Lipid disorders, especially hypercholesterolemia, are one of the most thoroughly investigated cardiovascular risk factors. Their correlation with biometeorological conditions has been reported, with authors stressing seasonal increases of total cholesterol (TC) levels, mostly occurring in winter. This study aims at determining the correlation between the level of lipid parameters (LP) and meteorological conditions, analyzing seasonal variations in LP levels, and attempting to answer the following questions: do changes in LP levels result from the organism’s response to cold or heat stress, or are they secondary to seasonal dietary variations? An observational study comprised ambulatory patients from the city of Olsztyn (Poland), for whom laboratory test were performed in 2016–2018, with 106,325 records of TC, high-density lipoprotein (HDL), and triglycerides (TG). LP levels were matched with atmospheric conditions on the day when the test was conducted and expressed by the universal thermal climate index (UTCI). We demonstrated seasonal increases of TC in cold stress (in wintertime) and of TG in heat stress (summer). The analysis of LP levels in specific periods revealed the increase of TC levels after holidays  in men by 4.56%, and the increase of TG levels in women by 13.46% in the same period. Our results suggest the secondary, diet-dependent underlying cause of the observed changes. This work contributes to the discussion concerning the impact of biometeorological factors on LP levels and may be of significance when planning population-dedicated preventive activities. Lipid disorders, especially hypercholesterolemia, are one of the most thoroughly investigated cardiovascular risk factors. Their epidemiology, apart from genetic predispositions, depends on diet, national income, and many other factors ,2. NumerMean population lipid parameters (LP) values demonstrate seasonal variations. Higher mean total cholesterol (TC) values in wintertime were reported by the authors of the 2016 European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) guidelines for the management of dyslipidemias . The autVedel-Krogh et al.  reportedDespite these reports, it is still unclear if the increase of TC levels results from the organism’s response to cold stress, or if the observed change is correlative to seasonal dietary variations. Considering entire populations, in climatic zones characterized by evident seasonality, dietary habits associated with a given season of the year are related to a higher supply of calories in winter and a higher intake of fats, which may result in increases of LP levels ,11. For The question formulated earlier may be addressed either by conducting a planned prospective study or by changing the approach to the studied issue. If variations in LP levels depend on the exposure to cold/heat stress, they should also appear during short-term weather changes in a given season, especially since the dietary impact on LP levels is not immediate. Hence, the possible evidence for the correlation between a few days of exposure of the organism to cold/heat stress and LP levels might indirectly prove that the described link is direct rather than secondary and dependent on other factors . In our It should also be remembered that dietary habits are culture-dependent and may result in significant, periodical dietary modifications leading to changes in LP levels. This is especially true for different holidays related to a given country’s tradition. It is quite commonly known that, for instance, in Muslim culture during Ramadan (fasting), high-density lipoprotein (HDL) levels increase, and LDL levels decrease . PeriodiIn Poland, Christmas celebrations begin on 24 December with Christmas Eve supper, traditionally consisting of 12 dishes, and last until 26 December. This is a time of family gatherings accompanied with hours of sitting at tables laden with food and eating. One Polish study, devoted to the calorie content of meals at Christmas time, reported an average intake of about 2400 kcal daily and an average weight gain by 420 g, the effect was comparable to that after Thanksgiving in the USA ,20.To describe local atmospheric conditions, a number of simple meteorological parameters may be used, such as: outside temperature , wind speed, atmospheric pressure, and many others. However, if we consider the level of energy required by a human organism, the biometeorological parameter of choice seems to be the universal thermal climate index (UTCI). This index comprehensively describes the impact of meteorological factors on the human organism and appears to be particularly useful for describing the organism’s response to thermal stress, including cold stress ,22,23,24The aim of this work is to determine the correlation between LP levels and biometeorological conditions expressed with the UTCI, to analyze seasonal variations in LP levels, and to answer the following question: do changes in LP levels result from the organism’s response to cold/heat stress, or are they secondary to seasonal dietary variations?This observational study was based on laboratory and meteorological data collected in the period 2016–2018 in Olsztyn, Poland. Olsztyn has a population of about 180,000 inhabitants and is located in a cold climate-type zone without a dry season with warm summer (Dfb) . In our An observational study comprised patients, aged between 18 and 99 years of age, for whom laboratory tests were performed . The results were obtained from two large laboratories located in Olsztyn: DIAGNOSTYKA limited liability company and the Municipal Hospital. The analysis involved the results of basic lipid tests: total cholesterol (TC) , high-density lipoprotein (HDL) , and triglycerides (TG) . The analyzed results contain both the assays from prophylactic examinations and routine follow ups of patients, including those who take hypolipidemic drugs. For the sake of this study, no personal details concerning the patients were processed. To assess thermal stress, the UTCI values based on data recorded at 12.00 were used, calculated for consecutive days of 2016–2018. Input data were obtained from the Olsztyn weather station belonging to the Institute of Meteorology and Water Management. The obtained UTCI values were classified to appropriate thermal conditions classes, including cold stress class (UTCI ≤ 9.0 °C), thermoneutral conditions (UTCI from 9.1 to 26 °C), and heat stress class (UTCI > 26 °C) . Cold stress dominated in the analyzed period, found for 52% (n = 570) of days, thermoneutral conditions occurred on 38.05% (n = 417) of days, and heat stress on 9.95% (n = 109) of days.Consistent with the suggestion of Vedel-Krogh et al. , the impTo assess the impact of biometeorological conditions during the studied 3 years on the results of LP levels, we used 7 two-week long periods characterized by a significant change in meteorological parameters, in which the average UTCI value for the previous week was more than 10 °C lower, as compared to the following week, and 7 periods when the average UTCI value for the previous week was more than 10 °C higher than in the following week. We selected these periods to assess the impact of warmer and colder outdoor temperature on LP values in the patients.t-test was used, and the Mann–Whitney U test was used when the equality of variances was not met. The statistical significance level was assumed at p ≤ 0.05.Statistical analysis was performed with the use of Statistica  13.3 version . To assess the distribution of the analyzed variables, the Shapiro–Wilk test was used, and to assess the equality of variances, Levene’s test was employed. The comparison of weekly, monthly, and thermal variability  was performed with the analysis of variance (ANOVA) test and with the use of the Least Significant Difference (LSD) test as a post hoc procedure. When the equality of variance was not met, the Kruskal–Wallis test was used with multiple comparisons of median ranks. To compare the impact of holidays  and colder/warmer outdoor temperature, Student’s The mean TC level in our dataset was 203.18 mg% (standard deviation (SD) = 45.07), the mean value of TG amounted to 132.68 mg% (SD = 97.03), and of HDL, 61.08 mg% (SD = 17.96). The analysis of lipid data revealed a decrease of the mean TC level in consecutive years .The decrease of TC levels in consecutive years is not a correlative of the population undergoing laboratory tests ‘getting younger’ . After lp < 0.001), while the mean TG level was higher in males . It should be remembered, however, that in the Polish climatic zone (Dfb), meteorological conditions in specific months are characterized by large variabilities in consecutive years. Seasonal variations of LP levels are presented in In the seasonal analysis, in a month-to-month assessment , some stThe decrease of TC levels in December and high TG values in August merit attention. In summer months (July–September), high TG values were observed more often (TG > 400 mg%), in total there were 150 cases (35%) and in August, 12% (n = 58).p < 0.001) mean TC values  as compared to cold stress conditions  The comparative analysis of LP levels in females and males under cold stress conditions, thermally neutral conditions, and heat stress, revealed statistically significant differences . Patientp < 0.05), while in males, the difference was not statistically significant (200.04 mg% versus 202.1 mg% p = 0.34). The analysis of special situations—the impact of a short-term (one-week-long) change in weather conditions, performed for all 14 periods together, revealed higher TC values ‘on the cold side’ of the analysis. In seven periods when the weather became colder, TC increased substantially in females  and HDL by 7.25% (p < 0.0007) were observed in males in the post-holiday period, and significantly higher mean TG levels by 13.46% (p = 0.0210) in females in the post-holiday period, as compared to the levels before the holidays , significantly higher mean TC values by 4.56%  is always burdened with some risk of indirect correlations. For instance, a larger number of cardiovascular deaths in the winter season may be attributed to the direct response of the organism to cold stress , may be secondary to seasonal increases in respiratory tract infections, or may be associated with decreases in vitamin D3 levels in winter ,30,31,32The correlation presented in Yet, explanations referring to the direct response of the organism to cold/heat stress cannot be ignored either. It is commonly known that the organism’s responses to a drop in outdoor temperature involve increased basic metabolism, increased activity of the brown adipose tissue, and improved LP levels ,37,38. IThe analysis of special situations , Table 4As for the ongoing discussion, conclusions that may be drawn from the response to a short-term change in weather conditions seem more important. It may be hypothesized that the increase of TC levels on ‘the cold side’ of the analysis in females  and the absence of this effect in males, may be related to a higher sensitivity of females to cold stress (the difference in the body surface to body mass ratio) . This isHigh TG values in August are difficult to interpret . TG valup < 0.001), we consider these values as consistent with data from the available literature [Decreased mean TC levels in consecutive years  may resuterature .When planning this study, we primarily considered its practical dimension. Seasonal variations in LP levels lead to the question as to when, from the point of view of public health, primary preventive activities should be most beneficial, i.e., screening for hyperlipidemia. Because cold stress dominates (52%) in the Polish climatic zone, it appears that such activities should be undertaken in the autumn–winter season, excluding special situations (pre- and post-public holiday periods) which may influence the obtained population values. Unfortunately, the mentioned special situations are correlative to culture-dependent conditions and may prove different in other countries.LP levels reveal seasonal variations. TC values are statistically significantly higher in cold stress conditions, i.e., in wintertime. However, these variations are most likely secondary to seasonal dietary changes. LP variations in the peri-holiday periods should be taken into consideration when planning screening examinations. This study is based on a large dataset; however, the data come from one center  collected over a relatively short time period (three years). This limitation was related to the change in laboratory assaying systems in both laboratories and changes in information technology systems that made it practically impossible to make use of earlier data. This study is, however, easily reproducible in a different center, most beneficially in a different climatic zone and culture. Its confirmation might end the discussion concerning the impact of weather conditions on LP values. The analysis does not consider LDL levels due to methodological reasons: some results are taken from the direct assay, the majority from Fridewald’s formula . From a The factor that may interfere with the achieved results, yet lowering the values rather than inflating them, especially with regard to the analysis of cold stress, is the avoidance of thermal stress by remaining indoors. We are unable, however, to indicate the reason why this would occur in any specific winter month and not any other. Moreover, since the study is based on raw data referring to lipid parameters and on the material that did not contain any patients’ clinical details, such as: diet, drugs, co-existing diseases, etc., it is possible that its duplication conducted on a selected subpopulation may yield different results. Consequently, in our study, we operated only on the analysis of mean values. However, with such a large dataset collected in one region, our results may be considered to be population values.


Morphea is an inflammatory disease of the connective tissue that may lead to thickening and hardening of the skin due to fibrosis. The aim of this study was to document magnetic resonance imaging (MRI) changes in patients with linear morphea who were treated with methotrexate (MTX) and high-dose corticosteroid. This study was conducted on 33 patients from the outpatient's dermatology clinic of our institute, who fulfilled the inclusion criteria. Patients received 15 mg/week of MTX and monthly pulses of methylprednisolone for three days in six months. The effectiveness of the treatment was evaluated by MRI, modified LS skin severity index (mLoSSI), and localized scleroderma damage index (LoSDI). All parameters of mLoSSI and LoSDI including erythema, skin thickness, new lesion/lesion extension, dermal atrophy, subcutaneous atrophy, and dyspigmentation were also noticeably improved after treatment. Subcutaneous fat enhancement was the most common finding in MRI. MRI scores were significantly associated with clinical markers both before and after the treatment with the exception of skin thickness and new lesion/lesion extension which were not associated with MRI scores before and after the treatment, respectively. The lack of correlative laboratory disease activity markers, control group, and clearly defined criteria to judge the MRI changes. MRI could be a promising tool for the assessment of musculoskeletal and dermal involvement and also monitoring treatment response in patients with morphea. Morphea, localized scleroderma (LS), is an inflammatory connective tissue disease that may lead to skin thickening and hardening due to fibrosis. The course of LS includes an early inflammatory stage. It starts with hyperaemia of the skin and is followed by fibrosis, sclerosis, and, finally, atrophy . LS has Morphea affects the underlying structures , in whicAlthough numerous therapeutic modalities including methotrexate (MTX) in combination with systemic corticosteroid have been discussed for these debilitating forms of morphea, optimal treatment is unknown maybe due to a lack of consensus as to the methods of evaluation and monitoring of treatment response –13.Although several clinical and paraclinical diagnostic and assessment tools including the modified LS skin severity index (mLoSSI), the localized scleroderma cutaneous assessment tool (LoSCAT), ultrasonography (US), elastography, and skin biopsy have been documented, all of them have some limitations; for example, only a limited subset of the clinical parameters is evaluated by each mLoSSI and LoSCAT, or elastography is so hard to perform, US is usually not so helpful on the scalp/face due to a thin tissue, and finally no one really wants to biopsy the face. Magnetic Resonance Imaging (MRI) has recently been shown to be a useful diagnostic tool for identifying the musculoskeletal involvement in patients with morphea –16.The aim of this study was to document the MRI changes in patients with morphea who were treated with MTX and high-dose corticosteroid.The study was approved by the ethics committee of Shahid Beheshti University of Medical Sciences. Informed consent was sought from the patients in accordance with legal requirements.9/l, thrombocytopenia <100 × 109/l, liver transaminase levels more than twice the upper limit of normal, or renal impairment defined as creatinine clearance <90 ml/min/1.73 m2, osteopenia, and osteoporosis, or if the patient was unwilling or unable to adhere to the protocol.This study was conducted on 33 patients from the outpatient's dermatology clinic, who fulfilled the inclusion criteria. The inclusion criteria were immunocompetent patients 10 years old or older with confirmed morphea , normal bone mineral density, and being negative for latent infections, endocrinopathies, and cardiovascular, renal, and pulmonary disorders. The patients were excluded if they had systemic sclerosis, major concomitant medical conditions, leukopenia <3.0 × 10Morphea diagnosis was confirmed by histological examination. Owing to the activation of latent infections during immunosuppressive treatment regimens, the patients were also examined for tuberculosis, viral hepatitis, and HIV infections.2) per pulse, up to a maximum dose of 1 g intravenous methylprednisolone (or 2 mg/kg/day of prednisolone with a maximum dose of 60 mg and 1 mg/kg/week of MTX with a maximum dose of 15 mg/week in pediatrics). On the other hand, all patients were followed up to 18 months and methotrexate (15 mg/wk) was continued in this period.Treatment protocol and duration encompassed six months and, in this period, the patients received MTX, methylprednisolone, and folic acid. MTX was started with a weekly oral dosage of 15 mg, and 1 mg of daily folic acid was prescribed to diminish its toxicity. At the beginning of each month, patients were hospitalized for three days to administer 20–30 mg/kg  assesses 18 cutaneous anatomic sites, capturing both disease activity and damage parameters. Scores for each site are based on the most severe score for each parameter. To minimize intersubject variability, all skin changes are compared with the contralateral or ipsilateral skin area.The modified LS skin severity index (mLoSSI) includes the total of three separate activity scores as follows: (A) erythema (ER), (B) skin thickness (ST), and (C) new lesion/lesion extension (N/E). Three cutaneous damage domains are summated to obtain the localized scleroderma damage index (LoSDI) as follows: (A) dermal atrophy (DAT), (B) subcutaneous atrophy (SAT), and (C) dyspigmentation (DP) .μs; maximum slew rate, 200 T/m/s) with integrated parallel acquisition techniques in three spatial directions. The imaging protocol consisted of gradient-echo localizers on each table position, followed by coronal whole-body STIR images for assessment of pathological signal changes occurring in the musculoskeletal system. MRI images were graded from 0 to 10 by an experienced and blinded radiologist. Also MRI scores (before and after treatment) were compared and scored from 0 (no improvement) to 10  by investigators.Patients were visited monthly with complete laboratory data to check for probable adverse side-effects. Efficacy of the treatment was assessed clinically by mLoSSI and LoSDI before starting the medication. MRI was also performed before and after 6 months of the treatment by 1.5T closed-bore MRI body scanner which elucidates the depth and thickness of the soft-tissue structures and the degree of inflammation and edema. MRI scans were performed for all patients using high-performance gradients  and 95% confidence interval (CI). P-values which were adjusted with Benjamini–Hochberg method to control the false discovery rate lower than 0.05 were considered statistically significant. SPSS software for Windows  was used to perform all statistical analyses.The variables were checked for having normal distribution by using Shapiro-Wilk test. According to nonparametric clinical variables , the Wilcoxon signed-rank test was used instead of paired-samples25-75 of 19.00 to 37.50, with an age range of 10–61 years. Eight patients (24.2%) were <18 years. The mean duration of skin stiffness or atrophy was 5.81 ± 3.31 months, and the minimum and maximum durations were two and 13 months, respectively. Linear morphea was diagnosed in 28 cases that all of them had the en coup de sabre subtype; none of these patients had neurological involvement. The remaining five individuals were diagnosed with generalized type.In present study, the female to male ratio was 5.6:1 (28 women and five men). The median age was 29.00 with IQRAs mentioned previously, the efficacy of the treatment was evaluated by mLoSSI, LoSDI, and MRI, which is shown in According to mLoSSI, erythema, skin thickness, and new lesion/lesion extension were significantly improved after the treatment. Furthermore, all parameters of LoSDI including dermal atrophy, subcutaneous atrophy, and dyspigmentation were also noticeably improved after treatment. The treatment regimen was evaluated to be an effective method according to MRI by a P-value <0.001 . The resAmong the 33 patients who received treatment, all of them experienced some adverse side-effects. According to the precise inclusion criteria, which excluded patients with latent infection, none of them experienced any severe adverse effect of immunosuppression.Weight gain and acne vulgaris were the most prevalent side-effects, detected in 26 and 23 patients, respectively. These were primarily due to high dosages of glucocorticoid. Constitutional side-effects such as fatigue (n=13), nausea (n=11), and headache (n=5) were also reported in less than half of the patients, which could probably be due to MTX. Striae rubrae and alopecia were two cosmetically important adverse effects, respectively, observed in seven and six patients. Secondary Cushing syndrome was observed in approximately 10% of the patients  as the most important adverse effect in this study. Finally, hypokalemia (n=8), leukopenia (n=2), and anorexia (n=1) were other reported side-effects.It is worth noting that this study demonstrated the effectiveness and sensitivity of MRI to treatment and its association with LoSCAT that would definitely be more novel and unique in the treatment of these patients.Over the years, a variety of therapeutic options has been reported for morphea, topical and systemic corticosteroids, topical and systemic calcipotriol, topical tacrolimus, phototherapy, and MTX , 18–23. 2/week of MTX were given to 34 patients. The effectiveness of the treatment was measured by thermography and clinical criteria, and, ultimately, 71% of patients had entered the remission phase [In the study conducted by Kreuter et al., fourteen LS patients were treated with 15 mg/week of MTX and monthly methylprednisolone pulse (1000 mg for three days) for six months. The effectiveness of the treatment was evaluated by ultrasound (US) and histological findings. Almost all of the patients had achieved clinical improvement, which was confirmed by paraclinical criteria . In anoton phase .Several clinical and laboratory methods have been reported to measure morphea disease activity. One of these criteria is LoSCAT. Arkachaisri et al.  in 2008 In 2010, a new standard was designed for the measurement of damage that was composed of DT, SAT, and DP. The reliability of this score with mLoSSL and PGA was acceptable. In our study, mLoSSI and LoSDI were significantly improved after treatment. Similar to earlier studies , we alsoAn important issue is the lack of a universal agreement on the optimal tools to be used for assessment of disease activity and damage severity or monitoring of the treatment response. Skin scores and recently more sensitive tools including laser Doppler flowmetry, Doppler US, and MRI have been used for evaluation and monitoring of the lesions .Ultrasonography has been utilized for assessment of the superficial linear and circumscribed lesions because of its availability and excellent soft-tissue resolution, but evaluation of deep tissues may be impossible by US  and alsoThe data clearly show that MRI plays a key role and is able to document both dermal and musculoskeletal involvement at the initial presentation, as well as the changes occurring during these therapies. A valuable follow-up instrument should be able to differentiate between therapy responders, patients with stable disease, and those who are unresponsive to treatment. In our series, we found treatment success, which is in line with previous studies. Schanz et al.  showed tSchanz et al.  mentioneThis study is subject to a number of important limitations: the lack of correlative laboratory disease activity markers and clearly defined criteria to judge the MRI changes; lack of a control group can be mentioned as another limitation, but it should be noted that it is inconsistent with ethical principles for patients not treated for several months.We demonstrate the ability of MRI to capture disease improvement in patients with linear morphea responding to a methotrexate and corticosteroid regimen as defined by a significant change in the mLoSSI and LoSDI scores. Larger and comparative studies are needed to elucidate the diagnostic and monitoring applications of MRI in different types of morphea.


Drowning is a leading cause of accidental death in children under 14 years of age in Guangdong, China. We developed a statistical model to classify the risk of drowning among children based on the risk factors.P value of 0.1 for multivariable model. Three-quarters of the participants were randomly selected as a training sample to establish the model, and the remaining were treated as a testing sample to validate the model.A multiple-stage cluster random sampling was employed to select the students in Grades 3 to 9 in two townships in Qingyuan, Guangdong. Questionnaire was a self-reported measure consisting of general information, knowledge, attitudes and activities. A univariate logistic regression model was used to preliminarily select the independent variables at a P = 0.65).A total of 8390 children were included in this study, about 12.18% (1013) experienced drowning during the past one year. In the univariate logistic regression model, introvert personality, unclear distributions of water areas on the way to school, and bad relationships with their classmates and families were positively associated with drowning. However, females, older age and lower swimming skills were negatively associated with drowning. After employing the prediction model with these factors to estimate drowning risk of the students in the testing samples, the results of Hosmer-Lemeshow tests showed non-significant differences between the predictive results and actual risk (χ2 = 5.97, Male, younger children, higher swimming skills, bad relationship with their classmates and families, introvert personality and unclear distributions of water areas on the way to school were important risk factors of non-fatal drowning among children. The prediction model based on these variables has an acceptable predictive ability. Drowning in children is a serious public health concern around the world, with an average of 372,000 death from drowning every year . DrowninAlthough a series of intervention measures has been implemented in China, drowning in children remains an important public health issue , 6. MostWe conducted this study in two rural townships in Qingyuan City of Guangdong Province because of the high mortality rate due of drowning and abundant natural and man-made open water bodies (unprotected nature or man-made water bodies). The findings from this study will provide important insights to the future prevention and control of drowning among children.Students were selected using multiple-stage cluster random sampling  in GuangThis study was approved by the Ethics Review Committee of the National Center for Chronic and Noncommunicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention (No: 201318). Agreement was obtained from every participant.The questionnaire used in this study was developed based on our previous project of integrated intervention for prevention of non-fatal drowning in children in Guangdong Province, 2006–2008 . The varWe collected the potential drowning-related risk factors including general information , education levels of their parents, relationships between their family members, their own swimming skill levels, risk perception on drowning, high-risk behaviors , environment  and disease burden on drowning  , 11, 14.The study participants were randomly divided into training and testing groups. The distributions of age, gender, and prevalence of drowning was similar in the two groups. We used training group to establish the model, and testing group to evaluate the model. Training group including three-quarters of all subjects was used to examine the significant variables of drowning and establish the prediction model. Testing group was used to evaluate the predictive effect of the model. Univariate logistic regression model was used to establish a predictive model by selecting significant variables of drowning. The receiver operating characteristic (ROC) curve and Hosmer-Lemeshow (H.L) Chi-square test were employed to test the sensitivity and specificity of the prediction model.Variable selection: We used univariate logistic regression model to examine the relationship between the potential risk factors and drowning, and select significant variables at a P value of 0.1 for multivariable logistic regression model [Modeling evaluation: We used the established prediction model to predict student’s drowning risk in the testing group, and evaluated the predictive effect of the prediction model by the area under the ROC curve (AUC) [(1) on model , 16. Theve (AUC) . All theA total of 8390 students were initially recruited in this study, after excluding 73 students due to the missing information, with 4367 males and 3950 females. The mean age was 12.43 ± 1.84 years. The risk of exposure to water activities (such as playing in or around open water) was 48.74%. A total of 1013 (12.18%) students experienced non-fatal drowning in the one year before the survey.Younger students, males, higher swimming skill, introvert personality, unclear distributions of water areas on the way to school, bad relationships with classmates and family were significantly associated with drowning risk in the univariate regression analyses Table .Table 2UDrowning risk was significantly lower in females, students with older age and lower swimming skills. However, introvert personality, unclear distributions of water areas on their way to school, bad relationships with their classmates and families could significantly increase drowning risk in the multivariate analyses. In the final identified regression model, trend tests were also performed by including ordinal variables as continuous measures Table .Table 3MThe prediction model for drowning risk in children was established based on the variables of multivariate analysis.The drowning probability of 0.15 was set as a cutoff point. Students with drowning probability equal to or larger than 0.15 were defined as high drowning risk group, and students with drowning probability lower than 0.15 were categorized as low drowning risk group , indicating a high goodness of fit of the model. The sensitivity of the model was 49.44%, specificity was 74.76%, and the AUC was 0.680 (95% CI: 0.66~0.78), indicating that the model fits the data well , family  and social factors  , 8. AlthThe established model could divide students into high-risk and low-risk groups according to the drowning risks in children. We should pay more attention to the high-risk group when we run integrated intervention for prevention of children drowning.The multivariate regression model is a widely-used method to establish a risk prediction model . It can Based on our previous studies , 11, 23,In the present study, we established a prediction model including seven independent variables based on the binary unconditional logistic regression model. According to the cutoff point, all the included children were divided into two groups. The test results in the test sample indicated that the model in predicting the risk of non-fatal drowning in students was acceptable, with an area under the ROC curve (AUC) of 0.680. Generally speaking, the AUC is around 0.7 in the population-based prediction models of a certain event , 30, andA few limitations should be noted. The cross-sectional study has limitation in ascertaining causal relationship between the risk factors and drowning. Recall bias may exist in the cross-sectional study because most of the variables were measured by self-report, especially occurrence of drowning, the personality of the participants, the relationships with classmates and family. As one important factor associated with the risk of drowning, the information of water exposure was just simply collected in this survey. This might be the underlying reason for the higher drowning rate among the students with higher swimming skill observed in this study, this issue will be further investigated in future studies.In summary, male, younger children, higher swimming skills, bad relationship with their classmates and families, introvert personality and unclear distributions of water areas on their ways to school might be important risk factors of non-fatal drowning among children, and the prediction model based on these variables has an acceptable predictive ability.


More than one hundred years have passed since the development of the first microbial inoculant for plants. Nowadays, the use of microbial inoculants in agriculture is spread worldwide for different crops and carrying different microorganisms. In the last decades, impressive progress has been achieved in the production, commercialization and use of inoculants. Nowadays, farmers are more receptive to the use of inoculants mainly because high-quality products and multi-purpose elite strains are available at the market, improving yields at low cost in comparison to chemical fertilizers. In the context of a more sustainable agriculture, microbial inoculants also help to mitigate environmental impacts caused by agrochemicals. Challenges rely on the production of microbial inoculants for a broader range of crops, and the expansion of the inoculated area worldwide, in addition to the search for innovative microbial solutions in areas subjected to increasing episodes of environmental stresses. In this review, we explore the world market for inoculants, showing which bacteria are prominent as inoculants in different countries, and we discuss the main research strategies that might contribute to improve the use of microbial inoculants in agriculture. Humanity has always been concerned about food production to attend the increasing population and, for a long time, the solution was to expand agriculture to new areas. However, this scenario has changed in recent decades, first due to limitations of unexplored cultivable land, but also reinforced by the development of new technologies that allow higher yields, in addition to increasing environmental concerns, leading to agricultural practices aiming at achieving sustainable production. Therefore, although the global demand for food continues to increase, the concepts of agriculture sustainability, recovery of degraded areas, and mitigation of environmental impacts are gaining more respect  or plant-growth-promoting rhizobacteria (PGPR), as they may benefit the plants by a variety of single or combined processes, including the production of phytohormones, siderophores, phosphate solubilization, induction of plant intrinsic systemic resistance to abiotic and biotic stresses, among others , which very often can fully supply the plant´s demands on N. Moreover, other diazotrophic bacteria, such as Glycine max (L.) Merr.) is the most inoculant-consuming crop worldwide, carrying bacteria belonging to the genus Bradyrhizobium. Brazil is probably the global leader in the use of inoculants for the soybean crop (Hungria and Mendes Phaseolus vulgaris L.), cowpea (Vigna unguiculata (L.) Walp.), maize (Zea mays L.) and co-inoculation of soybean and common bean with rhizobia and Azospirillum have also increased in Brazil  and phytohormone production , solubilization of phosphate (e.g. Bacillus spp.), or biological control . If the microorganisms cannot be combined in a single product, they are manufactured separately and the bags containing each one are sold in the same package.Particularly in the last decade, the use of inoculants containing microorganisms of “different type” has expanded. The idea is of combining strains or species acting in different microbial processes, so that the combined benefits of each one would result in higher benefits and, ultimately, yields. Examples of mixed inoculant are those combining microorganisms whose major processes are BNF , and to the plant genotype. Therefore, research is needed to generate knowledge aiming at the production of new formulations for commercial inoculants with mixed bacteria , for the soybean crop single inoculation of Bradyrhizobium resulted in mean increases of 8.4% in grain yield compared with the naturalized population, whereas the co-inoculation with A. brasilense promoted an “upgrade” to 16.1%; for common beans, single inoculation with R. tropici increased yield by 8.3%, whereas the co-inoculation improved the yield by 19.6%  and surface polysaccharides that stimulate root nodulation by R. tropici, improving the efficiency of BNF.In addition to Rhizobium strain IITA-PAU 987 and Bacillus megaterium increased nodulation, shoot dry weight and had 31% increase in BNF when compared with the single inoculation with Rhizobium.Co-inoculation has also been shown to be efficient under several limiting conditions, such as in low phosphate soils. Generally, the BNF is compromised under these situations, but the co-inoculation with phosphate-solubilizing microorganisms can make it available for plant nutrition and, in the case of legumes, help to ensure the benefits of BNF , B. diazoefficiens SEMIA 5080 (= CPAC 7), B. elkanii SEMIA 5019 (= 29w) and SEMIA 587). The legislation still establishes a minimum concentration of viable cells (1 × 109 viable cells/g or mL) of the inoculant until the expiration date, which must be at least 6 months, and void of contaminants at the 1 × 10−5 dilution  or “promiscuous” soybeans  region has developed, over the years, strategies for the use of beneficial microorganisms in soybean adapted to local environment and social characteristics. As consequence of the lack of local production and difficulties in the importation of inoculants in the 1970s, the International Institute of Tropical Agriculture (IITA) launched a breeding program aiming at developing high-yielding tropical soybean varieties capable of nodulating with indigenous rhizobial strains. These new varieties were named “TGx”  are cropped worldwide, representing the most important source of protein in several countries, especially in South and Central America and Africa  of R. tropici have been used in commercial inoculants in Brazil since 1998 and 2004, respectively, in addition to R. tropici CIAT 899, originally isolated in Colombia by Dr. Peter H. Graham  is the major legume cropped in many African countries, responsible for more than 95% of the world’s production   is still controversial  that induced plant protection against salinity, leading to increases in nodulation, plant biomass and N content, confirming that indigenous species may have excellent results when inoculated in fava beans.In saline soils in Morocco, Benidire et al.  reportedLegumes are generally part of the food base of people and animals throughout the world. In addition to soybeans and various types of beans, other crops are also important sources of protein and nutrients and serve as raw materials for many industrialized products. Therefore, raising the yield of these crops under a variety of environments, by means of inoculation with elite rhizobial strains has been the subject of several studies in several countries.Bradyrhizobium sp. strain SEMIA 6144, originally from Africa, has been used in commercial inoculants for peanut (Arachis hypogaea); however, inoculation is not a common practice for this crop in the country, attributed to the lack of response, due to the high population of indigenous rhizobia. Indeed, peanut is a very promiscuous species capable of nodulating with a broad range of soil rhizobia  is a highly nutritive legume cropped mainly in India, but also in more than fifty other countries  is a legume that has gained prominence in global agriculture due to several industrial uses, as their seeds are rich in galactomannan gum, which can be used as lubricant, binder, thickener and emulsifier. It is cultivated in several semi-arid regions such as in India, Pakistan and the United States  is a native grass from Central America  in Brazil , and convert it to a soluble form (Fe2+) available for plants  was released in 2019, with great acceptance by the farmers.The use of A. brasilense   is estimated at least 130 million years ago in Asia and has spread over the years all over the planet , Pseudomonas fluorescens (1N) and Citrobacter freundii (3C) , B. subtilis (B9), Bacillus amyloliquafaciens (E19) and a soil yeast, Candida tropicalis (HY)   on sugarcane growth. After 15 days of planting, a 50% increase in dry mass of inoculated roots was observed.After the isolation and description of sugarcane-associated diazotrophic bacteria, and in view of the observed benefits of bacterial/plant association for other cultures, research has been intensified in Brazil. Dos Santos et al.  observed−1 in the first site and 38.0 Mg ha−1 in the second site compared to the control. The variety RB72454 showed increases of 16.7 and 37.5 Mg ha−1, respectively.The same group of bacteria was used in hydroponic sugarcane cultivation for 59 days under different concentrations of N. Two varieties of sugarcane were used: RB867515 (adapted to low fertility soils) and IACSP95-5000 (adapted to medium to high fertility soils). The authors reported that the two sugarcane varieties, when inoculated with the bacterial mix, presented different results regarding the activity of enzymes related to the assimilation of N. Under low N concentration, nitrate reductase activity was increased in RB867515 by 26% in the shoots, and by 48% in the roots, while glutamine synthetase activity was 21% higher than the control. For the IACSP95-5000 under low N concentration, nitrate reductase activity decreased by 62% in roots, and glutamine synthetase activity was increased by 16%  can raise productivity with economy. In 2019 the first commercial inoculant for the sugarcane was released in Brazil, carrying Nitrospirillum amazonense strain.Optimum yield results via inoculation with the same bacterial mix suggest reduced N-fertilizer application. Pereira et al.  considerEstimates are that the global pasture area covers 26% of the ice-free land surface, but in many of these places, the pastures are degraded and insufficient to provide nutrients to the animals, demanding new areas  representing the main component  increased biomass production by 15% and of protein by 25% in comparison to the control receiving only N-fertilizer   grasses with promising characteristics for pastures. The isolated bacteria were studied in vitro and selected for their plant-growth promotion properties, such as the production of auxins, siderophores and P solubilization.In New Zealand, Monk et al.  isolatedPennisetum clandestinum (kikuyo) was inoculated with two PGPB strains of Stenotrophomonas sp. and Pseudomonas sp. able to synthesize indole compounds, to fix nitrogen and to solubilize phosphate in vitro. Under greenhouse conditions, significant increases in the biomass and root dry weight were observed in comparison to the non-inoculated control.In Colombia, Trifolium spp., Arachis pintoi, Medicago sativa L., Stylosanthes spp. are important examples. Dozens of studies have been performed with PGPB with those legumes. Trifolium repens and Trifolium pratense are two clovers species broadly used in pastures in Uruguay. To ensure good development there is a recommendation, since 1967, of inoculation of both clovers with R. leguminosarum sv. trifolii strain U204, a commercial inoculant strain introduced from the USA  is present in pastures in temperate and subtropical, and arid and semi-arid areas. Buntić et al. (Sinorhizobium (= Ensifer) meliloti strain L3Si allowing better shelf life, pre-inoculation and performance in alfalfa, as there were no liquid inoculants available with this strain. Shoot N content of plants originated from seeds pre-inoculated 1 month before sowing ranged from 3.72 to 4.19%, whereas the control with N-fertilizer had 4.03%; the highest SDW value was of 27.12 mg/plant in the inoculated plants, higher than the control with N-fertilizer (20.20 mg/plant), indicating a high effectiveness of the liquid formulation , carotenoids, N, P and K contents, plant height, leaf-to-stem ratio and fresh and dry weight in comparison to the non-inoculated control. However, one major consideration in this and in several other studies is the need of regulation to avoid potentially pathogenic strains in microbial inoculants, such as Acinetobacter, Enterobacter and even some species of Bacillus.Interest in increasing alfalfa production has also growing in Saudi Arabia. Daur et al.  isolatedA. pintoi) and Stylosanthes spp. are the most commonly used legumes in pastures. For A. pintoi, two Bradyrhizobium spp. strains are used in commercial inoculants, SEMIA 6439 (= MGAP 13) and SEMIA 6440 (= NC 230). In a field experiment that resulted in the selection of these two strains, they increased shoot dry weight, in comparison to the non-inoculated controls, without and with N-fertilizer, by 63 and 47%, respectively  and SEMIA 6154 (= BR 446); recently, SEMIA 6154 was recognized as the type strain of a new species, Bradyrhizobium stylosanthis  in savanna areas in Roraima, Brazil, increased the shoot biomass and N of Stylosanthes capitata cv. Lavradeiro under greenhouse conditions.Despite the widespread use of Trifolium spp.  takes part in the diet of million people, consumed in salads, as ingredient of hot dishes and with great application in the industry as raw material in the manufacture of many products, mainly sauces    (Mangmang et al. Several other vegetables have been reported as responsive to microbial inoculants, including lettuce (Enterobacter spp., of the Burkholderia cepacia complex, Pseudomonas aeruginosa, among others, can be isolated from soils and have the capacity of promoting plant growth (e.g. Adesemoye et al. Attention should be paid to some threats that appear from the increased scientific and commercial interest on microbial inoculants. Several studies are reporting plant-growth promoting benefits in studies with bacteria that may be harmful to plants, animals and humans. Analyzing these studies, there is no doubt that several strains of In relation to agronomic practices, the compatibility with agrochemicals used for seeds treatments, with an emphasis on pesticides represents a major limitation to the survival of bacteria (e.g. Campo et al. Amazingly, information about the benefits of microorganisms on plant growth is leading some farmers to the production of their own microbial inoculants and products for biological control. It is not difficult to perceive the threat that such practice can result to the agriculture. Production of microbial inoculants require specific requirements not easily followed even under specialized conditions (Hungria et al. Research on inoculants and inoculation with rhizobia and legumes raised great interest from researchers and companies in the 1970s. In the following decades, although several reports of benefits of new PGPB and the advances achieved at the inoculant industry, modest interest from research and industry has been observed. However, nowadays, increased demand for food, interest in sustainable agriculture and increasing reports on pests and pathogens resistance to agrochemicals are exponentially raising the global interest on microbial inoculants. Based on the information presented in this brief review, it is possible to perceive the increased number of studies that have been carried out about the development of new inoculants (Santos et al. One challenge to the development of new inoculants relies on the increasing concerns about climate changes. The expected increases in temperature and dry periods in the next years will have major impacts on agriculture. According to Ramirez-Villegas and Thornton , in trop


Schizophrenic patients have serious impairments in social cognition, which often persists after significant reduction in clinical symptoms. Community-based psychosocial treatments aim to recover social functioning for mentally ill individuals. Our aim was to examine prospective changes in social cognition and functional outcomes in two groups of schizophrenic patients involved in two forms of community-based psychosocial treatments namely case management (CM) and community-based club (CC) compared to a matched, treatment as usual (TAU) group of patients. We hypothesized that CC and CM groups would exhibit better functional and social cognitive outcomes after a 6-month long psychosocial treatment period. Seventy-five patients participated either in CC, CM or TAU. Both CC and CM took part in community-based psychosocial treatment programs including trainings, such as communication and assertiveness trainings. In addition, CC provided group therapeutic treatments and a continuously available day care where patients had the possibility to participate in various social interactions. All participants were in remission, and on maintenance antipsychotic treatment. Participants were assessed on all study variables at two time points: baseline and after 6 months with a battery of questionnaires that examined affective face perception, affective prosody perception, pragmatic language comprehension and ToM. Our results showed that functional outcomes improved significantly in the CC as well as in the CM groups, in contrast to the TAU group. While analyzing summary scores of social cognition, it was found that only the CC group increased its performance in social cognition. In addition, a significant between-group difference in social cognitive function was found after 6 months between the three groups, with the CC group performing best. When investigating associations between changes in social cognition and changes in functional outcomes during a 6-month long treatment period, we found significant correlations between the two variables both in the CC and in the CM groups. Based on our results, we suggest that a rich interpersonal network and social support have highly beneficial effects on social cognition and we would like to emphasize the necessity of offering community-based psychosocial treatments beside antipsychotic medications as early as possible as a crucial part of the complex therapy of schizophrenia. Schizophrenia is still one of the most disabling disorders throughout the world. With a prevalence of approximately 1%, it is a serious economic and social burden on communities . A meta-Several researches reported that functional outcomes in schizophrenia are affected by numerous factors, including clinical symptoms, functional capacity, social cognition and neurocognition  versionFor the correlation analysis, we used summary scores for the social cognition variable, because we were interested in global, rather than specific effects in these analyses . SummaryAs gender, education, age, and duration of illness were matched between the three groups, there were no significant differences between them at baseline Table .At baseline the mean value of PANSS total remission score was 14.46 (2.02 S.D.) in the CC group, 15.76 (2.88 S.D.) in the CM group and 14.82 (2.02 S.D.) in the TAU group. After 6 months it was 13.96 (1.98 S.D.) in the CC group, 15.15 (3.27 S.D.) in the CM group and 15.39 (2.29 S.D.) in the TAU group. All the patients remained in remission during the 6 months. No significant symptom worsening, relapse or hospitalization were detected during the observation.p = 0.001) as well as after 6 months (p < 0.001). In addition, compared to baseline GAF scores increased significantly after 6 months both in the CC group (p < 0.001) and in the CM group , while in the between-group analysis significant differences were found between the three groups at 6 months (p = 0.041). The last significant difference between the three groups disappeared after Bonferroni correction. No statistical differences were found regarding the summary response time during the social cognitive tasks between the three groups at baseline or after 6 months.In the within-group analysis of the summary social cognitive scores the CC group was found to have increased their performance significantly (CC group increased significantly in the irony task (p < 0.001), in the metaphor task (p = 0.031) and in the emotional prosody task (p = 0.001). The CM group also showed better results in the irony task (p = 0.01) and in the metaphor task (p = 0.033), however, they showed worse results in the face test (p = 0.012). Interestingly, the TAU group showed better performance only in the irony task (p = 0.001), and their performance in FP task (p = 0.03), as well as in face perception (p = 0.016) deteriorated significantly.While analyzing the data of social cognition task performance in details, in the within-group analysis task performance of the However, significant improvement of the CC in the metaphor task, and significant improvement of the CM in the irony and in the metaphor task disappeared after Bonferroni correction. The significant decline of the TAU in the FP task and in the face test as well as significant decline of the CM in the face test also disappeared after Bonferroni correction.p = 0.01), but this significant difference between the three groups disappeared after Bonferroni correction.In the between-group comparison, there were no significant differences regarding any of the task performances at baseline. The evaluations 6 months later showed significant differences in the metaphor tasks (CC group showed significant acceleration in the metaphor tasks (p = 0.019). Interestingly, the CM group showed deceleration in the irony task (p = 0.005), while the TAU group also showed deceleration in the irony task (p = 0.011) as well as in the face test (p < 0.001) between baseline and after 6 months.While analyzing response times of social cognition tasks in detail in the within group differences, the After the Bonferroni correction, the acceleration in the metaphor task in the CC group, as well as the deceleration in the irony task in the TAU group ceased to be significant.p < 0.001) and in the face test (p = 0.005). Besides, response time in the irony task remained significant (p = 0.01) after 6 months. However, the latter significant difference between the three groups disappeared after Bonferroni correction.On the between group-level, at baseline, the three groups differed significantly in their response times in the metaphor task  as well as in the CM group . However, in the TAU group this correlation was not significant .We found significant positive correlations between changes in GAF scores and changes in summary social cognition scores during the 6-month long treatment period in the CC group  . Since sWe found modest positive correlations between prospective changes in summary social cognition scores and functional outcomes both in the CC as well as in the CM groups. However, there was no such relationship observed in the TAU group. In the biosocial model of functional outcomes in schizophrenia , social CC group, as they showed strong significant prospective changes in irony comprehension, emotional prosody processing and summary social cognition, as well as a moderate prospective improvement in metaphor comprehension. Moreover, a significant between-group difference was found after 6 months in the metaphor tasks with the CC group performing at the highest rate. Importantly, the CC group also significantly reduced their response times in the metaphor tasks. According to our previous study (The most prominent changes in social cognitive functions were detected in the us study , for adaRegarding the results of the CC group, we propose that with a sufficiently effective psychosocial rehabilitation program, patients with schizophrenia are able to meaningfully improve their social cognitive performance. In line with Medalia and Saperstein  we propoRegarding the CM group, we observed moderate prospective improvements in irony and metaphor comprehension, together with a moderate decline in affective face perception. Additionally, there was a significant deceleration of response time in irony comprehension. Our results also show that the TAU group significantly improved response rates, together with a moderate deceleration in response times, in the irony tasks. Their performance also moderately declined in the faux pas tasks as well as in the face test. Regarding the differences observed between the three groups after 6 months of treatment, it can be observed, that the TAU group had the lowest scores in summary social cognition, in the metaphor tasks, and in the GAF scale. In addition, their performance was the slowest in the irony tasks.We cannot ignore the fact that all three groups improved their performance significantly in the irony tasks. Additionally, both the CM and the TAU increased their response times, which resulted in a significant between-group difference in response times of the irony tasks after 6 months treatment. In Varga et al.  we have As far as we know, the present investigation is the first to assess the efficacy of two forms of community-based psychosocial treatments available for schizophrenic patients and compared them to a treatment as usual group of patients. According to our present findings, we believe that community-based psychosocial treatments are able to facilitate functional outcomes in schizophrenia. Regarding social cognition, we found that the most prominent prospective change could be achieved with the program of community-based clubs. Our results indicate that this is due to a supportive social milieu, in which various social interactions can be practiced as well as new social roles can be learned, which provide aspecific improving effect to social cognition and help patients find their way to the society. Additionally, our present results clearly show that in order to meaningfully improve the social cognitive performance of patients, it is important for them to get involved in community-based clubs. According to our present and previous  findingsTo summarize, our results underline the necessity of offering community-based psychosocial treatments beside antipsychotic pharmacological treatments , 67. ComOur study has several limitations. First of all, there is a wide range of community-based psychosocial treatment models in the literature, and the generalization of our present results across different models could be problematic. However, as far as we know, our research was the first that examined different aspects of community-based rehabilitation separately.As we mentioned earlier we used only GAF for estimating functionality, and a more detailed assessment of these domains would have eventuated in more reliable results. We should have also considered other areas referring to functionality such as self-care, independent living, work or supported work, etc.We did not assess potential relations between neurocognitive factors, social cognition, functional outcomes, clinical symptoms and vocational status. Future studies should address the effects between these factors. In addition, other aspects of social cognition such as attributional style as well as social perception should be reflected in future measures.Another important limitation is the use of different antipsychotic medications. All patients with schizophrenia were on maintenance antipsychotic medication. However, it was found that antipsychotics have little reliable effect on social cognition , and earEV: study design, stimulus construction, data analysis, writing article, manuscript revision; SE: project idea, study design, data collection, data analysis, writing article; TB: writing software, software development, data analysis; TT: writing article, manuscript revision; RH: project idea, writing article, manuscript revision.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.


N = 107 couples). Participants  independently completed twice-daily ecological momentary assessments (EMA) via smartphone for 14 consecutive days. Items assessed RS and communication . Linear mixed models employing an Actor Partner Interdependence Model were used to examine concurrent, time-lagged, and cross-lagged associations between communication and RS. Expressing one's feelings was unassociated with RS. Holding back from doing so, in contrast, was associated with lower RS for both patients and spouses in concurrent models. These effects were both intrapersonal and interpersonal, meaning that when individuals held back from expressing their feelings, they reported lower RS and so too did their partner. Giving and receiving support were associated with one's own higher RS for both patients and spouses in concurrent models, and for patients in lagged models. Conversely, criticizing one's partner and feeling criticized were maladaptive, associated with lower RS . Cross-lagged analyses (evening RS to next-day afternoon communication) yielded virtually no effects, suggesting that communication may have a stronger influence on short-term RS than the reverse. Findings underscore the importance of responsive communication, more so than expression per se, in explaining both concurrent and later relationship adjustment. In addition, a focus on holding back from expressing feelings may enhance the understanding of RS for couples coping with cancer.Cancer treatment poses significant challenges not just for those diagnosed with the disease but also for their intimate partners. Evidence suggests that couples' communication plays a major role in the adjustment of both individuals and in the quality of their relationship. Most descriptive studies linking communication to adjustment have relied on traditional questionnaire methodologies and cross-sectional designs, limiting external validity and discernment of temporal patterns. Using the systemic-transactional model of dyadic coping as a framework, we examined intra- and inter-personal associations between communication (both enacted and perceived) and relationship satisfaction (RS) among patients with stage II–IV breast or colorectal cancer and their spouses ( A diagnosis of cancer poses great challenges for both patients and their loved ones. Patients with cancer often experience significant emotional distress including anxiety and worry, depression, and fears of disease progression and death  is encoded and interpreted by the other dyad member, who may or may not respond. If the response conveys empathic understanding, validation and support, emotion-focused positive supportive dyadic coping is said to be occurring. If the response conveys hostility or ambivalence, negative dyadic coping is said to be occurring. Research on these specific elements of dyadic coping indicate positive associations between emotion-focused positive supportive dyadic coping and relationship satisfaction (RS), and inverse associations between negative dyadic coping and RS , emotion-focused positive supportive dyadic coping, and negative dyadic coping at a given point in time and RS at (a) the same time and (b) a later point in time using ecological momentary assessment (EMA) methods. To date, most descriptive studies linking communication to adjustment in cancer have relied on cross-sectional designs which limit our ability to discern temporal patterns and do not allow for optimal tests of hypotheses regarding transactional causality in dyadic interactions. Few longitudinal studies exist, particularly those in which data are collected in real-time and in naturalistic settings. EMA offers a number of advantages. First, it minimizes recall biases inherent in global, retrospective measures which require participants not just to remember but also to summarize their behavior . When considering such questions, individuals use a variety of heuristics to estimate their answers, leading to systematic biases influenced, for example, by current mood . Conversely, being critical and feeling criticized would be inversely associated with concurrent and later RS (both own and partner's), as would holding back from expressing one's feelings. We also examined the cross-lagged effects of RS on next-day communication to explore the possibility of these reciprocal effects.All procedures, including screening and approach processes, were approved by the Institutional Review Boards of Arizona State University  and Duke University School of Medicine . Participants were recruited from two different cancer centers, the Duke Cancer Institute in Durham, NC and the Seattle Cancer Care Alliance in Seattle, WA . The Institutional Review Board of Arizona State University served as the IRB of record for the Seattle site, with IRB authorization agreements held by the Fred Hutchinson Cancer Research Center and the University of Washington. All subjects gave written informed consent in accordance with the Declaration of Helsinki.Inclusion criteria for patients were: age 18 or older; stage II–IV breast, colon, or rectal cancer; currently receiving or having received chemotherapy and/or hormone therapy; within 2 years of diagnosis of current cancer stage; life expectancy of at least 6 months per primary oncologist; married or in a committed, cohabiting relationship with someone of the same or opposite sex; and ability to speak and comprehend English. Inclusion criteria for spouses were: age 18 or older; married to or in a committed, cohabiting relationship with the patient; and ability to speak and comprehend English. Please note that the term “spouse” is used throughout but encompasses both spouses and non-married cohabiting partners. This is to avoid confusion with the term “partner” as used in the EMA item wording and in the statistical sense (partner effect).N = 944), 396 were deemed initially eligible based on medical records. Among the 396, 268 were contacted, further screened, and deemed fully eligible. Among those, 136 agreed to a face-to-face study visit with their partner, a 50.7% agreement rate. The most common reasons for refusal were lack of interest in the study or simply being too busy. Twenty of the 136 scheduled appointments were beyond the time frame of analysis for the present manuscript. Among the 116 couples seen face-to-face at the time of data extraction, 115 signed consent forms (separate forms for patients and spouses). Three of the 115 couples signed consent forms for the study in general but elected not to participate in the EMA portion of the study, due to discomfort with technology (EMA questions were posed via smartphone). Five of the 112 were excluded from the current analyses because of either insufficient data provision due to technological problems (n = 2 couples) or because they had not yet reached the end of the EMA phase at the time of data extraction (n = 3 couples), yielding an analytic sample of 107 couples.Among patients screened for the protocol at the time of data extraction , were asked to identify a convenient time for a 90-min in-person visit, often scheduled around their next medical appointment to minimize additional travel to the clinic. Couples met with the site research coordinator in a private room at or near the site clinic. Written consent was obtained separately from patients and spouses following a detailed description of study procedures, risks and benefits, and assuring that any and all questions or concerns were addressed. After consent, participants completed other study activities not included in this report  and then downloaded the free smartphone application.The smartphone application was created using lifedatacorp.com, a web-based application development platform. The application is compatible with iOS and Android cell telephones. Participants used their personal phones unless they owned a different kind of phone or did not own a phone, in which case they were lent an iPod Touch device for study use. This was the case for 15 individuals. Participants who borrowed an iPod Touch completed the activity using the device as they would a smartphone. The application download was conducted in the same manner as with smartphones and application interfaces and participant views were comparable.The lifedatacorp.com system allows users to receive questions via notification once the application has been downloaded on participants' mobile devices and they have signed up as individual users. The site research coordinators guided participants through the application download process. Upon download and required user registration, participants began receiving notifications to complete assessments twice daily for 14 days: once at 12:00 p.m. (afternoon assessment) and once at 8:00 p.m. (evening assessment). The response window was set for 2 h from the time of the first notification for both assessment periods. If participants did not begin to complete the assessment within the 2-h response window, the notification expired.Participants received a Frequently Asked Questions user handout developed for the smartphone portion of the study and were provided with site research coordinator contact information in case of any technical difficulties. Participants were contacted 2–3 days after the application download to check in and provide assistance as needed. At the completion of the 14-day EMA, participants were sent a $75 check or gift card if they had completed 85% or more of the notifications received. If <85% of assessments were completed, participants were paid $3 per notification completed.Demographic characteristics  were assessed via questionnaire using Research Electronic Data Capture (REDCap), a secure web-based tracking and on-line data acquisition system ? The second item assessed perceived importance: How important was this conversation to you ?Participants were asked whether or not they had talked to their partner since awakening (afternoon assessment) or since the last notification (evening assessment). What constituted “talking” was not defined and therefore left up to interpretation by participants. Accordingly, participants may have counted telephone calls or text messages with their partner as conversations, but this was not measured r = 0.54, p < 0.001 for patients and r = 0.58, p < 0.001 for spouses [holding back]; and r = 0.16, p = 0.102 for patients and r = 0.08, p = 0.419 for spouses [disclosure]. These associations provide some support for validity, more so for the holding back item. Note that overlap is not expected to be great given that one set of ratings is necessarily cancer-related and the other is not. Parallel EMA items assessed perceptions of partner communicative behavior (Table Remaining items (listed in Table r = 0.73 and 0.67 from two different studies) and valid, i.e., able to discriminate persons classified as adjusted vs. distressed using the total scale score excluding item #31.Following Auger  in patients' and spouses' RS responses, we computed intraclass correlation coefficients (ICCs), adjusting for temporal autocorrelation. ICC values for patients and spouses were nearly identical . These values indicate that approximately 40% of the total variation in RS was at the within-person level .In the present study, we administered the full DAS to patients and spouses as part of a baseline battery of questionnaires. Baseline ratings of item #31  were positively associated with EMA ratings of the same item (relationship happiness today), Descriptive statistics were used to characterize the sample with respect to demographic, clinical and relationship adjustment characteristics. Ecological momentary assessment response and completion rates, frequency of having talked to one's partner, whether or not a conversation was about the cancer, and perceived importance of a conversation were summarized separately by afternoon and evening. Correlational analyses examining associations among key study variables also were conducted , (2) models predicting each dyad member's RS from that member's report of his/her own communication and perceptions of his/her partner's communication in the afternoon of the same day (lagged models), and (3) models predicting each dyad member's afternoon reports of communication and perceptions of his/her partner's communication from that member's report and his/ her partner's report of RS from the preceding evening (cross-lagged models). In concurrent and lagged models, four effects of substantive interest were estimated, depicted in the top two panels of Figure 11); (2) spouse's reports of communication/perceived communication predicting his/her own RS ; (3) patient's reports of communication/ perceived communication predicting the spouse's RS ; and (4) spouse's reports of communication/perceived communication predicting the patient's RS . Parallel actor and partner effects were estimated in cross-lagged models, but with communication/ perceived communication being predicted from the preceding day's RS; see bottom panel of Figure Associations between communication variables and RS were estimated using linear mixed models within an Actor-Partner Interdependence Model (APIM) framework for dyads with distinguishable members. Three sets of APIM analyses were conducted: 1) models predicting each dyad member's RS from that member's report of his/her own communication and perceptions of his/her partner's communication on  models pIn concurrent and lagged models, each dyad member's RS on a given evening was predicted from two dummy vectors coding for dyad member  and four two-way interactions between these dummy vectors and person mean-centered evening (or afternoon) communication/perceived communication variables, each capturing one of the four effects of substantive interest. Four parallel between-person interaction terms were included. Cross-lagged models paralleled concurrent and lagged models in their general form, but with each day's afternoon communication/perceptions of communication being predicted from the preceding evening's RS. Except where noted in tables of model coefficients, intercepts and actor and partner effects were estimated as random. An AR(1) variance/covariance structure was specified for day-level residuals. Results from analyses conducted adjusting for cancer diagnosis stage (stage II vs. stage III or IV) did not differ from those based on analyses described above. Results from the more parsimonious models  are reported here. Descriptive analyses were conducted in SPSS 24.0 and SAS/STAT 14.1. Linear mixed models were estimated via restricted maximum likelihood using all available data in SAS/STAT 14.1 PROC MIXED. Given the large number of APIM model effects analyzed, α was set at 0.01 for these tests.Table With regard to clinical characteristics, 44% of patients had been diagnosed with breast cancer, 32% with colon cancer, and 24% with rectal cancer. Across diagnostic groups, 64% were coping with advanced cancer, stage III or IV. The breast cancer group was characterized by more lower stage disease (55% stage II) whereas the colon cancer group was characterized by more higher stage disease (56% stage IV). The rectal group was more evenly distributed in this respect .Table p-values from linear mixed models predicting evening RS from same-day evening communication. Intercepts represent the adjusted sample means for RS for patients and spouses . Labels for patient- and spouse-specific actor and partner effect coefficients  correspond to those in the top panel of Figure p < 0.01) effects.Table s e.g., a1 correspActor effects showed associations between self-reported enacted communication and one's own RS. For both patients and spouses, providing support to one's partner was positively associated with one's own RS. Holding back from expressing one's feelings, in contrast, and criticizing one's partner, were negatively associated with one's own RS. With respect to perceived partner communication, for both patients and spouses, feeling supported was positively associated with one's own RS, and feeling criticized was negatively associated with one's own RS.felt supported, their patient partner reported higher RS.Partner effects were also found. For both patients and spouses, their own holding back was negatively associated with their partners' RS. In addition, spouses' support of the patient was positively associated with the patients' RS, while their criticism of the patient was negatively associated with the patient's RS. Lastly, when spouses p-values from linear mixed models treating afternoon communication as the predictor and same-day evening RS as the criterion. As in the concurrent models, intercepts represent the adjusted sample means of RS for patients and spouses. Significant actor effects were found only for patients. For patients, supporting one's partner in the afternoon was associated with one's own higher RS that evening. For patients, there were also intrapersonal effects of feeling supported, and feeling criticized. If patients felt supported in the afternoon, their own RS was higher that evening. Conversely, if patients felt criticized in the afternoon, their own RS was lower that evening.Table Partner effects were obtained for being critical (patients only) and feeling criticized (spouses only). If patients criticized their spouse in the afternoon, the spouse reported lower RS that same evening, and if spouses felt criticized by their patient in the afternoon, their patient reported lower RS that evening.Table Results indicate that the nature and quality of communications between patients with cancer and their spouses were, as predicted, associated with concurrent ratings of RS and, to a lesser extent, later-day ratings of RS. The study used a heuristic framework based largely on the systemic transactional model, adapted to define communication broadly as not only stress-related, but also incorporating the construct of holding back from disclosure given its relevance to this population as demonstrated in prior studies  than did the lagged (afternoon to same-day evening). Communication and RS may have been more closely connected in the lagged situation, in which the two variables were measured more proximally in time. In the cross-lagged situation, a full night and much of the following day separated ratings of RS and communication, and intervening events may have affected both variables in unknown ways.r = 0.39, p < 0.01), and spouse report of feeling criticized in the afternoon was positively correlated with patient report of having been critical at that same time . All eight relevant correlations (four for enacted and perceived support and criticism rated in the afternoon and four for enacted and perceived support and criticism rated in the evening) were positive in sign and statistically significant at the p < 0.01 level. This suggests that appraisals were in fact attuned to partner behavior  and is commensurate with previous work demonstrating the value of partner-reports in couple research  were relatively high overall, certainly above the midpoint; see intercepts in Tables Collectively, our findings are consistent with previous studies that point to the importance of conceptualizing cancer as a “we-disease” , in part to minimize participant burden but also because we assumed that this variable would be relatively stable over the course of a day. Accordingly, we could not examine concurrent associations between communication and RS at the afternoon time point. Second, we did not assess conversational topic or valence of disclosures. We did, however, ask participants to rate the degree to which the topic was related to cancer and the importance of the conversation. Responses suggested that many conversations couples reported on may not have been directly cancer-related, but they were deemed relatively important. Thus, despite the rigors associated with treatment and recovery, couples frequently discuss important topics and concerns that may be unrelated to the cancer. It is unclear whether, in the context of cancer, there may be different communication patterns when discussing cancer vs. non-cancer topics, and whether these are differentially important for couples' RS. It is likely that couples infrequently engage in conversations specifically focused on the cancer in the absence of precipitating events, such as a doctor's visit or receipt of test results. Thus, studies using EMA methods may have difficulty capturing such conversations. Future studies could be designed to assess couples around the time of such events or could assess couples over multiple time periods  to increase the likelihood of capturing important cancer-related conversations. Future studies might also incorporate more specific questions about the topic of conversations and valence (positivity or negativity) of disclosures. A third limitation of this study is that our analyses were limited to same and next-day effects. Examining longer time lags may yield important information regarding the degree to which communication behaviors affect RS over time. Lastly, the fact that the couples in this study were relatively well-adjusted may limit generalizability.Despite these limitations, the present study has several notable strengths. First, the sample size was fairly large for this population and, unlike much of the literature on couple communication in cancer, includes a subset of patients coping with advanced disease (64%). Second, our sample includes both male and female patients and was drawn from two different geographical regions across the United States. Third, our response rate was quite high (90%), as was our completion rate (89%), thus demonstrating that smartphone-enabled EMA is feasible, even for an arguably stressed and vulnerable population. Fourth, the inclusion of reports not just of one's own behavior but of perceptions of one's partner's behavior add significantly to our understanding of the role of appraisal in the context of dyadic coping.In conclusion, findings from this EMA study underscore the importance of responsive communication in explaining day-to-day relationship adjustment among patients with cancer and their caregiving partners. These findings confirm predictions of the systemic transactional model with regard to emotion-focused positive supportive dyadic coping and negative dyadic coping (Bodenmann, SL, LP, JR, FK, TS, KS, JWB, JBB, NB, JG, VS, KW, and SZ secured funding for the study. SL, LP, JR, FK, TS, KS, JWB, JBB, and NB contributed to study conception and design. NG and BP recruited and consented participants, trained participants in the smartphone application, and tracked data collection. JG, VS, KW, and SZ supported and facilitated patient recruitment. MT performed statistical analyses. SL, MT, LP, JR, TS, and NG wrote the first draft of the manuscript. All authors reviewed and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.