Histological chorioamnionitis (HCA) is an infection of fetal membranes and complicates 5.2% to 28.5% of all live births. HCA is associated with increased mortality and morbidity in both premature and term neonates. Exposure to HCA may have long-term consequences, including an increased risk for allergic disorders and asthma later in childhood, the mechanism(s) of which are still not yet well understood. The objective of this study was to determine the mRNA transcriptome of cord blood mononuclear leukocytes from term neonates to identify key genes and pathways involved in HCA. We found 366 differentially expressed probe IDs with exposure to HCA . These transcriptomes included novel genes and pathways associated with exposure to HCA. The differential gene expression included key genes regulating inflammatory, immune, respiratory and neurological pathways, which may contribute to disorders in those pathways in neonates exposed to HCA. Our data may lead to understanding of the role of key genes and pathways identified on the long-term sequelae related to exposure to HCA, as well as to identifying potential markers and therapies to prevent HCA-associated complications. The prevalence of histological CA (HCA) in term neonates with spontaneous labor is 23.6–28.7%3. Approximately 500,000 to one million infants in the United States are born each year to mothers diagnosed with HCA. Exposure to HCA may have long-term consequences, including an increased risk for allergic disorders and asthma later in childhood6. Additionally, studies have demonstrated that exposure to HCA can also lead to developmental delay and cerebral palsy in preterm and term infants9. Asthma and other allergic chronic diseases during childhood affect greater than 7 million children in the United States10. Although HCA is associated with the development of asthma, allergic disorders, and neurodevelopmental impairment, the exact mechanism for these complications is unknown. Exposure to infection during late fetal life is likely to incite epigenetic changes, which may modulate the immune and neurological systems and increase the risk for development of neurological and allergic disorders later in life.Chorioamnionitis (CA) is an infection of the fetal membranes and placenta that complicates 5.2% of all live births12. More recently, differential gene expression in whole blood from preterm neonates exposed to HCA has been published13. However, fetal inflammatory and immune response to microbial infection differ between preterm (born before 37 weeks gestation) and term infants16. The effects of HCA on gene expression profile on cord blood mononuclear leukocytes in human term neonates have not been characterized. Our objective was to determine the mRNA transcriptome of cord blood mononuclear leukocytes from term neonates and identify key genes and pathways involved in HCA.Gene expression studies of cells and tissues have become a major tool for discovery in the pathogenesis of various diseases. Global gene expression by transcriptomic analysis can uncover gene signatures and help delineate molecular pathways involved in the development of asthma, allergy, and neurodevelopmental impairment in neonates born to mothers with HCA. Previous studies have reported differential gene expression patterns associated with preterm labor and lipopolysaccharide (LPS) stimulation of cord blood leukocytesTen term infants were enrolled in the study. Five infants had histological chorioamnionitis (HCA group), and five infants with no evidence of histological chorioamnionitis on placental histopathology served as the control group.18. The top down-regulated genes included two important antimicrobial proteins, lactoferrin (LTF) and cathelicidin antimicrobial peptide (CAMP).Comparison of the HCA group array data with the control group using transcriptome array console software revealed that 366 probe IDs were differentially expressed with a fold change ≥ 1.5 (p < 0.05). Of these, 198 probe IDs were significantly up-regulated  by loading 366 probe sets that were differentially expressed with HCA19. Seventy-three functions were modified by differential gene expression with exposure to HCA. Important functions modified with the exposure to HCA are listed in Table Pathway analysis was performed using Ingenuity Pathway Analysis (IPA) software 25.Based on fold change, the top up-regulated genes included chemokine receptor CCR2, T-cell receptor gamma variable-3 (TRGV3), and TRGV4. CCR2 is an important chemokine receptor that induces macrophage and monocytes recruitment to sites of inflammationIn utero exposure to HCA leads to fetal inflammatory response syndrome. Understanding the effects of the fetal inflammatory response on the programming of immune, respiratory, and neurological systems in neonates could lead to new ways of modulating these responses and improving long-term consequences. We have identified several key genes involved in immune function, inflammation, and lung development that are expressed differentially after exposure to HCA. These candidate genes are likely to play a critical role in long-term consequences including bronchopulmonary dysplasia (BPD), asthma, allergy, and immunological disorders in neonates exposed to HCA. This warrants further functional investigation.26. RTKN2 may prolong survival of inflammatory cells and contribute to an exaggerated inflammatory response in neonates exposed to HCA. CD99 is a cell surface protein involved in cell adhesion, migration, differentiation, and apoptosis, and influences processes associated with inflammation and immune response27. GIMAP family members play a role in T-helper cell differentiation28. GIMAP4 and GIMAP5 have a role in T-cell survival. GIMAP7 is also a regulator of lymphocyte survival and homeostasis29. NR4A3, a gene involved in protein coding that regulates Treg cell development through activation of FoxP3, and which may have potential for therapeutic target for immune disorders, was down-regulated30. NR4A3 also positively regulates neutrophil survival and homeostasis31.We report that several important genes involved in the immune system are up-regulated in cord blood mononuclear cells after exposure to HCA. RTKN2 has anti-apoptotic properties, is highly expressed in T-cells, and plays a role as a key signaling switch for regulation of genes involved in T-cell survival32. CXCL1 is a potent neutrophil chemoattractant that plays a role in the development of BPD33. IRAK2 forms a Myddosome complex with Myd88 and IRAK4, activating downstream NF-kB and MAPKs P38 and JNK, leading to inflammatory response34. The roles of these pro-inflammatory mediators downregulated by exposure to HCA need further investigation.Our data indicate that several key pro-inflammatory mediators are down-regulated in cord blood mononuclear leukocytes after exposure to HCA. The down-regulation of a few pro-inflammatory mediators likely is a modulating mechanism for the exaggerated inflammatory response induced by HCA. The inflammatory mediators downregulated by HCA include PDE4B, CXCL1, TARM1, and IRAK2. PDE4B degrades cyclic AMP, a second messenger involved in inflammatory process. Selective inhibition of PDE4B is a therapeutic target for inflammatory and allergic disorders36, and inhibition of CHRNA7 is an important therapeutic target for asthma36. Amphiregulin (AREG) is a member of the epidermal growth factor family and contributes to the regulation of cell proliferation. Recombinant AREG suppresses epithelial cell apoptosis in LPS-induced lung injury in mice37. Down-regulation of AREG by HCA may contribute to the development of BPD by increasing epithelial cell apoptosis. CAMP plays a critical role in innate immunity against invasive bacterial infections. CAMP is an important host defense against respiratory pathogens. Suppression of CAMP by HCA may increase the risk for recurrent respiratory infections in neonates exposed to HCA. Ramos-Martinez et al. showed that treatment with vitamin D reduced respiratory infections in patients with asthma, and this effect was mediated by increase in CAMP38. LTF is an important mucosal antimicrobial protein that is also downregulated in neonates exposed to HCA. Revenis showed that the level of LTF was lower in tracheal aspirate samples from premature infants who developed BPD39. Additionally, LTF can down-regulate allergic airway inflammation in asthma40. In an animal model of allergic rhinitis, LTF administration in the nostril alleviated allergic rhinitis and its mechanisms41. NFIL3 is the most strongly induced transcription factor by IL-4 stimulation and is a critical regulator of IgE production and airway hyper-responsiveness43. The target genes  for the canonical Wnt/B-catenin pathway are down-regulated after exposure to HCA. These target genes of Wnt/B-catenin pathways play a role in the pathogenesis of asthma46. Peng et al. demonstrated that Zc3h12a-knockout mice have severe spontaneous lung inflammation with an increase in IL-5- and IL-13-producing cells in the lung45. ZNF331 was expressed differentially in bronchial alveolar lavage cells from patients with asthma46. PTEN regulates airway smooth muscle contraction in allergic asthma47. Epithelial-mesenchymal transition (EMT) accounts for accumulation of subepithelial mesenchymal cells and contributes to airway hyper-responsiveness and remodeling48. Up-regulating expression of PTEN inhibits EMT and may be protective on airway modeling in asthma and BPD. PTGS2/COX2 increases lung inflammation and impairs lung development49. HBEGF overexpression is associated with airway remodeling and asthma50. Interestingly, we found that expression of PTGS2 and HBEGF was down-regulated in cord blood mononuclear cells after exposure to HCA. HBEGF was also downregulated in lung tissue after intra-amniotic LPS administration in an animal model of HCA51. The role of PTGS2 and HBEGF on lung development and lung inflammation needs further investigation.We also report that several key genes involved in lung development, BPD, and asthma are expressed differentially in cord blood mononuclear cells after exposure to HCA. Exposure to HCA upregulates CHRNA7, a key mediator of the biological effects of nicotine. CHRNA7 plays a critical role in lung development as well in the pathogenesis of asthma9. Our pathway analysis indicates that exposure to HCA affects genes involved in nervous system development, neurological disease, behavioral, developmental, and psychological disorders. Allard et al. showed that female rats exposed to in utero placental inflammation showed hyperactive behavior after puberty52. IPA analysis of our data indicates that HCA differentially expressed genes in the IL-17 signaling pathway, IL-17A signaling in airway cells, and IL-17A signaling in fibroblasts. Recent findings suggests that IL-17A in the fetal and maternal inflammatory response leads to fetal brain injury and neurological sequelae including cerebral palsy and potentially autism, schizophrenia, and multiple sclerosis later in life53.Infants and children born to mothers with HCA are at not only an increased risk for development of inflammatory, immune, and allergic diseases, but they are also predisposed to abnormal neurodevelopmental disordersOur study has several strengths. This is the first study reporting differential gene expression in cord blood from term neonates exposed to HCA. A similar study reported differential gene expression after exposure to HCA in preterm infants using whole blood, which does not allow distinction of the relative contribution of leukocytes. Our study is unique as global gene expression was performed in cord blood mononuclear leukocytes, not in whole blood. Further, our global gene expression data were validated by Real-Time PCR for the identified target genes. Six out of seven genes validated with Real-Time PCR showed significant change in the same direction as microarray data, with the seventh gene displaying trends in the same direction. Neonates are vulnerable subjects, and drawing a large amount of blood from them is ethically unacceptable. By using umbilical cord blood, we were able to collect a large amount of blood non-invasively without additional risks to the neonates.54. There is an inherent chance of finding differences in the gene expression due to multiple comparison; however, our results were validated by using Real-Time PCR.Our study also has several limitations. Our sample size of 10 neonates is small, but similar sample sizes have been used commonly in studies investigating differential gene expression using microarrayIn conclusion, HCA induces differential gene expression in cord blood mononuclear leukocytes from term neonates. We found novel genes and pathways associated with exposure to HCA, including key genes regulating inflammatory, immune, respiratory and neurological pathways. This differential gene expression may contribute to inflammatory, immunological, and neurological disorders in neonates exposed to HCA. Future studies can further validate differential expression of target genes in a larger cohort of neonates exposed to HCA. Our data may lead to understanding the role of key genes and pathways identified in this study on the long-term sequelae related to exposure to HCA. Functional studies on the identified genes and pathways could lead to the development of potential markers for the diseases caused by exposure to HCA and possible therapy to prevent those complications.All human protocols and procedures described in this study were approved by the Institutional Review Board of Thomas Jefferson University Hospital. All experiments performed in this study were approved and in accordance with the Nemours Institutional Biosafety Committee. The Institutional Review Board waived informed consent as this study was performed on discarded blood and placental tissue samples.This is a prospective observational study that examines differential gene expression in mononuclear leukocytes isolated from cord blood of term infants born to mothers with HCA. Cord blood and fetal membranes were collected from term neonates (37–40 weeks of gestation). Exclusion criteria were maternal infections other than HCA and complications of pregnancy including diabetes, hypertension, major congenital/chromosomal anomalies, and intrauterine growth restriction.et al.55. In brief, collected blood was diluted with an equal amount of phosphate buffered saline (PBS). 1 ml of PBS was mixed thoroughly with 16 ml of Ficoll-Paque plus and used as density gradient. 25 to 30 ml of diluted blood was layered on top of the Ficoll mixture and centrifuged at 400xg for 30 minutes. The upper plasma layer was collected and centrifuged to remove platelets. The cellular interface was then collected in a separate tube and washed with PBS containing 1 mM EDTA. Cells were washed with autologous plasma to remove platelets. Finally, the mononuclear leukocytes were washed with PBS, and 2 million packed cells per vial were saved at −80 °C for RNA isolation and microarray analysis.At the time of delivery, the umbilical cord was disinfected and cut at the placental side of the clamp. Cord blood was collected in sterile EDTA tubes, mixed thoroughly, and checked for blood clots. Mononuclear leukocytes were isolated by Ficoll-Paque Plus density gradient , following the manufacturer’s protocol and the method of Normann 56.Small pieces of fetal membranes tissue were washed with cold PBS and fixed in 10% neutral buffered formalin for 24–48 hours. Membrane pieces were processed and paraffin embedded in Histoplast LP . Samples were sectioned at 5 µm on a Leica RM2255 microtome  and floated onto Superfrost® Plus slides . The sections were heat immobilized for 60 minutes at 60 °C and were subsequently equilibrated to room temperature prior to staining. The slides were placed on Tissue-Tek Prizma stainer  and were deparaffinized with xylene, hydrated through a graded series of alcohols, and hydrated to water. Finally, the slides were stained with Harris hematoxylin  and eosin  and were dehydrated, cleared, and mounted in Permount® . Tissue samples were processed by the Nemours Histochemistry and Tissue Processing Core using standard workflows and operating procedures. The stained slides were examined by a pathologist (JC) and classified either as HCA  or no HCA Total RNA was isolated using Qiagen miRNeasy Mini Kit . RNA was quantified on a Nanodrop ND-2000 spectrophotometer , and quality was assessed by an Agilent 2200 TapeStation . 100 ng of RNA was used from each sample to prepare fragmented biotin-labeled cDNA by GeneChip WT PLUS reagent kit . The Affymetrix gene chips and Human Transcriptome Array 2.0 were hybridized with 5 µg of fragmented biotin-labeled cDNA in 220 µl hybridization cocktail, followed by target denaturation at 99 °C for 5 min and then 45 °C for 5 min. Hybridization was performed for 16 hours at 45 °C with a rotation of 60 rpm. An Affymetrix GeneChip hybridization wash and stain kit was used to wash and stain the arrays in GeneChip Fluidic Station 450. Chips were scanned on an Affymetrix GeneChip Scanner 3000 using Command Console Software . Expression Console Software v1.4.1 was used to perform quality control.Selected genes from microarray data were validated by Quantitative Real Time PCR with TaqMan Gene Expression Assay Mix from Applied Biosystems  following the manufacturer’s protocol. In brief, 200 ng of total RNA was reverse transcribed with a High-Capacity cDNA RT kit  in a total reaction volume of 20 µl. Real-Time PCR was performed in duplicate wells with 0.5 µl of cDNA preparation using TaqMan Universal PCR Master Mix and TaqMan Gene Expression Assay mixes specific for different genes. Actin B was used as a housekeeping gene, and data were collected by Quant Studio 12K Flex Thermal Cycler .https://www.qiagenbioinformatics.com/products/ingenuitypathway-analysis)19. Real-Time data were compared using Student t-test or Wilcoxon signed rank test between the HCA and control group.Expression Console Software was used to generate a Chp file from Affymetrix after sst-rma normalization. The HCA Group was compared with the control group using Transcriptome array console software v 1.4.1 . Genes with fold change ≥1.5 and p < 0.05 were identified as differentially expressed. Student t-test was performed for comparison of the two groups. Gene expression data are available at the Gene Expression Omnibus (GEO) database of the NIH under accession number GSE120855. Data were analyzed through the use of IPA (QIAGEN Inc., Supplementary Tables


We simulate a non-human primate’s alcohol drinking pattern in order to better understand temporal patterning of alcoholic drinks that can lead to the excessive intakes associated with alcohol use disorder. A stochastic mathematical model of alcohol consumption pattern is developed, where model parameters are calibrated to an individual monkey’s drinking history. The model predicts a time series that simulates a monkey’s alcohol intake in time, and we analyze this drinking pattern to understand the variations in day and night drinking, the lengths of drinks (intake in 5 or more consecutive secs), and lengths of bouts (1 or more drinks per 5 min occasion). This time series can predict a lifetime categorical drinking level , thus correlating an individual monkey’s parameters with distinct long term drinking classifications. The trajectories from a person’s first alcoholic drink to a diagnosis of AUD is an active area of research for diagnostic and prevention purposes , 12. To SIR models used to predict the onset of epidemics [In this paper we present a mathematical model that describes the drinking behavior of individual monkeys using data collected as part of the Monkey Alcohol Tissue Research Resource (MATRR) , a tissupidemics . A modifpidemics , where apidemics  where thCompartment models describe the behavior of a population using averages over a typically small number of subgroups. Agent-based models, such as the one described in Gorman et al. , can incOther models attempt to predict addictive behavior, for both alcohol and tobacco consumption, based on an individual monkey’s features , 21 . Ou2.2.1.2.1.1.Macaca mulatta) collected as part of larger animal cohort studies from the Oregon National Primate Research Center (ONPRC). This study includes cohorts designated “4,” “5,” and “7b,” Models were constructed from twenty-three rhesus monkeys  and remained in social groups until a minimum of three months prior to the onset of oral ethanol self-administration. At that time they were transitioned to individual cages according to established protocols .2.1.2.The alcohol self-administration protocol was reviewed and approved by the Oregon Health & Science University Animal Care and Use Committee and was in accordance with the guidelines for the care and use of laboratory animals .2.1.3.Adapted from the rodent literature, Schedule Induced Polydipsia (SIP) in primates has been an effective protocol to establish voluntary ethanol consumption  through the use of interval schedules of food delivery . Briefly2.2.2.2.1.Drinking panels with custom acquisition interfaces were used to capture self-administration data and food intake patterns , 22. Eac2.2.2.heavy drinking category. BD and LD are likewise collapsed into a single non-heavy category. This increases statistical power of the collapsed category for model testing and circumvents the need for including BEC as a discriminating factor as BEC data availability is currently not included in the predictive modeling.Each animal was classified into one of four well-defined drinking categories  based on percentage of open-access days of thresholded intake volumes, modified slightly from previously described methodology . VHD ani2.2.3.drinks. Drinks have a minimum effective resolution of 0.1 second and 0.1 mg of fluid, and continue as a single episode until the completion of an event. Less than 5 seconds between events is considered a single drink. A bout is defined as the volume of ethanol consumed without a 5-minute lapse between drinks, as defined by a previous principle component analysis of drinking patterns [Intake of ethanol and water are discretized events called patterns .2.2.4.http://www.matrr.com. It aims to maximize the use of NHP resources by limiting experimental redundancy, provide a repository of uniformly derived tissues and data imperative for long term alcohol research, and enhance cross-discipline integration. Data include drinking behavior on a per-second basis, blood protein and hormone information, molecular and genome data, imaging, and animal meta data among others. Previous research has used publicly available data to classify stable drinking categories in NHP [The Monkey Alcohol Tissue Research Resource  can be fs in NHP  and enabs in NHP .2.2.5.All data was collated and analyzed on the MATRR computing servers, twin computers, each running 4 Intel Xeon E5620 processors  at 2.4 GHz, having 4 cores per processor (16 cores per server), with 47 GB of memory. Statistical analysis and data processing was performed using Python and R.3.non-heavy or heavy drinker as described in non-heavy category is sub-divided into light drinkers (LD) and binge drinkers (BD), while the heavy category is made up of heavy drinkers (HD), and very heavy drinkers (VHD). These sub-categories are calculated from the average daily ethanol intake (ADEI) as described in The mathematical model of the drinking features that we develop in this section is a stochastic process that predicts second by second drinking of an individual monkey. At each time point, a monkey is in one of four states: not drinking (state 1), low (state 2), medium (state 3), or high (state 4) drinking. Transitions between each state, as well as the time spent in a given state, are described by random variables whose distributions can be calibrated to each individual monkey. Once a monkey’s drinking is simulated, the average daily alcohol consumption is calculated to classify the monkey as a 3.1.rate process determines the time spent in each state. In this model, there are two sets of rate processes, depending on whether a monkey enters a bout or not. A bout is a sequence of drinks such that the time between drinks is less than 300 seconds. If the time between drinks is more than 300 seconds, the bout has ended, and the decision to enter a new bout or not is made according to a fixed probability, p. The lengths of the bouts is described by the distribution, bQ(t). A diagram illustrating the model flow is shown in We describe the drinking process as a continuous time Markov process on the four states: not-drinking, drinking at a low, medium or high rate. The transitions between these states are given by a set of probabilities that depend only on the current state, and not on the past history. In addition, a stochastic i to to state j with Prob(i ↦ j) = P is:nlP, nmP and nhP, as well as the distributions giving the time spent in each state, can be estimated from the drinks taken by each individual monkey. In order to implement the model, we will need to estimate these transition probabilities, as well as the time spent in each state. Based on the experimental data, we choose to use five different probability distributions for the times between states. The distributions dT(t) and bT(t) describe the time spent between drinks in a bout or between bouts, respectively. The distributions iQ(t) describe the time spent in drinking state i, where i = 2 (low drinking rate), 3 (medium drinking rate) and 4 (high drinking rate) (see The Markov transition matrix describing the probabilities of moving from state ate) see .3.2.njP and to estimate the parameters of the distributions describing the times spent in each state, we start by examining the data for 31 monkeys, showing 22 hours of drinking per day for a year. We filter out drinks that are 1 second long and contain 0.2 mL of alcohol consumption. These drinks represent the lowest possible value that can be recorded and could be an indicator of slight disturbances in the balances, such as air bubbles in the tubing. As seen in the histogram in low drink; any drink between (and including) 0.6 and 1.1 is considered a medium drink; drinks with a rate above 1.1 are considered high drinks. In the simulations, we use the median values of each of the bins. We used the binned data to estimate the transition probabilities  as the fraction of drinks that were in each category, as well as the probability of entering a bout (p). Note that we are assuming that the probability of entering a given drinking state  is independent of the past drinking history.To estimate the transition probabilities, shape of the distribution. Thus, if the shape parameter is 1, the Weibull is the same as an exponential distribution. If the shape parameter is greater than one, it means that the rate of events increases with time; in our context, it means that a monkey who is drinking is more likely to stop drinking in the next second as the drink length increases. As shown in dT, the time between single drinks, defined as times less than 300 seconds, and the bT, the time between bouts, defined as non-drinking times greater than 300 seconds.For each drinking and non-drinking state we extract from the experimental data the corresponding drink lengths and breaks between drinks. A first exploration of the distributions of these data showed that the time spent in each drinking state was well-described by a Weibull distribution. This makes sense, since a Weibull distribution models a process for which the average number of events per unit time (the rate) is a power of the amount elapsed. The value of this power is called the ik) and rate (λi) parameters for each of the drinking states: 1 (not drinking), 2 (low drinking rate), 3 (medium drinking rate), and 4 (high drinking rate). We note that bQ (length of bouts), bT and dT had shape parameters equal to 1, i.e., they are well-described by an exponential distribution.We fit the parameters of the corresponding distribution to the data using a best-fit function in R. 4.We test the model described in For each of the 23 monkeys, we calculate the average rate of ethanol consumption and the average daily ethanol intake. The average daily ethanol intake is calculated in g/kg to account for the different monkey weights. As seen in Next we looked at the accuracy of the simulation by simulating 23 monkeys, comprised of 8 light drinkers, 6 binge drinkers, 5 heavy drinkers, and 4 very heavy drinkers. We ran the simulation 100 times and calculated the monkey’s drinking category in each simulation as described in 5.non-heavy, (LD or BD) or heavy, (HD or VHD). We can see from this table that the simulations of light drinkers are accurately classified in both cases, while the other categories show some inconsistencies. In fact, 100% of the light drinkers are classified correctly 100% of the time and three out of four of the very heavy drinkers are correctly identified 100 % of the time when the drinking categories are collapsed into heavy and non-heavy drinkers. Overall, approximately 80% of the monkeys are classified correctly in at least 95% of the simulations. The binge category has the lowest accuracy and is one of the hardest to classify. The definition of a binge drinker requires the monkey to have at least one binge which is represented by a BEC above 80 mg/dl. Our current model does not include a BEC model, thus for our future work we plan on incorporating a BEC model . In the next iteration of the model, we plan to add BEC to the model output by incorporating a pharmakokinetic-pharmakodynamic (PKPD) model of ethanol metabolism and elimination. PKPD models that describe BEC as a function of ethanol intake have been developed for humans –26. The In addition, we would like to extend our working model for male rhesus monkeys to include female monkeys. Ethanol consumption of female monkeys is impacted by menses, having a strong correlation with progesterone . By inclIn addition, both human and non-human primates are social beings, and drinking behavior among humans has been shown to be affected by social circumstances . Social n feature characteristics: F =  and we want to estimate the three transition probabilities, nlP, nmP and nhP which give the probabilities of transitioning from the non-drinking state to the low, medium and high drinking states, respectively. We might assume that the relationship between the features and these probabilities takes the form:D1, D2 and D3 will be estimated using an optimization procedure such as a maximum likelihood estimate (MLE).Now that we have a calibrated model of drinking behavior, we wish to use it to predict drinking behavior from physiological characteristics. In order to do this, we will use data as described in Baker et al.  and an uin silico, explore the occurrence and impact of AUDs, and, ultimately, provide a framework to rapidly evaluate pharmacological and behavioral interventions.Our belief is that a general, feature-driven probabilistic model of drinking behavior will help us understand the factors that lead to AUDs. Ultimately, we hope to use the model to independently test the impact of individual characteristics on drinking


Background: Video lectures are an increasingly popular format. They allow an individual choice of time, place and speed of learning.Objective: The aim of the present study was to compare whether video lectures are as effective as live lectures to impart the complete contents of the clinical part of the medical exam. The study also examines whether students prefer live or video lectures and for what reason.Design: In 2014, a preparatory course was held at the University of Göttingen to train medical students for the clinical part of the medical exams. Three-quarters of the participants received 41 four-hour lessons live, while the same lessons were shown on video to the remaining quarter. The assignment to the video group changed daily, so that all students saw both live and video lectures. To compare the effectiveness, it was evaluated for 205 students how video and live students answered the 301 multiple choice questions of the medical exam.Results: There is hardly any difference regarding effectiveness. 36,735 of 46,926 questions (78.283%) were correctly answered by the live group, while 11,617 of 14,779 questions (78.605%) were correctly answered by the video group . There were some differences in subjective evaluation: 48% of students preferred live lessons, 27% preferred video lessons and 25% stated ‘neutral’. The items ‘learning atmosphere’, ‘ability to concentrate’, ‘presence of other students’ and ‘acoustic intelligibility’ were assessed significantly better for the video courses than for the live courses. No item of the live course was rated better than in the video course.Conclusions: Video and live lectures are equally effective in preparation for the clinical part of the medical exams. Video lectures offer many benefits for the students and for the faculties, and may complement and partly replace conventional live events. Video recordings of lectures offer various benefits to the user. He can repeat the lecture subsequently at any time and place . StudentThe speed in which the lecture proceeds can be determined by the student himself . This isn = 59 4th-year medical students, 129 multiple-choice questions, average score and standard deviation live/video 87.56 (+4.80) vs 87.99 (+6.46)). Subjectively, however, the students thought they had learned more from the live lectures.Paegle et al.  comparedn = 66 medical students, 34 multiple-choice questions, live/video 90.2% vs 87.8%, p = 0.15). But while 88% of the students rated the live performance as very good, the video presentation was rated equally well by only 62%.Schreiber et al.  came to Spickard et al.  also foun = 85 students of dentistry, average score and standard deviation live/video 74.9 (+14.9) vs 68.6 (+16.3)). In their subjective assessment, however, 97% of the participants felt an improvement of their clinical abilities by the videos. Only 78.8% felt an improvement of their clinical abilities by the live lessons.Ramlogan et al.  came to In a study about the use of video lectures in pharmacology, Fernandes et al.  found beMost of the studies that compared live and video lectures in the medical field focused on a quite restricted part of the medical curriculum and use only a small number of test questions for the comparison of live and video lessons.For example, Paegle et al.  showed aThe purpose of this study is to evaluate whether video lectures for exam candidates for the second section of the medical examination have the same effect on the test results as live lectures. In addition, it is supposed to be investigated how the exam candidates evaluate the video compared to the live lectures.complete subject matter of the clinical section of the medical examination.What is new is that not only the effect of video and live courses as teaching methods is studied on a few, selected subjects, but that a comparison is made about the Do students gain the same results in their exams after taking part in video lectures as they do after attending live lectures?Are video lectures and live lectures subjectively assessed as equal by the students?How are video lectures perceived compared to live lectures regarding the learning atmosphere, the ability to concentrate, the usefulness for examinations, the intelligibility, the clarity and the tempo? How fascinating are video compared to live lectures?The following questions are supposed to be answered by the study:In Germany, the examination for the second section of the medical state examination is a uniform multiple-choice test (Type A questions), which is held twice a year at all medical faculties. A total of 320 exam items enclose the clinical fields as well as pharmacology, pathology, forensic medicine, social medicine and occupational medicine. The examination is passed if at least 60% of the questions have been answered correctly.In the spring of 2014, MEDI-LEARN was entrusted by the University of Göttingen to conduct a 41-day course to prepare students for the second part of the medical examination. Each day includes 4 h of lecture.A total of 296 students were registered for the Göttingen MEDI-LEARN course. As the largest available lecture hall was only designed for 272 listeners, the lecture had to be shown in parallel in a second lecture theater.For this purpose, MEDI-LEARN has recorded all teaching units on video before. The lecturers were asked to give the same lecture they usually give in the live course. In almost every case, the lecturers of the live course could be won for the video recording, exceptions were the two cardiology and the infectiology videos. In the background, the same PowerPoint® presentation was displayed that later was shown on a monitor (SmartBoard®) in the live course. The lecturers were shown from the head to the hip in the picture; next to the lecturer, the monitor with the presentation was visible.When the course scripts were dispersed at the start of the course, the students were distributed randomly to four counters. The groups should later be assigned either to live or video lectures.the lecturer (exceptions see above)date, time and approximate duration of the lecturethe Powerpoint® presentation usedaccompanying lecture notestransmission of the sound via the audio system of the lecture hallbreaksAt the introductory event, participants were given their timetable. Each lesson was offered simultaneously in two lecture halls: once live and once on video. Thus, the video could be shown under nearly equal conditions as the live lessons. The following features were the same for both events:Since most lecturers held two or more classes, the students often saw a topic of the lecturer live, another topic of the same lecturer on video. On each course day, three of the four groups saw the live lecture, while one group attended the video lecture. On the first day of the course, group 1 saw the video, on the second day group 2 and so on.As a result, each group saw a quarter of the lectures on video and three quarters live, with each group having seen a different course on video. In turn, this crossover setting was also used to evaluate every day of the lessons, both by video and live participants  according to the following criteria:The data were statistically evaluated with the software SPSS 24.p value ≤ 0.05 significantly.To test for independence of the characteristics correct/false and live/video readings, we performed a Chi-square test, p value ≤ 0.05, to assess the significance.In the study of the preference, we performed a Wilcoxon signed rank test on a sample, Since many items (and therefore hypotheses) were tested, we performed a Bonferroni correction and an α of Three hundred and one out of 320 questions could be assigned to the teaching units presented in the course. Of the 205 study participants, all the answers to these 301 questions are available, and it is known which of these contents were presented as part of a live video interview and which were taught in a video lecture.Thus, of the total of 61,705 questions, the contents of 14,779 questions were conveyed to the participants in a video lecture, while the contents of 46,926 questions were presented in a live lecture.A total of 36,735 of 46,926 questions (78.283%) were correctly answered by the live group, while 11,617 of 14,799 questions (78.605%) were correctly answered by the video group.The video students of this study were on average 0.332 percentage points better – the difference was therefore very small.One hundred and thirty out of 271 (48%) prefer live lessons, 69 (25%) rated ‘neutral’ and 72 (27%) prefer the video lessons. This shows that the students obviously prefer live lessons see .In the differentiated course evaluation, different picture emerges than in the case of preference: Here, the characteristics learning atmosphere, concentration capacity, presence of other students and the acoustical intelligibility in the video lectures are assessed significantly better than in the live lectures, but vice versa no feature of the live lectures is assessed better than in the video lectures.Previous studies have produced contradictory results regarding the effect of video readings compared to live lectures.Paegle et al.  found onp = 0.049 in the variance analysis). However, the results were reached after a lesson in dental examination techniques. Perhaps, the clinical practical topic of this study explains that the live listeners performed better.In contrast to this, Ramlogan et al.  found siPrevious studies about the efficacy of medical video lectures were only on few, selected subjects. Paegle et al.  comparedThe present study is based on more than 160 lectures on the almost complete contents of the clinical section of the medical examination. It was also confirmed with this range of material that live and video lectures have the same effect on the examination performance.n = 61,705. The effect strength in this study was ω = 0.003337 significantly smaller. If there is a difference between live and video students, it is negligible.For an α = 0.05 and an assumed β of 0.2, an effect strength of only ω = 0.012128 could have been measured at p <0.0003). In Spickard et al. [p = 0.03). Schreiber et al. [In the subjective evaluation of the students, the live course was judged better than the video course in most studies. In Paegle et al. , studentd et al. , 96% werr et al. , as wellr et al. , found iKalwitzki et al.  came to In this study, the question of preference for live or video course comes to the following result: 48% decide for the live, 27% for the video course and 25% are neutral on this question. This result is consistent with most previous studies. In this study, however, the course evaluation gives a different picture than it emerges from the preference: Here, the characteristics of the learning atmosphere, the ability to concentrate, the presence of other students and the acoustical intelligibility in video conferencing are assessed significantly better than live, but vice versa no feature of the live course is judged better than in the video course.A weakness of the present study is that because of voluntary participation, a selection of the sample cannot be ruled out. But since almost the whole of the year took part in the course, the students of the Göttingen University can be regarded as an almost complete and sufficiently representative sample.In addition, the course was intended exclusively for candidates in the Second Section of the Medical Examination. The course covers all major clinical subjects, but it conveys theoretical and less clinical practical knowledge. According to Davis et al. , resultsAs most of the other investigations on video and live lectures, this study comes to the conclusion that both formats are equally effective.Video lectures could increase the quality of the teaching, focus the university lectures more on the mediation of research and even improve the practical training through the possibilities of the distance learning. And finally, a video lecture is more expensive in the production than a single live lecture, but it can be repeated as often and for as many students as desired, which would ultimately result in a considerable cost savings.


The authors wish to make the following corrections in their published paper in Sensors .−4 RIU by tracking sharp fringes appearing in the slow-light regime near the edge of the guided band.” The last name of the first author and the detection limit value are incorrect. It should be revised as follows: “Later, in 2010, García-Rupérez et al. achieved an improved DL of 3.5 × 10−6 RIU by tracking sharp fringes appearing in the slow-light regime near the edge of the guided band.”In the last paragraph of page 8, the original article printed “Later, in 2010, Skivesen et al. achieved an improved DL of 6.75 × 10In the reference section, reference number 116 was incorrect. It was printed as “Joannopoulos, J.D.; Johnson, S.G.; Winn, J.N.; Meade, R.D. Photonic Crystals: Molding the Flow of Light; Princeton University Press: Princeton, NJ, USA, 2011.” It should be revised as follows: “Popović, M. Theory and design of high-index-contrast microphotonic circuits. PhD Thesis, Massachusetts Institute of Technology, Cambridge, MA, USA, 2008.”Opt. Fiber Technol.2018, 40, 13–17.” It should be revised as follows: “Yoshida, S.; Ishihara, S.; Arakawa, T.; Kokubun, Y. Highly sensitive optical biosensor based on silicon-microring-resonator-loaded Mach–Zehnder interferometer. Jpn J. Appl. Phys.2017, 56, 04CH08.”Reference number 193 was incorrect. It was printed as “Martincek, I.; Kacik, D. A PDMS microfiber Mach–Zehnder interferometer and determination of nanometer displacements. The authors would like to sincerely apologize for any inconvenience caused to the readers by these changes. References


Importantly, the video also significantly reduced negative attitudes (p < 0.05), and attitudinal ambivalence (p < 0.001). The culturally targeted video shows preliminary evidence in improving psychosocial outcomes related to GCT uptake in Latinas at risk for HBOC. This intervention is a promising easily-disseminable strategy to address disparities in GCT utilization.Latina women at risk of hereditary breast and ovarian cancer (HBOC) have lower awareness, knowledge, and use of genetic counseling and testing services (GCT) than non-Latina Whites. Few interventions have been developed to reduce these disparities among at-risk Latinas. This pilot study assessed the impact of a culturally targeted narrative video developed by our team. The study included 40 Latina immigrants living in the United States who were at risk of HBOC, including affected and unaffected women. We assessed pre-post differences in psychosocial outcomes. Participants were 47.35 years old on average (SD = 9.48). Most (70%) were unaffected with cancer, had an annual income of $40,000 or less (65%), an education of High School or less (62.5%), and were uninsured (77.5%). The video significantly enhanced knowledge ( BRCA1/2 gene mutations are the most commonly identified mutations that increase the risk of hereditary breast and ovarian cancer (HBOC) [BRCA1/2 mutations are three times more likely to develop contralateral breast cancer than non-carriers [BRCA1/2 gene test result impacts treatment choices in women diagnosed with cancer and risk management in women with and without a cancer diagnosis [r (HBOC) ,4. Breascarriers . Nationacarriers ,7. Genetiagnosis , includiiagnosis . Risk-reiagnosis ,11, and iagnosis . BRCA1/2 mutations is at least double that of the general population. [Breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death in Latinas . Among Lulation.  Despite ulation. ,16,17,18ulation. . Disparities in GCT awareness are pervasive . In a poEnsuring that complex genetic information is understandable and culturally appropriate is critical, especially for the most vulnerable subgroup of Latina immigrants with low education, low health literacy, and limited English proficiency. Substantial evidence documents at-risk Latinas’ preference for interventions and education materials in Spanish that include plain language, visual aids, and a narrative format ,28,29. EWe developed a culturally targeted Spanish-language narrative video for at-risk Latinas. The development process is reported elsewhere . BrieflyIn addition to TPB constructs, we targeted other constructs that have emerged from prior literature. Prior research suggests that once informed, Latinos tend to hold positive attitudes towards GCT ,29,38. HThis paper presents psychosocial outcomes from a pre-post pilot study of the culturally targeted video described above. Guided by the key psychosocial variables within the expanded TPB, we assessed change in knowledge as a primary outcome and change in attitudes, subjective norms, perceived control, behavioral intentions, anticipatory emotions, and ambivalence as secondary outcomes. We hypothesized that, after viewing the video, women would exhibit increased knowledge, subjective norms, perceived control, and behavioral intentions toward GCT and more positive attitudes compared to their reports immediately before watching the video. We also hypothesized that watching the video would enhance favorable anticipatory emotions and reduce ambivalence towards participating in GCT. The goals of this paper are to (1) report immediate pre-post differences in knowledge and other psychosocial outcomes and (2) explore whether education and health literacy were related to changes in knowledge.Our primary recruitment method was through partnerships with two community-based organizations (CBOs) that provide patient navigation services to Latinas in the mid-Atlantic area of the U.S. Additionally, we conducted community outreach via flyers and radio, and contacted women from a research registry who had agreed to be contacted for future studies . In the At the in-person meeting, the RAs obtained participants’ verbal consent and administered verbally a pre-video baseline survey that lasted between 20–30 min. All assessments were completed individually, in a private room, and in Spanish. After completing the pre-video survey, participants watched the 18 min video. Immediately after the video, the RAs administered verbally a post-intervention survey that lasted between 20–30 min. Participants received a $30 gift card. Interested participants were referred to free or low cost GCT through patient navigators at our partner CBOs. The Georgetown University Institutional Review Board approved all the study procedures. We assessed sociodemographic factors in the pre-video survey, including age, race, country of birth, years of education, marital status, income, and insurance status. Participants answered Yes/No to “In the past year, have you needed to visit a doctor, but could not go because of cost?”, and also answered “How difficult is it for you/your family to meet monthly bill payments?” with response options ranging from 1—not at all difficult to 5—extremely difficult . We asseWe used a 4-item scale to assess GCT awareness . ParticiWe assessed psychosocial outcomes immediately before and after the video, including knowledge, behavioral intentions, attitudes, perceived control, subjective norms, anticipatory emotions, and attitudinal ambivalence.Knowledge: We measured three distinct types of knowledge. We assessed breast cancer genetics knowledge with Erblich and colleagues’ (2005)  validateBehavioral Intentions: We used two items validated with this population to assess participants’ intentions/likelihood of having genetic counseling and testing, respectively, in the next three months with response options ranging from 1—not at all likely to 5—extremely likely . Based on recommended guidelines  we develAttitudes: Positive attitudes were assessed with two items  on a 7-point Likert-type response (from 1—strongly disagree to 7—strongly agree). Higher scores indicated higher favorable attitudes. Negative attitudes were measured with two items  on a 7-point Likert-type response (from 1—strongly disagree to 7—strongly agree). Higher scores indicated higher negative attitudes.Perceived control: Perceived control was measured with two items on a 7-point Likert-type response (from 1—strongly disagree to 7—strongly agree) . Higher scores indicated higher perceived control. Since the alpha was low, we analyzed each item separately (α = 0.75 pre and α = 0.30 post).The people I care about would approve of me going to GCT”) while descriptive norms measured participants’ beliefs about genetic counseling uptake of the majority of people like them (“Most people like me (at-risk of HBOC) receive GCT”). Higher scores indicated higher injunctive and descriptive norm, respectively.Subjective Norms: Subjective norms were measured with two items on a 7-point Likert-type response (from 1—strongly disagree to 7—strongly agree). Injunctive norms evaluated to what extent loved ones approve that participants receive genetic counseling in the next three months . One item captured the cognitive aspect of attitudes , and the other item measured the affective aspects of attitudes . Higher scores indicated higher cognitive and affective ambivalence, respectively.Anticipatory Emotions: Participants rated to what extent they felt six different positive emotions ‘right now’  and six negative emotions  when thinking about participating in genetic counseling in the next three months on a 7-point Likert-type response (from 1—strongly disagree to 7—strongly agree). Following prior studies ,56,57, wp < 0.050. All statistical analyses were performed using SPSS 25 [We used descriptive statistics to summarize the sociodemographic data, and clinical data, genetic counseling awareness, and genetic counseling/testing referrals. We conducted paired t-tests to evaluate changes (from before the video to after the video) in the psychosocial factors. To examine changes in the proportion of correct responses on the items from the main information knowledge scale, we conducted a binomial Mc Nemar test. To assess whether changes in the three knowledge scales varied by education and health literacy, we stratified the sample into participants with low vs. high education (High School or below (n = 25) vs. some college and more (n = 15) and low (n = 16) vs. high (n = 24) health literacy . Then conducted paired t-tests to evaluate changes in knowledge separately for each stratum. The significance threshold was set at  SPSS 25 . Participants had an average age of 47.35 (SD = 9.48), and most were born in El Salvador (52.5%), followed by Peru (15%). Most were married (60%), had an education of High School or lower (62.5%), annual household income of $40,000 or lower (65%), and were uninsured (77.5%). Additionally, 40% reported feeling not comfortable/kind of comfortable completing medical forms by themselves. Most were unaffected with cancer (70%). Among the 12 women affected with cancer, 10 were diagnosed with breast cancer and two with ovarian cancer. Awareness was very low as 83.9%, and 83.3% of participants had heard almost nothing or relatively little about genetic counseling for hereditary breast cancer and for hereditary ovarian cancer risk, respectively. No participants had been referred to genetic counseling, and only 10% had been referred to genetic testing but had never received the genetic testing see .D.” After the video, knowledge significantly increased in the three distinct knowledge measures including breast cancer genetics knowledge  = 6.81, p < 0.001), genetic counseling knowledge  = 3.78, p = 0.001), and the main information knowledge scale  = 9.26, p < 0.001) (see p < 0.001). Also, the proportion of the sample (50% correct responses) who correctly identified breast cancer diagnosis at 50 or younger as a risk factor of HBOC increased significantly (95% correct responses) after the video (p < 0.001). Additionally, the three knowledge measures significantly increased in women with low and high education and in women with low and high health literacy (see Knowledge levels were low to moderate before the video. The estimated mean differences between pre and post are denoted by “001) see . The vidracy see .Attitudes: lthough participants held initial positive attitudes, watching the video significantly increased favorable attitude towards receiving genetic counseling  = 2.12, p = 0.04) and significantly reduced negative attitudes  = −2.33, p = 0.02). Behavioral intentions: The video significantly enhanced intentions to participate in counseling  = 3.62, p = 0.001) but there were no statistically significant differences in intentions to participate in genetic testing  = 0.21, p = 0.84). TPB Outcomes: Participants had high ratings for most TPB variables  before watching the video, potentially creating a ceiling effect for some of the variables. D = 0.16, t (37) = 1.97, p = 0.057). Descriptive norm presented a similar significance tendency  = 1.71, p = 0.09). Perceived control: Participants did not significantly change their confidence to be able to go to a genetic counseling session after watching the video  = 0.68, p = 0.50). A non-significant result was also obtained when we evaluated how much going to a genetic counseling session in the next three months depended on them  = 1.00, p = 0.32) (see Subjective norms: The video increased the injunctive norm approaching significance (.32) see . D = −1.10, t (38) = −2.62, p = 0.012) and the affective ambivalence  = −2.02, p = 0.050)  and mixed feelings  towards participating in counseling. The video significantly reduced both the cognitive (050) see .D = 0.22, t (39) = 2.10, p = 0.04) while the negative emotions remained low and similar  = −1.54, p = 0.13)  = 2.16, p = 0.037) and pride  = 2.56, p = 0.014). Hopefulness approached significance  = 1.98, p = 0.054).Anticipatory Emotions: Despite having high initial ratings of positive anticipatory emotions, watching the video significantly improved the positive anticipatory emotions (.13) see . The posOur culturally targeted narrative video constitutes one of the few psychoeducational interventions about HBOC targeted to Spanish-preferring, at-risk Latina women ,59,60. TAt-risk Latina women are significantly less likely to use GCT services compared to NHWs ,17,18. IIn addition to knowledge gains, our video enhanced other psychosocial outcomes that have been associated with GCT uptake . AlthougStudy participants had moderate levels of ambivalence at baseline , but watching the video significantly reduced ambivalence towards GCT participation. It is important to highlight that the relationship between attitudes-intentions-behavior is weaker for people who score high on ambivalence ,42. The The emotional reactions after the video are important, considering that the affective components are especially relevant when studying health-risk behaviors . Future-Results from this study also highlight the potential of the video to target historically identified barriers that Latinas in the U.S face for reception of GCT, including language barriers and suboptimal referrals ,21,47,69This culturally targeted narrative video constitutes one of the few psychoeducational interventions about HBOC targeted to at-risk Latina women. Our video contributes to and expands prior interventions for at-risk Latinas such as flip charts, or presentations that had only been piloted in small focus groups ,16. We pDespite the strengths, the study also has some limitations. The small sample size precluded us from conducting multivariate analysis and may have impacted the power to detect significant differences. Future studies with larger samples are warranted. The completion of the pre and post surveys at the same study visit could have resulted in a response burden. However, the use of a less cognitive burdensome mode of administration   and the Our culturally targeted educational video can help overcome several barriers that Latinos face to participation in GCT. Given the scarcity of materials in Spanish, low awareness of GCT, and limited knowledge, our easy-to-disseminate video represents a promising strategy to reduce disparities in GCT uptake.


Marriage, a marker event for the transition from adolescence to young adulthood, brings with it many changes, including shifts in values, new roles, and adjustments in a couple’s relationship. Marriage also appears to generate shifts in alcohol use and alcohol consumption, changes that can occur even before the marriage ceremony takes place. Alcohol plays a role in marital violence, marital quality, and marital disruptions. However, high levels of individual alcohol consumption in a marriage do not uniformly lead to lower marital quality. Rather, it may be the nature of a couple’s drinking partnership  that has the most effect on the health of a marriage. One of the most important transitions in life, both generally and from an alcohol-problems perspective, is marriage. Marriage not only involves major changes but also serves as a marker event for the transition from adolescence to young adulthood. Often, but not uniformly, marriage occurs with other milestones, such as stable adult employment and parenthood. As a developmental transition, marriage carries with it a variety of tasks that can fundamentally alter both the individual’s view of him- or herself and the way in which the broader social network behaves toward the individual and the couple. Newly married people often demonstrate a marked shift away from more individualistic values and toward more interdependent and socially positive values , consistent with the adoption of the new role of spouse. Major tasks that come with marriage involve the establishment of a mutually satisfactory relationship and the reestablishment or redefinition of ties, both as individuals and as a couple, with each member’s extended family and peer network . AlthougMarriage also appears to engender a vital transition for newlyweds with respect to alcohol use and alcohol problems. Although much has been written on alcohol’s effect on married life, little research has taken place on the role of alcohol during the transition to and early years of marriage. This article attempts to shed some light on this important developmental time period.Alcohol use, particularly heavy alcohol use,Alcohol use might play a role in how people select their partners: Considerable research suggests that alcoholics are likely to be married to alcoholic spouses see . HoweverThe effect of marriage on drinking is apparent even before the marriage ceremony has been completed. For those couples who marry at a developmentally normative age , researchers have observed drinking changes in the year preceding the marriage. For example, These declines continue into the first year of married life. The Buffalo Newlywed Study (BNS), a 3-year prospective study of couples applying for marriage licenses, has provided a more detailed description of the changes in drinking behavior that occur during the time period preceding marriage. The BNS assessed more than 500 couples at the time they applied for their marriage license, at their first anniversary, and at their third anniversary. Couples were evaluated with respect to drinking behavior, marital characteristics , and personality characteristics . The drinking changes that occurred in the first year of marriage were not simply a generalized reduction in average alcohol consumption; context-specific changes also took place. Although the proportion of time that the husband drank at home increased significantly over the first year, the relative amount of time he spent drinking with his wife present did not change. In addition, the typical amount he drank with his wife present declined, but the typical amount he drank in her absence did not. Thus, for men, the changes in drinking patterns related to marriage may be restricted to occasions in which the husband drinks with his wife present and to drinking in a less risky context, such as in the home. Similarly, the proportion of time that the wife drank at home also increased during the first year of marriage. Unlike the husbands, however, the wives reduced their typical quantity both when the husband was present as well as when the husband was absent. For women, then, the effect of marriage on drinking may be independent of their husband’s presence.Despite the overall reduction in drinking and drinking problems, a sizable proportion of the married men and women did not change their alcohol consumption after marriage; some even increased their drinking during the first year of married life. Although marriage affects drinking and drinking problems, drinking also has an effect on marital quality. It is commonly assumed that frequent or heavy drinking has a detrimental impact on marital conflict and satisfaction, but this pattern is not uniformly the case. Evidence suggests that drinking may have both positive and negative effects on a marriage.prospectively predicts the extent of marital violence early in marriage; and that this predictive relationship cannot be attributed to sociodemographic , personality , or relationship  variables  in understanding the effects of drinking on marriage. The establishment of a shared household increases each partner’s sphere of influence over the other. Each partner becomes a salient feature of the other’s drinking context, both through direct modeling as well as through the explicit or subtle communication of attitudes and values about drinking. Marriage thus profoundly alters a person’s drinking context: With marriage, a “drinking partnership” is molded from the separate premarital drinking habits of each partner. Together, couples establish norms about such things as whether alcohol is served with meals, whether the refrigerator or alcohol cabinet is kept stocked, whether guests are offered drinks, and so on. Drinking partnerships may vary from a pattern in which the partners have one or two drinks together each night in the privacy of their home to one in which each partner separately drinks one night per week at a bar with his or her own friends. Drinking is incorporated into the fabric of a marriage in diverse ways. It may be the partnership, rather than the independent effects of one partner’s drinking, that is critical to marital functioning.nondiscrepant) to those of their husbands. When both the husband and the wife drank either frequently or infrequently, marital adjustment was higher. Nondiscrepant drinking quantities , however, were not predictive of higher marital quality for either husbands or wives.Analyses of the BNS data  have supdiscrepant partner consumption patterns. In both of these profiles, the spouse who consumed more alcohol showed a pattern of higher quantity than frequency of consumption. The significant relationships between drinking partnership profiles and marital functioning held after statistically controlling for each partner’s average daily consumption. This result strongly suggests that the nature of a couple’s drinking partnership affects both husbands’ and wives’ marital quality independent of alcohol consumption.To capture more fully the complexity of the notion of a drinking partnership, The empirical research suggests that the transition to marriage in early adulthood is associated with declines in alcohol consumption and alcohol-related problems. This transition also is associated with major structural and psychological changes at the individual, couple, and social-network levels. It is unclear, however, which of these changes are responsible for the “protective” effects of marriage on alcohol consumption. Furthermore, it is critical that research not uniformly view drinking as completely inimical to marriage. Clear risks to the relationship are associated with problem drinking. However, an assessment of the functional requirements of a marriage, along with an examination of how individual drinking patterns and, most critically, the drinking partnership affect those requirements, would further a thorough understanding of the effect of alcohol use on marriage.


No consensus exists regarding the best reconstruction style after total gastrectomy (TG). Roux-en-Y oesophagojejunostomy is a simple option for gastrointestinal tract reconstruction. Recently, jejunal pouch reconstruction has been suggested as an appropriate approach. We compared the postoperative outcomes of the two surgical approaches using a well-characterized cohort of gastric carcinoma patients.A total of 60 patients who underwent TG were divided into two groups according to the reconstruction style. Both groups were compared regarding patient characteristics, perioperative data and quality of life (QoL), which was assessed using the Spitzer QoL index (QLI) and Visick grade. The incidence of long-term surgery-related complications, including reflux oesophagitis, dumping syndrome, and retention syndrome, was also compared to evaluate postoperative restoration.p < 0.05).Both study groups were comparable with respect to general patient characteristics. No mortality or no significant differences in surgery-related data were found except in the operation time. Compared to Orr Roux-en-Y reconstruction, pouch reconstruction was associated with a longer procedure time, a lower incidence of dumping/retention syndrome and better QoL parameters (In this study, jejunal pouch reconstruction after TG was superior to the traditional Roux-n-Y oesophagojejunostomy with respect to improved dietary intake and QoL. Gastric cancer is a common gastrointestinal (GI) tract malignant tumour disorder with high morbidity and mortality , and surIn 1952, Hunt and Cope , 9 firstSixty patients who underwent abdominal TG with jejunal pouch reconstruction or simple Roux-en-Y anastomosis at three tertiary hospitals between January 2010 and December 2015 were reviewed. The clinicopathological data are shown in Table To evaluate postoperative recovery, two validated and internationally accepted tools were employed in this research for data collection: the modified Spitzer quality of life index (QLI) and the Visick grade , 13. Thep-value of < 0.05 was considered statistically significant.Variables that fulfilled the criteria for a normal distribution were analysed using the Kolmogorov–Smirnov test.Normally distributed data are expressed as the mean ± SD and were analysed by two-tailed Student’s t tests.The chi-square test was used to assess categorical data. Statistical analyses were performed using SPSS software, version 19.0.A difference between groups with a p = 0.01).Other severe surgery-related complications, such as pancreatic fistula and abdominal abscess, were not found in our cohort. Patients were generally satisfied with the surgical outcomes, and the vast majority of patients reiterated that under the same circumstances, they would opt for pouch reconstruction again(78.1%).Up to 3 months after the operation, significantly less abdominal discomfort, appetite loss and weight loss were observed in the jejunal pouch group than in the conventional Orr-RY group.Similar results were observed again during the follow-up period . Interestingly, both sets of data related to postoperative rehabilitation improved over time in these patients, probably due to general improvements in diet control and the adaptive capacity of body over the long term .However, at the last follow-up time point, the jejunal pouch procedure was no longer superior to Orr Roux-en-Y with respect to the Visick grade (I/IIIvsIII/IV at 12 months: p = 0.137).Regarding prognostic indicators, the PNI was better in the jejunal pouch group, although the difference was not significant  of the reconstruction style to the intrinsic properties of the particular surgical technique. Moreover, with the greater application of the reconstruction technique, surgeons will become more proficient, and the operation times will become shorter. In recent years, with the application of stapling, the reconstruction procedure has become rapid, safe and practical .With resIn our opinion, jejunal pouch reconstruction has several advantages. It may alleviate postoperative gastric-related complications because the resulting curvature has valve-like characteristics that mitigate reflux disease and effectively change the direction of food,thereby giving the chyme more time to be assimilated.Additionally, this reconstruction style is not restricted by the intestinal diameter, thereby reducing the risk of strictures. Moreover, the OrrRoux-en-Y procedure produces a distal closed loop of jejunal bowel near the anastomotic site, easily leading to pouchitis. Thus, the pouch technique appears to be a more physiological reconstruction method for application in patients undergoing TG.There were certain limitations in our research. First, the short follow-up period—just 12 months—was a limitation, and the data analysed were inferior to data more indicative of the dynamic state; additionally, the sample size was small. Second, a relatively simple questionnaire was involved in the data analysis, and other parameters might also influence the analysed outcomes. Clearly, the perceptions of the definition of functional recovery may also lead to an unconscious bias among participants completing the modified Spitzer QLI questionnaire and the Visick grade self-assessment form; thus, the data rely on the individual understanding of each patient. Finally, the exact mechanism mediating the reduced incidence of dumping syndrome and retention syndrome and the improved daily QoL after pouch reconstruction was not clear. Regarding the latter, the morphological similarity of the reconstruction might play a critical role in this process.In summary,TG with jejunal pouch reconstruction for gastric cancer is feasible and safe.It combines the advantages of improved digestive absorption and storage and improved QoL. Based on our results, jejunal pouch reconstruction appears to be a superior surgical approach. However, more randomized controlled clinical studies are essential to verify the benefits of this procedure.


Video magnification reveals important and informative subtle variations in the world. These signals are often combined with large motions which result in significant blurring artifacts and haloes when conventional video magnification approaches are used. To counter these issues, this paper presents an amplitude-based filtering algorithm that can magnify small changes in video in presence of large motions. We seek to understand the amplitude characteristic of small changes and large motions with the goal of extracting accurate signals for visualization. Based on spectrum amplitude filtering, the large motions can be removed while small changes can still be magnified by Eulerian approach. An advantage of this algorithm is that it can handle large motions, whether they are linear or nonlinear. Our experimental results show that the proposed method can amplify subtle variations in the presence of large motion, as well as significantly reduce artifacts. We demonstrate the presented algorithm by comparing to the state-of-the-art and provide subjective and objective evidence for the proposed method. Video magnification techniques are useful for enhancing tiny variations, which extends to a series of applications. Consider, for instance, detecting respiratory rate either from fluctuation of chest or from skin color changes ,2, estimVideo magnification technique acts like a microscope for revealing small signals which would otherwise be invisible to the naked eye. Recently proposed methods mainly follow a Eulerian perspective that is a terminology borrowed from fluid mechanics. Compared to Lagrangian approaches , EuleriaSeveral recent methods are proposed to deal with the large motion while still enhancing small signals, such as the dynamic video magnification (DVMAG) , the depIn this paper, we present an amplitude-based filtering algorithm for small signals magnification in the presence of large motion. The method does not require manual drawn pixels of interest and additional information such as depth information. Instead, our algorithm copes with large motions by the amplitude-based filtering while still amplifies the small changes in video. We show that, by applying the linear EVM  and phasThis paper is structured as follows. In There are two main parts in video motion magnification: (1) motion expression and (2) small motion signal extraction or separation. For motion expression in video, existing approaches are divided into two main categories: Lagrangian perspective and Eulerian perspective. In a Lagrangian approach, the motion of image pixels or patches is tracked over time and computed based on optical flow. In contrast, video magnification from Eulerian perspective characterizes motion by looking at temporal signals at fixed image locations.x and time t. An advantage of the Eulerian approach is that it is more efficient and less prone to error than the Lagrangian. On the other hand, in Eulerian approaches, the temporal filters are widely used to extract the signal of interest for magnification, such as classical band-pass filter and second-order Laplacian filter. Consider a general case of subtle motion in video containing position displacement, rotation or illumination variation. We formalize this by a special case of one-dimensional signal which is described as a composite function under constant lighting. This analysis generalizes directly to motion in two dimension. In , the genx, and as such the motion or color changes can be expressed as Based on this model, the linear magnification method  assumes near EVM  uses theZhang et al.  presenteInspired by the Eulerian approaches, we aim to extend these methods to handle the large motion while still magnifying the small changes. In the next section, we present an amplitude-based filtering algorithm for video magnification within large motion.x with respect to a composite function We first assume that the input video records a stationary scene containing small changes and other large motion. To give intuition that the image intensity variations correspond to motion, we also consider one-dimensional temporal signal as a composite displacement function. For the input signal Equation (2)IThis is a special case of Equation  and an eEquation  as EquatEquation (3)θ(t)=δnear EVM  and the The goal of video magnification is to synthesize the output signal as Equation (4)I˜IThat is, the pixel at each position in video is linearly related to the deviation around t, as Equation (We are interested in the difference at each pixel between frames of the video at times 0 and Equation (6)DBecause near EVM . DissimiAfter applying frequency domain filters, we can capture the small deformation Equation (8)I^I^:(10)SDWA,ω=For video motion magnification, phase-based Eulerian approach  has subst and a reference frame is computed as Consider a case of one-dimensional signal under global translation over time. For the image intensity Equation )(12)I Core(TM) i7-3770 CPU and 8 GB RAM. For all videos, we process the video frames in YIQ color space. We provide representative videos and results for depicting our magnification method in this study. We compare our algorithm against three video magnification approaches: the linear EVM , PVM 1212 and EuWe apply the improved linear EVM for color magnification and the modified phase-based approach for motion processing. For color magnification, we use a Gaussian pyramid to decompose each frame into different spatial frequency bands and process the intensity changes in the frequency domain. For motion magnification, we decompose each frame to get magnitude and phase information, using the complex steerable pyramid with half-octave bandwidth filters and eight orientations, and only deal with the phase changes temporally.https://www.youtube.com/channel/UCqt_KRqgK0CNeI27gs9Dm8g.In addition, we provide the qualitative evaluation on real sequences and quantitative evaluation against ground-truth on synthetic ones. We also provide all experimental results, including real videos and synthetic ones, on Youtube: near EVM  reveals near EVM  can magnnear EVM   , root meOur results are similar to the motion acceleration magnification  when theThe disadvantage of the presented algorithm is that the magnification results are sensitive to the parameter (amplitude threshold) of the amplitude-based filter. If the maximum threshold is too large, the undesirable large motion components will be introduced which are magnified as well. A maximum threshold with too small value may cause another problem that it will suppress the signal of interest components. Another limitation of the presented algorithm is that it is hard to reveal the small motions mixed with large motions. Even though we can amplify such small motions in video, the magnification results are still hard to be seen with the naked eye because the large motions overwhelm them, such as the pulse amplification in We propose amplitude-based filtering as a pre-processing step to improve signal extraction from video within large motion. By applying the linear Eulerian method and phase-based motion magnification, we show that artifacts can be reduced dramatically. The DVMAG approach needs users to select a ROI, and depth-aware magnification requires RGB + D cameras to acquire depth information. Current acceleration magnification can only deal with linear large motion, otherwise, it will generate significant artifacts and blurs. We use an amplitude-based filter on pixels over time at different pyramid layers. Results show that our algorithm can handle linear or nonlinear large motions when the subtle variations in video are amplified.In addition, future work will handle multiple different motions while still magnifying useful small changes. More efforts will be given to improve the performance of algorithm under different real situations and expand the applications of video magnification.