development in dynamic downscaling methods has led to an important step forward in this regard.Paleo studies of GrIS evolution have focused on modelling past warm periods that may help to understand ice sheet behaviour in a warmer than present climate. However, large uncertainties in the climate forcing for the LIG and the mid-Pliocene warm period limit the ability to constrain past ice sheet behaviour and consequently inferences for the long-term future of the ice sheet.Large challenges remain concerning how to combine “the best of both worlds” from long-term spin-up and data assimilation techniques. The goal would be to produce modern ice sheet initial conditions that are close to observations and at the same time include long-term processes like bedrock adjustment and evolving thermodynamics that contain the  memory of past climate changes. This likely requires joint efforts from different corners of the ice sheet modelling community and integration of time series of observations. A big step in this direction would be to define physically based descriptions of basal processes that could replace the inversion for basal drag by deterministic modelling.An emerging development that is expected soon is two-way coupling of GrIS models with regional climate models for future projections. Several groups are currently working on what represents an important step forward to explicitly simulate interactions between evolving ice sheet and climate. Direct coupling between ice sheet models and AOGCMs is underway and should over the next few years become available for multi-centennial future projections, on time-scales where ice-climate feedbacks play an important role.The global ice sheet modelling community has grown significantly in the last several years, leading to new approaches and models with larger user bases. Tighter collaboration between groups across intra-community boundaries should be continued, exemplified by intercomparison exercises like ISMIP6 , MISOMIP


A symptomatic arcuate line hernia should be considered in patients with acute lower abdominal complaints. This rare internal herniation is caused by a sharp ending of the posterior aponeurotic sheath of the rectus muscle, rather than the more common gradual delineation, and can cause strangulation or incarceration of abdominal contents. Intra‐oWhich type of anatomical variation was found?2An arcuate line hernia was found Figure . ArcuateThe prevalence of arcuate line hernias is low. In a retrospective review of computed tomography in 315 unselected patients, arcuate line hernia was found in 2.2% of the patients.Treatment consists of reduction of the hernia with mesh placement over the defect. Laparoscopic approach is preferable because this allows inspection of hernia contents and concomitant hernias, and allows for intra‐ or preperitoneal mesh placement to cover the defect.Although rare, symptomatic arcuate line hernias should be considered in patients presenting with complaints of the lower abdomen.None declared.AB: contributed to writing and editing of the manuscript and literature search. MK: involved in writing and editing of the manuscript and editing images and figures. JK: contributed to proofreading of the manuscript and literature search. FA: involved in proofreading of the manuscript and literature search. FJV: contributed to proofreading of the manuscript and editing images and figures.


The increase in bacterial resistance to one or several antibiotics has become a global health problem. Recently, nanomaterials have become a tool against multidrug-resistant bacteria. The metal and metal oxide nanoparticles are one of the most studied nanomaterials against multidrug-resistant bacteria. Several in vitro studies report that metal nanoparticles have antimicrobial properties against a broad spectrum of bacterial species. However, until recently, the bacterial resistance mechanisms to the bactericidal action of the nanoparticles had not been investigated. Some of the recently reported resistance mechanisms include electrostatic repulsion, ion efflux pumps, expression of extracellular matrices, and the adaptation of biofilms and mutations. The objective of this review is to summarize the recent findings regarding the mechanisms used by bacteria to counteract the antimicrobial effects of nanoparticles. The increase in bacterial resistance to one or several antibiotics has become a global health problem . The antRecommendations have been suggested to avoid the constant appearance of resistance to antibiotics; these recommendations include: Improve sanitation and prevent the spread of infection, reduce unnecessary use of antimicrobials, improve global surveillance of drug resistance and antimicrobial consumption and promote rapid diagnostics techniques to reduce unnecessary use of antimicrobials. Likewise, new options for compounds with antimicrobial properties are continually being sought .Recently, nanomaterials have become a tool against multidrug-resistant bacteria. These nanomaterials can be used as nano-drugs that can act individually or in synergism with antimicrobial compounds against resistant bacteria. Nanomaterials are also used as drug delivery systems that provide greater therapeutic efficacy and enhanced physicochemical characteristics. The metal and metal oxide nanoparticles are one of the most studied nanomaterials against multidrug-resistant bacteria. These nanoparticles can be synthesized from metals and metal oxides as gold, silver, titanium, copper, zinc, and aluminum; as well as silver oxide, copper oxide, magnesium oxide, calcium oxide, and zinc oxide.Several in vitro studies report that metal nanoparticles have antimicrobial properties against a broad spectrum of bacterial species. This is due to the special characteristics of metal and metal oxide nanoparticles. These special characteristics include increased surface/volume ratio of the nanoparticles with a decrease in the particle size, nanoparticle stability, van der walls forces or hydrophobic interactions and, electrostatic attraction. These characteristics allow nanoparticles to exercise their antimicrobial activity through multiple mechanisms. These antimicrobial mechanisms include damage to the membrane and bacterial cell wall, damage to proteins and internal components of bacteria, release of ions, DNA damage and oxidative stress .The great diversity of antimicrobial mechanisms exerted by nanoparticles suggests that bacteria are unlikely to generate resistance to nanoparticles . HoweverThe objective of this review is to summarize the recent findings regarding the mechanisms used by bacteria to counteract the antimicrobial effects of nanoparticles.2O3 NPs) had a size of 28 nm. The bactericidal power of these three types of nanoparticles was evaluated against Gram-positive (Bacillus subtilis and Staphylococcus aureus) and Gram-negative (Pseudomonas aeruginosa and Escherichia coli) bacteria. Of the three types of nanoparticles, those with the smallest size (ZnO NPs—18 nm) had the highest bactericidal activity, while the nanoparticles with the largest size (Fe2O3 NPs–28 nm) showed the lowest bactericidal activity. Some studies suggest that the size of nanoparticles is one of the main factors of their antimicrobial power, although this may also depend on the type of synthesis, precursors and parameters used. For example, Raza et al. synthesized silver nanoparticles with different size and shape. They synthesized Ag NPs with spherical shape and diameters from 15 to 90 nm, while the triangular-shaped Ag NPs had approximate sizes at 150 nm. The evaluation of the antibacterial effect of both types of nanoparticles showed that the spherical and smaller nanoparticles had the greatest antibacterial power against Gram-negative bacteria . Bi. BiSilG nd SeMet . In morpal shape . All theal shape .E.coli cultures and aquatic microbiota to sublethal concentrations of ZnO NPs. This type of exposure facilitated the conjugative transfer of antibiotic resistance plasmids. The exposure to sublethal concentrations of ZnO NPs increased the permeability of the cell membranes and this, in turn, increased the horizontal gene transfer frequency [E. coli to high concentrations of titanium dioxide nanoparticles (TiO2 NPs), and observed that this caused a decrease in bacterial growth rate and an increase the conjugative transfer rate of antibiotic resistance genes [On the other hand, the widespread use of metal and metal oxide nanoparticles seems to stimulate the co-selection and co-expression of antibiotic resistance genes. This represents an important adverse side effect of the use of nanoparticles. Wang et al. exposed pure requency . In a prce genes .E), three different 2-component regulatory systems (like the pilus expression (Cpx) response, the regulation of capsular synthesis (Rcs) phosphorelay and the bacterial adaptive response (Bae)) and the phage shock protein response (PSP).The ESR also participates in the regulation of the mechanisms of defense against the electrical charge, ion release and the size presented by the different types of metal and metal oxide nanoparticles. The ESR in Gram-negative bacteria consists of an alternative sigma factor  is induced by conditions that can disrupt the cell envelope and control the production of macromolecular envelope structures and the envelope homeostasis. Finally, the bacterial adaptive response regulates the expression of different types of efflux pumps while the phage shock protein response maintains the proton motive force and prevents mislocalized secretin toxicity.The ESR in Gram-positive bacteria is formed by three systems. The first system regulates the response to specific noxious stimuli. The second system is activated by harmful agents present in the cell wall. These systems include extracytoplasmic function (ECF) σ factors and 2-component regulatory systems. The third system is not induced by cell wall damage but does play a role in controlling cell envelope integrity. These three systems regulate the cell envelope charge, cell wall metabolism, and expression of efflux pumps .The generation of reactive oxygen species (ROS) during the interaction of metal and metal oxide with bacteria is another mechanism of the bactericidal activity of these types of nanoparticles. The degree of ROS generation depends on the metal or metal oxide from which the nanoparticle is synthesized, and their ion release rates. The nanoparticles like ZnO NP, CuO NP, and Ag NP present a wide range of ion release and ROS production when interacting with bacteria ,58. Whil2 NPs cause the disruption of the cell membrane of bacteria [E. coli was exposed to Ag NPs under anaerobic conditions, the nanoparticles had no bactericidal effect [P. aeruginosa to Ag NPs under aerobic and anaerobic conditions. They observed a similar release of silver ions in the two evaluated conditions; this contradicts the reported by Xiu et al. However, the Ag NPs studied by Chen et al. also showed a lower bactericidal effect in anaerobic conditions. This is due to the fact that under anaerobic conditions there is a lower production of ROS and although the nanoparticles affect the bacterium the lack of the deleterious mechanisms induced by ROS diminishes its bactericidal activity [The ability of nanoparticles to induce ROS can be affected by their interactions with the environment in which they are used . These ibacteria . Xiu et l effect . Chen etactivity . This isactivity .Sublethal concentrations of ROS stimulates the expression of defense mechanisms in bacteria, a process which is called hormesis . HormesiThe second level is the long-term adaptation. The long-term adaptation is made up of two sub-levels: Transcriptional and genomic level. In the transcriptional level, ROS induces adaptation by upregulating the antioxidant mechanisms within hours to days . At the The genes that activate the mechanisms of resistance to oxidative stress are upregulated by two regulons: SoxR and oxyR. OxyR responds to the stress induced by hydrogen peroxide, while soxR responds to superoxide anion . For exa2 NPs [2 NPs) were trapped in the surface of Pseudomonas fluorescens and Mycobacterium smegmatis biofilms, while bacterial cells in the deepest part of the biofilms were not affected [In general, biofilms are a set of diverse bacteria within a matrix of extracellular polymers (ECP). The bacterial diversity presented in them results in the union of the various resistance mechanisms present in the different bacterial species to assemble a protective response against nanoparticles. Biofilms have already proven to be resistant to prolonged exposures to nanoparticles . The ver2 NPs ,75. Ther2 NPs . The ECP2 NPs . Peulen 2 NPs . While, affected . The degaffected . The divaffected .Pseudomonas aeruginosa PAO1 was exposed to a nonlethal concentration of polyvinylpyrrolidone-coated silver nanoparticles (PVP-AgNPs), the bacteria presented an increase in biofilm formation, lipopolysaccharide biosynthesis, increased extracellular polymeric substances and upregulation of antibiotic resistance genes (ARGs) [2 NP) caused an increase in the production of ECP and quorum sensing through oxidative stress [Exposure of biofilms to non-lethal concentrations of nanoparticles can also generate hormesis processes. For example, when s (ARGs) . In anote stress .Pseudomonas aeruginosa CCM 3955 and Escherichia coli 013 have resistance to Ag NPs through the production of flagellin [Pseudomonas aeruginosa produces pyocyanin, pyochelin, and pyoverdin to protect itself against nanoparticles [Enterobacter cloacae, Enterococcus sp., Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis and Staphylococcus aureus can express efflux complexes related to nanoparticle resistance [The bacterial diversity of the biofilms and the different mechanisms of resistance of each of the species to the nanoparticles can contribute to the resistance of the biofilm in general. For example, lagellin . Pseudomarticles . While, sistance .Competibacter spp.  due to the exposure to ZnO NPs. Accumulibacter spp. replaced the bacteria previously lost and its function within the biofilm [Biofilms also have functional redundancy; this is the ability to maintain their ecosystem despite the change in their microbial composition by harmful agents, as when a biofilm loses  biofilm . The exp biofilm .Enterococcus spp., Escherichia coli, coagulase-negative Staphylococci spp., Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans on their surface [E. coli and S. aureus biofilms. In addition, the glass surfaces covered with nanoparticles had a great potential for use in industrial and medical settings [It is estimate that biofilms cause 80% of infectious diseases, therefore, preventing the development of biofilm in clinical and industrial environments is a matter of great importance. One of the strategies in the combat of biofilms is to prevent their early stages of formation such as the adhesion of microorganisms to surfaces . Various surface . Gomez-C surface . Applerosettings . AlthougDespite the increasing knowledge on the antimicrobial activity of metal and metal oxide nanoparticles, much remains unknown about the impact of its use on the environment and global health. Scarce literature has been commissioned to study the mechanisms of adaptation of bacteria to the exposure of nanoparticles. It is important to understand these mechanisms to avoid the indiscriminate use of nanoparticles in different materials, as well as the appearance or increase of infections resistant to treatment. The authors of this paper called into action, the need for a better understanding of the mechanisms of adaptation and resistance to nanoparticles and how these can affect the environment and the health of people.The authors recommend that future studies should offer more information on the mechanisms and adverse effects of the appearance of bacterial resistance to nanoparticles.


Visual analogue scale (VAS), anxiety, and depression scale were administered. Participants underwent an MRI scan  on the same day. The results showed that BMS patients had higher depression and anxiety levels than controls. BMS patients showed lower gray matter volume (GMV) in the bilateral ventromedial prefrontal cortex (VMPFC) and increased functional connectivity between this region and the bilateral amygdala. Region of interest (ROI) analysis suggested that the functional connectivity between the bilateral VMPFC and amygdala correlated with the years of BMS illness in patients. The brain measures could predict the years of symptoms in the BMS group. These results suggest A potential neuromarker for the diagnosis and treatment of BMS.Featuring a burning sensation in the tongue or other oral sites in the absence of observable lesions or laboratory findings, burning mouth syndrome (BMS) is a chronic intraoral pain disorder, which is one of the most common medically unexplained oral symptoms/syndromes. Previous studies have suggested that brain changes are involved in BMS; however, the small number of participants in these studies limited the conclusions that could be drawn. The present study aimed to further elucidate the brain anatomical and functional changes in BMS with a relatively large sample. Fifty-three patients (26 BMS patients and 27 gender- and age-matched controls) were recruited. Demographic information was collected  Burning mouth syndrome (BMS) is a chronic intraoral pain disorder featuring a burning sensation in the tongue or other oral sites in the absence of observable lesions or laboratory findings . Patientper se , when there were severe symptoms and a larger change in brain activity . Trait at(51) = 0.50, p > 0.05]. The subjects were screened for neurological and psychiatric disorders by a qualified physician using the Mini-Mental State Examination (MMSE). They were also screened for any condition that could disqualify them from fMRI scanning. All research protocols were explained to the participants, and they signed the written consent form approved by the Medical Ethical Committee of the Xiangya Hospital of Central South University of Hunan Province, Changsha, China. Those patients who did not agree to participate in the study were excluded.The participants were 26 patients with BMS  and 27 gender- and age-matched control subjects . They were recruited from the outpatient department in Xiangya Hospital of Central South University in Changsha. The BMS patients met the inclusion criteria: an intraoral burning sensation or dysesthesia; recurring daily for more than 2 h per day over more than 3 months; without clinically evident causative lesions. The control group was recruited from a healthy population. These two groups did not differ in term of age .VBM results suggested that there were two clusters ,B showinTBSS did not reveal any significant difference between patients and controls with regard to FA and MD.r(26) = 0.71, p < 0.001; right: r(26) = 0.68, p < 0.001].Using the left and right VMPFC as the seed region, whole-brain connectivity analysis suggested that the bilateral amygdala had increased functional connectivity with the bilateral VMPFC region ,D in patFor the present study, we recruited 26 BMS patients and 27 healthy controls to investigate the possible deficits of brain structure and function in BMS patients. The results revealed that BMS patients had higher levels of depression and anxiety than controls. BMS patients showed lower GMV in the bilateral VMPFC and increased functional connectivity between this region and the bilateral amygdala. Region of interest (ROI) analysis suggested that the functional connectivity between the bilateral VMPFC and amygdala correlated with the years of BMS illness in patients. The brain measures could predict the years of symptoms in the BMS group.These results replicated those of previous studies on the mood problems in BMS patients . In our Additionally, our results suggested that BMS patients had lower GMV in the bilateral VMPFC region, and the GMV of this region was inversely correlated with the severity of BMS. These results partially replicated the results of Our results further indicated that the functional connectivity between the VMPFC and amygdala was increased in BMS patients, and this phenomenon was associated with the severity of BMS. This is consistent with previous studies  showing Three limitations of the current study should be noted. First, the study used a relatively large sample but without a balance of males and females. Although BMS is a female-dominated disease, future studies should include more male participants to generalize the findings to the whole population. Second, the cross-sectional methods used in this study limit our inference of the causality. Future studies with different data samples collected during the day or longitudinal studies would be very useful because of the dynamic changes in BMS symptoms. Meanwhile, further longitudinal studies should be conducted to replicate and expand on the findings of this study. Third, this study only investigated the stable brain signals ; future studies should use fMRI designs with different types of stimulation to investigate the dynamic patterns of brain activity.All datasets generated for this study are included in the manuscript and/or the supplementary files.All participants were aware of the purpose of the study and signed an informed consent before the study. All research protocols were explained to the participants, and they signed the written consent form approved by the Medical Ethical Committee of the Xiangya Hospital of Central South University of Hunan Province, Changsha, China. Informed consent was obtained from all individual participants included in the study.YT and LK conceived and designed the experiments. YT, XW, and JC conducted the experiments and collected the data. LK and ZQ analyzed the results. LK and ZQ wrote the main manuscript text. All authors reviewed 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.


Stroke is a leading cause of death and disability worldwide. Identifying the aetiology of ischaemic stroke is essential in order to initiate appropriate and timely secondary prevention measures to reduce the risk of recurrence. For the majority of ischaemic strokes, the aetiology can be readily identified, but in at least 30% of cases, the exact aetiology cannot be determined using existing investigative protocols. Such strokes are classed as ‘cryptogenic’ or as a stroke of unknown origin. However, there exists substantial variation in clinical practice when investigating cases of seemingly cryptogenic stroke, often reflecting local service availability and the preferences of treating clinicians. This variation in practice is compounded by the lack of international consensus as to the optimum level and timing of investigations required following a stroke. To address this gap, we aim to systematically review and compare recommendations in evidence-based clinical practice guidelines (CPGs) that relate to the assessment and investigation of the aetiology of ischaemic stroke, and any subsequent diagnosis of cryptogenic stroke.We will search for CPGs using electronic databases , EMBASE, and CINAHL), relevant websites and search engines  and hand-searching of bibliographies and reference lists. Two reviewers will independently screen titles, abstracts and CPGs using a pre-defined relevance criteria form. From each included CPG, we will extract definitions and terms for cryptogenic stroke; recommendations related to assessment and investigation of the aetiology of stroke, including the grade of recommendations and underpinning evidence. The quality of the included CPGs will be assessed using the AGREE II  tool. Recommendations across the CPGs will be summarised descriptively highlighting areas of convergence and divergence between CPGs.To our knowledge, this will be the first review to systematically compare recommendations of international CPGs on investigating the aetiology of ischaemic stroke. The findings will allow for a better understanding of international perspectives on the optimum level of investigations required following a stroke and thus contribute to achieving greater international consensus on best practice in this important and complex area.CRD42019127822.PROSPERO  Globally, stroke is the second most common cause of death  and the Although most ischaemic strokes are caused by atherosclerosis or arteriosclerosis of the blood vessels within the brain, or embolism originating from the heart or the major extracranial blood vessels, in at least 30% of cases, the exact aetiology of an ischaemic stroke is not identifiable by existing investigative protocols ; this isDiagnostic workup in cases of seemingly cryptogenic stroke is highly complex, and from existing guidelines, it is difficult to discern specific recommendations for diagnostic pathways. Additionally, up to now, only one diagnostic algorithm has been proposed to classify cryptogenic stroke . This alAs such, while some guidelines and published diagnostic algorithms have been proposed to facilitate the identification of the aetiology of ischaemic stroke, there does not yet exist international consensus on the optimum level and timing of investigations required following a stroke. Therefore, we aim to review international clinical practice guidelines (CPGs) to compare recommendations and pathways for the diagnostic workup necessary before arriving at the diagnosis of cryptogenic stroke, to understand where there are agreement, disagreement and conflicting recommendations. The review findings will inform prioritisation of future research in this emerging field of inquiry.The aim is to compare and appraise recommendations in evidence-based international clinical practice guidelines (CPGs) that relate to the assessment and investigation of the aetiology of ischaemic stroke and any subsequent diagnosis of cryptogenic stroke.The review has been designed based on input from experts in stroke and systematic review methodology and in accordance with the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) guidance. A PRISMA-P reporting checklist is provided in Additional file Have been endorsed by a national and/or international organisation Include recommendations related to the assessment and investigation of the aetiology of ischaemic stroke and any subsequent diagnosis of cryptogenic strokeWere published from January 2009 onwards (to ensure only the most up-to-date guidelines were included)Are available in EnglishWe will include CPGs thatCPGs focused exclusively on treatment and rehabilitation of stroke will be excluded.https://www.aan.com/), the Cochrane Library, Guidelines International Network (www.g-i-n.net); National Institute for Health and Care Excellence (https://www.nice.org.uk/), Scottish Intercollegiate Guidelines Network (https://www.sign.ac.uk/) and along with grey literature repositories (e.g. Open Grey (http://www.opengrey.eu/)). We will use keywords in the search utilities of each website to identify potentially relevant guidelines and conduct targeted searches by country. We will screen all relevant results retrieved through these searches. A final list of all relevant CPGs identified through this search strategy will be shared with the expert steering group to identify any additional CPGs that could contribute to the review aims and/or confirm that no relevant CPGs, of which the steering group members are already aware, have been omitted.Relevant CPGs will be retrieved using a combination of search strategies: (1) searching electronic databases, 2) searching relevant websites, (3) targeted searches by country and (4) hand-searching reference lists of included guidelines. Medical Subject Headings and text words such as ‘clinical practice guidelines’ and ‘stroke’ will be used to search electronic databases MEDLINE, Health Management Information Consortium (HMIC), EMBASE, and CINAHL. A draft search strategy for MEDLINE is provided in Additional file  searchinOne reviewer (NMcM) will collate all retrieved citations into reference management software for screening. Two reviewers (NMcM/MB) will independently screen all retrieved citations using a pre-defined relevance criteria form. For potentially relevant CPGs, the full texts will be obtained and independently assessed by two reviewers (from NMcM/MB/EB/RG/JG), including at least one with extensive experience of working in a clinical role in stroke care. Disagreements at any stage will be resolved through discussion with a third reviewer.A bespoke data extraction form will be developed, piloted and modified as necessary. One reviewer will extract all relevant information using this form. A second reviewer will perform a full check of the data extraction for all included guidelines to verify the accuracy of data extraction. Any disagreements will be resolved through discussion with a third reviewer. We will extract the following information from each CPG: year of dissemination; country/region; organisation; development team; funding; definition or terms used to describe cryptogenic stroke; recommendations related to assessment, investigation and diagnosis of stroke aetiology (including the recommended timing and order of investigations); recommendations related to the diagnosis of cryptogenic stroke; research evidence cited; and qualifying terms (such as level of evidence or grade of recommendation) used to summarise the strength of recommendations and their underpinning evidence.We will appraise the quality of the included CPGs using the Appraisal of Guidelines Research and Evaluation (AGREE) II  tool whiRecommendations related to assessment, investigation and diagnosis of stroke aetiology and diagnosis of cryptogenic stroke will be summarised descriptively. We will evaluate whether guidelines made specific recommendations and, in the cases where this is done, we will describe the grade of the recommendation, the level of evidence supporting the recommendation, and where the level of details allows, the nature and quality of studies supporting/refuting the recommendation. We will organise the identified recommendations into categories using a recently published identification and diagnostic evaluation algorithm  and prodThis review forms part of a wider programme of work exploring the optimisation of assessment and investigation of the aetiology of ischaemic stroke and the diagnosis of cryptogenic stroke. To our knowledge, this will be the first systematic review to compare the content of recommendations in relevant international CPGs. The review findings will allow for a better understanding of similarities and differences in international recommendations for identifying the aetiology of a stroke, the optimum level of investigations required following a stroke and the quality of evidence underpinning practice recommendations. Additionally, the review findings will have practical implications for the detection and management of patients with cryptogenic stroke. This review will follow a robust systematic method to identify all relevant publications. It will however only include English language publications which are a limitation.Additional file 1. PRISMA-P-checklistAdditional file 2. MEDLINE search strategyAdditional file 3. Confirmation of funding


The design of phase-change material (PCM)-based thermal energy storage (TES) systems is challenging since a lot of PCMs have low thermal conductivities and a considerable volume change during phase-change. The low thermal conductivity restricts energy transport due to the increasing thermal resistance of the progressing phase boundary and hence large heat transfer areas or temperature differences are required to achieve sufficient storage power. An additional volume has to be considered in the storage system to compensate for volume change. Macro-encapsulation of the PCM is one method to overcome these drawbacks. When designed as stiff containers with an air cushion, the macro-capsules compensate for volume change of the PCM which facilitates the design of PCM storage systems. The capsule walls provide a large surface for heat transfer and the thermal resistance is reduced due to the limited thickness of the capsules. Although the principles and advantages of macro-encapsulation have been well known for many years, no detailed analysis of the whole encapsulation process has been published yet. Therefore, this research proposes a detailed development strategy for the whole encapsulation process. Various possibilities for corrosion protection, fill and seal strategies and capsule geometries are studied. The proposed workflow is applied for the encapsulation of the salt hydrate magnesiumchloride hexahydrate (MCHH, MgCl Phase-change materials (PCMs) possess the ability to store large amounts of thermal energy when applied around their phase-change temperature. This enables the design of compact thermal energy storage systems (TES). As drawbacks, non-metallic PCMs have comparatively low thermal conductivities and a considerable volume expansion due to the phase-change . Furtherrcooling . Metals There are several studies concerning the encapsulation of inorganic PCM within metal capsules. Cylindrical steel capsules, filled with sodium nitrate   and 0.155W/(mK) ,36, respThere is only limited information about the application of corrosion inhibitors in PCMs in general and no literature for MCHH in particular. Lane  has explThe chosen PCM determines the fill and seal  process There are few studies about sealing methods for inorganics within metal capsules. Zheng et al.  have sealeischer  has propleischer  have appleischer .The desired capsule geometry  is restrThe arrangement  determinThe encapsulation concept presented in the previous chapter  is now aus paper  and someCompatibility investigations between the MCHH and different metal capsule materials have revealed that none of the metals is resistant at its pure form . TherefoDue to the aforementioned drawbacks, the following mechanical methods were applied to seal the capsules. A gasket made of FKM (fluoroelastomer) was applied as sealing element between the PCM and the ambient as this material is compatible with the selected materials and is stable up to the desired temperatures of 150 ∘C . Screws Seamless aluminium pipes were selected as base materials for the capsules, since they show good accessibility for the chosen corrosion protection and applicability of the sealing concept. A detailed view of the final encapsulation concept is depicted in The proposed cylindrical macro-capsules can be arranged in a storage system in various ways resulting in different storage powers and capacities. The highest storage capacities of cylinders of equal diameters can be achieved with uniform packings by applying a triangular alignment with a packing density of up to 90%. This type of capsule packing would result in a latent heat storage capacity of 135 From an economic point of view, the proposed encapsulation concept is very expensive. As depicted in Cost effective alternatives for the capsule shell can be products which are available as mass products on the market. Food cans are very cheap, but, in the available configuration, are not compatible with the PCM MCHH at elevated temperatures. Experiments with food cans revealed a decomposition of the lacquer layer and later corrosion and leakage of the shell. Typical cost of about .425d3m  and a deA development strategy for macro-encapsulation of PCM was presented. The procedure was discussed in detail with the focus on encapsulation of inorganic PCMs within metal capsules. The interactions between different process steps were discussed and examples were given. The analysis reveals that the final geometry of a macro-capsule is not necessarily a parameter of choice but a result of various upstream process steps.The proposed workflow was exemplarily applied to the encapsulation of the inorganic salt hydrate magnesiumchloride hexahydrate within metal capsules. The resulting macro-capsules consist of anodized aluminium pipes which are hermetically sealed with mechanical methods. From an economic point of view, the developed macro-capsules are still very expensive, which is mainly caused by the individual fabrication. Low cost encapsulation concepts applying food or aluminium cans manufactured in mass production are proposed as a cost-efficient alternative for future work.


Despite significant improvements in cardiopulmonary resuscitation, sudden cardiac arrest is one of the leading causes of mortality in the United States. Ultrasound is a widely available tool that can be used to evaluate the presence of cardiac wall motion during cardiac arrest. Several clinical studies have evaluated the use of ultrasound to visualize cardiac motion as a predictor of mortality in cardiac arrest patients. However, there are limited data summarizing the prognostic value of point of care ultrasound evaluation during resuscitation. We performed a systematic literature review of the existing evidence examining the clinical utility of point-of-care ultrasound evaluation of cardiac wall motion as a predictor of cardiac resuscitation outcomes.p <  0.001).We performed a systematic PubMed search of clinical studies up to July 23, 2019 evaluating point-of-care sonographic cardiac motion as a predictor of mortality following cardiac resuscitation. We included studies written in English that reviewed short-term outcomes and included adult populations. Fifteen clinical studies met inclusion criteria for assessing cardiac wall motion with point-of-care ultrasound and outcomes following cardiac resuscitation. Fourteen of the fifteen studies showed a statistically significant correlation between the presence of cardiac motion on ultrasound and short-term survival. This was most evident in patients with ventricular fibrillation or ventricular tachycardia as a presenting rhythm. Absence of cardiac motion non-survival. The data were pooled and the overall pooled odds ratio for return of spontaneous circulation in the presence of cardiac motion during CPR was 12.4 +/1 2.7 (Evaluation of cardiac motion on transthoracic echocardiogram is a valuable tool in the prediction of short-term cardiac resuscitation outcomes. Given the safety and availability of ultrasound in the emergency department, it is reasonable to apply point-of-care ultrasound to cardiopulmonary resuscitation as long as its use does not interrupt resuscitation. Sudden cardiac arrest is one of the leading causes of mortality and morbidity in the United States despite significant cardiopulmonary resuscitation (CPR) efforts in the Emergency Department. Out of hospital cardiac arrest (OHCA) survival rates have improved with the recent increase in bystander CPR and automated external defibrillator (AED) application . HoweverAs point-of-care ultrasound (POCUS) has gained popularity by physicians in the emergency department (ED) and other clinical settings. POCUS has been shown to demonstrate real time physiologic data reflecting dynamic changes in response to medical treatments. Additionally, it has been shown to offer prognostic information in patients with heart failure and atrial fibrillation. Additionally, this technology has begun to be used to aid in the assessment of patients with cardiac arrest. Ultrasound is used by physicians for both the etiologic diagnosis in cardiac arrest patients as well as in the prognosis of resuscitation outcomes. POCUS has been shown as favorable in assessing for the presence of reversible causes of cardiac arrest including cardiac tamponade, hypovolemia, myocardial infarction and pulmonary embolism . The ideSeveral clinical studies have evaluated the use of cardiac motion visualized with point-of-care ultrasound as a predictor of outcomes in cardiac arrest patients. We provide a systematic review of the existing literature to examine the reliability and accuracy of cardiac motion visualized with point-of-care ultrasonography as a predictor for mortality outcomes in cardiac arrest patients.We performed a systematic literature search in PubMed with search terms of “Emergency Ultrasound in Cardiac Arrest” And “Emergency Sonography in Cardiac Arrest” to identify primary clinical research studies that compared mortality outcomes in cardiac arrest resuscitations with and without the use of POCUS. Only clinical studies with adult populations that pertained to our objective and were published in English prior to June 23, 2019 were included in our review. For each study, we collected data on study design, patient population as well as major findings. Excluded from review were studies with outcomes unrelated to cardiac arrest, pediatric and fetal populations, and reviews, case reports and letters. Outcome data from all studies were pooled, and the Mantel-Haenszel test was utilized to estimate the odds of return of spontaneous circulation in the presence of detectable cardiac motion across all studies. Data were compiled and displayed using Excel (Microsoft corporation) and Graphpad Prism 8 (Graphpad Software inc).The initial literature review returned 729 journal articles. Of these, six pediatric and fetal ultrasound studies were excluded. Ninety-eight were excluded for being either a review article, case report, guideline article, editorial or letter and not a primary research study. Five were non-English publications. Six hundred twenty were deemed unrelated to the review objective. The fifteen remaining studies assessed cardiac movement with POCUS and outcomes after cardiac arrest resuscitation. The sample sizes ranged from 28 to 793 with a total of 2471 patients among all studies.Selection criteria did not specify the use of trans-thoracic echocardiogram (TTE) or trans-esophageal echocardiogram (TEE). However, only studies utilizing TTE were found. All studies utilized the subxiphoid  acoustic window for ultrasound image acquisition, either as the sole ultrasound window or in combination with additional windows. The additional acoustic windows included the parasternal, transthoracic and apical views. Imaging occurred in the ED in 13 studies and in the pre-hospital setting in the remaining 2 studies. Differences between studies include the probe type used, the types of cardiac arrest included, initial presenting cardiac rhythm and the timing of image acquisition during CPR. Imaging was performed upon ED arrival, upon initiation of resuscitation or during pauses in resuscitation. The definition of presence of cardiac motion was not standardized.  of patients without cardiac motion on point-of-care met criteria for a positive outcome.These results were further organized by presenting cardiac rhythm. Pooled data from all studies were organized by the fraction of positive or negative outcome over the presence or absence of cardiac motion. These data were stratified according to the presenting rhythm of pulseless electrical activity Table , AsystolA total of 414 patients, from eleven studies, were found to have pulseless electrical activity. Of these, 58.8% (133/226) of patients noted to have cardiac motion on POCUS and met criteria for a positive outcome. Conversely, 13.8% (26/188) of patients without cardiac motion on POCUS met criteria for a positive outcome of ROSC, survival to hospital admission or 24-h survival.A total of 600 patients, from eight studies, had asystole as the presenting rhythm. Table  Of theseA total of 140 patients, from six studies, were found to have with either ventricular fibrillation or ventricular tachycardia as the presenting rhythm. Table  Of theseThese data were further stratified according to outcome. Once again, data was organized by the percentage of positive or negative outcome over the presence or absence of cardiac motion. Only data for ROSC Table  and survTen studies, with a total of 1656 patients, studied return of spontaneous circulation (ROSC) in relation to the presence of cardiac motion on POCUS Table . The datSix studies, with a total of 1378 patients, studied survival to hospital admission in relation to the presence of cardiac motion on POCUS. (Table p < 0.001).Using ROSC as the primary outcome, the results of all studies were pooled using the Mantel Haenzel test to calculate the odds ratio and 95% confidence intervals for the presence of cardiac motion and the odds of ROSC. Fig. . The oveOur review of the data demonstrates a consistent relationship between the presence of cardiac motion on POCUS during cardiac arrest and “positive” outcomes of cardiac resuscitation. As cardiac motion is required for any positive survival outcome, it is not surprising that the presence of cardiac motion is associated with survival during resuscitation efforts. With current guideline directed clinical practice recommendations, the presence of cardiac or absence of cardiac motion seen with ultrasound is not an indication to alter management decisions. The negative predictive value of cardiac motion on positive outcomes may impact clinical practice. Across all studies, the absence of cardiac motion on ultrasound results in non-ROSC in 82% of patients. Furthermore, 94% of patients with absent cardiac motion did not survive to hospital admission. This suggests the potential for clinical utility in assessing cardiac motion at the initiation of or during pauses in cardiac resuscitation as a screening measure for patients presenting to the ED in cardiac arrest.Our review only included patients who received point-of-care echocardiograms either at the initiation of resuscitation or during the cardiac resuscitation. Jentzer et al. studied outcomes of cardiac arrest patients who underwent an echocardiogram within 24 h of hospital admission with an average time to ultrasound of 11.9 h . The invFurthermore, the pooled data support the use of serial ultrasound imaging in the evaluation of cardiac activity. Kim et al. studied the outcomes compared to cardiac activity seen on initial ultrasound as well as serial ultrasounds performed at two-minute increments during pulse checks . The posMost of the reviewed studies acquired echocardiographic data from the ED setting. However, two studies, Aichinger et al. and Briekreutz et al. examined echocardiographic cardiac motion in the pre-hospital setting using hand-held ultrasound devices , 16. ThePOCUS has the potential for real-time assessment of physiologic changes that may result from medical therapies and interventions by observing dynamic anatomic findings that are seen with ongoing patient treatments , 20. WhiThere are several limitations to the present study. Although we found a significant association between the presence of cardiac motion during resuscitation and ROSC, currently there is insufficient evidence to recommend abandoning resuscitative efforts based on the absence of cardiac motion alone. There are clearly certain instances when a lack of cardiac motion may not be predictive of failure of ROSC, especially in the setting of hypothermia or drug intoxication or in clinically induced cardiac standstill/cardiac arrest as in cardiac surgery for example . FurtherWith the increasing availability of affordable handheld POCUS devices, we believe there will likely be increased physician comfort and skill with the use of ultrasound in the ED and critical care setting. While these results suggest POCUS provides additional diagnostic and prognostic information in the management of cardiac arrest, with the current body of knowledge regarding POCUS in the setting of cardiac arrest, we believe it remains vitally important that point-of-care imaging does not interfere with standard advanced cardiac life support efforts. With further study and perhaps a randomized multicenter trial using POCUS during treatment of cardiac arrest, perhaps standardized POCUS data can be incorporated in the evidence-based treatment of patients suffering from cardiac arrest. Point-of-care assessment of cardiac motion has the potential to be informative as an additive clinical data point in the clinical assessment of patients suffering from cardiac arrest.