This study protocol describes a proposed randomized controlled trial that builds upon a successful pilot intervention study to address problematic and dangerous drinking among young adult college students studying abroad in foreign environments. Despite universities and colleges citing alcohol misuse as the most concerning issue for their students abroad, most institutions offer no empirically-based prevention efforts tailored to this at-risk population. The proposed intervention attempts to fill a major gap for the nearly 333,000 students completing study abroad programs each year by using empirically-based and theoretically-informed risk and protective factors to correct misperceived peer drinking norms and promote cultural engagement abroad. In addition to preventing heavy and problematic drinking, the intervention seeks to prevent risky sexual behaviors  and experience of sexual violence victimization, which are strikingly common among study abroad students and have the potential for lasting physical and psychological effects upon return home.We will conduct a randomized controlled trial of an intervention with a sample of 1200 college students studying abroad from approximately 50 US universities and colleges. The brief, online intervention is text and video based and contains evidence-based components of personalized normative feedback to correct students’ misperceived drinking norms, content to promote engagement with the cultural experience abroad and address difficulties adjusting to life in the foreign environment, and tips and strategies to prevent risky sexual behaviors and sexual violence victimization abroad. Participants will complete online surveys at five time points  to assess for intervention effects on drinking behavior, drinking consequences, risky sex, and sexual violence outcomes. We will examine whether the mechanisms targeted by the intervention  serve as mediators of intervention efficacy.The proposed study has the potential to fill an important gap in the research literature and provide empirical support for an online accessible, brief, and targeted approach that can easily be distributed to study abroad students to help prevent heavy alcohol use and sexual risk abroad.Trial registration ClinicalTrials.gov Identifier NCT03928067 The number of young adult students taking advantage of opportunities to study abroad during college is growing. Approximately 1 in 10 American undergraduate college students study abroad before graduating, with nearly 333,000 students completing study abroad experiences in the 2016/2017 academic year .Despite these benefits, American study abroad students represent a large and diverse population at-risk for increased and problematic drinking. Students more than double their weekly alcohol use while abroad and both pre-abroad inexperienced drinkers and the heaviest drinkers abroad return home drinking at higher levels than before they left –11. A suIn addition to heavy drinking, students are also exposed to a number of sexual risks while abroad, including risky sexual behaviors  and sexual violence  ; many ofThe literature on sexual risk abroad is only emerging, however, small cross sectional studies from single universities have shown that between 25 and 50% of male and female students report risky sexual behavior , 23, 24,A review of study abroad drinking revealed that while there is ample evidence showing that drinking in study abroad contexts is more problematic than domestic on-campus drinking, there has been little attention or targeted interventions aimed at this high-risk environment . In addiIncorrect perceptions of drinking abroad are a major factor contributing to increased and problematic drinking while studying abroad. Within the study abroad environment, perceived norms of study abroad peers are robustly associated with heavy drinking abroad and predict increases in drinking behavior from predeparture to during the abroad experience , 32, 33.Targeting misperceptions of peer alcohol use through personalized normative feedback (PNF) interventions can correct misperceptions and prevent heavy drinking during high-risk events. Correcting misperceptions of peer drinking norms through PNF has become one of the most prominent strategies for addressing excessive alcohol use among college students –38. InteIn our pilot work with a sample of 343 study abroad students from one university, we found that providing PNF focused on salient and proximal reference groups  prior to their departure helped students form more accurate beliefs about drinking within their host country and prevented escalation of drinking while abroad . HoweverPoor adjustment into the foreign environment and limited engagement with the local culture represent additional risk factors for heavy drinking while abroad. Theories of acculturation , 54 and,negative sojourner adjustment is associated with greater risk for heavy drinking and problems abroad [positive sojourner adjustment  protects students from heavy alcohol use and problems [Our research with American study abroad students suggests that those most at-risk for heavy drinking and consequences are those who separate themselves from the host environment , those who perceive the abroad culture as very different than their home culture, those who spend more time with other Americans while abroad, those who feel out of place being away from home, and those who experience anxiety about interacting in the foreign environment , 32. Oths abroad , 66. Conproblems . Thus, pproblems –69. Posiproblems , potentiAnimal House and Old School; discussions with friends about the parties that occurred). Yet study abroad students are entering a new environment with little to no context to make predictions about what drinking norms may look like in the foreign country . The promotion of cultural engagement in addition to PNF can help students better understand ways to engage in this new environment without the exclusive company of their American peers, affording valuable opportunities to observe that their perceptions of drinking may have been inaccurate. Our pilot work showed that students provided with sojourner adjustment feedback (SAF) in addition to PNF prior to departure abroad experienced significantly fewer alcohol-related consequences abroad compared to students in a control condition, with the greatest benefits for the most at-risk students—those reporting heavier consequences at predeparture [Our work has shown that study abroad students who greatly overestimated drinking behavior and who reported negative sojourner adjustment had the highest risk of drinking and consequences . It was eparture .Risk factors inherent to the abroad environment are also present and will likely impact any intervention effects on programming seeking to prevent heavy drinking and problems abroad. Many students may be going abroad before they turn 21 years old, which is the legal age to purchase and consume alcohol in the United States, but in nearly all countries that students travel to, the drinking age is lower. Thus, students may be studying abroad in cultures where it is now legal for them to access alcohol and research shows that those under 21 are at greater risk for increased drinking abroad , 72. MorExpanding on our promising pilot findings, we designed the present study to refine and further test the PNF + SAF intervention in five specific ways with a large sample of students across multiple diverse colleges and universities in the US. First, discussions with users of the pilot program indicated that the text-heavy feedback presented was too broad and difficult to absorb. Thus, we will update the normative content to reflect drinking in one’s specific country of study and make the SAF more interactive, including video testimonials from study abroad students discussing engaging in the culture and staying safe abroad. Second, given emerging research highlighting increased risk for study abroad alcohol-related risky sexual behavior and sexual victimization –26, we wThe present study will occur in two phases. Phase 1 will involve a large-scale documentation of the drinking patterns of a proposed 2500 students studying abroad and the video collection of testimonials/advice from a proposed 20 students who have previously studied abroad. Normative drinking content and video footage from study abroad students will be used to develop the intervention. In Phase 2, we will conduct a parallel group randomized controlled trial (RCT), where we will test the enhanced intervention among a different sample of 1200 students from approximately 50 US institutions. We will test the efficacy of the intervention on preventing problematic drinking behavior, risky sexual behaviors, and experiences of sexual violence in this high-risk environment during the first and last month abroad and on sustained effects once students return to campus at 1- month and 3- months post-return. The hypotheses are that those student participants who receive the intervention will drink less, experience fewer alcohol-related consequences, engage in fewer risky sexual behaviors, and experience lower rates of sexual violence abroad and back home on campus compared to student participants in a control group.Students will be deemed eligible to participate if they 1) are between the ages of 18 and 24, (2) are signed up to study abroad in one of the 12 most popular destinations  or a control condition (N = 600). Intervention participants will receive the 30 to 40 min intervention as described below. Control participants will receive a link to a general website offering study abroad advice and will be asked to spend at least 30 to 40 min reviewing their institution’s study abroad website content, including policies for drinking abroad. This control condition was selected as a form of “treatment as usual” as our conversations with study abroad personnel indicated this is the extent of typical information students receive about alcohol use abroad. Many students also attend predeparture informational orientation sessions where alcohol use and sexual risk may or may not be briefly discussed; we will control for receipt of orientation sessions that cover such topics in analyses.Participants will complete a survey approximately 2 weeks prior to departure, one survey during their first month abroad, one during their last month abroad, one during their first month back in the US, and a final follow up 3 months post-return to the US. The last survey completed abroad represents the final 30 days of the trip, which, for the majority of students in the study, will be the third month abroad. Length of program will be controlled for in analyses. Participants will receive a $20 Amazon gift card for each of these 15 to 20 min surveys that they complete. Email, text, and phone call reminders will assist with reducing attrition on surveys, which helped us retain 80% of participants in our pilot work and other RCTs , 76. A dIn the first phase of this project, we collected normative drinking data from 2650 study abroad students from 65 universities and colleges. Normative drinking by gender and by country will be presented in the intervention. Based on our prior work, we expected norms to be generally moderate and they will be displayed in a manner that documents that the majority of students abroad drink moderately rather than heavily. The PNF serves to correct misperceived norms and participants see that their intended drinking at predeparture, as well as their perceptions of peer drinking, may be more than the actual drinking of their peers abroad. In addition, we proposed to interview study abroad students about their experiences with drinking  and experiences with sojourner adjustment abroad. Selected clips from these interviews will be loaded into the intervention template so RCT student participants can hear about moderate drinking abroad, such as how local people view alcohol as a complement to a meal rather than as a means to get intoxicated, and how peers that spent most of their time in bars with other Americans risk missing out on meaningful social and cultural experiences.Video clips will also display students discussing ways in which they engaged with the culture while abroad, with content focused on facets of sojourner adjustment . For exaA sample of 1200 eligible students will be randomly assigned via computer-generated random numbers to complete the intervention (N = 600) or control (N = 600). Participants will be randomly selected from the interested students for inclusion and randomized to the intervention or control conditions in a stratified fashion to ensure equal cells by gender , age (21+ and under 21), host country (European vs. non-European), and institution type . If randomized to the intervention condition, participants will immediately receive the intervention after completing the predeparture survey. Participants can view their feedback again if they desire and will be resent a link to their feedback via email during their first and last month abroad.During the initial part of the intervention, participants will be asked to indicate how many drinks on average they think they will drink on a typical drinking day while abroad, as well as how many days in a typical month while abroad they will drink 5 or more for males/4 or more for females on an occasion (heavy drinking days). On-screen PNF will be presented containing information on the drinking behavior and attitudes about their gender- and country-specific study abroad peers in graphical and text format. As is standard in PNF interventions , a graphThe SAF-focused content of the intervention will be similar to what we used in our pilot work , which wBased on review evidence-based approaches for sexual violence prevention back on campus , 75, we We will analyze five outcomes  within a multilevel modeling framework, with the level 1 units being measurement occasions, the level 2 units being individuals, and the level 3 units being schools. Our models will include random effects for the individual students as well as schools to properly adjust for correlations among the repeated measures within an individual student and the students attending the same US school. By analyzing within a multilevel framework, we can investigate whether the intervention is differentially effective at different time points. The main analysis is to estimate the effect of the intervention compared to control at each follow-up time (the first and last month abroad and 1- and 3- months post-return). The N of 1200 was determined in a priori power analyses to be sufficient to detect small to moderate intervention effect sizes for all primary outcomes.Primary outcomes of the intervention are prevention of heavy and problematic drinking abroad, prevention of risky sexual behaviors abroad, and prevention of any sexual violence victimization abroad. Any observed intervention effects seen during abroad on the first and last month abroad surveys are anticipated to sustain through the first- and third-month post-return to the US, such that intervention participants will drink less, experience fewer problems, engage in fewer risky sexual behaviors, and experience fewer sexual violence events than control participants in the 3 months following return from abroad.Three prespecified drinking outcomes are total drinks per week, number of heavy drinking occasions, and number of alcohol-related consequences in the past 30 days. Drinking in the past 30 days will be assessed at all time points with the Daily Drinking Questionnaire , which Risky sex  in the past month will be assessed with the Sexual Risk Survey (SRS), a 23-item measure designed and validated with college student samples . The SRSSexual violence victimization will be assessed primarily with the Sexual Experiences Survey (SES) –86, valip-value.We will investigate the mechanisms of effects through mediation . Mediation will be investigated within the multilevel modeling framework, using bootstrapping to investigate the standard errors  of mediated effects –91. SecoThe intervention has two major components (PNF and SAF), and we have included measures to assess whether changes in perceptions and engagement in positive sojourner adjustment mediate observed effects of the intervention.Using a modified Drinking Norms Rating Form (DNRF)  participWe will use the 24-item Sojourner Adjustment Measure  to asseBased on prior work and pilot study findings, we hypothesize that younger students , men, those studying in Europe, those who drink for social and coping reasons abroad, those with expectancies that alcohol will play a large role in their experience while abroad, and baseline heavier drinkers will benefit most from the PNF + SAF intervention , 52, 72.We have considered alternative methodological approaches and attempted to address limitations to this study protocol. First, the use of longitudinal self-report measures collected via the Internet could be associated with attrition and bias. However, research suggests confidential surveys enhance reliability and that validity and response rates are higher for web than mailed surveys –99. In aonly a few students do it. Instead, we would combine this information with moderate drinkers and frame the message as “80% of students studying in Ireland report drinking less than 3 drinks on a typical night,” which conveys that moderate drinking is typical. This is how we framed normative drinking messages in our pilot work [Second, we considered potential iatrogenic effects from the PNF, but note that studies with college students have suggested that iatrogenic effects are rare in PNF interventions , 41. Liglot work .Third, we chose three primary drinking outcomes because it allows us to see nuanced heavy and problematic behavior. Frequency may increase as a function of the culture abroad  and may not be particularly problematic; thus heavy drinking in the form of total weekly quantity and frequency  and heavy drinking , as well as number of consequences, are our outcomes of interest. We also focus on 12 locations to allow us to personalize the content. These common host countries are skewed European; however, these sites represent 60% of all students abroad [Lastly, we primarily focus on sexual assault victimization and not perpetration as we will likely be underpowered to report any meaningful effects on the low base rate of admitted perpetration in the sample. Both men and women report sexual risk abroad  and we iIn sum, the proposed RCT innovatively extends normative feedback interventions by examining a tailored PNF-adapted intervention that uses additional content regarding SAF to reduce alcohol and sexual risk in young adults studying abroad—a significant and understudied high-risk group entering into a risky foreign context. Although study abroad and student affairs personnel recognize drinking abroad and sexual risk as major concerns and desire empirically-based programs for students as they enter a known period of risk, there currently are few targeted resources for this population. If the proposed intervention is efficacious, as hypothesized, it can be widely implemented at institutions across the country to help prevent the problematic drinking behavior abroad that negatively affects students and institutions, as well as serve as a model to address alcohol risk for other young adults living and traveling abroad.


The divers must acclimatize to these conditions during compression, and for up to 28 days until decompression is completed. During decompression, the ppO2 and ambient pressure are gradually decreased; then the divers must acclimatize again to breathing normal air in atmospheric pressure when they arrive at surface. We investigated 51 saturation divers’ subjective evaluation of the saturation and post-decompression phase via questionnaires and individual interviews. The questions were about decompression headaches and fatigue; and time before recovering to a pre-saturation state. Twenty-two (44%) of the divers who responded declared having headaches; near surface (44%) or after surfacing (56%). 71% reported post-saturation fatigue after their last saturation, 82% of them described it as typical and systematic after each saturation. Recovery was reported to normally take from 1 to 10 days. The fatigue and headaches observed are compatible with divers’ acclimatization to the changes in ppO2 levels during saturation and decompression. They appear to be reversible post- decompression.Commercial saturation diving involves divers living and working in an enclosed atmosphere with elevated partial pressure of oxygen (ppO Commercial saturation diving in the North Sea started with the emergence of the offshore oil and gas industry in 1969. The North Sea has depths from 100 to 180 meters of sea water (msw) that became the standard range of manned underwater operations. In 1980, the interest shifted to deeper diving in Norway and in Brazil. A series of contracts was awarded in Norway for validating diver interventions to 300–350 msw. During this period, outstanding developments were conducted at the Norwegian Underwater Technology Centre (NUTEC) in Bergen and several deep saturation dives were performed in the Norwegian fjords .However, at the turn of the 90s, the Norwegian media raised the issue of potential long-term health effects of deep diving. This became a national debate and in 1993, the Godøysund conference concluded that standard saturation diving in the Norwegian continental shelf should be limited. Today, NORSOK-U100 standards  that regThe limitation of diving depths in Norway was not the end of deep diving. The expertise was transferred from Norway to Brazil by companies like Comex that were operating internationally. In Brazil, deep diving to 200–240 msw became a routine . The key2), the effect of circulating venous gas on the lung function  and TechnipFMC Diving and Health services in Norway and United Kingdom divisions. Data collection was conducted according to the Declaration of Helsinki principles for ethical human experimentation . All parThe monitoring sessions were conducted onboard the Diving Support Vessel (DSV) Deep Arctic between 2015 and 2016. The study covered two operations; one in the Norwegian sector at 110 msw storage depth (121 msw working depth) and the other in the United Kingdom sector at 136 msw storage depth (155 msw working depth). In the two sectors, the divers used the same breathing gasses and equipment and performed the same type of work (well-intervention). However, the saturation procedures differed slightly because of local regulations.The study group consisted of male certified commercial saturation divers. All divers who were cleared for diving by the hyperbaric nurse during the pre-dive medical examination, were eligible for participation. The divers were organized in teams of three men. Each team was involved in one excursion per day during their 12 h-shift. The divers’ shift time was fixed over the saturation period, and the shifts were distributed over the day as the vessel operated a two-bells system for 24 h coverage. Bell run time was limited to 8 h and diver’s in-water time to 6 h; with a 30-min restitution break inside the bell in the middle of the in-water time. Table Saturation was conducted using heliox (helium and oxygen mixture) as breathing gas. Two saturation procedures were used, NORSOK U-100 saturation procedures  in Norwa2 was maintained between 21 and 45 kPa. The divers were pressurized to storage depth at a rate of 1 m/min. At storage depth, the chamber ppO2 was kept between 38 and 42 kPa. During the excursions, the breathing gas ppO2 varied from 60 to 80 kPa. During decompression, the chamber ppO2 was kept between 46 and 50 kPa in Norway and between 48 and 52 kPa in the United Kingdom . Close to surface, the chamber oxygen percentage was kept between 21 and 23% in both procedures.During compression, the chamber ppOThe decompression durations were 5 days and 4 h in the Norwegian project and 5 days 13 h in the United Kingdom project. The decompression durations differed by 9 h (5%). The maximum saturation durations are limited to 14-days bottom time in Norway and 28-days total time in the United Kingdom. The actual saturation durations varied according to the operational needs.The study was part of a larger project of divers’ monitoring, aiming at collecting information on divers’ high pressure nervous syndrome (HPNS) symptoms, fatigue, heat and cold exposure, stress, sleep, and hydration. The study was based on a questionnaire focusing on the diver’s subjective evaluation of oxygen acclimatization:-Diver’s experience of headaches during or after decompression,-Diver’s subjective evaluation of post-saturation fatigue,-Time required to return to normal pre-saturation state regarding the factors above,-Diver’s strategy to cope with return to normal life.The questionnaire included boxes to tick-off and, when relevant, a visual scale using a line of 10 cm (0 to 10) allowing a continuous evaluation. The divers were asked to complete the questionnaire within 12 h after surfacing from decompression. Some then went into structured interviews with the investigator in a separate room in the vessel’s hospital, one at a time. The objective was to provide explanations if needed and ensure that all the questions were answered. The interviewer did not influence or change the divers’ answers at any stage.Transthoracic ultrasound echography and Doppler examinations for circulating venous gas bubble detection were conducted within 2 h of the end of decompression. A Mindray M7 echocardiograph , equipped with a 2.5 MHz linear array transducer was used. Each diver was at rest on a bed in supine position for 3 min, before his heart was examined in an apical four chamber view as described in P-values < 0.05 were considered significant.Different statistical tests were adopted depending on the nature of the data. Two-sided Fisher exact tests were applied with categorical data. Pearson’s test was conducted to examine correlations between age and recovery time. n = 29 in the Norwegian sector, and n = 22 in the United Kingdom sector). The average saturation duration for the divers involved in the study was 19.7 ± 6.5 days. No bubbles were detected after saturation in any of the divers, either in the ultrasound images or by Doppler. The questions’ response rates and results are described in Tables The diving operations were concluded without any incidents. A total of 51 divers were invited to participate in the study, and all of them accepted and answered the questionnaire . The reported severity of the headaches differentiated two groups of divers; with one group describing headaches as light (grades 1 to 4) and the other group describing them as severe (scores 6 to 10). This last group also represented divers who reported being prone to migraines, thus there could be a link between their sensibility and the severity of the post-saturation headache effects.Headaches were frequently reported by the end of decompression. The headache score was 32% (question Q1). When combining the groups “often” and “sometimes” in question Q4, the score became 44%, no difference was found between Q1 and Q4  and after decompression (56%), which coincided with the reduction of the chamber ppOP = 0.5). The feeling of fatigue was presented in the following way:Most divers reported a feeling of fatigue, lasting up to 10 days after the end of decompression. It is reasonable to expect divers performing intense efforts 8 h a day, for several consecutive weeks, to experience physical fatigue. Several divers involved in night shift dives also mentioned the time required to readjust their circadian rhythms. However, if 71% of the divers reported post-saturation fatigue after their last saturation (question Q8), they also described it as typical and systematic (82% in question Q10). There is no difference between Q8 and Q10  than mental (question Q11). This feeling was generally described as a limitation to effort, like becoming breathless when climbing stairs.-The sense of fatigue remained within moderate levels on a scale from 1 (light) to 10 (severe) [mean ± standard deviation (SD) = 3.4 ± 1.92 in question Q9].-The overall well-being or mood, graded on a scale from 1 (bad) to 10 (excellent), was not affected (6.18 ± 1.56 in question Q12).-The capacity to focus or mental alertness, graded on a scale from 1 (bad) to 10 (excellent), was generally unaffected (6.23 ± 1.91 in question Q13). However, one diver mentioned difficulty to concentrate post-saturation.All the divers indicated a recovery process and reversible symptoms. However, their post- saturation sense of fatigue could last from 1 to 10 days (4.31 ± 2.92 days in question Q14). One diver reported a recovery in 3 days by comparing his bicycling performance on a regularly used circuit. After returning home, the divers adopted different strategies to manage this feeling of fatigue. Some said they immediately caught up with life and got intensely involved in sport, social life and auxiliary business. Others reported they preferred to take a relaxing week.An often-depicted relative paleness after decompression was observed on most of the divers. Some divers confirmed that this paleness was noticed by their families after their return home . The divers transferring from the chamber to surface instantly switched from breathing heliox to air. It is conceivable that their bodies may react to the relative drop in oxygen at this point. The transient isobaric counter diffusion and the counter fluxes of helium and nitrogen might have momentarily disturbed alveolar ventilation and reduced oxygen exchanges. The deprivation of sunlight may also contribute to the paleness of the divers.A study was conducted simultaneously onboard the same vessel in 2016, where hemoglobin and erythropoietin (EPO) levels were measured pre-saturation, immediately post-saturation and 24-h post-saturation . An incrConsidering that most of the saturation procedures used in the offshore industry were designed empirically in the 90s, knowledge obtained via research may contribute to their improvement. The benefit would not primarily be divers’ safety, since saturation diving is already relatively safe   but rath2 is linked to the ascent rate (2 protocol was used. The authors reported a case of decompression sickness and neurological deficit after this dive (2 is thus narrow, but there may still be room for improvement. Currently, the ppO2 used for the diving mixtures are specified within 60 to 80 kPa. This refers to the US Navy diving manual used in the early 70s, that authorized large excursion distances. These excursion distances have since been restricted to safer values, but the ppO2 has remained constant. It is possible that diving mixtures might be redefined according to new experience in the diving industry. The results from the present study may help mitigate some concerns of diving long-terms effects, by showing that some symptoms appear to be related to oxygen acclimatization with reversible short-term effects.During decompression from saturation, the chamber ppOent rate . An expehis dive . The marThis study has some limitations. When the interviewer was present, questions were answered with 100% compliance. However, in the interviewer’s absence some answers were missed. This is a known limitation; as already shown by other authors in evaluation of other aspects of saturation . The datWe conclude that post-saturation diving effects on headaches and fatigues include a dimension that is compatible with acclimatization to the higher than normal levels of oxygen experienced in saturation. This assumption is consistent with the hemoglobin concentration changes measured in similar conditions and supported by the subjective evaluation of saturation by the divers as assessed by the questionnaire. These effects appeared reversible post-decompression.It may be that parts of the alleged long-term effects of saturation diving, developed in 1993 at the Godøysund Conference, are in reality short-termed, reversible effects, associated with oxygen acclimatization.JI, CB, and ØL conception and design of research. JI, FK, and ØL collection of data. JI, FK, IE, and CB analysis and interpretation of data. All participated in the manuscript writing, review, and final approval.FK and ØL were employed by TechnipFMC in Norway. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


It indicated that morin was effective in delaying banana senescence.Banana is a climacteric fruit with desirable palatability and high nutritional value. It ripens rapidly accompanied with metabolite changes during postharvest storage. In this work, morin was applied to treat banana to delay senescence. Nuclear magnetic resonance (NMR) spectroscopy was used to monitor the changes of metabolite composition and levels in banana. The results showed that morin significantly delayed the changes of color and firmness. 1D and 2D NMR spectra reflected that the levels and composition of metabolites were changed with the senescence initiation. The principal component analysis revealed that the first principal components responsible for banana senescence were carbohydrates, amino acids, lipids and phenolics. Morin treatment delayed the transformation of starch to glucose, fructose and sucrose, accelerated the accumulations of alanine and γ-Amino-butyrate (GABA), postponed the generations of valine and  Banana fruit is an important horticultural crop with high nutritional value. It is rich in soluble sugars, vitamins, carotenoids, phenolics and minerals ,2. VarioStreptococcus mutans and other pathogens [Physicochemical and biochemical attributes of banana change during senescence. The surface color changes from green to yellow, and the texture softens. Starch degrades into sucrose and glucose leading to sweet taste. These changes contribute to banana with good appearance and desirable quality. However, banana is a typical climacteric fruit and deteriorates rapidly during the late phase of senescence. Therefore, an efficient preservation technique is required to maintain the quality and extend the shelf life of banana . A varieathogens . TherefoNuclear magnetic resonance (NMR) spectroscopy is a promising tool to identify and quantify complex metabolites from postharvest crops ,14. PrinThe current study aimed to investigate the preservative effects of morin on banana during postharvest storage. The color and firmness were measured to evaluate the ripeness of banana. The metabolites profiles at different ripening stages were determined by NMR spectroscopy. The principal metabolites responsible for the delayed senescence of morin-treated banana by analysed by PCA.d4 (CD3OD) was obtained from Energy Chemical . Morin was bought from Macklin Biochemical . Other reagents were of analytical grade.Fruits of banana (Musa AAA Giant Cavendish cv. Baxi) at green mature stage were collected from a local market in Guangzhou, China. Methanol-w/w) was applied to immerse bananas for three minutes. All fruits were stored at 25 °C. The skin color and firmness were tested after storing for 0, 10, 20 and 30 days. The metabolites profiles were analyzed by NMR.The fruit sample of uniform size, shape and maturity were selected and divided into two groups randomly. Morin was dissolved in ethanol and further diluted by water to a final concentration of 0.1%  according to the following formula:Skin color of banana sample was measured by a Minolta Chroma Meter CR-400 . Three fruit fingers were withdrawn randomly from each stage. Three equidistant points around the middle position of the surface were picked and used for the measurement of skin color. Three color scales of L*, a* and b* were recorded. L indicates the lightness or darkness, a* represents green to red color and b2).Fruit firmness was measured by a penetrometer  with a probe of 0.6 cm in diameter. Three fruit fingers were withdrawn randomly from each stage. Each finger was measured at three equidistant points around the middle position of the fruit. The force required to penetrate into the fruit was recorded. The final results were expressed as the ratio of the force to the applied force area  for NMR analysis. All assays were conducted in three replicates. Morin-treated group at four stages were sampled and named as Morin-0-1, Morin-0-2, Morin-0-3, Morin-10-1, Morin-10-2, Morin-10-3, Morin-20-1, Morin-20-2, Morin-20-3, Morin-30-1, Morin-30-2, Morin-30-3. Control group at four stages were sampled and named as CK-0-1, CK-0-2, CK-0-3, CK-10-1, CK-10-2, CK-10-3, CK-20-1, CK-20-2, CK-20-3, CK-30-1, CK-30-2 and CK-30-3.The fruit peel was frozen after liquid nitrogen treatment and was crushed into powder. 250 mg of sample were weighed and mixed with 1 mL of Methanol-1H NMR spectra were acquired from a BRUKER AVANCE III 500 spectrometer  at 500.13 MHz, equipped with Z-gradient system at 25 °C. Standard 2D NMR analyses were also performed for signal assignment including 1H-1H correlation spectroscopy (COSY), selective total correlation spectroscopy (1D-TOCSY), J-resolved spectroscopy (JRES), 1H-13C heteronuclear single quantum coherence spectroscopy (HSQC) and heteronuclear multiple bond correlation (HMBC). For COSY and 1D-TOCSY assays, 128 transients were collected into 1024 data points for each of 160 increments. Phase insensitive mode with gradient selection was employed in COSY assays. MLEV-17 functioned as the spin-lock scheme in the phase sensitive 1D-TOCSY assay with mixing time of 80 ms. A spectral width of 12.0 ppm was applied for every dimension. For JRES spectra, 128 transients were collected into 4096 data points for each of 80 increments. The spectral width was set as 6000 and 60 Hz for the acquisition and evolution dimension, respectively. For 1H-13C HSQC and HMBC assays, spectra were recorded by using the gradient selected sequences with 512 transients and 2048 data points for each of 128 increments. The spectral width was set as 6000, 27,500 and 20,625 Hz for 13C HSQC assays and 1H, 13C HMBC assays, respectively. All data were zero-filled to a 2048 × 2048 matrix with appropriate window functions prior to Fourier transformation.1H NMR spectra of banana peel extract. The chemical shift 3.31 ppm of MeOD-d4 functioned as a reference to calibrate phase and baseline distortions. Metabolites in methanol extract were determined according to proton and carbon signals in 1D and 2D NMR spectra. Their relative contents were calculated based on the area of characteristic peaks in 1H spectra, where a linear baseline scaling normalization approach was adopted. The baseline was constructed by calculating the median of each feature over all spectra. The scaling factor was measured for each spectrum as the mean intensity ratio of the baseline to the spectrum. The intensity of each spectra was multiplied by its particular scaling factor [2X and Q2 values were computed to reflect the explained variables and prediction ability of the model.TOPSPIN  was employed to analyze g factor . SIMCA 1p < 0.05.All experiments were arranged in completely randomized design. Triplicate assays were performed for the measurement of all parameters. The results were expressed as mean ± standard error and subjected to variance analysis. The least significant difference was set as −2) after being treated by 0.1% morin. Therefore, morin was effective to maintain banana quality and to delay the senescence of banana fruit and to inhibit fungal infection during postharvest storage.The appearances of banana fruit at four postharvest stages are shown in 1H NMR spectra of banana fruit with or without morin treatment were compared at four stages. The quantitative and qualitative differences were observed. Twenty-four compounds were identified. Their representative proton signals are marked in d-glucose, β-d-glucose, sucrose, fructose were the leading carbohydrates identified, while some free amino acids were observed, including alanine, asparagine, γ-aminobutyric acid, glutamine, isoleucine, l-aspartic acid, leucine and valine. Palmitic acid and linoleic acid were the lipids in banana peel. Three phenolics, dopamine, salsolinol and gallic acid were identified from specific ripening stages. Other small molecules were characterized as acetic acid, choline, ethanol, malic acid and phosphocholine.In this work, the metabolite profiles of banana fruit with or without morin treatment at four stages were analyzed by 1D and 2D NMR. The identified metabolites and their chemical shifts are presented in 1H NMR spectra, overlapped signals from 3.0 to 5.5 ppm were assigned to carbohydrates. Their major differences were characterized by their anomeric signals. An anomeric proton signal at 4.13 ppm  was assigned to fructose, signal at 4.52 ppm  was β-d-glucose, signal at 5.14 ppm  was α-d-glucose, signals at 5.40 ppm  was sucrose [In the  sucrose . Other pJ = 7.5 Hz), 2.98 ppm (J = 7.5 Hz) were assigned to three methylene groups of γ-aminobutyrate (GABA). Other free amino acids were identified by our previous work [J = 3.9 Hz) and 0.66 ppm  were assigned to saponin a. The single peek at 0.89, double peaks at 1.62 (J = 6.7 Hz), multiplets at 1.30–1.33 ppm were assigned to saponin b.The multiplets at 1.89 and triplets at 2.31 (ous work . Chemica1H NMR spectra were assigned to phenolics [J = 8.0 Hz), 6.73 , 6.62 ppm  indicated the existence of an important secondary metabolite. Further analysis of 1H-1H COSY spectra led to the identification of benzene ring with ABX spin system. In the HSQC experiments, H-5 (6.77 ppm) correlated with C-5 (115.5 ppm), H-2 (6.73 ppm) correlated with C-2 (115.8 ppm) and H-6 (6.62 ppm) correlated with C-6 (120.1 ppm). In the HMBC experiments, the 3J long-range correlations from H-2 and H-6 to C-7 (32.1 ppm) offered additional evidences. Thus, these three protons were assigned to dopamine. Surprisingly, these three protons disappeared completely and two aromatic protons at 6.68 (s) and 6.64 ppm (s) appeared subsequently in 1H NMR spectra after 30 days storage. Further analyses of HSQC confirmed the correlations from H-2 (6.66 ppm) to C-2 (114.5 ppm) and from H-5 (6.70 ppm) to C-5 (112.0 ppm). In the HMBC spectra, the long-range correlations from H-2 to C-7 (24.3 ppm), C-4 (144.2 ppm), C-6 (124.6 ppm) and from H-5 to C-9 (51.5 ppm), C-3 (145.1 ppm), C-1 (122.4 ppm) were observed, which confirmed the transformation of dopamine to salsolinol [Signals in the range of 6.5–8.0 ppm from henolics . Three alsolinol .J = 7.5 Hz) and 3.62 ppm (m) were identified as the signals of ethanol. Other single peaks were also assigned. The signal at 1.91 ppm was assigned to acetic acid, while 3.21 ppm was choline and 3.23 was phosphocholine. Other metabolites, e.g., malic acid and gallic acid, were also identified from banana peel extract.The peeks at 1.18  in the early 10 days but increased dramatically  in the later 20 days. Its growth rate in the morin-treated group was much slower than that in the control group as the final concentration of morin-treated banana was half of untreated banana. Starch is the major carbohydrate in green banana, but its content drops rapidly during climacteric periods accompanied with the accumulation of its hydrolysates, reducing sugars and sucrose [Carbohydrates are the principal components in banana fruits. Their metabolisms are tightly associated with the quality change during postharvest ripening . Their c sucrose . TherefoAmino acids are important nutrients in banana, and their metabolisms are dramatic during the postharvest storage. Alanine and glutamine were the two leading amino acids responsible for the metabolite changes. They increased remarkably from 0 to 30 days storage. The increasing rate of alanine was lower in the first 20 days but much higher in the last 10 d after morin treatment. While for glutamine, its increasing rate declined after morin treatment. The content of GABA changed insignificantly from 0 to 10 days storage but increased significantly after 10 days storage. At 30 days storage, the content of GABA in the morin-treated group was obviously higher than that in the control group. Since glutamine can turn into glutamate under the action of enzymes. GABA might be transformed from glutamate via glutamate decarboxylase. Therefore, the biosynthesis of GABA was in accordance with the ‘GABA shunt’ pathway . The glul-aspartic acid and valine were the other principal amino acids at four stages. The content of isoleucine decreased during storage. No significant differences were observed between the two groups. For l-aspartic acid, its content in the control group changed insignificantly from 0 to 10 days storage but decreased rapidly in the following storage, while in the morin-treated group, it decreased from 20 days storage onwards. For valine, the change trend was similar to that of l-aspartic acid. Therefore, amino acids in banana changed during storage, and the slower changes led to delayed senescence.Isoleucine, Lipid metabolism, especially membrane lipids metabolism, is responsible for plant senescence . LinoleiDopamine is an important phenolic compound in banana peel extract and exhibits strong antioxidant activity . It can Acetic acid, choline, gallic acid, malic acid and phosphocholine were the common primary metabolites in banana. These compounds belonged to the first two principal components in the loading plot, and might be associated with carbohydrate metabolism, protein metabolism and lipid metabolism mediated by a sequence of endogenous enzymes during senescence.d-glucose and β-d-glucose, the accelerated accumulation of alanine and GABA, the retarded formation of valine and l-aspartic acid, the suppressed degradation of saponin a. It suggested that morin was a promising preservative for banana to maintain the quality and extend shelf life.In conclusion, morin delayed the skin color change from green to yellow, slowed down senescence, and inhibited fungal infection. NMR was a useful tool to characterize the metabolites in banana. Twenty-four chemicals were identified, and their contents were determined. PCA analysis indicated that a significant effect of morin on metabolite changes occurred after 10 days storage, including the delayed accumulation of sucrose, fructose, α-


National surveys of adolescents, college students, and other young adults in the United States reveal high rates of alcohol use among these age groups as well as high rates of dangerous drinking practices such as binge drinking and daily drinking. Additional health-compromising behaviors such as tobacco use and drinking and driving often co-occur with alcohol use in these populations. The physical locations or drinking contexts where alcohol use occurs can predict drinking practices and consequences. This information can be used to identify appropriate targets for effective interventions and social policies. Alcohol use during adolescence and young adulthood remains a prominent public health problem in the United States. National survey results indicate that 28.6 percent of 12th graders and 40.1 percent of college students reported binge drinking  during the 2-week period preceding the survey a,b. AlcoIn 1999, more than 32 percent of young people reported beginning to drink before age 13 . EarlierFindings from the Monitoring the Future Survey (MFS) a—for whiResearchers have suggested that the differences in alcohol use between males and females are converging , but it Children attending alternative high schools constitute a distinctive subpopulation of adolescents who may be at increased risk for the development of serious alcohol problems. Alternative high schools serve students at risk for failing or dropping out of regular school and students who have been removed from their regular high schools because of behavior problems such as violence or substance use. About 2 percent  of all high school students attend alternative schools . GrunbauRates of drinking among college students and other young adults are also high. College students are often undergoing role transitions—such as moving away from the family home for the first time, residing with other students, and experiencing reduced adult supervision—that may increase the risk of alcohol use and abuse. College students also frequently reside in different physical and social environments and encounter new social and institutional factors  that may foster heavy alcohol use.As noted previously, the MFS followup b is limiAnother study of college drinking, the 1995 National College Health Risk Behavior Survey , investiBoth the prevalence of alcohol use during the last 30 days and the prevalence of binge drinking were higher among students at 4-year institutions than among students at 2-year institutions. The prevalence of daily drinking was slightly higher for women at 2-year institutions, compared with those at 4-year institutions, and was the same for men at the two types of institutions. Living conditions  and the increased role of fraternities and sororities on 4-year campuses compared with 2-year campuses may be important factors influencing the differences in rates of binge drinking and 30-day alcohol use at the two types of institutions.As reviewed above, survey data provide a consistent picture of high rates of alcohol use, binge drinking, and daily drinking on college campuses. Another important index of alcohol use by college students is the extent of alcohol-related adverse consequences. Standard surveys about the prevalence of alcohol use generally do not gather information about key situational or contextual conditions, such as the location of drinking. This information, however, may have a significant bearing on the interpretation of survey findings and on the identification of appropriate targets for effective interventions and social policies.Adolescents consume alcohol in a variety of contexts, including their own homes, homes of friends or acquaintances, bars or restaurants, outdoor settings , at school or work, and in moving cars or trucks. Based on a sample of 1,914 high school seniors, Several studies have indicated that living circumstances are a major contextual influence on college student drinking behaviors . For exaIn another study of drinking contexts, Alcohol use among adolescents co-occurs with a range of other risky behaviors including tobacco use, sexual activity, violence, drinking and driving, and suicide . Based oFindings from the National College Health Risk Behavior Survey  have alsEpidemiological findings on adolescent and young adult alcohol use reveal several disturbing trends. National data indicate not only that there are high rates of alcohol use among these age groups, but also that many adolescents and young adults engage in drinking practices  associated with major contributors to youth mortality  and with disruptions in significant contexts  that are important for healthy development. The findings also indicate that there are important secondary effects  for abstainers and nonbinge drinkers on college campuses with high rates of binge drinking. The findings regarding gender differences indicate that almost as many females as males are consuming alcohol, but that males in adolescent, college, and noncollege samples have a higher prevalence than females of more serious drinking patterns such as binge drinking and daily drinking. Racial/ethnic group differences indicate the highest prevalence of use among Whites, with Hispanics second, and African Americans at substantially lower levels. These racial/ethnic group findings were consistent across the multiple probability samples referred to in this article.In addition to the high rates of alcohol use among these youthful populations, survey data demonstrate the common co-occurrence of additional health-compromising behaviors  among heavier users. This information should be integrated in subsequent intervention efforts and social policies regarding the health and well-being of youth . These f


Dietary Mg2+ is absorbed in the intestine mediated through transcellular and paracellular pathways. However, there is little research into what factors upregulate Mg2+ absorption. We searched for food constituents that can increase the expression levels of Mg2+ transport carriers using mouse colonic epithelial MCE301 cells. Cyanidin, an anthocyanidin found in black beans and berries, increased the mRNA levels of Mg2+ transport carriers including transient receptor potential melastatin 6 (TRPM6) channel and cyclin M4 (CNNM4). The cyanidin-induced elevation of Mg2+ transport carriers was blocked by GW6471, a peroxisome proliferator-activated receptor α (PPARα) inhibitor, but not by PPARγ, PPARδ, and protein kinase A inhibitors. Cyanidin-3-glucoside showed similar results to cyanidin. Cyanidin increased the protein levels of TRPM6 and CNNM4, which were distributed in the apical and lateral membranes, respectively. The nuclear localization of PPARα and reporter activities of Mg2+ transport carriers were increased by cyanidin, which were inhibited by GW6471. The cyanidin-induced elevation of reporter activity was suppressed by a mutation in a PPAR-response element. Fluorescence measurements using KMG-20, an Mg2+ indicator, showed that Mg2+ influx and efflux from the cells were enhanced by cyanidin, and which were inhibited by GW6471. Furthermore, cyanidin increased paracellular Mg2+ flux without affecting transepithelial electrical resistance. We suggest that cyanidin increases intestinal Mg2+ absorption mediated by the elevation of TRPM6 and CNNM4 expression, and may constitute a phytochemical that can improve Mg2+ deficiency.Mg Over 300 enzymes, including those involved with oxidative phosphorylation and glycolysis, require Mg2+ for their activity. Chronic Mg2+ deficiency may be one of the causes of lifestyle-related diseases such as hypertension, cardiovascular diseases, and diabetes mellitus i) was determined using a Mg2+-sensitive fluorescent dye, KMG-20 AM. Cells cultured on 96-well plates were loaded with Hanks balanced salt solution (HBSS) containing 137 mM NaCl, 5.4 mM KCl, 4.2 mM NaHCO3, 3 mM Na2HPO4, 0.4 mM KH2PO4, 5 mM HEPES, 1 mM CaCl2, and 10 mM glucose supplemented with 2 μM KMG-20 at 37 °C for 30 min. The KMG-20-loaded cells were washed twice with dye-free HBSS and the fluorescence was measured every 20 s at 535 nm after excitation at 430 and 485 nm using a fluorescence reader . In the Mg2+ influx assay, MgCl2  was added to the nominally Mg2+-free HBSS immediately after measurement start. [Mg2+]i is represented as arbitrary units relative to a reference value measured at 0 min. The increases in fluorescence values for 5 min after measurement start (ΔA.U.) were compared in each group. In the Mg2+ efflux assay, the HBSS supplemented with 1 mM MgCl2 was replaced at the nominally Mg2+-free HBSS immediately after measurement started. The decreases in fluorescence values for 5 min after measurement start (ΔA.U.) were compared in each group. In the transepithelial Mg2+ flux assay, cells were cultured on Transwell plates. After forming the confluent monolayer, transepithelial electrical resistance (TER) was measured, as described previously [2+-free HBSS. After 60 min of 1 mM MgCl2 addition to the upper chamber, the lower chamber solution was collected. The concentration of Mg2+ was measured by a colorimetric method using xylidyl blue-I (XB-I). XB-I formed a 520 nm absorbance maximum complex upon Mg2+ binding in alkaline conditions. After calibration, the concentration of Mg2+ was calculated.The change in intracellular free Mgeviously . The uppt test. Significant differences were assumed at p < 0.05.Results are presented as mean ± standard error of the mean. Differences between groups were analyzed using a one-way analysis of variance, and corrections for multiple comparison were made using Tukey’s multiple comparison tests. Comparisons between two groups were made using Student’s 2+ absorption, we examined the effect of black bean components including genistein, cyanidin, and linoleic acid on the mRNA levels of Mg2+ transport carriers. Cyanidin significantly increased the mRNA levels of TRPM6 and CNNM4 without affecting that of TRPM7  is higher than those for PPARγ (KD: 24.50 μM) and PPARδ/β (KD: 389.01 μM). Another reason may be explained by the difference in expression levels of PPAR subtypes. The expression level of PPARα is higher than those of PPARβ and PPARγ in the intestine of adult rats [2+ transport carriers may mainly occur through the activation of PPARα.The cyanidin-induced elevation of TRPM6 and CNNM4 expression was inhibited by GW6471, but not by GW9662 and GSK3787, suggesting the involvement of PPARα. The nuclear trafficking of PPARα by cyanidin was blocked by GW6471, supporting the suggestion that cyanidin activates PPARα. Cyanidin binds directly to PPARα, PPARδ/β, and PPARγ, followed by activating the three PPAR subtypes-specific responsive genes . The affult rats . TherefoTRPM6 and CNNM4 genes have not been clarified in detail. Thus far, we reported that EGF, tumor necrosis factor-α, and PPARγ agonists increased the mRNA levels of TRPM6 in renal tubular epithelial cells [TRPM6 and CNNM4 genes mediated by the nuclear trafficking of PPARα and its binding to PPRE of the promoter region.The transcriptional mechanisms of al cells ,31,32. I2+ influx and efflux assays, cyanidin-3G and cyanidin significantly enhanced Mg2+ transport, which was blocked by GW6471 (2+ flux without affecting TER (2+ is negligible small compared to that of other ions, or cyanidin-3G and cyanidin can enhance the flux of anion. Anyway, we suggest that cyanidin-3G and cyanidin did not disrupt the paracellular barrier, but they can enhance Mg2+ absorption mediated through the transcellular pathway. The cell surface expression in the apical membrane of TRPM6 is regulated by Rac1, a small Rho GTPase [In the Mgy GW6471 . These rting TER . We do no GTPase . On the o GTPase . Immunof2+ influx and CNNM4-mediated Mg2+ efflux, resulting in the elevation of transepithelial Mg2+ absorption in the colon. The presumed action mechanism of cyanidine-3G and cyanidin is illustrated in 2+ deficiency.In the present study, we found that cyanidin-3G and cyanidin increase TRPM6 and CNNM4 expression in MCE301 cells. Cyanidin-induced nuclear trafficking and association of PPARα with the promoter regions of TRPM6 and CNNM4 were significantly inhibited by GW6471. In addition, cyanidin increased reporter activity of TRPM6 and CNNM4, which was inhibited by mutation in PPRE sequences. Cyanidin-3G and cyanidin might increase TRPM6-mediated Mg


The increasing adoption of hospital electronic prescribing and medication administration (ePA) systems has driven a wealth of research around the impact on patient safety. Yet relatively little research has sought to understand the effects on staff, particularly pharmacists. We aimed to investigate the effects of ePA on pharmacists’ activities, including interactions with patients and health professionals, and their perceptions of medication safety risks.A mixed methods study comprising quantitative direct observations of ward pharmacists before and after implementation of ePA in an English hospital, and semi-structured interviews post-ePA. Quantitative data comprised multi-dimensional work activity sampling to establish the proportion of time ward pharmacists spent on different tasks, with whom and where. These data were extrapolated to estimate task duration. Qualitative interviews with pharmacists explored perceived impact on (i) ward activities, (ii) interactions with patients and different health professionals, (iii) locations where tasks were carried out, and (iv) medication errors.p = 0.002), and searching for paper drug charts or computer decreased by 2 mins per 10 patients reviewed (p = 0.001). Pharmacists mainly worked alone , with patient interactions reducing from 5 to 2% of time (p = 0.03). Seven main themes were identified from the interviews, underpinned by a core explanatory concept around the enhanced and shifting role of the ward pharmacist post-ePA. Pharmacists perceived there to be a number of valuable safety features with ePA. However, paradoxically, some of these may have also inadvertently contributed to medication errors.Observations totalled 116 h and 50 min. Task duration analysis suggested screening inpatient medication increased by 16 mins per 10 patients reviewed  contains supplementary material, which is available to authorized users. The uptake of hospital inpatient electronic prescribing and medication administration (ePA) systems is increasing, with benefits cited as reduced adverse drug events, medication errors, length of stay, and healthcare costs, and more accurate communication among healthcare professionals –5. HowevIn England, pharmacists provide an important ward-based clinical service to inpatients and support to ward staff . The thrThis was an uncontrolled before-and-after study using an explanatory sequential mixed methods design . This deWe studied an acute admissions ward and a medicine-for-the-elderly ward in a large English NHS teaching hospital. These wards were purposively chosen to represent differences in patient length of stay, ward staff working practices, and pharmacy services. Typical UK hospital ward pharmacist activities were carried out on both wards, including taking medication histories, reconciling medications on admission, reviewing medication orders for clinical appropriateness, ordering medications, reviewing medications for discharge, patient counselling and some ward-based dispensing. On the acute admissions ward, pharmacy staff carried out these activities seven days a week as part of a ward-based service. This also included attendance at each of the two consultant-led ward rounds Mondays to Fridays, and one each Saturday and Sunday. In contrast, on the medicine-for-the-elderly ward, a single pharmacist provided a two hour ward visit Monday to Friday and attended one consultant-led ward round each week. The ePA system, a component of a commercial electronic health record system already in use at the hospital, was implemented on both study wards in March 2016 as part of the second phase of hospital-wide roll-out. Clinical decision support within the ePA system mainly comprised tools such documentation templates, condition-specific order sets, and medication-specific review reminders. Drug allergy alerts were in operation, but other computerised alerts such as drug-drug interactions were not activated. There was no formal change in ward pharmacy resources provided post-ePA.All eight pharmacists covering both study wards were invited to participate in the observations and interviews. Those willing to take part provided written consent and mutually convenient time(s) and day(s) for observations and interviews were agreed.Direct observations of pharmacists’ ward visits were planned for every 3–4 weekdays on each ward between January 2016 (approximately 1.5 months pre-ePA) and June 2016 (3 months post-ePA). One observation session typically lasted around two hours. Observations were scheduled to take place at two different times (after the morning ward round and late afternoon) on the acute admissions ward to capture potential variation in ward-based activities as it was impractical to observe the pharmacist for their entire eight-hour shift. As pharmacists on the medicine-for-the-elderly ward were not ward-based all day, observations were scheduled in the morning for the duration of their ward visit and they were asked to document any ward-related activities undertaken outside the ward visit using pre-piloted data collection forms on the days observed. Additionally, the presence of any other pharmacy staff on the ward was recorded.A standard random interval three-dimensional work sampling approach  was usedOne-to-one semi-structured interviews were carried out by GK in May 2016 (approximately seven weeks post-ePA) using a pre-piloted topic guide Additional file p-value of 0.0028 for assessing whether differences in task duration were statistically significant. We also compared median time per patient reviewed. Mann-Whitney U tests (for non-parametric data) and unpaired t-tests (for parametric data), with a two-tailed significance of 0.05, were used to explore potential differences between mean percentage of time spent on different tasks per observation, and mean percentage of time per observation with patients, different health professionals, and locations where tasks were carried out pre- and post-ePA.Quantitative analysis focused on the change in estimated time spent on value-added and non-value-added tasks on both wards. Estimates of time were based on ten patients reviewed to provide context with respect to implications for pharmacy services and to take into account any changes in numbers of patients reviewed. The percentage of time spent on each task overall was also calculated to provide an overview of how pharmacists spent their time. As this was an exploratory study, an a priori sample size was not calculated. We used the Bonferroni correction for multiple testing and adopted a Qualitative data were analysed using a deductive thematic approach with initial themes generated based on study objectives . One resFindings from the quantitative and qualitative data analyses were compared to explore areas of agreement and disagreement between measured and perceived impact of ePA on pharmacists’ activities. The modified Good Reporting of Mixed Methods Study guideline for pharmacy practice was used to support transparent reporting .p = 0.16). Six of the seven pharmacists covered both the admissions and medicine-for-the-elderly wards during the observation period; these six pharmacists also participated in the interviews (experience 1.5 to 6.5 years). Additional pharmacy support from at least one other team member was available for some or all of the time observed on the acute admissions ward (84% of 44 observations) and were mainly provided by a pharmacy technician (73% of observations). An additional pharmacist was available pre- (39% of observations) and post-ePA (62% of observations), and pre-registration trainee support (pre-ePA 28% and post-ePA 0% of observations) on the acute admissions ward. Additional ward-related activities carried outside of the ward visit by pharmacists on the medicine-for-the-elderly ward were reported for only one day pre-ePA and three days post-ePA; these data were therefore excluded from analysis.Seven of the eight pharmacists were observed, over a total of 116 h and 50 min (Table p = 0.62); screening inpatient medication ; and screening discharge medication  Additional file p = 0.02).Overall task analysis indicates that pharmacists spent most time on: professional communication , and searching for drug charts decreased by 2 mins per 10 patients reviewed (p = 0.001).There was no statistically significant difference in the total time spent on all tasks combined  per 10 patients reviewed post-ePA . Interactions with “other persons” included: ward clerk, occupational therapist, researcher, and information technology support staff.Pharmacists spent the majority of their time working solo Fig.  both preOn the acute admissions ward, pharmacists spent the majority of time observed working in the ward office, which changed little post-ePA Fig. A. In comOverall, we identified seven main themes from the interview transcripts: (i) more efficient and effective screening of medications post-ePA, (ii) more time-consuming daily work, (iii) fewer patient interactions and a less natural communication mode, (iv) more interactions with other health professionals but less face-to-face communication, (v) discussions with other health professionals and patients are more focused on problem solving, (vi) patients valued over medical records as a reliable source of medication history, and (vii) higher prevalence of medication errors. These were interlinked by a core concept: the enhanced and shifting role of the ward pharmacist post-ePA. We present this concept below as the primary finding from integration of quantitative and qualitative data. Selected verbatim quotes are included for illustrative purposes.“Our role has changed a lot more to be a person who updates the actual drug chart and updates the actual prescriptions. Because it is a new system the junior doctors, I think rely a lot more heavily on the fact that we can PC [amend on behalf of a “prescriber contacted”] amendments or changes, or additions. ………. now just on ward round alone, the drug chart screen is only really looked at by us [pharmacists]”. “Yeah, technical issues, …….. definitely I’ve got more questions from nurses about what things mean on [the ePA system], or can I help them find something. Or if they’ve signed for something accidentally, how do they reverse it and things like that. And then from a doctors’ point of view, I suppose just feeding back things that they can do differently”. A principal aspect of a ward pharmacist’s responsibilities is to clinically screen patients’ medications, ensuring accuracy as well as appropriateness and practicality for use. While this remains the case, interviews with pharmacists post-ePA suggest that they were also taking on more of a transcribing role by ordering medication based on a doctor’s verbal request plus an ePA support role for ward staff in general. Pharmacists reported being approached by doctors and other ward staff more frequently to make prescription changes on the ePA system, for advice on how to use the ePA system, and for troubleshooting.“….there’s a vast amount of information available now when I’m seeing those patients for a first time on ward round ….. that wasn’t available to me pre [ePA] … [the ePA system] allows everything to kind of be gathered into one… I find myself being able to screen a drug chart clinically with a lot more information on a ward round” “The time I think I spend putting information into [the ePA system] takes a lot longer post implementation. It takes a lot longer for me to do a drug history, do a meds rec’ [medicines reconciliation] and finish [with] a patient before I’m happy to move onto another one”. Despite their greater transcribing and additional technical support roles, pharmacists themselves strived to continue to provide a ‘typical’ clinical pharmacy service and recognised many advantages and disadvantages of ePA. Pharmacists believed that the ePA system enabled more efficient screening of drug charts and a greater propensity to make meaningful clinical contributions for optimising a patient’s medications. Specific features of the ePA system, including a pharmacy medicines management page, were highlighted as helpful for prioritising patients at each visit. However, pharmacists perceived some common routine tasks, such as taking a medication history, to be more time-consuming.“So I think first of all trying to get a computer is an issue. I work on one particular ward and they’ve basically put stickers on a lot of their computers-on-wheels saying ‘This is for nurses’ use’, which is really difficult for you as a pharmacist [……] you end up going and writing it all down on paper and then going back to a computer and sitting down and putting it all onto [the ePA system] and that’s really time consuming because you’re duplicating the work ….” Pharmacists who believed ePA facilitated clinical screening attributed this to having more convenient access to patient records that allowed them to review medications, laboratory results and medical notes concurrently. However, paradoxically, this meant pharmacists would sometimes spend more time reviewing a patient’s medications as they were reviewing the medical notes and laboratory results more frequently. Given that pharmacists reported little change in the way they prioritised their ward activities (i.e. reviewing new patients and those due to be discharged first), the consequence was that pharmacists carried out fewer patient reviews post-ePA for those who were not new or due to be discharged. This perceived reduction in the number of patients reviewed was further compounded by a lack of computer terminals, which was often reported as a rate-limiting step. One pharmacist mentioned the introduction of ‘computer ownership’ on the wards, whereby groups of staff would designate computers for their own use.“I definitely think it [the ePA system] cuts down on patient interaction … So, yeah, unfortunately I think it definitely cuts down on patient interactions and meaningful patient interactions … Previously you would have been seeing everyone on a daily basis at their bedside but now if you can’t find a computer you don’t do that and more commonly the purpose for going is to get the drug history or to ask questions rather than going along on a day to day basis and checking in with the patient”. “Taking a device to the bedside still kind of takes away a little bit from a natural conversation because of the inputting you’re doing at the same time as having a conversation with someone[…….] And I feel like with a chart pre [ePA] implementation, the conversation was a little bit more natural”. An important unintended consequence of ePA was that pharmacists perceived they were interacting with fewer patients, and that although the conversations held were more targeted (e.g. focused around a specific question), they were of a less natural mode.A prevalent belief was that ePA had increased the prevalence of medication errors (both minor and severe). Pharmacists also reported on examples of medication risks with ePA as compared with paper drug charts. Interview findings suggests the perceived increase in medication errors may be due to six types of situation: (i) ePA nudges users to do the ‘wrong’ thing, (ii) ePA indiscriminately defaults to specific actions, (iii) ePA makes error less visible compared to paper drug chart, (iv) ePA makes error more visible compared to paper drug chart, (v) ePA makes other key information less visible, and (vi) ePA clinical decision support does not meet users’ expectations. Examples are provided in Table “I'd like to think that, because there are lots of different teams looking at the prescriptions, not just one person, that errors will be identified, similar to if they were written incorrectly. So I don't think it’s any more or less dangerous than a paper chart…” Pharmacists also reported a number of ePA-based patient safety improvements e.g. every prescription is always clear and complete with medication order details, name and bleep number of the prescriber. This facilitates investigation of medication errors as well as feedback to those involved. The ePA system also prevents medications from being prescribed if there is a documented allergy to the drug concerned in the patient’s record. However, pharmacists believed that it was human safety nets, namely doctors, nurses and pharmacists looking at medication orders, which allowed errors to be rectified before they can cause severe harm.This study has revealed a number of effects of implementing ePA on ward pharmacists’ activities. Some routine tasks took longer while others reduced post-ePA, which corroborates previous research , 16. PhaOur findings suggest a key underlying change post-ePA was the enhanced and shifting role of the ward pharmacist. Pharmacists generally perceived an enhanced ability to review patients’ medications more comprehensively and efficiently (despite perceiving some tasks to take longer), a greater transcribing role in ordering new medications on behalf of some doctors and that they were seen as an ePA expert among ward staff.perception of error  as doctors and other ward staff. Given that ePA was implemented relatively recently in our study, it is possible that the pharmacist’s role is still changing. The additional ePA expert role may dissipate as greater ePA knowledge and experience becomes embedded among core staff across all disciplines.Patients play an important role in medication safety and can contribute to reducing medication error when health professionals involve patients in their care , 28. A cA strength of this study was the use of a planned explanatory mixed methods approach. This not only allowed us to triangulate our findings but also allowed us to gain a more in-depth understanding of contributing factors for post-ePA effects observed. In particular, the same pharmacists participated in both the quantitative and qualitative parts of the study, which ensured interviews were of maximum relevance to the observational data collected. Furthermore, there was a high level of engagement and involvement from pharmacy staff at multiple stages of the research .Limitations include lack of data on tasks carried out by pharmacists outside of the ward visit, not observing the acute admissions pharmacist for the whole day, a small sample of observations, data being collected starting immediately post-implementation which will therefore include any ‘settling in’ time, the presence of an observer potentially affecting the way the pharmacists worked, and lack of data on the tasks carried out by other pharmacy staff who were supporting the observed pharmacists. Our study was also conducted at one hospital and therefore may not be generalizable to other settings. Finally, we used a relatively large number of different task types, compared to other studies, that provided us with greater granularity of potential specific effects of ePA, but it also reduced the statistical power for detecting differences.It was recognised within the pharmacy department concerned that revision to existing guidance on clinical ward service provision was needed to better support individuals and teams to effectively prioritise and deliver high quality care post-ePA. Our findings support this and provide useful insights on how ePA has influenced pharmacists’ work processes on an acute admissions and a medicine-for–the-elderly ward. We suggest updating guidance on specific work processes  to maximise the efficiency of having a centralised system for written communication, and supporting pharmacists to involve patients routinely when reviewing their medications using a mobile computing device on the ward. We also suggest actively encouraging staff to report any difficulties or workarounds with ePA to the pharmacy ePA team to facilitate shared learning and identity actions as required to address any problems. Furthermore, we recommend increasing the number of mobile computing devices available to ward pharmacy staff, and a review of the location of computer terminals on the wards to facilitate greater access to the ePA system.The perceived increase in medication errors is a concern and we suggest future research to develop and evaluate methods to monitor the extent to which ePA-related and non-ePA errors are captured in routine practice. We also suggest capturing types of remedial actions to facilitate organisational learning and greater shared learning across the health sector. Finally, we suggest further research should seek to map and better understand the unintended consequences of ePA, particularly on how it may enhance  work for health professionals in order to improve patient safety. Any system design should also consider how users may change in the short, medium, and long term as appropriate. For example, pharmacists who have never worked with paper charts - and consequently never experienced how patient contact naturally arises from bedside screening of paper charts  or how rThis study provides quantitative and qualitative insights into the effects of implementing ePA on ward pharmacists’ activities. Some tasks took longer while others reduced, and our results suggest that pharmacists may spend less time with patients with ePA. Pharmacists valued a number of safety features associated with ePA but also perceived an overall increase in medication risk. Pharmacy staff demonstrated a degree of resilience to ensure ‘business as usual’ by enhancing and adapting their role.Additional file 1:Quantitative work-sampling task definitions with inclusion and exclusion examples, adapted from Schofield et al. . Additional file 3:Percentage of time spent on tasks pre- and post-electronic prescribing and medication administration (ePA). (PDF 410 kb)


In this paper, we introduce two methods to forecast apartment burglaries that are based on repeat and near repeat victimization. While the first approach, the “heuristic method” generates buffer areas around each new apartment burglary, the second approach concentrates on forecasting near repeat chain links. These near repeat chain links are events that follow a near repeat pair of an originating and (near) repeat event that is close in space and in time. We name this approach the “near repeat chain method”. This research analyzes apartment burglaries from November 2013 to November 2016 in Vienna, Austria. The overall research goal is to investigate whether the near repeat chain method shows better prediction efficiencies (using a capture rate and the prediction accuracy index) while producing fewer prediction areas. Results show that the near repeat chain method proves to be the more efficient compared to the heuristic method for all bandwidth combinations analyzed in this research. Early scientific studies showed that crime events are spatially concentrated Guerry . In recepermanently deploy police resources to these locations. For example, research suggests that (some) crime clusters are unstable and may move between different locations  around each apartment burglary that occurs. Based on the “boost” account, it is assumed that offenders will return to the same and nearby locations of these incidents. These forecasted areas are valid for just a few days, because the risk of another event taking place is assumed to be elevated close to a previous event but for a limited period of time. The prediction accuracy of this method is first evaluated by comparing it to expectation, assuming that there is no pattern to the timing and location apartment burglaries. This first approach is similar to the method carried out by Fielding and Jones  in theirResults from the first method are compared to a second approach, which is motivated by the concept of near repeat chains. This second approach was tested as the first created many prediction areas, due to there being a large number of apartment burglaries that occurred in Vienna each day. To narrow down the number of prediction areas, the second technique relies on the assumption that following a first near repeat, subsequent near repeats are more likely to occur. For this method, buffer areas are hence derived for every near repeat (as opposed to every event). An important research question is whether the near repeat chain technique results in similar or better prediction accuracies than the first approach. A second research question analyzes whether the prediction accuracy of each techniques differs from chance expectation. Although we know that crime is not randomly distributed, the comparison with chance expectation is a fundamental baseline of most statistical approaches. We know that crime is not random nor should comparison prediction areas be random. However, police resource allocation in Austria is somewhat arbitrary and this approach is still common practice. The approach of randomly placing prediction areas is designed to approximate arbitrary resource allocation. It is hypothesized that non-random prediction areas show better prediction accuracies. To the best of our knowledge, an extensive analysis of the predictive accuracy of an approach based on near repeat chains and their potential to forecast future residential burglaries has not been researched before.The remainder of the paper is organized as follows: “Vienna is home to approx. 1.85 million people, which is about one-fifth of all residents in Austria. Austria records approximately 550,000 reported crime incidents per year, of which 38%  occur in Vienna  developed by Ratcliffe , which iThe NRC requires the user to select the spatial and temporal bandwidths used for analysis. The spatial bandwidth is a threshold distance used to define which events are considered to have occurred close to a previous event. The temporal bandwidth is the time span between sequential events. In previous research, many different spatial and temporal parameters have been used to analyze near repeat patterns. Johnson et al.  reviewedAs discussed, the research focuses on the evaluation of two methods for forecasting future crime events. The first involves creating geographical buffer areas around each incident for a given time frame. For example, for today’s forecast of future burglary events, dissolved buffer areas of (say) 300 m radius were generated around all burglaries that occurred on the previous (say) 3 days Fig. . The bufThe second method takes a slightly different approach for which the number of prediction areas produced per day is reduced compared to the first method. For example, if 15 new apartment burglaries occur every day, 15 new prediction areas need to be generated using the heuristic method. If the forecasting period is 5 days long, then about 75 predictions are generated. In fact, it is challenging to develop preventive strategies for so many prediction areas. Therefore, another approach is introduced that is based on near repeat chains. This approach identifies near repeat pairs that are both close in space and time. Dissolved buffer areas are then created around the near repeat events (the second event in the event pair), so that these near repeats act as originating events for subsequent near repeats. Hereafter, we refer to this approach as the “near repeat chain method”. Figure To evaluate the predictive accuracy of both approaches, a comparison is made to a random distribution of prediction areas which are generated in the following way. Prediction areas are sampled at random using data about the unique locations of all 14,551 apartment burglaries located in the study area. In each case, the same amount of prediction areas that were generated using either the heuristic or the near repeat chain method are selected at random from all historic apartment burglary locations (from November 2013 to October 2016) across Vienna. This represents a simple Poisson process and doing this once provides an estimate of the expected accuracy, assuming that prediction accuracy reflects nothing more than a random process. However, one sample may be misleading and hence a Monte Carlo simulation is used to repeat the process 99 times, which allows us to test the likelihood of observing a particular result with a level of statistical significance equal to 0.01. This level of statistical significance would suggest that the pattern observed would be expected to occur by chance only once in one hundred times  are used. These spatial and temporal parameters represent various bandwidths that are within the range of bandwidths used in earlier studies  speaks to efficiency—how many offenses are captured per percentage of study area, whereas the capture rate tells what fraction of offenses might be prevented.The capture rate represents the proportion of predicted events from the total number of events in the dataset. The larger the proportion, the larger the possible reduction in events due to possible crime prevention strategies employed by the police. Because this rate does not take the size of prediction areas into account, the PAI is additionally calculated to evaluate predictive accuracy. First introduced by Chainey et al. , this inAll calculations were automatically processed using a Python script using the ArcPy site-package of Esri’s ArcGIS. For each of the spatial and temporal parameter combinations, the script calculated the number and sizes of the prediction areas generated per day, and analyzed which “future” events occurred within prediction areas, flagging these events as predicted events. Based on these results, the two evaluation indices (capture rate and PAI) were calculated. Examining the findings for the different methods for different spatial and temporal bandwidths enables an assessment of the sensitivity of the approach to different parameter combinations and provides an assessment of the optimal parameter settings.In this section, we investigate whether there is a pattern of repeat and/or near repeat victimization for apartment burglaries in Vienna. Given observed patterns elsewhere, it is expected that apartment burglaries will cluster in space and in time. Table The value in upper-left of Table This section focuses on the accuracy of the repeat and near repeat forecasting approach that uses the heuristic method. Essentially, for each apartment burglary in the dataset, the routine written searches for subsequent burglaries that occur within a given space and time of the burgled home. As discussed, different parameter values were used to define what is considered close in space , and time . This routine is repeated for each day for which data exists and flags apartment burglaries that are identified as “near repeats”. Of course, a single event cannot be predicted more than once and it should be noted that—as with previous studies of this kind—predictions are produced for the day after the interval used to generate predictions.Table 2). As a rule of thumb, 1 ha is often referred to as the size of one soccer field. This means that on average, prediction areas generated using a 100 m bandwidths and a 1 day forecasting period  and the predictive accuracy (PAI). In this research, both evaluation metrics can be combined by using threshold values. For example, with a capture rate of at least 10%, meaning that at least 10% of apartment burglaries can be predicted, which of the spatial and temporal parameter combinations yields the largest PAI value? To give an example, the combination of up to 300 m spatial bandwidth combined with a forecasting period of up to 3 days shows the highest PAI value of 6.4 Table . For theThe approach of comparing observed patterns of prediction areas to randomized prediction areas and their potential to predict apartment burglaries reveals significant differences, when using different spatial and temporal bandwidths. The shorter the spatial and temporal bandwidths are, the more statistically significant are both evaluation indices for the observed compared to the random distribution of apartment burglaries. In contrast, no statistical significance in the prediction accuracy can be observed, when using the heuristic method with larger spatial and temporal bandwidths. In Tables The near repeat chain method is designed to reduce the number of prediction areas, by preselecting areas that are already prone to near repeats. As discussed, rather than assuming near repeats will following every burglary, the near repeat chain method identifies existing repeat and near repeat pairs and assumes that a future (near) repeat is more likely near to one or both of these events , statistically significant repeat and near repeat patterns were identified. This research revealed that a high proportion of all apartment burglaries in Vienna can be attributed to repeat and near repeat apartment burglary victimizations. General results from this research match findings from comparable international studies  are obtained with the shortest bandwidth combinations for both the heuristic and the near repeat chain method. However, additional analysis shows that using the shortest bandwidth for both prediction measures would have decreased the potential prevention (capture rate) of predicted apartment burglaries by the least amount. Unfortunately, no measure currently exists that takes both predictive accuracy, as calculated with the PAI, and predictive power  into account. However, this research proposes a possible solution to this shortcoming, by defining an optimal spatial and temporal threshold value for calculating the capture rate. After some testing, a spatial bandwidth threshold of 300 m and a temporal bandwidth threshold (both for finding near repeat pairs and for the forecast period) of 3 days was found to be most appropriate. Capture rates for this optimal bandwidth combination resulted in a value of 14.7% for the heuristic method and 4.6% for the near repeat chain method, respectively.Overall, the near repeat chain method proves to be the more efficient of the two evaluation methods, since it resulted in higher PAI values than the heuristic method for all bandwidth combinations analyzed here. While for the heuristic method only the originating event is needed to make a forecast, a near repeat is additionally required to make a forecast using the near repeat chain method.The results of this research suggest that there is considerable potential for law enforcement in the city of Vienna to employ the concepts of repeat and near repeat victimization to forecast future apartment burglaries. The approaches discussed in this study can easily be interpreted by analysts and by police officers. Using automated workflows, the calculation of the results from these predictive analytic methods only takes a few minutes per day. While these methods work well for apartment burglaries, it does not necessarily mean that the principle of repeat and near repeat victimization is also suitable for other types of crime in the selected study area. The predictive methods investigated in this research may also only be applicable to the city of Vienna and may not show similar results in other cities around the world. Future research might thus test these methods for other types of crime and for other cities.The analysis of repeat and near repeat victimization presents many opportunities for future research. As an alternative and a possible enhancement of the proposed predictive methods could be to do the analysis based on administrative boundaries, such as districts or police beats, in order to assess which level of aggregation or size of enumeration unit is more suitable in predicting near repeats. First tests at the district level show that districts that are closer to the city center experiencing higher risks and therefore more suitable for predicting apartment burglaries than districts further away. But underlying enumeration units do not necessarily have to be administrative units. It is also imaginable to define specific areas of interest, such as spatial and temporal hotspots of apartment burglaries and focus the analysis on areas where crime is clustered in both space and time. In addition, an alternative selection for a study area could be to use high-risk areas identified by the risk terrain modeling approach.This research (and studies like it) does not include information on serial offenders. If this information were available, then a possible enhancement of the near repeat chain method would be to define prediction areas by serial offenders that committed crimes at both the originating and near repeat locations. Of course, such information is unlikely to be available at the present time given the time it takes to catch offenders and universally low rates of detection. However, prediction areas might only be created if both crime events of the near repeat pair share the same method of entry into an apartment (see Bowers and Johnson Of course, the effectiveness of predictive policing relies not only on efficient forecasting methods, but also effective crime prevention strategies. Santos and Santos  suggest