The aim of this study was to investigate whether some associations between histological chorioamnionitis (HCA) and favorable neonatal outcomes might be linked to those of antenatal steroids (AS) by determining the separate as well as the combined associations of HCA and AS with neonatal outcomes in very low birth weight infants (VLBWIs).This was a population-based study of VLBWIs born at 20–33 weeks’ gestation between January 2013 and December 2015 from the Korean Neonatal Network. A total of 4652 VLBWIs were enrolled for prevalence study. Of these, 2900 singleton VLBWIs were used for outcome analyses to evaluate individual associations of HCA and AS simultaneously with correction for potential perinatal factors and an interaction term of HCA and AS.P = 0.022), AS were associated with reduction in mortality  and neonatal seizure , and a combination of HCA and AS was associated with remarkably lowered severe intraventricular hemorrhage by interacting with each other .The overall prevalence of HCA was 34.9% (1623 VLBWIs). Multivariable logistic regression demonstrated that HCA was associated with decreased mortality (adjusted odds ratio [aOR], 0.51; 95% confidence interval [CI], 0.29–0.91; We suggest that in VLBWIs HCA and AS may be favorable independent factors for neonatal outcome and may also work in synergy for neuroprotection. Histological chorioamnionitis (HCA) is defined as an acute inflammation of chorionic and amniotic layers of fetal membranes, many cases of which are clinically silent ,2. The pAntenatal steroids (AS) have been accepted as standard medications given to women with imminent preterm parturition because of its effectiveness in preventing newborn outcomes such as RDS, intracranial hemorrhage, necrotizing enterocolitis (NEC), and death ,17. UnliThe reported favorable results of HCA in some of neonatal outcomes from the adjusted analyses of large preterm cohorts under high coverage rates of AS have been shown to overlap with those of AS previously published ,10,12–14This study was a retrospective analysis of prospectively collected clinical data on VLBWIs  born at < 34 weeks’ gestation between January 2013 and December 2015 who were admitted to neonatal intensive-care units (NICU) of perinatal centers registered for the KNN . After eThe KNN is a nationwide database on VLBWIs in NICU hospitalization of up to 60 participating facilities (December 2015) during the inclusion period. This accounts for approximately 70% of overall admissions of VLBWIs in South Korea . The curet al’ criteria by Yoon et al [HCA was defined as the presence of acute inflammatory change of polymorphonuclear leukocyte infiltration in any part of the amnion, chorionic decidua, umbilical cord, and the chorionic plate based on pathologic review of the placenta by pathologists at each participating facility according to the modified Salafia on et al ,26. GA won et al . RDS wason et al . IVH wason et al . The higon et al . NEC wason et al   were performed with or without an interaction term (HCA × AS). Multivariable models accounted for perinatal characteristics as possible confounder covariates in 2 ways: after excluding 1- and 5-min Apgar scores from the baseline perinatal variables, 1) the seven variables that were significantly different between the HCA+ and HCA–groups and 2) all the eleven variables. Goodness-of-fit Chi-square statistics were ascertained for model fit [P < 0.05 was considered statistically significant.All statistical analyses were performed using SPSS 17.0 software . Data are expressed as number (%) or median (interquartile range). Univariable analyses were conducted using χodel fit . A two-tThis study was approved by the Samsung medical center institutional review board (2013-03-002). Data registration in the KNN was approved by the institutional review board at each participating hospital. Written informed consent was obtained from parents of infants upon enrollment by NICU staff at each hospital. All methods were carried out in accordance with the institutional review board-approved protocol and in compliance with relevant guidelines and regulations.+1 and 33+6 weeks of gestation during the study period and registered in the KNN. Among them, 4652 (83.4%) infants born at 20+1–33+6 weeks’ gestation had available data on pathological examination of the placenta and were included in the first population for prevalence study. Of the 4652 infants, 2900 (62.3%) infants born at gestational ages between 20+1 and 33+6 weeks were enrolled in the second study population for final outcome analyses after excluding 139 infants with major congenital malformations, 1623 infants from a multiple pregnancy, and 63 infants born outside the participant centers. These 2900 infants were then categorized into HCA+ and HCA–groups depending on the placental pathology of HCA and AS+ and AS–groups according to AS exposure.Among 4652 VLBWIs with available placental histopathology data, 1623 (34.9%) were exposed to maternal HCA .Ps < 0.001). Infants exposed to AS had higher 1- and 5-min Apgar scores  than those unexposed. Mothers with HCA had greater parity (P = 0.004), lower rates of maternal hypertension (P < 0.001), and higher occurrence of prolonged rupture of membranes (> 18 hours) (P < 0.001) than those without HCA. Mothers with AS administration had less gravidity and parity  and higher occurrence of prolonged rupture of membranes (> 18 hours) (P < 0.001) than those without AS administration. There was no significant difference in the rate of AS exposure between HCA+ and HCA–groups or in the prevalence of HCA between AS+ and AS–groups.P < 0.001), BPD , total IVH (P = 0.007), neonatal seizure (P < 0.001), early-onset sepsis (P = 0.025), and severe ROP (P < 0.001) (P = 0.004), severe IVH (P < 0.001), PVL (P = 0.045) and neonatal seizure (P < 0.001) (P = 0.005), severe IVH , cystic PVL , and NEC (stage ≥ 2)  (P = 0.022), RDS , severe IVH  and neonatal seizure   . The use< 0.001) . Multiva= 0.020) . The use= 0.001) . When an= 0.001) . The othThe current study of VLBWIs demonstrated that the higher risk of HCA for some adverse neonatal outcomes  shown in unadjusted analyses was not significant any longer in multivariable logistic regression analyses . In the To date, a variety of underlying mechanisms have been suggested to explain the advantages of AS therapy for preterm birth. These include acceleration of fetal organ maturation , cerebraet al. [in utero infection/inflammation is expected to induce dual opposite effects on the developing fetus. In light of hemodynamics in early postnatal period of VLBWIs, it has been reported that chorioamnionitis increases the risk of hypotension [In contrast, studies on roles of HCA in premature infants have been largely focused on the harmful effects of intrauterine infection/inflammation, including cytokine-related organ injury ,5,39 andet al.  have peret al. ,5. Thereotension  whereas otension .Taken together, in VLBWIs exposed to both maternal HCA and AS the following mechanisms may be hypothesized. Prenatal inflammation may induce secretion of vasoactive or neurotoxic pro-inflammatory cytokines and may decrease systemic blood pressure in the early postnatal period, with endogenous cortisol secretion as a host defense. Corticosteroids may suppress the pro-inflammatory cytokines and may improve the lowered blood pressure, leading to intermediate cytokine and blood pressure levels, in addition to other benefits of neuroprotection as mentioned above. Accordingly, it is postulated that the cooperation of HCA and AS may complement the harmful weak points of each other to the brain and lead to more stable cerebral vascular environments regarding blood pressure and flow, which may result in protection from IVH related to fluctuating cerebral flow velocity  and elevThe overall incidence of HCA in the first study population of VLBWIs registered in the KNN was 34.9% (1623 of 4652 infants) . This waOur study had the strength in that it was based on a nationwide population (up to approximately 70% of VLBWIs in South Korea). In addition, it is the first report to evaluate the combined associations of HCA and AS with neonatal outcomes in VLBWIs via the use of an interaction term. This study also has limitations. The observational nature of the study inherently restricts causal inference despite prospective data were collected under the same strict guidelines of the KNN. Other limitations include potential sources of substantial bias to the results such as physicians’ choices of the use of AS and the relatively high unavailable placental pathology of 16.6%. The lack of data on prenatal antibiotics and the distribution of cases according to the severity and extent of HCA including fetal vasculitis/funicitis should be considered in data interpretation.In conclusion, our results suggest that in VLBWIs HCA may decrease mortality and AS may reduce mortality and be protective against neonatal seizure while the HCA and AS may work synergistically to prevent severe IVH.


This study evaluates the unique and combined effects of three complementary ICT-based extension methods ― interactive radio, mobile SMS messages and village-based video screenings ― on farmers’ knowledge and management of fall armyworm (FAW), an invasive pest of maize that is threatening food security in sub-Saharan Africa and Asia. Building on a survey of maize farmers in western Uganda and using various selection-on-observables estimators, we find consistent evidence that participation in the ICT-based extension campaigns significantly increases farmers’ knowledge about FAW and stimulates the adoption of agricultural technologies and practices for the management of the pest. We also show that exposure to multiple campaign channels yields significantly higher outcomes than exposure to a single channel, with some evidence of additive effects. These results are robust to alternative estimators and also to hidden bias. Results further suggest that among the three ICT channels, radio has greater reach, video exerts a stronger impact on the outcome measures, and greater gains are achieved when video is complemented by radio. Our findings imply that complementary ICT-based extension campaigns  hold great potential to improve farmers’ knowledge and trigger behavioural changes in the identification, monitoring and sustainable management of a new invasive pest, such as FAW. Spodoptera frugiperda) is a devastating crop pest native to tropical and sub-tropical regions of the Americas. It was first detected in West Africa in early 2016 [Fall armyworm  that is wreaking havoc across SSA. Furthermore, we add to the literature by comparing three ICTs― mobile phone, radio and video. Most previous studies on the impact of ICT-mediated interventions have analysed these three ICT tools in isolation. In contrast, our study is based on an intervention that allows us to explore their unique and combined effects. The research questions addressed in this study include: (1) what factors influence participation in the ICT-mediated extension campaign on FAW?; (2) does participation in the campaign enhance farmers’ knowledge on how to identify, monitor and manage FAW?; (3) what is the impact of the campaign on the adoption of agricultural technologies and practices for the management of FAW?; (4) does exposure to multiple ICT-enabled campaign channels result in larger gains (in terms of knowledge and management of FAW) than exposure to only one channel?; and (5) to what extent are there differential effects of the three ICT-enabled extension approaches used in the FAW campaign?The FAW pest was first detected in Uganda in June 2016, and by the end of 2017, it had spread to all the districts of the country . As partA technical brief on FAW monitoring, identification and management options was developed by the campaign team and subsequently validated by the Uganda FAW National Task Force, forming the basis for the messaging communicated through the campaign. The technical brief reflected nationally agreed recommendations as well as farmers’ information needs on the FAW pest. Prior to the launch of the campaign, a stakeholder consultation meeting was held among the implementing partners to design the campaign messages. The communication channels used for the campaign include interactive radio, video screenings and mobile SMS messaging, which were led by FRI, PVI and Hamwe, respectively. The three partners worked closely together to complement and promote each other’s’ activities in the campaign.FRI developed a 10-week interactive series that ran on Radio Kitara, and was aired in Runyoro, the dominant language in mid-western Uganda. The campaign consisted of a one-hour live interactive radio programme and a repeat broadcast per week for 10 weeks; and around eight short spot messages per week. Each broadcast featured recorded information about an aspect of FAW, live interviews with two experts, as well as with farmers’ who shared their experiences about the pest. This was followed by phone-ins during which the experts responded to farmers’ queries. The radio series also publicised the video screening locations and schedules and advertised the SMS short code for participating in the SMS campaign. The radio campaign is estimated to have reached nearly 330,000 farmers .Kibanda Boda and CrowdPullerz. Kibanda Boda is a solar powered micro cinema that is mounted to the back of a motorcycle, and is able to reach farmers in remote communities. A typical Kibanda Boda video screening in a community was attended by 25–32 farmers, who were facilitated by a FAW content expert. Screening sessions lasted between 60 to 90 minutes, allowing ample time for question and answer sessions to ensure full comprehension of the topics among all participants. CrowdPullerz, on other hand, is an edutainment DVD-video that featured latest popular local music videos interspaced with a four-part video on FAW prevention, monitoring, and management as well as safe use of chemicals. The DVDs were distributed freely to 1,043 public screens  in the three campaign districts. Attendance lists from the Kibanda Boda screenings indicate that 4287 people participated in the video screenings, while the CrowdPullerz distribution lists suggest that about 36344 people watched the video through this platform across the three districts.PVI produced and disseminated an eight minute video (in both English and Runyoro) on FAW through community–based screenings in the three campaign districts using two media delivery tools: A total of 45 structured SMS messages in Runyoro language were pushed to a pre-existing database of 30,000 farmers by Hamwe. The database contained mobile phone numbers of some farmers in the study region who had already subscribed to receive maize-related contents from Hamwe. Additionally, a call-to-action approach was used where farmers were informed through the radio and video campaigns to send the word ‘FAW’ to a specified short code to receive FAW-related information, and about 2500 farmers did so. The farmers received three to five text messages per week consistently over a 10-week period.Data for this study were collected between October and November 2018 through a survey of 607 maize producing households in mid-western Uganda, where the FAW campaign was implemented. The campaign was concentrated in three districts, namely Kiryandongo, Masindi and Buliisa. A multi-stage sampling approach, involving purposive sampling of districts, sub-counties, and random sampling of communities and farm households was adopted in this study. First, Masindi and Buliisa were selected from the three campaign districts because the inhabitants speak Runyoro, which was the primary language for the campaign. Kiryandongo district was excluded, as language barrier could have affected the quality of the campaign in this district, given that five different languages are spoken in the district. Within each district, we purposively selected three sub-counties based on the importance of maize production and the geographic coverage of Radio Kitara, which aired the radio campaign messages. The selected sub-counties include Bwijanga, Mirya and Pakanyi in Masindi district, and Biiso, Kihungya and Ngwedo in Buliisa district. Within each sub-county, we randomly selected between four to eight communities based on the size of the sub-county. Our data show that there were video screenings in at least two of the selected communities per sub-county. Finally, we randomly selected and interviewed about 10 to 20 farm households per community depending on the size of the community. In total, our sample consists of 202 and 405 households from Buliisa and Masindi districts, respectively. The sample households cultivate maize and had experienced FAW attack on their maize plots prior to the campaign.The data were collected by 16 trained enumerators using a structured questionnaire that was pre-tested in Kigumba sub-county in Kiryandongo district. The questionnaire  and dataAs is typical of impact assessments, the challenge of analysing the impact of the FAW campaign is determining what would have happened in the absence of the campaign. For any differences in the outcomes of interest to be attributed to the FAW campaign, the control group (non-participants) would need to be similar to the treatment group (campaign participants), except they would have not received the FAW campaign messages. Thus, both the treatment and control groups should have a similar range of observable characteristics  and unobservable characteristics, such as entrepreneurial ability and motivation. The best way to obtain these comparable groups is to use an experimental design in which prior to the beginning of the extension campaign, farmers are randomly assigned to treatments groups (those who will receive information on FAW through one of the communication channels) and a control group (those who will not participate in the campaign). The experimental approach was, however, not possible in our case as farmers were not randomly assigned to participate in the extension campaign. Instead, our study is based on observational data where households self-selected into the extension campaign. We use propensity score matching (PSM) and doubly robust estimators to mitigate selection bias when evaluating the impact of the FAW extension campaign.In this study, we are interested in assessing if FAW extension campaign increased farmers’ knowledge of FAW and their likelihood of adopting management practices. To address this objective, we first pool all the households that were exposed to the campaign regardless of the channels into one treatment group and compared them with households that were not exposed to any of the campaign channels (control group). We then separated the treatment group into subgroups based on the campaign channel(s) which the households were exposed to, and compared each of these subgroups to the control group. Thus, the second part of our analysis comprises multiple treatment assignments, as households who participated in the extension campaign had the possibility of obtaining the campaign messages through the following channels: (1) radio only; (2) SMS only; (3) video only; (4) radio and SMS only (Radio+SMS); (5) radio and video only (Radio+Video); (6) SMS and video only (SMS+Video); and (7) the three platforms of radio, SMS and video (Radio+SMS+Video). Our estimation techniques—PSM and doubly robust estimator― can handle both binary and multi-valued treatments.PSM involves identifying non-participants of the campaign who are similar to participants in their observable characteristics. In the first stage of the PSM procedure, we generate propensity scores from a logit regression, which indicate the probability of a farm household participating in the FAW campaign. In the PSM with multi-valued treatments approach, we follow Lechner  by estimOur second estimation technique, the doubly robust estimator, models the treatment and outcome simultaneously to attenuate selection bias from non-random treatment assignment . Among tY(1) and Y(0) are the outcomes for the campaign participants and non-participants, respectively; C denotes participating in the FAW campaign. Note that in the case of multi-valued treatments, C indicates participation in a particular campaign channel.In both the PSM and doubly robust estimators, we are interested in estimating the average treatment effect on the treated (ATT), which measures how the FAW extension campaign affects the outcomes for households who decided to participate in the campaign. This can be expressed as:The impact of the extension campaign was assessed on outcome indicators related to farmers’ knowledge of FAW and the subsequent adoption of management practices. To assess FAW knowledge, the sample farmers were asked to respond to 30 questions related to FAW awareness, identification, monitoring and management. We generate four different knowledge scores from the 30 FAW knowledge questions. The first score includes a subset of 10 questions that relate to common myths about FAW, key morphological features of FAW and visible signs of damage caused by the pest. We refer to this score simply as the FAW identification score. The second score, which we term FAW monitoring score, includes a subset of five questions on when and how to monitor maize farms for the presence of FAW. A subset of 15 questions related to the integrated management of FAW forms the third score, and is referred to as the FAW management score. Ten of the 15 questions in this subset are related to the safe use of pesticides, given that pesticides are the most commonly applied FAW management option by African farmers , but areOne of the key objectives of the extension campaign was to foster the uptake of appropriate FAW management practices among farmers in the study region. To this end, the campaign participants were advised to use a combination of prevention and control practices to effectively manage the FAW pest. Following the principles of integrated pest management (IPM) , the recThe descriptive statistics for the knowledge questions and scores are reported in The probability of participation in the campaign increases with ownership of radio and mobile phones, contact with extension agents and membership in farmer groups. This is unsurprising, given that multiple information channels were used to create widespread awareness of the FAW campaign. The coefficient on the PPI variable is negative and statistically significant, indicating that after controlling for other covariates, poorer households have a higher probability of participating in the campaign. A possible explanation is that agricultural information flows are already biased towards richer households, and this can decrease their likelihood of making efforts to acquire information through, for instance, a video campaign, which appears to be driving this result. Results also indicate that households located in Masindi district have a higher propensity to participate in the campaign than those located in Buliisa. This may be related to geographic proximity to information source, considering that the radio campaign, which generated the most coverage among the three campaign channels, was broadcasted through Radio Kitara, which is situated in Masindi district.2, reduced mean bias and insignificant log-likelihood values after matching, and these are all indications of matching quality [Before estimating the treatment effects of the FAW campaign, we first check if the common support and covariate balancing conditions are fulfilled.  quality . We also quality , and theThe results in As mentioned earlier, the reliability of our impact estimates using PSM depends on selection on observables, and thus our results would be biased if there is unobserved heterogeneity (hidden bias) between the campaign participants and non-participants that affect our outcomes of interest. We check the sensitivity of the ATT estimates to unobserved heterogeneity by computing the Rosenbaum bounds , which measure how large the difference in unobserved variables that influence the decision to participate in the campaign would have to be in order to affect the estimated impacts. In general, the results of the critical gamma levels (Γ) in We also test the robustness of our ATT results using two alternative PSM estimatorsꟷ nearest neighbour (NN) matching and radius matching with a calliper of 0.05. Detailed descriptions and discussions on the advantages and disadvantages of the different matching algorithms can be found in . The resSo far we have shown that households that participated in any of the campaigns outperformed the non-participants in knowledge about FAW and the adoption of management practices. An important follow-up question then is how do the different campaigns compare against each other? We address this question by restricting our sample to households who participated in the campaign, and assess the incremental impact of the campaigns over the radio only campaign, which is the common campaign option. By limiting the sample to campaign participants, we reduce bias due to unobserved heterogeneity in the propensity to participate in the campaign.Results further indicate that when households are exposed to both radio and video, it leads to significant increases in both FAW knowledge and the implementation of management practices. Conversely, we find no robust significant effects of exposure to both radio and SMS over radio alone. We also find that concurrent exposure to all three channels produces the highest effect on the adoption of management practices, and this is likely to be driven by the video campaign, given that the SMS campaign did not exhibit significant incremental effect over the radio campaign. Taken together, these results suggest that among the three channels, video was the most effective in terms of achieving the goals of the campaign; however, it achieves greater impacts when combined with radio.This article explored the effects of ICT-based extension services on farmers’ knowledge and management of FAW, a serious invasive pest of maize in Africa. The study is based on an intervention in western Uganda that used three complementary ICT-based channels  with the aims of increasing farmers’ awareness on the identification, prevention and sustainable management of FAW, and improving farmers’ practices in managing FAW on their farms.Using the doubly robust and various propensity score matching estimators, we found consistent evidence that participation in the ICT-based extension campaigns significantly increased farmers’ knowledge about FAW and stimulated the adoption of agricultural technologies and practices for the management of the pest. Even the most conservative estimates suggest that the campaign contributed to a 17% increase in knowledge related to FAW identification, monitoring and management, which translated into the adoption of two additional FAW management practices. The sensitivity analysis of hidden bias shows that our results are not likely driven by unobservable household characteristics. When analysing the unique and combined effects of the three ICT-based channels, we found that exposure to multiple campaign channels leads to higher impacts on FAW knowledge scores and the adoption of management practices than exposure to a single campaign. We also found differential outcomes between the three channels. For example, radio proved most effective in achieving widespread coverage; and while the observed impacts on FAW knowledge and management appear to be considerably driven by video, greater gains are achieved when it is complemented by radio.Overall, our findings imply that in the ongoing battle against FAW in SSA, ICT-based extension campaigns hold great potential to improve farmers’ knowledge on how to identify, monitor and manage the pest, which, in turn, can trigger the adoption of complementary management strategies. The results also imply that to achieve higher awareness and knowledge of FAW that will also translate into behavioural changes, using complementary ICT channels that repeat and reinforce messages is worthwhile. However, in a low-literacy population, as in our case, ICT applications that allow both verbal and visual communication (such as village-based video screenings) should be prioritised when an array of channels are being considered. Our data did not permit analysis of the unique effects of SMS, but the results generally point to a weak to no impact of SMS relative to the other two campaign channels. The SMS campaign under study relied mostly on push-based messages, which has the risk of being seen as spam . MoreoveA limitation of this study is that we have relied on cross-sectional data. While we have tried to control for observable confounding factors using various selection-on-observables estimators and also confirmed that our results are robust to hidden bias using Rosenbaum bounds sensitivity analysis, further research involving experimental or panel data designs would be needed to properly account for potential bias from unobserved heterogeneity and to test our findings. Moreover, there is a possibility of positive FAW knowledge spillovers from the campaign participants to non-participants, and thus the exact magnitudes of the estimated effects of campaign participation relative to non-participants could even be larger than those reported. Finally, we have focused on the role of complementary ICT-enabled extension services in improving farmers’ knowledge and management of FAW. It would also be interesting to study the complementarities between ICT-based and conventional extension approaches such as farmer training and demonstrations in achieving the outcomes of interest, particularly in the current context in Uganda where agricultural extension services have been reformed and extension-farmer ratios are improving , and we S1 File(DOCX)Click here for additional data file.S2 File(CSV)Click here for additional data file.S1 Table(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.S3 Table(DOCX)Click here for additional data file.S4 Table(DOCX)Click here for additional data file.S5 Table(DOCX)Click here for additional data file.S1 Fig(TIFF)Click here for additional data file.


This study examining the impact of increasing the minimum legal drinking age (MLDA) in Massachusetts beautifully illustrates the complexity of measuring the effects of changes in public policy in the midst of other concurrent changes and historical trends. Hingson and colleagues performed their study during a time of transition, when some States had implemented increases in the drinking age whereas others had not. Moreover, States with an increased MLDA already in effect had not been studied extensively using longitudinal evaluation; thus, many unanswered questions remained. For example: How would MLDA’s eventually affect drinking levels of different age groups? How would the differences in MLDA affect population subgroups such as women? And how would differences in MLDA’s of adjacent States affect regional drinking behavior?When Hingson and colleagues undertook this study, there was a great need for objective, comprehensive evaluation of how, and if, raising the MLDA would affect drinking behavior and, more specifically, drinking and driving behavior among young people. Since their study, more research has been conducted on this topic. And although many public health and traffic safety experts today accept that the decrease in alcohol-related motor vehicle fatalities for young drivers was causally related to nationwide increases in the MLDA e.g., , other eHingson and colleagues compared the drinking behavior of teenagers in Massachusetts with those in New York (excluding New York City and Nassau County). The two States had similar critical variables, such as laws concerning the age at which drivers could obtain their drivers’ licenses and penalties for driving while intoxicated as well as similar weather conditions. However, Massachusetts raised the MLDA from age 18 to 20 and New York retained age 18 as the MLDA. In the study, researchers compiled data from telephone surveys, crash data, arrest data, and interviews with law enforcement and other officials. They found that after raising the MLDA, the frequency of teen drinking in bars and clubs and the percentage of teens likely to purchase alcohol in liquor and grocery stores declined in Massachusetts, compared with New York. Still, a surprising 40 percent of the Massachusetts teenagers surveyed reported that they had attempted to purchase alcohol after the legislative change. Of the teenagers who continued to purchase alcohol, one-third were never asked for identification, and very few were arrested. Other Massachusetts teenagers readily adapted to the new law by getting older friends to purchase alcohol for them. When asked about drinking and driving, teenagers from Massachusetts and New York reported similar frequencies of driving after heavy drinking . However, the number of teenagers who reported that they drove after any drinking declined significantly more in Massachusetts.Hingson and colleagues analyzed survey data on drinking, driving after drinking, and nonfatal accidents and found that the incidence of drinking and driving among older Massachusetts teenagers , who had previously been entitled to drink, was not significantly different from drinking and driving among younger teenagers . Nighttime single vehicle fatal crashes showed a greater decline for Massachusetts teenagers ages 18 and 19 than for teenagers of the same ages in New York, but no differences were found for younger teenagers in both States.In their article, Hingson and colleagues noted that by raising the MLDA, officials in the State of Massachusetts provided a “symbolic statement” to teenagers that the citizens of that State disapproved of teen drinking and feared that accidents may result as a consequence of teen drinking. However, the researchers also acknowledged that enforcement of the new MLDA law was uneven across Massachusetts, with many police officers and other officials reluctant to impose sanctions. Police interviews conducted by Hingson and colleagues revealed that lack of personnel and competing priorities were the reasons most often cited for the uneven enforcement. Other comments offered by police officers showed that many of them did not heartily support the law. Indeed, the researchers reported that many officers did not perceive teenage purchasing of alcohol or drinking as a “sufficiently serious crime to stigmatize juveniles by putting an arrest on their records.” Enforcement of sanctions against retailers who sold to underage customers was even more lax; liquor license revocations by the State did not increase in frequency after the law’s passage.Hingson and colleagues’ study focused on only a single State, with a second State used as a comparison. Subsequent studies combining larger numbers of States appear to show clearly the impact of increases in the MLDA in reducing teenage drinking and driving and involvement in alcohol-related crashes. Hingson and colleagues also were among the first to raise cautionary flags concerning interpretation of the impact of such strategies in reducing nonfatal and fatal crashes. As the researchers pointed out, it is not sufficient simply to enact legislation. If the public and, in particular, the law enforcement community, do not completely support the legislation, its effectiveness is diluted.The study performed by Hingson and colleagues exemplified the limitations of one strategy in reducing drinking and alcohol-related crashes among teenagers. Strategies designed to reduce drinking and driving are affected by and, in turn, affect the public’s attitude toward drivers who drink. The gradual improvement seen in traffic safety is undoubtedly a function of many strategies that have reinforced each other to bring about change.


The linseed oil glyceride (LOG) was synthesized by using a transesterification process with a glycerol/linseed oil molar ratio of 1.0. The waterborne urethane oil (WUO) wood coating was prepared by acetone process. First, dimethylolpropionic acid was reacted with hexamethylene diisocyanate (HDI) or isophorone diisocyanate (IPDI), followed by adding LOG at various NCO/OH molars of 0.7, 0.8, and 0.9, respectively, and the COOH-containing prepolymer was obtained. Then, the ionomer which was prepared by neutralizing prepolymer with trimethylamine, was dispersed by adding deionized water, and the water–acetone dispersion was obtained. Finally, the acetone was removed by vacuum distillation. In the whole synthesized process, the LOG and COOH-containing prepolymer could be steadily synthesized by FTIR analysis, and the weight-average molecular weight and polydispersity of COOH-containing prepolymer increased with an increase of NCO/OH molar ratios. During the water dispersion process of the ionomer acetone solution, the point of phase inversion was prolonged, meaning the solid content decreased with an increase of NCO/OH molar ratios. After acetone was removed, the color of WUO was milky-white, and it was weakly alkaline and possessed a pseudoplastic fluid behavior. The particle size of WUO increased with increasing of NCO/OH molar ratios, however, the storage stability was extended for HDI and shortened for IPDI synthesized with increasing of NCO/OH molar ratios. The application of coatings to wood surfaces protects the wood from damage, prolongs the lifecycle and carbon fixation duration of wood products, enables wood utilization to conform with principles of regeneration and sustainability, and enhances the value of the wood products by improving their surface quality and functionality. With an increase in the number of wood buildings, wood-based recreational facilities, and high-quality wood furniture in Taiwan, penetrating oil for wood finishing has received increasing attention. However, such wood coatings are formulated using unsaturated triglycerides, such as linseed oil, with the addition of metal dryers, solvents, and other additives. Therefore, the physical properties of their films are poorer than those of traditional wood coatings such as polyurethane coatings. Urethane oil (UO) coatings are formed by the introduction of urethane linkages (–NHCOO–) into the molecular chains of an unsaturated drying oil. As a result, coatings with oxidative polymerization drying characteristics and urethane bonds are obtained, which can improve the physical properties of films and reduce the curing time of coating ,2. HowevWith the consumption of petrochemical raw materials, the use of natural and renewable resources as raw materials combines the principles of environmental protection and sustainable development, leads to cost reductions, and promotes the creation of comfortable, safe, and healthy environments for humans ,8,9. In Linseed oil (LO) was obtained from Chung-Hsing Chemical Co. Ltd.  with specific gravity: 0.97 (25 °C); viscosity: 57 cP (25 °C); iodine value: 175; saponification value: 185; and acid value: 0.7 . Acetone, xylene, calcium oxide, and glycerol (GL) were purchased from Union Chemical Works Ltd. , reagent grade. Hexamethylene diisocyanate (HDI) was purchased from ACROS Co. , reagent grade. Isophorone diisocyanate (IPDI) and dimethylolpropionic acid (DMPA) were purchased from Merck Taiwan Ltd. , reagent grade, and the DMPA was dried in an oven at 105 °C for 12 h and cooled before use. Molecular sieve, Type 4A (8–12 mesh), was purchased from J.T. Baker Co. . Methanol was purchased from Aencore Chemical Co. , reagent grade. Triethylamine (TEA) was purchased from Tedia Co., Inc. , reagent grade. Dibutyltin dilaurate (DBTDL) was obtained from An Fong Development Co. Ltd. , industrial grade. Deionized water was prepared in our laboratory. LOG was prepared following the method reported by previous reports ,14,15. A− + N–R groups. Acetone was added to adjust the solid content of the ionomer solution to 50 wt %, then the deionized water was added dropwise at a rate of 4 mL/min into the ionomer solution, which was stirred at a rate of 550 rpm. During the water dispersion process, the viscosity of the dispersion was monitored, and the point at which the mixture viscosity trend showed a sudden change, from a slow increase to an instant decrease, was identified as the phase inversion point, which is the transition point of the dispersed phase from an oil phase consisting of organic solvent to an aqueous phase. After the continued addition of deionized water to achieve the targeted solid content, acetone was removed by vacuum distillation, and the six WUOs were obtained, which were, respectively, named according to their synthesized diisocyanate type and mole ratio as HDI-0.7, HDI-0.8, HDI-0.9, IPDI-0.7, IPDI-0.8, and IPDI-0.9. The synthesis process of WUO is shown in HDI and IPDI were respectively mixed with DMPA at a mole ratio of 2:1 and placed in a four-neck reaction flask. The mixture was then diluted to 50 wt % with acetone, and allowed to react in a nitrogen environment at 60 °C. After the NCO content of the reaction mixture decreased to 50% of its initial NCO content, the LOG with various weights calculated based on NCO groups/total hydroxyl groups of LOG mole ratios of 0.9, 0.8, and 0.7 were respectively added, and the temperature of the reaction was maintained at 60 °C for 5 h. Subsequently, 0.08 wt % DBTDL was added, and the temperature was held at 60 °C for another 2 h. Carboxyl (COOH)-containing prepolymers were obtained as the reaction products, and TEA was added to achieve 100% neutralization to obtain ionomers containing R–COOMw), number-average molecular weight (Mn), and polydispersity.The molecular weight of LOG was performed by gel permeation chromatography  with a Shodex KF-802.5 column  and Hitachi L-4000 UV detector  at a detection wavelength of 254 nm. Each sample was diluted to 0.1% using tetrahydrofuran (THF), and the elution was performed using THF with sample injection volumes of 20 μL and a flow rate of 1 mL/min. The polystyrene standards, with molecular weights of 168; 578; 1080; 2450; 5050; 10,100; and 22,000 g/mol, were used to establish a calibration curve for the measurement of weight-average molecular weight (v/v) with acetone, coated on a potassium bromide (KBr) disc, dried, and scanned 16 times using transmission mode with a scan range of 4000–450 cm−1 and resolution of 4 cm−1.FTIR spectra were obtained using a Perkin-Elmer Spectrum 100 spectromete . Each sample was diluted to 5% .The FTIR spectra were obtained as described in The instrument settings and measured properties were as described in Solid contents were determined in accordance with CNS 5133 . The mass retention of 3 g sample in the 105 °C oven for 3 h was determined.Solid contents were determined as described in −1/min for 180 s. The rheological properties of the dispersions were measured using a shear rate range of 0–300 s−1 and a shear rate acceleration of 100 s−1/min.The variation of viscosity during ionomer transition was measured with a Brookfield R/S Plus rheometer  using a C50-1 spindle  and a fixed shear rate of 30 sThe pH values were measured using a Suntex pH meter  under 25 °C.Dynamic light scattering (DLS) using a Malvern Zetasizer Nano-ZS system  with a 4 mW helium/neon laser as the light source, a scattering angle of 173°, and a detection range of 0.66 nm–6 μm, was employed to analyze the z-average diameter and polydispersity index (PDI) of the suspension particles.Each WUO was placed in a capped 1 L polyethylene bottle, and stored away from sunlight at 25 °C. The liquid in each bottle was visually inspected for signs of gelation, precipitation, discoloration, or stratification.Mw, Mn, and polydispersity of LOG were 871 g/mol, 620 g/mol, and 1.32, respectively, while they were 1275 g/mol, 968 g/mol, and 1.40 for LO, respectively. The results show that the Mw and Mn of LOG were both lower than of LO, which indicates that most of the LO already transesterificated to form linseed oil monoglyceride and diglyceride.The main fatty acid component of linseed oil (LO) is linolenic acid (53.2%), followed by oleic acid (18.5%), while other constituents include linoleic acid (17.3%), palmitic acid (6.6%), stearic acid (4.4%), and a small amount of other fatty acids . However−1, which indicates the absence of OH groups, while the spectrum of LOG formed after transesterification had a broad absorption peak at 3423 cm−1, which indicates the presence of OH groups in LOG. Absorption peaks indicating the stretching and bending vibrations of cis C=C–H bonds in fatty acids were observed at 3009 and 715 cm−1 in the spectra of LO and LOG, which shows that unsaturated fatty acid structures were still present in LOG. In the absorption spectrum of LO, absorption peaks representing C=O and C–O–C were observed at 1744 and 1165–1158 cm−1, respectively; however, the intensities of the corresponding peaks in the LOG spectrum were reduced. This is due to the replacement of fatty acids in linseed oil by OH groups after the transesterification reaction [The FTIR spectra of LO and LOG are shown in reaction ,17,18. T−1, which represents the stretching vibrations of OH groups, had a lower intensity compared with the corresponding peak in the LOG spectrum. In addition, an absorption peak corresponding to the stretching vibrations of N–H could be observed in the prepolymer spectra at 3350 cm−1, which represents the characteristic peak of N–H in the urethane linkages (–NHCOO–) formed from the reaction between OH groups in LOG and diisocyanate. The absorption peak at 1710–1730 cm−1 corresponds to the stretching vibrations of carbonyl groups (C=O), while the peaks at 1534 and 774 cm−1 correspond to the bending vibrations of N–H, and the peaks at 1245 and 1040 cm−1 correspond to the stretching and vibration peaks of C–O. It was also observed that the C=O absorption peak in the LOG spectrum at 1745 cm−1 shifted to a lower wavenumber range of 1740–1660 cm−1 in the prepolymer spectra. This is consistent with the results obtained in a study on castor-oil-based two-component waterborne polyurethane coatings [−1, which proves that the prepolymers contained the COOH structure of DMPA [−1 in the spectra, which shows that the NCO groups completely consumed.The FTIR spectra of COOH-containing prepolymers respectively synthesized by the reactions of different diisocyanates (HDI or IPDI), DMPA, and different weights of LOG based on different NCO/OH mole ratios, are shown in coatings . Based o of DMPA . These r−1, respectively [−1 corresponding to the stretching vibrations of N–H remained unchanged. However, from the spectra of the COOH-containing prepolymers synthesized using IPDI and different NCO/OH mole ratios shown in −1, while the maximum values for IPDI-0.8 and IPDI-0.9 were located at 3340 cm−1 and 3330 cm−1, respectively. Therefore, with an increase in the NCO/OH mole ratio, the N–H absorption peak shifted towards a lower wavenumber, which indicates an increase in hydrogen bonding between urethane linkages in the hard segments of the COOH-containing prepolymers. In −1 corresponds to C=O affected by hydrogen bonds, while the absorption peak at 1740 cm−1 corresponds to the stretching vibrations of free C=O groups. It was observed that the locations of the absorption peaks for the three NCO/OH mole ratios were unchanged. However, the peak intensity at 1700–1740 cm−1 increased as the NCO/OH mole ratio increased, which indicates that urethane linkages within the molecular chains increased with an increase in the NCO/OH mole ratio. In the spectra of prepolymers synthesized using IPDI and different NCO/OH mole ratios in −1 increased with an increase in the NCO/OH mole ratio. In view of the results described above, the number of N–H and C=O groups affected by hydrogen bonds in the COOH-containing prepolymers synthesized using HDI were independent of the NCO/OH mole ratio. This is because HDI, which contains alkane chains, has greater compatibility with the fatty acid chains of the glyceride, resulting in a less orderly arrangement of molecules in the hard and soft segments of the polyurethane prepolymers. Therefore, the hydrogen bonds were not affected by the NCO/OH mole ratio used during synthesis. By contrast, IPDI has a lower compatibility with the fatty acid chains of glyceride due to the alicyclic structure in IPDI. Therefore, the prepolymers synthesized using IPDI had a more orderly arrangement of molecules in the hard and soft segments, i.e., the microphase-separated structure formed from the arrangement of soft and hard segments was more distinct. As a result, an increase in the NCO/OH mole ratio led to an increase in the number of N–H and C=O groups affected by hydrogen bonds in the prepolymers [The previous study reported that the free N–H and C=O absorption peaks in urethane linkages were located at 3440–3450 and 1730–1740 cmectively . Howeverpolymers .Mw and Mn of 4214 and 1631 g/mol, respectively, followed by HDI-0.8 with Mw and Mn of 7181 and 1678 g/mol, while the highest Mw and Mn of 10,734 and 1682 g/mol were obtained in HDI-0.9. For the prepolymers synthesized by HDI, the Mw, Mn, and polydispersity increased as the NCO/OH mole ratio increased. Similar trends were observed in the molecular weights and polydispersity of prepolymers synthesized by IPDI, whereby IPDI-0.7 had the lowest Mw of 2962 g/mol, followed by IPDI-0.8 with a Mw of 5861 g/mol, and IPDI-0.9 with a Mw of 6126 g/mol. Due to the reactive difference of two NCO groups in IPDI, the IPDI-based prepolymer, which was obtained through two-step addition reaction, is more homogeneous than the HDI-based prepolymer. Therefore, the IPDI-based prepolymers had a lower Mw and polydispersity than the IPDI-based prepolymers.Results of GPC analysis of the COOH-containing prepolymers synthesized using different diisocyanates and NCO/OH mole ratios are shown in As shown in The viscosity variation for the water–acetone dispersions of HDI ionomers in The viscosities of the water–acetone dispersions during the water dispersion process of HDI ionomers were higher than that of the IPDI ionomers. For example, the maximum viscosity of HDI-0.9 was 2224 cps, which was much higher than the maximum viscosity of 1106 cps of IPDI-0.9. This is because the prepolymers synthesized by HDI had higher molecular weights than those synthesized by IPDI. Similarly, the TEA-neutralized HDI ionomers also had higher molecular weights compared with the IPDI ionomers. Additionally, HDI is mainly composed of long alkane chains, while IPDI is an alicyclic compound. Therefore, under the same shear force, the molecular chains synthesized by using HDI were more flexible and easier to entangle, which led to higher viscosities. As IPDI molecules are more rigid, the synthesized molecular chains had lower activities, which led to a lower tendency of the chains to entangle, or compress to form spherical particles. Consequently, the viscosity variations were smaller, and the overall viscosity of the ionomer–acetone continuous phase during the initial water dispersion process was higher. When the phase inversion point of the water–acetone dispersion was reached, the continuous phase changed to an aqueous phase. However, as the water molecules of the continuous phase mostly encased the dispersed phase in the form of bound water, the suspension particles of the dispersed phase still easily entangled, which resulted in a slower reduction in the viscosity of the water–acetone dispersion of HDI-0.9 compared with IPDI-0.9. The six ionomers exhibited a clear yellow color. However, as the added amount of deionized water increased, the water–acetone dispersions became cloudy and milky. After the water dispersion process was complete, the acetone was removed from the water–acetone dispersion by vacuum distillation to obtain the respective waterborne urethane oils (WUOs) synthesized by using different diisocyanates and NCO/OH mole ratios, with all WUOs exhibiting a milky-white color.The basic properties of WUOs synthesized by using two types of diisocyanates and different NCO/OH mole ratios are shown in The particle size distributions of the WUOs obtained by dynamic light scattering (DLS) are shown in The synthesized WUOs were respectively placed in 1 L polyethylene bottles and observed for signs of gelation, precipitation, discoloration, or stratification. The durations for which the WUOs remained stable are shown in The rheological properties of the WUOs were measured by a rheometer, and the results are shown in In the present study, transesterification of LO with GL was performed to obtain OH-containing LOG, which were subsequently reacted using different NCO/OH mole ratios  with acetone and DMPA, HDI, or IPDI, to obtain COOH-containing prepolymers. The prepolymers were then neutralized with TEA to form ionomers, and were dispersed into water to form water–acetone dispersions. Finally, acetone removal was performed by vacuum distillation to obtain WUOs. From the FTIR spectra of the prepolymers synthesized by HDI and IPDI, it was found that the intensity of the OH absorption peak decreased, the NCO absorption peak was absent, and characteristic absorption peaks corresponding to the urethane structure and COOH were presented, which show that the diisocyanates, LOG, and DMPA successfully reacted to form prepolymers. In addition, the Mw and polydispersity of the prepolymers increased with an increase in the NCO/OH mole ratio. After neutralization of the ionomer solution with TEA, the phase inversion point during the water dispersion process occurred later when the NCO/OH mole ratio was increased, which led to a decrease in solid content. The WUOs obtained after acetone removal had milky-white appearances, were weakly alkaline, and exhibited pseudoplastic behaviors. For the WUOs synthesized by HDI, particle size and storage stability increased as the NCO/OH mole ratio increase. Similarly, the particle sizes of the WUOs synthesized by IPDI increased with increasing NCO/OH mole ratio. However, the storage stability decreased as the NCO/OH mole ratio increased. In addition, the films properties of the WUOs for wood coatings have been examined and will be submitted in the future report.


The recommended drug regimen for elimination of lymphatic filariasis outsidesub-Saharan Africa is single dose of diethylcarbamazine (DEC) plusalbendazole (ALB). Multiple annual treatments are required for eliminationsince this regimen does not sustainably reduce blood microfilaria (Mf)counts below the threshold required to interrupt transmission. This studytested the efficacy of a single dose of ivermectin (IVM) combined withDEC/ALB. Wuchereria bancrofti-infected adults in Papua NewGuinea were assigned to treatment with DEC/ALB once (n=61), DEC/ALB twice and IVM/DEC/ALB once (n=60). The primary outcomewas complete clearance of blood Mf at 24 months.We conducted an open label, randomized clinical trial in whichAt 24 months 96% of participants treated with IVM/DEC/ALB wereamicrofilaremic compared to 56% after single dose DEC/ALB  and 75% after two annual dosesof DEC/ALB .Filarial antigen levels decreased markedly and to a similar degree aftertreatment with all 3 regimens. Moderate adverse events were more commonafter the triple than the two-drug regimen . Therewere no serious adverse events.Treatment with a single dose of IVM/DEC/ALB was superior to a single dose ortwo annual doses of DEC/ALB for clearing Mf. There were no significantsafety concerns. Widespread use of IVM/DEC/ALB could greatly accelerateelimination of lymphatic filariasis.   Wuchereria bancrofti and to a lesser extent,Brugia spp., infect more than 100 million people in 73countries with another one billion at risk Lymphatic filariasis (LF), an infectious disease caused by mosquito-borne nematodeparasites, is characterized by lymphedema of the extremities (“elephantiasis”),hydroceles and chronic disability. The life cycle of the parasite requires uptake ofmicrofilariae (Mf) by mosquitoes with their blood meal and development of Mf in themosquito to infective larvae that are the transmission stage for new infections inhumans We recently reported results of a small pilot study that compared thepharmacokinetics and efficacy of a single dose of co-administered IVM/DEC/ALB versusDEC/ALB for bancroftian filariasis in Papua New Guinea A randomized, controlled, study was performed with participants recruited from 12villages in Dreikikir district, East Sepik Province, Papua New Guinea. None ofthe participants had received previous treatment for LF. Institutional ReviewBoards at University Hospitals Cleveland Medical Center, Cleveland, OH(#04-12-33) and the Papua New Guinea Institute of Medical Research (#1220) andMedical Research Advisory Committee (#12.35) of Papua New Guinea approved thestudy protocols and documents. All participants provided written informedconsent.319 circulating filarial antigen (CFA) test positive individuals were screenedfor blood Mf levels. 182 participants met the inclusion criteria of >50Mf/mL, age 18-65 years, no recent illness by history, non-pregnant, no priortreatment with DEC or ALB, no significant biochemical or hematologicabnormalities and no significant proteinuria, hematuria or glucosuria .Eligible and consenting participants were randomized 1:1:1 to one of threetreatment arms using a computer-generated randomization table: i) DEC 6mg/kg + ALB 400mg  administered once at study initiation; ii) DEC 6mg/kg + ALB 400mg atstudy initiation and at 12 months, and iii) IVM 200 µg/kg  + DEC 6mg/kg + ALB 400mg once at study initiation. Adesignated individual administered medications under direct observation toassure all pills were swallowed. Participants were unaware of the treatment arm.Blood samples were labelled only with ID numbers. Individuals counting Mf andevaluating adverse events (AEs) were blinded to treatment assignment. Screening and initial treatment were performed at the Dreikikir health centerunder direct observation for ten hours and monitored for AEs over the next twodays. A symptom questionnaire was administered and vital signs obtained andrepeated after treatment. A symptom-directed physical examination was performedif moderate or severe subjective AEs were reported. New or worsening symptoms,changes in vital signs and new abnormal physical examination findings wereconsidered to be drug-related AEs and scored using a modified version of theNational Cancer Institute Common Terminology Criteria for Adverse Events,v4.0.Microfilaremia was assessed by passing two mL of heparinized blood (collected byvenipuncture between 9 p.m. and 1 a.m.) through two 5 μm polycarbonate filters. Filters were washed, placed on glassslides, dried, stained with Giemsa and read by microscopy for the presence of Mfas previously described Circulating filarial antigen levels were measured by ELISA at baseline, 12 and 24months, as previously described The primary outcome was percent of individuals with total Mf clearance at 24months post- treatment. Secondary outcomes were percent Mf clearance at 12months, reduction in Mf counts, percent of individuals who cleared CFA andpercent reduction in CFA relative to baseline.The primary hypothesis was that IVM/DEC/ALB given once would achieve 75% Mfclearance at 36 months compared to 50% Mf clearance with a single dose DEC/ALB.A second hypothesis is that single dose of IVM/DEC/ALB would be non-inferior toDEC/ALB given annually with a confidence margin of 15%. For alpha=0.05 and powerof 0.8 we estimated 46 and 54 individuals would be required for each arm to testthe first and second hypotheses respectively. Additional participants wererecruited to account for potential dropout. We conducted an unplanned 24- monthinterim analysis based on the unexpectedly high efficacy of IVM/DEC/ALB at 24months observed in a separate pilot study The study sponsor had no role in study design, data collection, analysis,interpretation, or writing of the report.Participants were enrolled between June 11 and December 13, 2014. Baselinedemographics, Mf counts, and CFA levels were similar among the three treatmentgroups . PretreaWith respect to the primary outcome at 24 months , a singlWith respect to missing data, if we assumed all missing participants in theIVM/DEC/ALB arm were Mf positive  and that all individual missed in the two DEC/ALB arms were Mf negative(complete clearance in 36 of 61 participants [59%] after DEC/ALBx1 and in 47 of61 [77%] after DEC/ALBx2), IVM/DEC/ALB would still have had significantly higherMf clearance rates at 24 months than either DEC/ALB treatment arms .The geometric mean (GM) Mf count in individuals with persistent Mf at 24 monthsfollowing a single dose of DEC/ALB was 12 Mf/mL (range 1-671); four participantsof the total number of persons tested at 24 months (7%) had >50 Mf/mL . The GM CFA levels decreased significantly by 12 months after treatment relative tobaseline in all treatment groups with further reductions between 12 and 24months. The DEC/ALB once and DEC/ALB twice treatment groups had similarreductions in CFA levels of 58%-59% and 70%- 71% at 12 and 24 months,respectively. These values were less than the 67% and 75% reductions observed at12 and 24 months after IVM/DEC/ALB treatment, but the differences were notstatistically significant. More people in the IVM/DEC/ALB treatment arm had CFAlevels reduced to below the assay’s limit of detection at 24 months (14 of 42 or32%) than those in the other treatment groups (10 of 48 or 21% in the DEC/ALB x1 group and 11 of 45 or 24% in the DEC/ALB x 2 treatment group), but thesedifferences were not significant. Relative CFA levels after treatment were notsignificantly lower in individuals who completely cleared Mf after treatmentcompared to individuals with persistent Mf at 12 and 24 months (p = 0.07 and0.30).All individuals were actively observed for up to 10 hours post-treatment for AE,and 73% of participants were assessed for AEs between 24 to 36 hours afterreturning to their villages .Five paW. bancrofti bloodMf than treatment with standard MDA of DEC/ALB in LF-endemic areas outside ofsub-Saharan Africa. Participants in this clinical trial had not been previouslytreated for LF, and they had moderate to very high blood levels of W.bancrofti Mf and filarial antigenemia. A single dose of triple drugtherapy cleared Mf from almost all participants, and the effects persisted for atleast 24 months. This regimen was superior for clearing Mf compared to a single doseor two annual doses of DEC/ALB. Results observed after DEC/ALB treatment wereconsistent with those reported from previous trials These results show that a single dose of the new triple drug regimen consisting ofIVM/DEC/ALB was much more effective for clearing Adverse events were more frequent after treatment with IVM/DEC/ALB. This result isconsistent with observations in a pilot study performed by our group Simulation-modeling studies suggest that MDA with IVM/DEC/ALB should significantlyreduce the number of rounds of MDA required to reach elimination targets Supplementary Materials


To assess the risk of recurrent ipsilateral ischemic stroke in patients with symptomatic near-occlusion with and without full collapse.n = 266), near-occlusion without full collapse (n = 57) and near-occlusion with full collapse (n = 42). The risk of preoperative recurrent ipsilateral ischemic stroke was analyzed, or, for cases not revascularized within 90 days, 90-day risk was analyzed.Included were consecutive patients eligible for revascularization, grouped into symptomatic conventional ≥ 50% carotid stenosis . In multivariate analysis, near-occlusion with full collapse had a higher risk of recurrent ipsilateral ischemic stroke  and near-occlusion without full collapse tended to have a higher risk  than conventional ≥ 50% stenosis. Only 24% of near-occlusion with full collapse underwent revascularization, common causes for abstaining were misdiagnosis as occlusion (31%), deemed surgically unfeasible (21%) and low perceived benefit (10%).The risk of a preoperative recurrent ipsilateral ischemic stroke or ipsilateral retinal artery occlusion was 15% (95% CI 9–20%) for conventional ≥ 50% stenosis, 22% (95% CI 6–38%) among near-occlusion without full collapse and 30% (95% CI 16–44%) among near-occlusion with full collapse (Symptomatic carotid near-occlusion has a high short-term risk of recurrent ipsilateral ischemic stroke, especially near-occlusion with full collapse. Carotid near-occlusion is a severe carotid stenosis that causes a reduction of the size of the internal carotid artery (ICA) distal to the stenosis –3. The sIn the pooled analysis of NASCET and ECST, 246 of 262 cases with near-occlusions were without full collapse and only 16 had criteria for near occlusions with full collapse . These tThe purpose of this study was to analyze the short-term risk of ipsilateral ischemic stroke among a consecutive series of patients with symptomatic near-occlusion with and without full collapse diagnosed by CT angiography (CTA).We re-evaluated consecutive carotid CTAs performed or sent to the department of radiology at Norrland University Hospital during the period January 2010 to December 2014 (4440 CTA examinations from 4067 patients). Inclusion criteria were symptomatic ≥ 50% stenosis on CTA and being suitable candidates for evaluation for revascularization. Hence, exclusion criteria were severe co-morbidity , major stroke as presenting event and > 6 months delay between presenting event and CTA; however, cases that did not undergo revascularization due to other causes, such as major recurrent stroke occurring after presentation and perceived poor risk/benefit after detailed evaluation were included.Umeå Stroke Center is the only center performing carotid interventions in northern Sweden, with 11 referring hospitals covering a population of 880,000. Two clinicians with stroke experience  reviewed the medical records, blinded to the CTA findings except for side of stenosis. With standardized referral pathways from the 11 referring hospitals and universal use of digital medical records, access to information was excellent. As the preoperative evaluation routinely includes well-documented examinations by a specialist in neurology and internal medicine, data availability for events and co-morbidities was robust. Vascular baseline parameters, management, imaging findings and detailed descriptions of cerebrovascular events (previous and up to 90 days after presenting event) were collected. As clinical routine, post-operative assessments included neurological consult day 1–4, face-to-face stroke physician visit at day 30 or telephone with vascular surgery nurse in cases with missing 30-day data.n = 2, both awake procedures), previous CEA (n = 2) and for access when treating an early stroke recurrence with thrombectomy (n = 1).Patients were routinely prescribed antiplatelet therapy after the presenting event, but dual antiplatelet therapy with Clopidogrel was most often not given before CEA due to concerns of cervical hematoma. CEA in general anesthesia was the routine method. CEA indications were  ≥ 50% stenosis and recently (< 2 weeks) symptomatic and overall reasonable surgical candidates when considering cardiovascular risk profile, age (> 85 years rarely accepted), size of neurological deficit and other co-morbidities. Beyond 2 weeks after the last event, individual assessments were made with shorter delay, increasing age > 65 years), severe conventional stenosis (≥ 70%) and male sex being markers for CEA indication. Based on preliminary local results [5 years, The history and signs of all cerebrovascular events were critically assessed to adhere to our event definitions. Cases with multiple causes of stroke, such as concurrent atrial fibrillation, were only considered to have asymptomatic stenosis  if there was sufficient evidence that the stenosis was clearly not the cause, such as clinical and/or radiological evidence of recent ischemia in one or more territories not supplied by the carotid artery. To adhere to conservative approach, occipital events were considered as posterior circulation events regardless of Circle of Willis status.The CTAs were performed using several scanners and protocols reflecting standard of care imaging at each referring site. All cases were screened for eligibility by one reviewer (EJ) while all CTAs were reviewed by a second reviewer , blinded to each other and to clinical information. Disagreements were resolved by consensus. Inter-rater reliability for near-occlusion was good: kappa 0.80, intra-rater reliability was kappa 0.75 and 0.88 for each observer. Near-occlusion was diagnosed when the carotid artery distal to the stenosis was judged to be reduced in size because of the stenosis. This was assessed using an interpretive approach weighing the information of four features  to find the best possible explanation for the findings : The ICACases with contrast visible distal to the stenosis, but had not yet reached skull base at time of image capture were diagnosed as near-occlusion with full collapse, whereas occlusion was diagnosed when no contrast was seen beyond the lesion. Among the near-occlusions, full collapse was defined as a threadlike distal lumen, whereas those without full collapse had a normal-appearing albeit small distal ICA , 2. AmonThe presenting event was the last event before seeking healthcare. The ipsilateral side was defined as the side of the presenting event. Stroke was defined according to the conservative 1976 WHOs definition . TIA wasThe primary endpoint was a preoperative recurrent ipsilateral ischemic stroke or ipsilateral retinal artery occlusion. Among cases that had not undergone revascularization within 90 days after presenting event, only events occurring within 90 days after presenting event were considered for the primary endpoint. Secondary endpoints were (1) ipsilateral ischemic stroke (2) any preoperative recurrent ipsilateral ischemic event  and (3) any preoperative stroke. Safety endpoint was any stroke or death within 30 days after carotid revascularization.χ2-test, ANOVA, and Kruskal–Wallis test as appropriate. The primary endpoint and secondary endpoints of ipsilateral ischemic stroke and any preoperative ipsilateral ischemic event were analyzed with Kaplan–Meier curves with log rank test. The presenting event was index time; cases not reaching the endpoint were censored at carotid revascularization, death or 90 days. Bivariate and multivariate Cox regression was performed with the same index time and censoring as the Kaplan–Meier analysis, producing hazard ratios (HR). After bivariate analysis of all co-variates, a multivariate model was created using possible confounders, identified as associated (p < 0.1) with near-occlusion at baseline and/or with the primary outcome. Check for curve crossing, co-linearity and interaction revealed no relevant findings among included co-variates. Statistically significance was determined by p < 0.05. All analyses were performed in SPSS v24.0.This was the pre-specified primary analysis of this cohort. We used mean, median, standard deviation (SD), intra-quartile range (IQR), 95% confidence intervals (95% CI), two-sided n = 6), major stroke as presenting event (n = 11) and > 6 months delay between presenting event and CTA (n = 2). Five cases had two distinctly separate symptomatic episodes and were therefore included twice. These were three conventional ≥ 50% stenosis and two near-occlusions ; the two episodes were either > 6 months apart and contralateral (n = 2) or were > 1 year apart and ipsilateral, but did not undergo surgery for the first episode (n = 3). The final cohort therefore comprised of 365 incidents from 360 patients, all undergoing CTA within 6 months post presenting event (n = 362) or within 90 days before the presenting event and not repeated (n = 3).Of the screened 4067 patients, 642 had a ≥ 50% carotid stenosis, of which 379 were symptomatic. 19 patients were excluded due to severe co-morbidity .Of included cases, 99  had near-occlusion, remaining 266 conventional ≥ 50% stenosis. Of near-occlusions, 42  were with full collapse, remaining 57 were without full collapse. Of conventional stenoses, 146 were 50–69%, 116 were ≥ 70%, and 4 were too calcified to categorize beyond being ≥ 50%. Cases with near-occlusion were younger and received fewer lipid lowering treatments at presentation than conventional ≥ 50% stenosis (Table n = 214), death (n = 4) or 90 days (n = 147). During the 90-days follow-up period, a total of 46 patients reached the primary endpoint of a preoperative recurrent ipsilateral ischemic stroke or ipsilateral retinal artery occlusion . There was only one clinically suspected retinal artery occlusion, confirmed with acute retinal exam. This occurred in 15% among conventional ≥ 50% stenosis, 22% among near-occlusion without full collapse and 30% among near-occlusion with full collapse, p = 0.012  or dichotomized into 50–69% (14%) and ≥ 70% . When limiting the analysis to the 140 cases not undergoing revascularization, 11 of 32 near-occlusions with full collapse suffered the primary outcome; 7, 14, and 90 day risks were 25%, 28% and 34% for near-occlusion with full collapse and with statistical difference in risk between the three stenosis groups .Forty-four cases did not undergo revascularization as they were interpreted as < 50% by the clinician Table . The 42 Comprehensive searches of local databases revealed that during the study period, 149 patients with symptomatic ≥ 50% stenosis were evaluated, but examined with ultrasound alone. Hence, 71% (365/514) of cases with symptomatic ≥ 50% stenosis during the study period were included as CTA was required for analysis.The main finding of this study was that the risk of recurrent ipsilateral ischemic stroke was high among all patients with symptomatic near-occlusion, especially near-occlusion with full collapse. This confirms the high risk reported from a recent single-center study .There are both similarities and differences between the current study and the pooled analysis of near-occlusions in NASCET and ECST . SimilarAs presented in a recent meta-analysis , cases wp = 0.06) to be a risk factor, but degree of stenosis was not (p = 0.66) [p = 0.06). Near-occlusion could not be analyzed in the pooled cohort due to differences in diagnostics between the centers, but were merged into the ≥ 70% stenosis category [A recent pooled analysis of three cohorts  studying the risk of preoperative ipsilateral ischemic stroke within 90 days found that increasing age was a risk factor, cerebral presenting event tended (adjusted  = 0.66) . We coulcategory . In contWith the high risk of recurrent ipsilateral ischemic stroke in all near-occlusion and particularly in near-occlusion with full collapse, the possibility of treatment should be assessed in a randomized trial. However, some improvements seem reasonable before launching such a trial: Further work into prognosis is warranted to define optimal inclusion criteria. Many of the high-risk near-occlusion with full collapse cases were mistaken for occlusions in routine practice imaging (but correctly diagnosed by experts in retrospect), an issue likely not limited to our center, warranting improvements in diagnostics. Also, many of the high-risk near-occlusions were deemed technically unfeasible to treat and had a high risk of stroke when treated; similar risk has been suggested elsewhere —pathophyA limitation of this study is the non-randomized design. By virtue of the retrospective approach not all symptomatic stenosis cases during the study period underwent CTA, with 149 cases examined with ultrasound alone, the coverage was 71%. CTA was required in this analysis due to the poor sensitivity of carotid ultrasound as near-occlusion often have high flow velocity on ultrasound ; we noteIn summary, the short-term preoperative risk of recurrent ipsilateral ischemic stroke is high among all symptomatic near-occlusions, particularly near-occlusion with full collapse. As these findings question the current guideline recommendations of best medical treatment for symptomatic near-occlusion , 5, rand


Mental well-being and excessive alcohol consumption each represent a significant public health concern, and evidence suggests an association between them. Furthermore, drinking motivations associated with harmful drinking have been studied, but not systematically in the UK population. A representative sample of 6174 UK adults aged 18–75 were surveyed online. Low risk drinkers were found to have higher mental well-being than hazardous, harmful, and, probable, dependence drinkers. Using a hierarchical multiple regression analysis, it was found that just over 5% of the variance in well-being scores was accounted for by the level of harmful drinking and drinking motivation; the most significant contribution was drinking to cope. Among people drinking to cope, those drinking in more harmful ways were statistically significantly more likely to have low well-being compared to less harmful drinkers. In the UK adult population there is a clear association between poor mental well-being and harmful drinking. Furthermore, coping was a significant motivation to drink for many with low mental well-being. While mental well-being was found to be directly linked with levels of harmful drinking, the motivation for drinking was a stronger predictor of mental well-being. With alcohol being a leading cause of death worldwide it is a considerable public health concern , and theeudaimonic and hedonic aspects of mental well-being [Hazardous alcohol intake has been found to be associated with low mental well-being ,9,10,11.ll-being ,14. Mentll-being , as beinll-being , and it ll-being .Internationally, a body of research is emerging on mental well-being and alcohol consumption. One study from New Zealand found that there was a negative correlation between aggregate population eudaimonic well-being and alcohol consumption, and this correlation was strengthened as drinking became more problematic . The resA study in England looking at the relationship between alcohol and well-being found that abstainers and heavy drinkers were more likely to experience low well-being . The stuIt has been suggested that the link between high levels of alcohol consumption and the mental health conditions of anxiety and depression can, at least in part, be explained by “self-medication” , wherebyFurthermore, some studies on the association between alcohol consumption and mental well-being have identified an “abstainer effect”, where abstainers were found to be more likely to experience lower well-being and higher levels of distress than low risk or moderate drinkers . The absThese studies examining drinking motivations, mental health, and levels of alcohol consumption offer valuable insights to inform the development of targeted interventions and messages. However, to our knowledge, there is no published research examining motivations for drinking in a representative, adult UK drinking population, and linking this to aspects of mental well-being and levels of harmful drinking. This study aims to understand these interrelations, which may help inform efforts both to identify individuals who could be more effectively supported to reduce their drinking through higher mental well-being, and to engage individuals to take steps to reduce their alcohol consumption through the prospect of experiencing higher well-being.Data was used from the 2017 Drinkaware Monitor survey, which investigated drinking behaviours, occasions and motivations, harmful drinking behaviours, and moderation techniques across the UK . The surThe following standardized tools included in the survey were used in the analysis for this study.The AUDIT tool was developed by the World Health Organization , with thThe Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS), developed by Warwick and Edinburgh Universities, was developed as a way to assess mental well-being in the general population . The WEMThe Drinking Motive Questionnaire: Revised Short Form (DMQ-R SF)  consistsParticipants were asked to indicate their age, gender, education, and occupation. Age was calculated from the participant’s date of birth. Education level was calculated from a list where participants were asked to choose their highest completed education. Social grade was calculated based on the occupation (or pension situation) of the chief income earner in the household.The data used in this study was analysed using IBM SPSS Statistics version 22.0  . StatistThe first hypothesis is that harmful drinking is significantly related to mental well-being. Relative percentages are reported for the categorical variables included within the analysis and are reported in the cross-tabulation . The sigTo test the second hypothesis, that there is a relationship between well-being, drinking motivations, and harmful drinking in the UK population, a chi-squared statistical test was used to test the significance of the relationship between the categorical variables of the harmful drinking category and drinking motivation . A hiera2 (8) = 65.203, p < 0.001, with a very small effect size (V = 0.073). Harmful drinking is significantly related to low well-being. As can be seen by the frequencies cross tabulated in Low risk drinkers are significantly more likely to have higher well-being (14.1%) than hazardous (9.4%) and harmful (7.3%) drinkers. Whilst 14.7% of low risk drinkers have low mental well-being, this rises to 27.3% among probable dependence drinkers. However, abstainers are less likely to have high well-being (11.7%) compared to low risk drinkers, yet they are more likely to have higher well-being than hazardous and above drinkers .There is a relationship between mental well-being, drinking motivations, and harmful drinking in the UK population. Motivations for drinking were grouped into four categories within the dataset: Coping reasons, conformity reasons, social reasons, and enhancement reasons. Findings show that the largest difference between mental well-being categories is between those who drink for coping reasons, followed by those who drink for conformity reasons. Almost three quarters (72.8%) of those with low mental well-being drank for coping reasons, compared to 35.1% of those with high mental well-being. Over half (53.1%) of those with low mental well-being drank for conformity reasons, compared to 33.2% of those with high mental well-being. 2 (2) = 222.352, p < 0.001, V = 0.203) or to conform (X2 (2) = 63.274, p < 0.001, V = 0.108) decreases. The relationship is not as strong, demonstrated by the small effect sizes, but it is also significant for those who drink for social (X2 (2) = 26.339, p < 0.001, V = 0.070) or enhancement (X2 (2) = 16.933, p < 0.001, V = 0.056) reasons.p < 0.001) and explained 5.4% of the variance in the well-being score. Age, education level, and social grade all made a significant unique contribution to the model, but gender did not . There were no violations of assumptions. In the first step of the hierarchical multiple regression, four control predictors were entered based on previous research demonstrating their relationship with well-being: gender, age, education level, and social grade ,34,35. T not see . p < 0.001). The introduction of the AUDIT score explained an additional 0.6% of the variance in the well-being score, after controlling for demographic variables  = 32.767, p < 0.001). In the second step, the raw AUDIT score variable was entered and the total variance explained by the model as a whole was 6%  = 68.687, p < 0.001). Taking into consideration drinking motivations explained an additional 4.5% of the variance in the well-being score after controlling for demographic variables and the AUDIT score  = 67.681, p < 0.001).Drinking motivation was added in the third step and the total variance explained by the model as a whole was 10.5%  = 70.130, p < 0.001) than the other predictor variables. In the final adjusted model, seven out of the nine predictor variables were statistically significant, with coping reasons for drinking recording a higher Beta value  low risk drinkers report high mental wellbeing in contrast to one in fourteen (7.3%) harmful drinkers and less than one in ten hazardous and probable dependence drinkers (9.4% and 9.3%). Similarly, low mental well-being is more prevalent the more harmful the drinking is, rising from 14.7% among low risk drinkers to more than one in four (27.3%) among probable dependence drinkers. These findings are supported by previous literature, which has found that binge drinking, hazardous drinking, and high-volume drinking are associated with poorer mental health . Our examination of how mental wellbeing and drinking motivations are interlinked in the UK adult population showed that the largest difference between mental well-being categories was between those who drink to cope followed by those who drink to conform. Among people with low mental well-being, almost three in four (72.8%) drank to cope, compared to just over a third (35.1%) of those with high mental well-being. The finding that a large proportion of those with low mental well-being drink for coping reasons are in line with previous research examining the link between low mood and drinking to cope . By examUniquely, the study examined the extent to which a range of factors predicted mental well-being. It was found that, while the level of harmful drinking explained some of the variance (0.6%), the single biggest predictor of well-being was a person’s drinking motivation (4.5%). In addition, it was found that age, education level, and social grade combined explained just over 5% of the difference in mental well-being, whereas gender was found not to have any effect. This finding shows that, although mental well-being is directly linked with levels of harmful drinking, the motivation for drinking is a stronger predictor of mental well-being.Possible implications of these findings are that understanding people’s motivations for drinking should be a key consideration in efforts not only for reducing harmful drinking, but also to improve their mental well-being. In particular, alcohol may be used as “self-medication” to cope with low mental well-being, and it should be considered whether alternative support and guidance could be provided to reduce the incidence of harmful drinking resulting from this.A key strength of this study is the large sample size (over 6000) offering a representative sample of the UK population aged 18–75 and the use of standardized and validated tools to measure harmful drinking (AUDIT), mental well-being (SWEMWBS), and drinking motivations (DMQ-R SF). This has allowed a detailed investigation of the interrelation between these factors, adding to the literature in the field, and, potentially, informing future alcohol harm reduction interventions. Limitations of the study mainly relate to the study methodology, being an online panel survey relying on self-selection and self-completion. Although issues of representativeness have been adjusted for in the analysis through weighting the data according to age, gender, region, and social grade, it has been suggested that using alternative methodologies may more effectively engage hard-to-reach groups  . AlthougTo our knowledge, this is the first time a study has looked at how mental well-being, harmful drinking, and drinking motivation are represented and interlinked in the UK adult population. The findings reveal a clear association between poor well-being and harmful drinking. Drinking for coping reasons was found to be a significant motivation to drink for many with low mental well-being. Furthermore, it was found that, while mental well-being is directly linked with levels of harmful drinking, the motivation for drinking is a stronger predictor of mental well-being.Understanding these interrelations between mental well-being, harmful drinking, and drinking motivations may help inform efforts both to identify individuals who could be more effectively supported to reduce their drinking through better mental health and to engage individuals to take steps to reduce their alcohol consumption through the prospect of experiencing higher well-being. In particular, it should be considered whether alternative support and guidance could be provided to reduce the incidence of harmful drinking resulting from people drinking to cope with poor mental well-being. Further research may explore how such interventions could be designed to effectively engage key target audiences and support them to drink in less harmful ways.