Recent climate change is affecting the earth system to an unprecedented extent and intensity and has the potential to cause severe ecological and socioeconomic consequences. To understand natural and anthropogenic induced processes, feedbacks, trends, and dynamics in the climate system, it is also essential to consider longer timescales. In this context, annually resolved tree-ring data are often used to reconstruct past temperature or precipitation variability as well as atmospheric or oceanic indices such as the North Atlantic Oscillation (NAO) or the Atlantic Multidecadal Oscillation (AMO). The aim of this study is to assess weather-type sensitivity across the Northern Atlantic region based on two tree-ring width networks. Our results indicate that nonstationarities in superordinate space and time scales of the climate system  can affect the climate sensitivity of tree-rings in subordinate levels of the system . This scale bias effect has the capability to impact even large multiproxy networks and the ability of these networks to provide information about past climate conditions. To avoid scale biases in climate reconstructions, interdependencies between the different scales in the climate system must be considered, especially internal ocean/atmosphere dynamics. Dense proxy networks are often used to reconstruct temperature123571213Much effort has been made to improve climate reconstructions by including larger multiproxy datasets for both hemispheres and by the comparison of results31720Besides these efforts for several locations temporally unstable climate/growth relationships, a reduced sensitivity of tree-rings to single climate elements22In addition to these issues our results demonstrate that phenomena operating on the synoptic to global scale  of the climate system can affect the climate sensitivity of tree-rings for phenomena in subordinate levels of the climate system . This scale bias effect can be generally defined as a reduced climate sensitivity of proxies for phenomena in subordinate levels of the climate system, caused by nonstationarities in superordinate scales of the climate system. For instance, a reduced climate sensitivity of proxies for phenomena in the micro scale of the climate system can also be referred to as scale bias if it is caused by nonstationarities in the meso-, synoptic-, or global scale of the climate system.The scale bias effect has the capability to severely impact climate reconstructions11In this study, we utilise nine weather-/circulation-type classifications in combination with two tree-ring datasets to demonstrate the scale bias effect.The study is based on nine weather-type classifications, the subjective  Hess Brezowsky (H/B)th Century Reanalysis data archive30k-means clustering) –15. Both classification approaches were conducted in two variants, producing 18 and 27 classes (types) respectively. Consequently, a total of eight classifications were computed – two pressure levels, two classification methods, two variants (18 or 27 classes).The weather-type classifications for the period 1871–2010 have been derived by applying the cost733class classification softwareThe first classification approach is the Grosswettertypes (GWT) or Prototype classification3015Two tree-ring datasets were used to determine the influence of scale bias effects in tree-ring networks. Tree-ring dataset-1 is based on 21 beech and 29 oak chronologies which were taken from an already published tree-ring width network1235To calculate site chronologies a bi-weight robust mean was used. The values of the statistical parameters, expressed population signal (EPS)et. al.We used dataset-2 to verify the results derived from dataset-1. Dataset-2 is a subsample of the dataset gathered by Babst The atmospheric circulation tree-ring index (ACTI)An ACTI time series is computed for each weather-type classification and for every site chronology.The values of the ACTI time series are defined as springtime sums of the weighted weather-type frequencies during the period 1891 to 1990 (for tree-ring dataset-1) and 1881 to 1980 (for tree-ring dataset-2), respectively. As an example, 27 weather-type weights are needed to calculate ACTI for a weather-type classification with 27 classes/types. These weights are computed, based on a Monte Carlo simulation with 1 million simulation runs. In each Monte Carlo run a random number set which contains 27  normal distributed random numbers is used to compute a randomly weighted weather-type index. In each run 60 discontinuous calibration years are selected and different measures of coherence are computed between all tree-ring chronologies and the weather-type index. Since several hypotheses are tested (1 million simulation runs), the experimentwise error rate is larger than the individual error rateFor tree-ring dataset-2 this proceeding is not useful due to the vast spatial domain and the large number of tree species  gridded E-Obs 10 datasetp < 0.001) computed between ACTIm and gridded climate datasets indicate that the tree-ring network (dataset-1) used in this study is sufficiently large enough in order to capture large-scale climate signals across the Northern Atlantic region. As stated previously, ACTI is always positively correlated with the corresponding tree-ring chronologiesr < -0.6, r > 0.6 r < -0.6 Based on tree-ring dataset-1 for each weather-type classification an ACTI time series for the period 1891 to 1990 was computed. Additionally, a mean curve (ACTIm) was derived from the nine resulting ACTI time series. Therefore the results are based on a weather-type ensemble to ensure that the detected instability between weather-types and tree-ring chronologies is not a statistical artefact in the weather-type data. Also the temporal stability of the relationships between ACTI and climate data and the spatial structure of the correlation patterns are investigated. In To investigate the temporal stability of the statistical coherence between climate datasets and ACTI, the region showing the strongest statistical coherence between ACTIm, pressure and temperature  is used r = 0.36 to r = 0.73) for the year 1951 (correlation window 1934–1968). The black curve in p < 0.05).In contrast to the results above, the moving correlation analysis (35-year window) between ACTI time series and tree-ring chronologies indicates synchronous fluctuations in weather-type sensitivity . Additiop <= 0.01 and for one curve 0.01< p < 0.05. All curves especially the objective weather-type classifications show a decline in statistical relationship in 1911. The GWL C29 H/B shows another sharp decrease in 1916. The lowest variability between the curves shown in p > 0.01). After 1918 a positive trend is observable until 1965. Towards the end of the time series the statistical relationship between ACTI time series and tree-ring chronologies decreases again, especially for the objective weather-type classifications.In the beginning of the time series (1908) nine out of ten curves indicate a significant relationship between ACTI and tree-ring chronologies. For eight curves p < 0.01) in SST_N and SST_S areas .A spatial correlation analysis between gridded Hadley Centre SST data and the NAO index shows negative correlation coefficients ( finding . Both NA finding  and in gr = 0.26 (p < 0.01), but in a 17-yr moving correlation window only two longer periods 1923–1932 and 1968–1975 show significant correlation coefficients (p <= 0.05) especially in 1925 and 1926  used for The observed SST sensitivity of the tree-ring network first observed for 1923 can be seen as the reason for the already described decline in weather-type sensitivity in the beginning of the 20th century the weather-type sensitivity of the tree-ring width network decreases, whereas a significant statistical relationship with SST occurs. At the end of the time series (1971) AMO is again in its negative phase but no distinct SST/NAO correlations are observable only the relationship between NAO_Azo and SST_S  and their associated tree-ring width chronologies were used to compute a mean curve. Hence the PCA is only applied to group ACTI and tree-ring width chronologies according to their weather-type response and to extract the common signals from the tree-ring network. For tree-ring dataset-2 649 out of 726 chronologies showed at least for one weather-type classification a significant weather-type response for spring, for dataset-1 49 out of 50 chronologies. For each weather-type classification and for both tree-ring datasets the number of chronologies with significant weather-type response for spring are shown in To verify the results shown in th century. Even though a larger dataset  and different calibration years for the weather-type procedure were used, the curves The moving correlation analysis (35-year window) between the ten ACTI time series  and the ten mean tree-ring chronologies dived from tree-ring dataset-2, indicates similar fluctuations in weather-type sensitivity  as alreath century are within a period with stronger NAO/SST  and Southern Annular Mode (SAM) demonstrate the need to quantify the effect of nonstationarities in paleoclimate reconstructionsth Century Reanalysis dataset which is declared to be homogeneousIn fact there is a certain within-type variation within each single weather-typeOur study gives evidence that more attention is needed to understand scale effects in climate reconstructions and raises the question how uncertain due to scale biases climate reconstructions are. Further research is needed to understand how processes or phenomena on different space and time scales of the climate system interact and which underlying processes or phenomena in the climate system, besides NAO and AMO, can cause changes in climate sensitivity of proxies.Based on our results we conclude and state the following theses: Multiproxy networks are vulnerable to scale biases not only due to their tree-ring dominance, but it is also extremely likely that other climate proxies such as corals lake and sea sediments are affected as well. To reduce uncertainties in climate reconstructions the interdependencies between the processes and phenomena which act on different scales of the climate system must be considered to a greater extent. Our results confirm the need to consider ocean-atmosphere interactionExamining scale bias from an inverse perspective leads to the conclusion that it hinders the assessment of the influence of past climate conditions on climate proxies. As a result, the estimation of the influence of scale bias within future climate scenarios is even more complicated as it relies on assumptions that are derived from physical observations. To improve the understanding of interdependencies and feedbacks in the climate/earth system the role of scale effects must be re-assessed.How to cite this article: Schultz, J. A. et al. Sensitivity of proxies on non-linear interactions in the climate system. Sci. Rep.5, 18560; doi: 10.1038/srep18560 (2015).


There is increasing interest in using smartphones as stand-alone physical activity monitors via their built-in accelerometers, but there is presently limited data on the validity of this approach.The purpose of this work was to determine the validity and reliability of 3 Android smartphones for measuring physical activity among midlife and older adults.A laboratory (study 1) and a free-living (study 2) protocol were conducted. In study 1, individuals engaged in prescribed activities including sedentary , light (sweeping), moderate , and vigorous  activity over a 2-hour period wearing both an ActiGraph and 3 Android smartphones . In the free-living study, individuals engaged in usual daily activities over 7 days while wearing an Android smartphone (Google Nexus One) and an ActiGraph.P<.001) between the raw ActiGraph counts/minute and the phone’s raw counts/minute and a strong correlation on minutes of moderate-to-vigorous physical activity . Results from Bland-Altman plots suggested close mean absolute estimates of sedentary (mean difference=–26 min/day of sedentary behavior) and MVPA (mean difference=–1.3 min/day of MVPA) although there was large variation.Study 1 included 15 participants . Correlations between the ActiGraph and the 3 phones were strong to very strong (ρ=.77-.82). Further, after excluding bicycling and standing, cut-point derived classifications of activities yielded a high percentage of activities classified correctly according to intensity level  that were similar to the ActiGraph’s percent correctly classified . Study 2 included 23 participants . Within the free-living context, results suggested a moderate correlation (ie, ρ=.59, Overall, results suggest that an Android smartphone can provide comparable estimates of physical activity to an ActiGraph in both a laboratory-based and free-living context for estimating sedentary and MVPA and that different Android smartphones may reliably confer similar estimates. Reduced sitting time and increased moderate-to-vigorous physical activity (MVPA) confers an array of health benefits -3. IdentOne potentially cost-efficient and low-burden mechanism for tracking daily physical activity is the smartphone ,7. The sAt present, there is relatively little systematic research exploring how accurately physical activity can be tracked via smartphones. Some studies have explored the utility of ecological momentary assessment (EMA) via smartphones , activitThe purpose of this work was to determine the validity and reliability of Android smartphones for tracking physical activity utilizing cut-point–based methods of activity classification. In particular, we sought to determine the validity of Android smartphones for categorizing physical activity into sedentary, light physical activity, and moderate-to-vigorous levels of physical activity in a laboratory setting. We also explored interdevice reliability by comparing the estimates from 3 Android phones used simultaneously in the laboratory. Finally, we sought to determine the validity of the smartphones by comparing daily estimates of physical activity between the ActiGraph and an Android smartphone in a free-living context.We conducted both a laboratory-based and free-living study. In the laboratory-based study (study 1), individuals engaged in prescribed activities of various intensities over a 2-hour period wearing both an ActiGraph and 3 Android smartphones  all worn both on the hip and in the pocket. In the free-living study (study 2), individuals engaged in usual daily activities that were tracked over a 7-day period via an Android smartphone (Google Nexus One) and an ActiGraph.Participants were a convenience sample of 15 midlife and older adults living in the San Francisco Bay area in California. Midlife and older adults  were chosen because they represent an understudied population for activity classification and because the algorithms developed were explicitly being developed for a smartphone-based physical activity intervention . ParticiThe procedures for this study were similar to previously published work conducted by the study investigators . SpecifiThe ActiGraph GT3X+ is a small, electronic, triaxial device that is worn on the waist and measures activity “counts”  ,22. The We chose to include 3 different Android smartphones to gauge the reliability and validity across manufacturers  and within manufacturer by using different firmware versions of Android . After attaching the devices, participants were asked to engage in a series of activities while wearing the ActiGraph and the Android phones  and moderate-to-vigorous intensity physical activity (>1951) [00 countsWe first calculated an intraclass coefficient (ICC) reflecting the effect of individual variability on observed counts. Our analyses found that the within-subject variance was effectively zero across all possible comparisons using a leave-one-out cross-validation method for each mixed model analysis described subsequently. Based on this and that the counts were not normally distributed, Spearman rank order correlations were deemed an acceptable method for determining these associations. Mixed model analyses  were conAs previously mentioned, we used fairly standardized cut-point values for ActiGraph counts of sedentary physical activity   and MVPAWe used standard conventions for labeling the strength of our Spearman correlations . WithinParticipants were a subsample from the previously reported Mobile Interventions for Lifestyle Exercise and eating at Stanford (MILES) study and, thus, recruitment procedures have been reported previously . In brieFor this validation study, only the baseline phase  from the MILES intervention study was used. Participants were requested to continue with their normal physical activity during the baseline phase. All participants (N=23) were provided a Nexus One smartphone equipped with a custom app for tracking physical activity via the built-in accelerometer and also wore an ActiGraph (GT3X+), utilizing standard quality control procedures for the ActiGraph . ParticiData compliance and cleaning procedures for the ActiGraph and smartphone were consistent with other large-scale cross-sectional accelerometer studies ,30, suchAlthough ICC were originally used, we again found minimal within-person variation. As such, Spearman rank order correlations were calculated between the ActiGraph and smartphone. In addition, Bland-Altman plots  were cre=.90). There were a total of 15 participants  who participated in study 1. A list of the activities in the laboratory study can be found in ). P<.001; sedentary: ρ=44, P<.001; MVPA: ρ=.67, P<.001) and weak correlations for light physical activity . These correlations were nearly the same as the no bike and standing correlations .There were 23 participants who had acceptable data for comparing the phone accelerometer to the ActiGraph . On average, participants had approximately 5 days of valid wear time for both the ActiGraph and smartphone accelerometry data  Android smartphone raw counts are strongly correlated to ActiGraph counts in a laboratory-based and free-living setting suggesting the accelerometers provide similar estimates regardless of the activity classification algorithm used, (2) Android smartphone raw counts were strongly correlated with one another suggesting that different Android phones reliably provide similar estimates before any algorithm, (3) placement in the pocket versus on the hip both in a laboratory-based and free-living context did not detrimentally impact estimates suggesting that phones can reliably be worn in either location, and (4) absolute classifications of activity intensity between the phone and ActiGraph were comparable both in-laboratory (based on similar correct classification percentages of known activities) and free-living context (based on absolute mean difference estimates via Bland-Altman plots) for sedentary and MVPA estimates but not light physical activity.Results indicating that the phone accelerometers and ActiGraph are strongly correlated have important implications for not only cut-point-based activity classification strategies, but also any classification strategy utilizing an accelerometer. In particular, because the effective raw signals are providing similar information, it is quite plausible that similar algorithm strategies can be used between devices with similar effects, assuming some degree of calibration. This is important because it suggests other activity recognition strategies, such as machine learning/neural network analyses -13, can Results suggesting phone placement did not impact sedentary and MVPA estimates have important implications for usability. Specifically, we found an almost even split in preferences related to wearing the phone, with some desiring to wear it on the hip and others desiring to keep it in their pockets. A phone will likely be worn if it fits into a person’s daily life. As such, allowing individuals to wear the device in whatever way they so desire increases the likelihood of continuing to gather the data in the long-term . Our reFinally, our results suggesting that the phones gave similar absolute estimates of sedentary and MVPA activities to an ActiGraph in both in-laboratory and free-living studies has important implications for epidemiologic and intervention research. At present, there is far more data supporting the linkage between cut-point-derived estimates of physical activity with health outcomes compared to the other data analytic techniques ,15,33. BThe ActiGraph was utilized as our primary comparison metric. Although the ActiGraph is acceptable for field-based research, it is not a gold-standard activity monitoring device. This is particularly important to be mindful of when interpreting the Bland-Altman plots because the Bland-Altman plots are designed to support comparison of a new measure to a previous gold-standard metric. The Bland-Altman plots revealed good mean-level differences but poor confidence interval estimates between the smartphone and ActiGraph. Because the ActiGraph is not a gold-standard measure, it is quite plausible that the high confidence intervals can be attributed not only to variance from the smartphone but also the ActiGraph. As such, the confidence intervals from the Bland-Altman plots need to be interpreted with caution. Further, the ActiGraph cut-points utilized incorporated only the vertical axis whereas the phones used all 3 axes, thus establishing another potential source of error between the two.A second limitation of our work is that we utilized a cut-point-based strategy for activity classification rather than newer strategies such as neural network analysis or machine learning techniques -13. AlthAnother limitation is the brands of the smartphones we studied. In 2009, HTC and Motorola were among the most important manufacturers of Android smartphones, but at this point Samsung has become the primary Android phone manufacturer. Unfortunately, our study cannot provide any insights on the quality of Samsung devices. Further, although the data were comparable across our phones, it is impossible to determine if the phone estimates would remain comparable in newer phones. That said, based on the plethora of different Android phones available, our data at least increases confidence that different manufacturers and running different firmware versions of Android may provide similar estimates of physical activity based on the accelerometry.Strengths of this research were that data are available from both an in-laboratory and free-living context. Further, the samples used to create the estimates are in-line with other physical activity assessment/validation protocols. Finally, validation occurred via direct observation of activities in laboratory.Overall, our results suggest that an Android smartphone appears to be an acceptable alternative for estimating sedentary and moderate-to-vigorous intensity physical activity to an ActiGraph accelerometer in both a laboratory-based and free-living context. This suggests that smartphones might be an effective mechanism, by themselves, for tracking physical activity. Future work should explore other potential analytic techniques  for further improving the classification.


One of the main reasons why a non-cancer drug may prove effective against cancer is that not all of its biological targets may have been identified when the drug was originally developed. Until recently, the main focus in oncology drug development has been on the tumor cell — first with traditional chemotherapy and then with more targeted agents. But much of the focus has now shifted to targeting the tumor micro-environment, especially its key role in metastasis and drug resistance.Research on existing FDA-approved drugs is increasing in the field of anti-cancer drug development. Drug repurposing may allow progressing through the drug development process more quickly as well as reducing project costs compared to traditional in vivo experiment, a four-day pre-treatment followed by a 30-day oral administration of the quadruplet drug combination to mice inoculated with melanoma cells produced significant inhibition of cancer metastasis in the lung dose-dependently without any marked side effects. In addition, the authors confirmed that all the four of these drugs were required for inhibition of cancer metastasis.Wan L. et al. proposed that initiation of circulating tumor cell adhesion to the local vascular endothelium is an important first step for circulating tumor cells to start the metastatic cascade. They showed that a combination of 3 FDA-approved drugs, the over-the-counter drug aspirin, the well-known antibiotic doxycycline and mifepristone (a progesterone receptor antagonist known as an abortifacient pill) used together with the amino acid lysine could effectively and safely prevent cancer metastasis Figure . 1]. Th. Th1]. TAspirin, a widely used anti-inflammatory drug, a potent COX-2 inhibitor and an antiaggregant has been recently shown that its regular intake might reduce long-term risk of colorectal, oesophageal, gastric, biliary, and breast cancers and the risk of distant metastasis as well .We proposed a novel strategy for the treatment of primary tumors and advanced metastases via the selective targeting of cancer stem-like cells and identified a conserved phenotypic weak point - a strict dependence on mitochondrial biogenesis. Given that mitochondria have a bacterial origin, antibiotics also target mitochondrial translation and impair mitochondrial function. In our study we have shown that treatment with 4-5 different classes of FDA-approved antibiotics, especially doxycycline can be used to eradicate cancer stem-like cells in several tumor types Figure  [4].in vitro and in a mouse xenograft model. Importantly, this effect may be achievable in human sera with a therapeutic dose of the drug [Pulvino et al. describe in their paper that a connectivity map  analysis uncovered several tetracycline antibiotics. Among them doxycycline as the most potent inhibitor of NF-κB signaling. Also, doxycycline successfully inhibited the growth of diffuse large B-cell lymphoma the drug .in vivo in a subcutaneous model of two human melanoma cell lines (A375 and MV3) in nude mice [Hu et al. showed that tigecycline, another tetracycline antibiotic, suppressed cell proliferation, cell invasion and migration in melanoma Figure . It induude mice .Cancer is a leading cause of death worldwide and despite the investment of millions of dollars of large pharmaceutical companies and governments into anti-cancer drug development, the current chemotherapeutic approaches are highly costly while their efficacy is not universally effective in all patients. These factors are leading to repurposing of well-known FDA-approved drugs, which can bypass the early stages of drug development, even Phase I clinical trials in some cases, thus reducing project costs and time. Taken together, the previously mentioned studies show that FDA approved drugs can be successfully applied in tumor therapies.


Molecular image-guided therapy has been demonstrated to be effective in improving diagnosis, prognosis, planning, and monitoring of personalized medication. Molecular imaging modalities include positron emission tomography (PET), single-photon emission-computed tomography (SPECT), magnetic resonance imaging (MRI), computed tomography (CT), ultrasound (US), and optical imaging . Among clinical molecular imaging modalities, radionuclide imaging technique is the most sensitive one which could provide target-specific information as well as function, pathway activities, and cell migration in the intact organism. For instance, the radiotracer could noninvasively assess diseases treatment endpoints which are used to rely almost exclusively on biopsies and histopathological assays. New leads on the development of personalized theranostic (image and treat) agents would allow for more accuracy in the selection of patients who may respond to treatment.18F-FDG PET/CT. Their study demonstrated that different types of adenocarcinoma with BAC features exhibited different 18F-FDG uptake patterns. False negative on 18F-FDG PET/CT mainly occurs in those lesions presented as the nonsolid nodule on CT, but not the solid nodule. Y. Dong and her coauthors from Zhejiang University evaluated the efficacy of PET/CT in association with serum tumor maker assays in the follow-up of patients with breast cancer (BC). This study indicated that PET/CT was a highly efficient tool to follow-up patients with BC compared with CITs in terms of sensitivity and specificity, allowing for the detection of metastatic and/or recurrent cases. The high serum levels of CA 15-3 in confirmed positive PET/CT patients compared to negative ones indicated the clinical value of CA 15-3 in BC follow-up. H. Hou and his coauthors from the same institute reported a pilot study on the prognostic value of 99mTc-pertechnetate thyroid scintigraphy for predicting the outcomes of fixed dose (5 mCi) of radioiodine. A fixed dose of 5mCi radioiodine seems to be practical and effective for treating GD patients with thyroid mass ≤40.1 g and 99mTc-pertechnetate uptake ≤15.2%. This study demonstrates that 99mTc-pertechnetate thyroid scintigraphy is an important prognostic factor for predicting the outcomes of RIT.Topics covered in this special issue include advances in molecular imaging modalities in oncological disease management, image-guided approach of brain function, stem cell technology, and receptor based imaging approach. For example, Q. Wang's group at Nanfang Hospital of Southern Medical University reported a retrospective study on 51 consecutive patients to investigate what causes the false negative of adenocarcinoma with BAC features on Mesenchymal stem cells (MSCs) have been proposed as a promising cell population for cell therapy and regenerative medicine applications. However, the low retention and poor survival of engrafted cells hampered the therapeutic efficacy of engrafted MSCs. In this issue, F. Cao and her coauthors from Fourth Military Medical University and Chinese PLA General Hospital presented their work on the protective effects of ghrelin on engrafted adipose derived mesenchymal stem cells (ADMSCs) and its beneficial effects with cellular therapy in mice myocardial infarction (MI). Their study revealed that ghrelin may serve as a promising candidate for hormone-driven approaches to improve the efficacy of mesenchymal stem cell-based therapy for cardiac ischemic disease via PI3K/AKT pathway. hSSTr2 gene can act as not only a reporter gene for in vivo imaging, but also as a therapeutic gene for local radionuclide therapy. Even a second therapeutic gene can be transfected into the same tumor cells together with hSSTr2 reporter gene to obtain a synergistic effect.Recently, a number of tracers have been introduced due to the encouraging results from the applications of radiolabeled ligand-receptor system. The current status of somatostatin receptor based imaging and radionuclide therapy is summarized and discussed in the review paper by C. Xu and her coauthor. TheNeuroscience is a hot topic in recent years. Maladaptive use of the Internet results in Internet addiction (IA), which is associated with various negative consequences. Molecular and functional imaging approaches have been increasingly used for the analysis of neurobiological and neurochemical changes of the brain. Y. Zhu and his coauthors summarize the molecular and functional imaging findings on neurobiological mechanisms of IA, focusing on magnetic resonance imaging (MRI) and nuclear imaging modalities including positron emission tomography (PET) and single-photon emission-computed tomography (SPECT). MRI studies demonstrate that structural changes in frontal cortex are associated with functional abnormalities in Internet addicted subjects. Nuclear imaging findings indicate that IA is associated with dysfunction of the brain dopaminergic systems. Abnormal dopamine regulation of the prefrontal cortex (PFC) could underlie the enhanced motivational value and uncontrolled behavior over Internet overuse in addicted subjects.In summary, molecular imaging could be applied to target characterization, underlying disease progression and evaluation of therapeutic response and stem cell and brain function. This special issue provides a platform of the efficacy of personalized medication from molecular imaging technology which may have high impact on patient care.Hong ZhangMei TianIgnasi CarrioAli Cahid CivelekYasuhisa Fujibayashi


Integration of web-based educational tools into medical training has been shown to increase accessibility of resources and optimize teaching. We developed a web-based educational portal (WBEP) to support teaching of pediatric residents about newborn medicine by neonatology fellows.1) To compare residents’ attitudes about their fellow-led education in the NICU pre- and post-WBEP; including assessment of factors that impact their education and usefulness of teaching tools. 2) To compare fellow utilization of various teaching modalities pre- and post-WBEP.We queried residents about their attitudes regarding fellow-led education efforts and various teaching modalities in the NICU and logistics potentially impacting effectiveness. Based on these data, we introduced the WBEP – a repository of teaching tools  for use by fellows to supplement didactic sessions in a faculty-based curriculum. We surveyed residents about the effectiveness of fellow teaching pre- and post-WBEP implementation and the type of fellow-led teaching modalities that were used.p<0.0001) and journal articles .After analysis of survey responses, we identified that residents cited fellow level of interest as the most important factor impacting their education. Post-implementation, residents described greater utilization of various teaching modalities by fellows, including an increase in use of mock codes (14% to 76%, A web-based resource that supplements traditional curricula led to greater utilization of various teaching modalities by fellows and may encourage fellow involvement in resident teaching. Web-based tools are becoming critical supplements for training medical students, residents, and fellows. Benefits include the ability for standardization, flexibility for the student–teacher pair to select the time and place for learning, and ease of accessibility. These alternative teaching options are especially beneficial in the current environment of restricted resident work hours and decreased resident training time in Newborn Medicine per Accreditation Council for Graduate Medical Education (ACGME) guidelines. Studies have identified key subject areas best suited for Internet-based learning, including the critical care setting where learners can become familiar with rare events .Although web-based tools for critical care learning are available, quality varies considerably. Prior to developing Internet-based learning tools, educators need to consider availability, relevancy, redundancy, and an approach for system modification . One stuThe goals of subspecialty fellowship training include development of skills as clinical leaders, researchers, and teachers. The teaching role of fellows requires mastery of subjects and problem-solving skills when challenged by engaged learners. However, fellows have limited formal teaching instruction and rarely receive feedback about their teaching skills. In addition, successful resident learning is dependent on both the residents’ and fellows’ level of interest. Several studies have cited that trainees benefit specifically from teaching by fellows . HoweverWe created a web-based newborn medicine educational portal to enhance utilization of existing and newly created educational tools, and enhance the neonatology fellow teaching role. The specific aims of our project were 1) to compare residents’ attitudes about their fellow-led education in the NICU pre- and post-web-based educational portal (WBEP), including assessment of factors that impact their education and usefulness of teaching tools; 2) to compare fellow utilization of various teaching modalities pre- and post-WBEP.We recruited pediatric residents from a large neonatal intensive care unit (NICU) at the Brigham and Women's Hospital (BWH) in Boston, Massachusetts. Residents and fellows rotate through this NICU from an affiliated tertiary care children's hospital  from the Boston Children's Residency Program (BCRP) and the Harvard Neonatal–Perinatal Medicine Fellowship Program (HNPMFP).The BCRP is ACGME accredited and comprised 150 pediatric residents, most of whom are required to complete 2 four-week NICU rotations (one at the BWH). During pediatric internship , each PGY-1 rotated through this NICU as part of a team comprised of 1 neonatologist, 1 neonatology fellow, and 2–4 PGY-1s. This team provided clinical care to 16 Level 2 or 3 neonatal patients. Since 2011, the residency program has followed the ACGME 2011 Duty Hour Standard, limiting PGY-1 to a maximum of 16 continuous duty hours .The ACGME-accredited HNPMFP trained 18 neonatology fellows per year. The first year of fellowship, included four one-month BWH NICU rotations including daytime shifts and overnight call. The second and third fellowship years consisted of 2–3 months of BWH night call coverage. During the fellow-led daily work rounds and at the bedside, neonatology fellows spent significant time interacting directly with residents and played a major role in resident education. Fellow responsibilities included direct patient care and oversight of the pediatric residents’ training. No formal scheduled teaching time or teaching tools had been delegated for fellow-led resident education prior to our intervention. The contribution of the fellow-resident teaching interactions had not been previously formalized within the curriculum.Given the coupling of decreasing exposure to clinical time in the NICU and an increasing role of the neonatology fellow as the supervising physician who spends the most time with the resident, resident education in the BWH NICU was becoming increasingly dependent on neonatology fellow-led teaching.and utilization of teaching modalities, prior to implementation of our fellow-based teaching curriculum, we surveyed 49 residents who had rotated as PGY-1 residents during the 2009–2010 and 2010–2011 academic years. After characterizing resident teaching modality preferences during the 6 months prior to the intervention, a need was suggested for process improvement to develop a structured curriculum for fellow-led resident education.To assess both resident attitudes In the setting of the 2011 ACGME Duty Hour Standards altered duty hours for PGY-1 residents, we utilized a quality improvement Plan-Do-Study-Act (PDSA) tactical framework  to improWe designed, piloted, and revised a cross-sectional quality improvement survey to evaluate resident attitudes about current education and teaching practices and then developed content and populated the WBEP with material guided by ACGME-recommended goals. We specifically addressed our first objective by querying residents about factors that both positively and negatively impact fellow-led education as well as usefulness of various teaching modalities. For our second objective, we also asked residents to identify the teaching modalities used by fellows. Because a validated assessment instrument does not exist, we created our survey by establishing face validity. In this approach, authors used a consensus-building approach to establish key questions that were relevant to NICU education. Subsequently, we determined process measures that addressed the utility of the WBEP. We developed the WBEP to provide educational prompts for fellows to utilize during impromptu resident teaching and scheduled weekly fellow-run mock codes. Usually, one fellow was paired with 2–3 residents for these teaching opportunities. The WBEP served as an easily accessible platform for the fellows to utilize different types of teaching modalities to educate the residents. For example, the portal provided sentinel neonatology articles with discussion questions, scripted simulation exercises, and case vignettes for the fellows to describe and discuss with the residents. The teacher and learner team could choose which teaching modality they preferred for each session. We promoted the WBEP in bi-weekly fellow meetings including introduction to the portal, review of the available resources, and encouragement of use for resident teaching.The WBEP, a repository of resources, contained more than 110 resource pages including questions, case discussions, articles, mock codes, and knowledge tests . The resWe launched the WBEP in October 2011, 3 months after the 2011 ACGME Duty Hour Standards were implemented. The program was updated weekly and accessible to all BWH fellows and residents. The pre-implementation historical cohort was surveyed prior to the intervention in October 2011 and the post-implementation cohort was surveyed between October 2011 and June 2012.Our pre-implementation cohort included 49 pediatric residents who rotated in the BWH NICU during the 2009–10 or 2010–11 year as PGY-1 residents. The post-implementation cohort included 29 residents who were also PGY-1 residents who rotated in the BWH NICU after the implementation of the portal. All participants before and after the WBEP implementation were invited by e-mail to complete a cross-sectional quality improvement survey. Both samples were obtained by convenience sampling.The primary outcomes assessed were resident attitudes about the impact of various factors on their neonatology education and usefulness of various teaching modalities in their education and the PGY-1 resident report of fellow teaching modality utilization.We measured resident attitudes and teaching tool utilization using a 10-item cross-sectional quality improvement survey. The survey contained questions about participant characteristics, resident attitudes about factors impacting education, usefulness of teaching modalities, and rate of utilization of teaching modalities. After implementation of the WBEP, we surveyed the first 10 residents who had exposure to fellow-led use of the WBEP to complete our PDSA cycle 1. After examining resident feedback, we revised the WBEP by including additional PowerPoint presentations, journal articles, and clinical vignettes. We then recruited 19 additional residents who completed the cross-sectional quality improvement survey. We completed PDSA cycle 2 in June 2012. The same survey instrument was administered to the residents pre- and post-implementation to address both objective 1 and 2 of the study.t-tests for continuous variables. We used SAS version 9.3  for analyses.We conducted bivariate analyses to examine associations of predictors with outcomes using Chi-squared test for categorical and The study was deemed exempt from review by the Institutional Review Board because it was considered a quality improvement project.A total of 78 residents responded to the quality improvement education survey (51% response rate) – 49 (54%) pre-implementation and 29 (64%) post-implementation. Resident participant characteristics are presented in most positively  and most negatively  affected their NICU education. In addition, resident reflections showed that resident level of interest positively impacted their education (56%), while fellow responsibilities (51%) and resident schedules (46%) had a negative effect. The majority of residents (80%) rated fellow teaching as effective. Post-implementation, similar results were obtained as pre-implementation survey results, including a continued highlight on fellow level of interest as a critical component (see p=0.06).To address our first objective of comparing residents’ attitudes about their fellow-led education in the NICU pre- and post-WBEP, we surveyed residents about factors that positively and negatively affected their education during the NICU rotation including: patient acuity, fellow responsibilities, fellow level of interest, resident schedule, resident level of interest, attending presence on rounds, and lack of access to teaching tools. We specifically addressed attitudes toward both ‘fellow level of interest’ and ‘resident level of interest’ to assess impact of both members of the teacher/learner pair, as both are critical components of a successful educational experience. Interestingly in the pre-implementation survey, as demonstrated in nent see . Comparin=10) surveyed post-WBEP implementation identified the following modalities as useful: mock codes (100%), journal articles (70%), case-based discussions (100%), and bedside teaching (100%) (n=19) in our outcome analysis. Combining our results from PDSA cycle 1 and 2, we found that residents rated usefulness of journal articles more highly after the WBEP implementation .As a second component of our first objective to assess resident attitudes toward fellow-led education, we asked residents’ about the usefulness of various teaching modalities. After PDSA cycle 1, we found that residents (g (100%) . Given tn=49, post-intervention n=29), we found a significantly greater fellow-led utilization of several queried teaching modalities (p<0.0001) and journal articles  by fellows.To measure our second objective of comparing fellow utilization of various teaching modalities, we queried residents about the utilization of various teaching modalities both pre- and post-implementation. Interestingly, although the residents cited that each tool was useful, they also reported that they were not being utilized frequently (range between 12 and 33%) prior to WBEP implementation . Using odalities . SpecifiAccessibility of the WBEP. The WBEP was available online from any computer in the NICU to all fellows and residents.Straightforward user interface. The WBEP user interface was very easy to navigate for the fellow as teacher. The toolbars were highlighted in a different color making it simple to find various resources.Interactivity. Addition of ‘virtual patient’ cases provided a platform for interactive PGY-1 patient assessment and management with the fellow taking the role of facilitator.Accuracy and quality. The WBEP included neonatology focused high quality resources and tools. The computer-based program permitted weekly modifications, allowing incorporation of the most up-to-date evidence-based materials.Encouragement and recognition of the fellow teaching role. WBEP development and focus on the NICU fellow teaching role led to an increased emphasis on fellow teaching. This increased awareness and recognition alone likely contributed to the success of fellow-led resident teaching.We describe a successful educational quality improvement intervention, which created a structured teaching role for fellows to supplement an existing curriculum that led to increased utilization of various teaching modalities. We propose that the success of the intervention was the result of the following factors:Our first objective, comparing resident's attitudes toward fellow-led education pre- and post-intervention, identified fellow level of interest as a key factor affecting the resident NICU educational experience. While fellow level of interest in teaching is not an easily modifiable factor, we hypothesized that ease of WBEP accessibility, variety of available teaching tools, scheduled weekly teaching session and ongoing promotion of the WBEP may help foster fellow interest in education and lead to better resident education. The residents’ attitudes toward effective teaching tools likely depended on each fellow's modality preference for teaching. While this cannot be accounted for in our analysis, the generalizability remains robust as the WBEP is designed for a wide-range of fellow/teacher resident/learner pairs, both likely to have varied preferences. Our goal to provide a variety of reliable, accessible teaching tools where the teacher/learner pair can pick their modality appears achievable for application in clinical academic medical education.Our second objective compared the utilization of different teaching modalities by the fellows pre- and post-intervention and found an increased use of mock codes and journal articles post-intervention. The increased mock-code utilization may have been stimulated by providing a scheduled weekly blocked time for a potential mock-code session. The increased use of journal articles for teaching occurred at the discretion of the fellow/resident pair. We can hypothesize that the increased use of journal articles may have been due to ease of access to sentinel and state-of-the-art neonatology articles on the WBEP.One limitation of this intervention is that this is a single site study. However, the material provided in the WBEP could be generalizable and made accessible to other academic institutions to supplement their neonatology fellow teaching tools for resident education. Another limitation was that the survey measure was not piloted or administered to a focus group. However, it did have face validity as it was reviewed multiple times by the authors. The WBEP was specifically designed to focus on fellow-led teaching tools to enhance interactive teaching, rather than replacing faculty teaching or resident self-learning. While this set-up was by design, it could be seen as a limitation because of the missed opportunity for resident self-learning. However, the WBEP could be easily amended to include an additional self-learning focused section to address this issue.Each fellow/resident pair had different levels of exposure to the WBEP. The fellow teaching curriculum implemented with the WBEP included only one scheduled weekly session. The remainder of the fellow teaching time was dependent upon fellow and resident level of interest, acuity of patient responsibilities and time constraints. While a strict curriculum was not enforced, we believe that our intervention is generalizable to a realistic NICU teaching environment with opportunities for impromptu teaching sessions arising at different periods of time throughout a resident's rotation.Only a few publications address quality improvement initiatives in pediatric residency education –11. BaroWe demonstrated that a web-based resource that supplemented traditional curricula encouraged fellow-led utilization of various teaching modalities. Utilization of web-based teaching tools presents the opportunity for continued improvement in both fellow teaching skills and resident education. In our current age of technology, teaching using web-based resources will likely become a critical component of medical training. Ongoing work is needed to develop accurate, accessible resources to test the quality of these resources and to assess their impact on resident learning.


Malignant pleural mesothelioma (MPM) is a lethal disease with poor prognosis. The combination of cisplatin and pemetrexed has been confirmed as the standard of care for nonoperable MPM. Data have shown that the adoption of pemetrexed maintenance therapy (PMT) following first-line treatment appears extremely promising.We describe a 57-year-old man diagnosed as advanced MPM. We treated this patient with PMT after first-line cisplatin-based bevacizumab-containing chemotherapy and residual tumor disappeared after 6 course of PMT. A perfect response and a long progression-free survival (PFS) were reached with tumor mass disappearing and 14 months duration of PFS.This case suggests that adding bevacizumab to standard first-line chemotherapy is feasible and that PMT could be promising and useful for treating advanced MPM. We further entail a review of the literature on the first-line treatment, continuation maintenance therapy, switch maintenance therapy, and second-line treatment of patients with advanced MPM. So, progression-free survival (PFS) was not satisfied for patients with MPM.Malignant pleural mesothelioma (MPM) is a locally aggressive, usually fatal malignancy stemming from the pleural mesothelial surfaces, with a median survival of 4 to18 months after diagnosis.The efficacy of treatment of cisplatin-containing chemotherapy as SOC reaches a platform. It is difficult to further improve the prognosis of advanced MPM with mere standard combination schedule. Whether it can promote PFS or survival to add additional drug such as target therapy to first-line SOC? Besides, the role of pemetrexed maintenance therapy (PMT) in responding or stable patients with MPM after receiving first-line treatment has not been confirmed and the question of the benefits of PMT for MPM remains open. Is it reasonable and flexible to incorporate this new strategy before disease progression?We therefore report a case of advanced MPM treated with a combinational revenue of cisplatin, pemetrexed, and bevacizumab as first-line care and subsequent strategy of PMT with breaking though the SOC for advanced MPM, expecting to further improve PFS. The patient presented good response after 6 courses PMT and achieved a strikingly long duration of PFS.3N2M0).A 57-year-old man with a 5-year history of smoking from 30 years of his age was referred to community hospital and complained of right chest pain for about 1 month. The patient classified his pain as 2/10, which usually was worse with activity. Physical examination suggested no significant abnormalities. Laboratory findings were within normal range, except for the neuron-specific enolase (NSE) level of 48.04 ng/mL  in the serum. His computed tomography (CT) scan of the chest with contrast revealed a large right-sided pleural mass and other nodules lying in the costophrenic angle, suggestive of pleural malignancy  position-emission tomography (PET)-CT was performed and revealed the residual disease and metastasis of bone  analysis. The pathological diagnosis of the specimens was MPM Figure  and conf2), pemetrexed (500 mg/m2), and bevacizumab (7.5 mg/kg) as first-line chemotherapy was administered every 21 days for 6 cycles. Due to no pain of bone metastasis areas, only Ibandronate sodium in absence of radiotherapy was given monthly for skeletal-related events. Response evaluation was performed after every 2 cycles of chemotherapy according to the modified Response Evaluation Criteria in Solid Tumors criteria.5 The response after 2 courses, 4 courses, 6 courses was partial response (PR), PR, PR, respectively  for further treatment. His CT scan with contrast showed tumor residue Figure A. Bone my Figure B–D. Takiy Figure E.2) administered every 21 days after radiotherapy with another discussion by multidisciplinary team. The interval between the end of radiotherapy and the start of maintenance treatment was 1 month. After 6 courses of PMT, the residual mass disappeared .4 A combined first-line regimen using cisplatin and pemetrexed is therefore considered as the standard treatment for advanced MPM. Besides, the combination of pemetrexed and carboplatin was also active and well tolerated.6In advanced, nonoperable MPM, chemotherapy is still the groundwork of treatment, especially platinum-based regimens. A phase III randomized trial assessed cisplatin/pemetrexed versus cisplatin alone in patients who were not candidates for surgery. The combination of platinum–pemetrexed conferred 3 months median overall survival benefit over cisplatin alone  and its receptor (VEGFR) are highly presented in MPM.13 Unfortunately, however, this trial failed to achieve its primary end point of a 50% improvement in median PFS in comparison with standard pemetrexed/platinum combinations. Excitingly, the final results of the French randomized phase II/III trial  evaluating the addition of bevacizumab to standard chemotherapy has been reported in 2015 American Society of Clinical Oncology annual meeting.14 Bevacizumab addition to pemetrexed/cisplatin provides a significantly longer overall survival  and PFS  in advanced MPM patients with acceptable toxicity. The following reasons may account for this reverse results. The former trial has the limitation of a nonrandomized single-arm phase II design that has some potential bias. And this trial also had a crucial limitation of a small sample size (only 76 patients enrolled). While, MAPS is an open-label multicenter randomized trial with restrict inclusion and exclusion criteria. In this trial, 448 patients were included, which contributes to a great statistic power. The results of MAPS trial may be more convinced. The combination of bevacizumab and pemetrexed/cisplatin is very promising and makes this triplet a new treatment paradigm. This triplet may be new standard of fist-line therapy for unresectable MPM.The role of bevacizumab adding to the combination of cisplatin and pemetrexed remains indefinite. An open label phase II study (NCT00407459) was to assess the activity of bevacizumab combined with pemetrexed and carboplatin as first-line therapy in patients with MPM.15 Limited data are available to guide second-line therapy, although several agents are in clinical trials.16 Accordingly, the method of either by prescribing higher dose intensities or higher total doses of chemotherapy may be optimal for patients who are in the absence of disease progression after 4 to 6 cycles of initial therapy. Maintenance chemotherapy, which prolongs duration of chemotherapy either with the use of at least 1 of the agents given in the first line (continuation maintenance) or with the initiation of a different agent (switch maintenance), increases the total dose of chemotherapy.Although the response rates in first-line treatment were substantial, most patients experienced disease recurrence or progression during or after first-line treatment.P < 0.0001)17; 23% of patients with stable disease after induction therapy achieved a PR with maintenance therapy. In this investigation, no grade 4 toxicity was observed and the only nonhematological grade 3 toxicity during PMT was fatigue (15%). The safety of continuing single agent pemetrexed has also demonstrated. In addition, pemetrexed as a single agent to treat MPM has revealed activity in a phase II trial. The response rate and median overall survival were 14.1% and 10.7 months, respectively.18 On the basis of antitumor activity of pemetrexed, PMT strategy could be available in the current case.There existed many clinical investigations to explore the continuation maintenance treatment for patients with MPM. In a small trial with 27 patients, PMT until disease progression or unacceptable toxicity, compared with no maintenance after pemetrexed-based induction treatment, suggested both survival and time to progression benefit  (who are negative for sensitizing EGFR mutations or Anaplastic Lymphoma Kinase arrangements) beyond 4 to 6 cycles of initial therapy. Dual-agents maintenance therapy using bevacizumab/pemetrexed is also an option in patients with nonsquamous NSCLC.24 In consideration of good effect with single-agent or dual-agents maintenance therapy for NSCLC, the favorable response may also be presented in MPM. Researchers should launch clinical trials to assess the impact of bevacizumab with or without PMT. It may be difficult for the enrollment of patients as the incidence of MPM is low compared with NSCLC. The final results may be prospective at cost of many years.It is well acknowledged that single-agent bevacizumabContinuation maintenance with pemetrexed could achieve a good response, while switch maintenance may be disappointed.27 Recently, final results of the NVALT5, an open-label, multicenter, randomized phase 3 study, have been published, which explored thalidomide versus active supportive care for maintenance in patients with MPM after first-line chemotherapy. Patients were randomly assigned to receive thalidomide 200 mg/d plus best supportive care (BSC) or BSC alone until disease progression. Thalidomide did not suggest any positive effect in the maintenance setting in term of time to progression  with the addition of thalidomide maintenance to first-line chemotherapy.Thalidomide has shown antiangiogenetic activity and immunomodulation by inducing apoptosis of established new vasculature. Besides, it also has a striking bioavailability after oral administration and has shown an outstanding antitumor effect in hematological malignancies.In conclusion, the continuation maintenance treatment with pemetrexed may have advantages for patient with MPM, while the switch maintenance treatment with thalidomide yielded disappointing results. The more convenient administration of maintenance therapy in patients with MPM is still an open question. Thereby, further investigations are needed to confirm the effect of maintenance therapy.16 The only randomized clinical trial in this setting eliciting an improvement in PFS was undertaken before the widespread use of pemetrexed as first-line treatment, comparing second-line pemetrexed versus BSC.28 Pemetrexed alone or in combination with cisplatin could be available as second-line treatment in those patients who previously treated without pemetrexed.29 Furthermore, for pemetrexed pretreated patients, the combination of dual-agents treatment with gemcitabine–vinorelbine or gemcitabine–oxaliplatin are reasonable palliative options.31 Besides, re-treatment with pemetrexed is a feasible option in fit patients, especially in patients with longer PFS (>12 months) after first-line pemetrexed treatment.32 The efficacy of second-line therapy remains unanswered at present and it is still an unmet need in this patient population.Many patients may want second-line chemotherapy at the time of recurrence or progression. Second-line therapy is being progressively utilized in clinical practice, despite of the fact that there are none appropriate randomized controlled researches to show any survival benefit and the definitive optimal regimen is currently undefined.We described a case of MPM treated by PMT following cisplatin-based bevacizumab-containing first-line chemotherapy, with a perfect response and a long PFS. Although the standard first-line chemotherapy for advanced MPM is the combination of cisplatin and pemetrexed, addition of bevacizumab to standard first-line treatment tend to be favorable. PMT still remains experimental; however, the use of higher total dose of pemetrexed by adopting PMT following first-line treatment appears extremely promising. The administration of maintenance therapy in patients with MPM is still unclear and further investigation is urgently warranted to answer this question.


The article by van Kooyk et al. provides an introduction to glycan analytical tools   sialic acids illustrate how glycan structures can influence the adaptive immune response. Glycans, both families . As explactions) . Sialidaactions) . Not allll death , yet in n tumors .N-glycans of resting and activated cytolytic T lymphocytes (CTLs), with more galectin-3 ligands being present on activated CTLs, is an example where the density of a glycan structure regulates CTL function. In a galectin-3 rich milieu , reduced motility of galectin-3 cross-linked glycoproteins on activated infiltrating CTLs could explain the decreased CTL activity within tumors  binding motifs within their sequences . Many ofThe association of GAGs with inflammation extends beyond complement pathway regulation. Chemokine–HS interactions are known to establish chemokine gradients to direct leukocytes to inflammatory sites ; but theThe contribution of HS to human immunodeficiency virus (HIV-1) infection has come of age. Connell and Lortat-Jacob indicate how the elegant design of a potential drug developed through an appreciation of the molecular events involved in HIV-1 infection of CD4+ leukocytes . AlthougThese articles highlight the contribution of glycans to different aspects of the immune response, yet this is a “taster plate” of their total contribution. Contrary to the often held view, glycan structures frequently bind proteins with quite exquisite specificity; our lack of understanding of their binding modes and the nature of the protein conformations that are recognized cause the miss-interpretation. Reductionist thinking and analyses, although useful, in isolation are unlikely to reveal the truth. Repeatedly, it is the “context,” whether the presentation of glycan motifs, or the molecules (proteins and carbohydrates) of the surrounding microenvironment, which determines the outcome of glycan–protein interactions. It is fitting that the concluding article in this series  describeThe 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.


This systematic review sought to assess the costs and benefits of interventions preventing hospital-acquired infections and to evaluate methodological and reporting quality.We systematically searched Medline via PubMed and the National Health Service Economic Evaluation Database from 2009 to 2014. We included quasi-experimental and randomized trails published in English or German evaluating the economic impact of interventions preventing the four most frequent hospital-acquired infections . Characteristics and results of the included articles were extracted using a standardized data collection form. Study and reporting quality were evaluated using SIGN and CHEERS checklists. All costs were adjusted to 2013 US$. Savings-to-cost ratios and difference values with interquartile ranges (IQRs) per month were calculated, and the effects of study characteristics on the cost-benefit results were analyzed.Our search returned 2067 articles, of which 27 met the inclusion criteria. The median savings-to-cost ratio across all studies reporting both costs and savings values was US $7.0 (IQR 4.2–30.9), and the median net global saving was US $13,179  per month. The studies’ reporting quality was low. Only 14 articles reported more than half of CHEERS items appropriately. Similarly, an assessment of methodological quality found that only four studies (14.8%) were considered high quality.Prevention programs for hospital acquired infections have very positive cost-benefit ratios. Improved reporting quality in health economics publications is required. Hospital acquired infections (HAIs), also called nosocomial infections, are a serious public health problem and a major cause of morbidity and mortality. MoreoveTherefore, we conducted this systematic review to provide a cost-benefit estimation for HAI prevention and to examine the quality of economic studies and their reporting.Our systematic review conforms to recommendations in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement  10] and and10] aSearches of eligible studies were conducted in Medline via PubMed and the National Health Service Economic Evaluation Database (NHS EED) to identify relevant articles in English and German published in a five year period between January 2009 and January 2014 with an abstract available for review.We used several search terms, and keywords were matched to database-specific indexing terms (Mesh and ti). We used the operator AND to link keywords with different meanings and the operator OR for keywords with similar meanings. All studies found were reviewed for eligibility by applying the PICO  question format. Publications identified in the search of the two databases were combined and duplicates were removed.We included studies assessing interventions intended to prevent the four most common HAIs . There was no age or gender restriction in this systematic review.The interventions of interest were measures reducing person-to-person transmission ; measures preventing transmission from the environment ; and measures proven effective for the prevention of urinary tract infections, surgical site infections (SSI), pneumonia and vascular device infections that used the World Health Organization (WHO) guidelines for HAI prevention . StudiesWe included quasi-experimental and randomized trails, while articles without an explicitly formulated study design or method were excluded. We also excluded cross-sectional studies, reviews, guidelines, studies of pure mathematics, studies published as an abstract only and studies using a simulation or modeling published data.In this review, cost-effectiveness analyses (CEAs), cost-benefit analyses (CBAs), cost-minimization analyses (CMAs) and cost-utility analyses (CUAs) were included. Studies lacking quantitative economic parameters or reported outcomes were excluded.Two reviewers  independently applied inclusion and exclusion criteria and extracted the data from eligible studies by screening titles, abstracts and full-text articles. Differences were resolved by discussion with a third review author. The reviewers documented the reasons for excluding articles from the review.We extracted the characteristics and results of included health economics studies using a standardized data collection form . We alsoIn cases of missing information concerning inflation adjustment, we assumed that the costs were adjusted to the last year of the study period. Moreover, if a low/high range of intervention costs or savings was reported, we used the average cost for our analysis.The methodological quality of the economic evaluations was assessed based on the methodology checklist recommended by SIGN (Scottish Intercollegiate Guidelines Network). Additionally, for an overall assessment of studies we answered one question from selection 2 of the SIGN statement, “How well was the study conducted?”, with the following coding: “++” denotes that all or most of the criteria have been fulfilled, “+”that some of the criteria have been fulfilled, and “−” that few or no criteria were fulfilled .We used the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement to assess the reporting quality of studies , althougIntervention costs and cost savings following the intervention were recalculated as costs per month during the intervention period and during the length of follow-up, respectively. We estimated the savings-to-cost ratio and the save–cost difference adjusted to 2013 US$. A savings-to-cost ratio larger than 1 indicated savings exceeding costs, and a positive save–cost difference value indicated net savings. Both intervention costs and cost savings were adjusted to 2013 values using an annual country-specific consumer price index . After aThrough our searches, a total of 1992 potentially relevant citations were identified, of which twenty-seven articles fulfilled the inclusion criteria –44. A flMost of the studies were performed in North America or Europe . Approximately 63% of identified studies on the prevention of HAIs were performed in surgical departments  or intensive care units . The studies employed several methods to calculate effectiveness; 37.0% were randomized control studies (n = 10) and 63.0% were quasi-experimental (n = 17). More than half of the studies  stated that they used the definitions of HAIs provided by the Centers for Disease Control and Prevention (CDC). Five studies focused on more than one site of HAI (18.5%). Most interventions aimed to prevent HAIs by reducing person-to-person transmission , primarily by hand decontamination . The mosWe assessed the reporting quality of 26 studies using the CHEERS statement. Of these, we were able to identify 13 studies as economic evaluations based on the title (50.0%). Most articles presented a clear study question and an explicit statement of the background for the study . Studies generally reported the target population and subgroups well . Statements regarding the perspective of the study and its relation to costs were missing in 17 studies (65.4%). The majority of studies did not include a statement on the choice of discount rates  or included poor reporting on the choice . Only 9 studies properly described what approaches were used to estimate resources and costs (34.6%). A price date, the method of price adjustment and the currency used were not noted in 10 studies (38.5%). Half of the selected studies did not report conflicts of interest .Most of the 27 economic studies included in the method quality assessment defined an answerable study question , but few papers included all costs relevant to the viewpoint of the study . In the Common cost components included nurse/physician time, antimicrobials, administration costs and pharmaceuticals. Intervention costs were usually reported as the global costs of the intervention . Extra costs of an HAI and costs of extra hospitalization days due to HAIs were the major cost components used for cost savings calculations.The median savings-to-cost ratio across the 18 studies reporting both values was US $7.0 (IQR 4.2–30.9), and the median net global saving of the 19 studies was US $13,179  per month. The median cost across the 20 studies reporting intervention costs was US $1,114 (IQR 174–6234) per month. The median saving across the 24 studies reporting this figure was US $12,519  per month. Most of the 18 articles reporting both intervention and saved costs calculated a savings-to-cost ratio >1 and a positive save–cost difference, and only one study showed that infection control interventions were not economically justified because the savings-to-cost ratio was < 1 or the save–cost difference was negative .The effects of study characteristics on the savings-to-cost ratios and net savings were very diverse. Higher savings-to-cost ratios were observed in studies that focused on pneumonia prevention compared with prevention programs focusing on other infections. However, the studies that considered several types of infections in their infection prevention program calculated a higher savings-to-cost ratio compared with studies dedicated to a single type of HAI. Savings-to-cost ratios were higher in studies with smaller number of patients. Larger hospitals  with shorter intervention durations (≤12 months compared with longer durations) exhibited higher savings-to-cost ratios. Nevertheless, savings-to-cost ratios were considerably lower in multi-center studies. Programs for prevention of HAIs in surgical units have higher savings-to-cost ratios compared with prevention programs for HAIs in intensive care units or in hospital-wide studies. Savings-to-cost ratios were much higher in studies that did not report or poorly addressed costs and had inappropriate measurement and evaluation, compared with studies addressing these factors adequately or well. This result shows that studies without complete identification and measurement of relevant costs overestimate the savings-to-cost ratios. We found similar savings-to-cost ratios among studies that were assigned an overall assessment of “-” .We systematically reviewed and assessed the quality of the methods and reporting of selected economic evaluation studies regarding HAI prevention interventions and their economic benefits. Prevention interventions for HAIs were reported as statistically significantly efficacious in many studies, and our analysis shows that these interventions have significant economic benefits. On average, the savings of a prevention program were 11 times greater than the costs. The highest save–cost difference was identified in a study by Harris et al., which used improvement practices of hand hygiene, oral care and central-line catheter care in a single hospital . Only VaInterventions targeting several types of HAIs or HAIs in general were associated with higher economic benefits than prevention interventions for a single type of infection. A strong association was identified between intervention duration and cost benefit. The median save–cost difference among studies with intervention periods of 12 months or less was 9 times greater than that among studies with longer intervention durations. Higher savings-to-cost ratios were found in larger hospitals. These ratios were very low in multi-center studies; however, the median save–cost difference in such studies was high. Multi-center trials are usually very expensive to implement and much more complex than single-center studies. Nevertheless, multi-center prevention programs exhibit a better net-savings than single-center programs.The quality of reporting in the studies was low. Only fourteen articles reported more than half of the CHEERS items appropriately, and only seven studies reported 70% or more of these items well. We found similar results in our assessment of methodological quality. Various studies had low internal validity; for example, several studies did not include some of the relevant costs in the economic evaluation that could have a substantial impact on the results. Discounting future costs and outcomes was necessary in most of the selected studies; nevertheless, such discounting was often not performed. The quality of economic studies is directly related to the presence of a sensitivity analysis. Therefore, the Oxford Centre for Evidence-based Medicine (OCEBM) classified economic studies without a sensitivity analysis as level IV evidence . NeverthHigher quality studies fulfilling all or most of the methodology criteria have higher savings-to-cost ratios compared with studies of intermediate quality, but the savings-to-cost ratios in low-quality studies fulfilling few or no criteria were extremely large. This may represent overestimation due to inappropriate designs for economic evaluations or the failure to consider some relevant costs. Low-quality clinical trials inflated the estimated treatment efficacy by 30–50%, according Moher et al. . An overStaphylococcus aureus (MRSA) in a study that was methodologically similar to our systematic review. They found that the median savings-to-cost ratio among 18 MRSA studies was US $7.16 (IQR 1.37–16), which is similar to the present findings. Their study observed that interventions with longer durations (>6 months) had higher savings-to-cost ratios compared with interventions of shorter duration. In contrast, the present study found higher savings-to-cost ratios for interventions with a duration of 12 months or shorter compared with interventions with longer durations.Only a small number of systematic reviews examined the economic impact of interventions for HAI prevention ,12,13. FOur study has some limitations, as is true of all systematic reviews of economic evaluations. Due to the wide variety of terminology in the fields of full economic evaluations, hospital acquired infections and prevention interventions, some relevant articles may have been missed in our review of the literature. However, we used two large literature databases, and a variety of keywords were matched to database-specific indexing terms. In this review, databases were searched based on the English and German languages. Therefore, publications in other languages were not detected using this search strategy. Because various types of interventions and various combinations of interventions were included and because some intervention cost components were lacking, we could not classify the interventions’ effects with respect to economic benefits. The distribution of cost values was not normal, and the homogeneity of costs was not high; therefore, we were unable to perform a formal meta-analysis. One further limitation of our study is a potential publication bias. Studies with a negative save to cost ratio are unlikely to get published compared to studies with a positive result and these studies are not included in our review.In conclusion, the included studies indicate that HAI prevention interventions yield very positive cost-benefit estimations. The quality of economic evaluations should be improved to provide better information to healthcare policy makers and clinicians. International standardization of cost estimations for HAIs would enable economic evaluation studies to perform more precise assessments of economic benefits and cost changes associated with HAI prevention programs.S1 Table(PDF)Click here for additional data file.S2 Table(PDF)Click here for additional data file.S3 Table(PDF)Click here for additional data file.S4 Table(PDF)Click here for additional data file.


Cat DPP-Pd. The SiliaCat DPP-Pd catalyst is air-stable and the method does not require the use of inert conditions. The use of non-toxic isopropanol or 2-butanol as reaction solvent further adds to the environmental benefits of this new green synthetic methodology.Unsymmetrically coupled biaryls are synthesized in high yield starting from different aryl bromides and bis(pinacolato)diboron by carrying out the Miyaura borylation reaction followed by the Suzuki–Miyaura reaction in the same reaction pot over 1–2 mol % Silia The rea2(dppf) is air stable. This made the method more versatile and provided a long awaited easy way to synthesize a broad range of boronic esters that are conveniently used in place of boronic acids in the Suzuki–Miyaura reaction when reactive functional groups are present in the electrophilic aryl halides [In contrast to a number of Pd catalysts that are air sensitive, PdCl halides –4.Several homogeneous palladium catalysts of enhanced versatility for the cross-coupling of pinacolborane with aryl halides have since been introduced, for example by Buchwald and co-workers –6. Of diYet, it remains desirable to efficiently heterogenize palladium catalytic species used in cross-coupling reactions with the aim to prevent product contamination with palladium, reuse the expensive catalyst and streamline the whole synthetic process . FurtherCat DPP-Pd catalyst .The catalyst, which is highly active in C–C coupling reactions , has typCat DPP-Pd in the synthesis of boronic acid pinacol esters has been recently shown elsewhere [The leach-proof and truly heterogeneous nature of Silialsewhere , whereinCat DPP-Pd catalyst mediates the borylation and the subsequent Suzuki–Miyaura reaction in an elegant one-pot sequential synthesis. Hence, an aryl bromide is first converted into the boronic acid pinacol ester diboron by carrying out the Miyaura borylation reaction followed by the Suzuki–Miyaura reaction over 1–2 mol % catalytic amount of the sol–gel entrapped catalyst SiliaFinally, the use of isopropanol or 2-butanol as reaction solvents further points out the environmental benefits of the method. As the fine chemicals and pharmaceutical industries are eventually adopting green chemistry synthetic methodologies , this me


This study is designed to address the need for evidence-based HIV/STI prevention approaches for drug-involved women under criminal justice community supervision.We tested the efficacy of a group-based traditional and multimedia HIV/STI prevention intervention  among drug-involved women under community supervision.We randomized 306 women recruited from community supervision settings to receive either: (1) a four-session traditional group-based HIV/STI prevention intervention ; (2) a four-session multimedia group-based HIV/STI prevention intervention that covered the same content as traditional WORTH but was delivered in a computerized format; or (3) a four-session group-based Wellness Promotion intervention that served as an attention control condition. The study examined whether the traditional or multimedia WORTH intervention was more efficacious in reducing risks when compared to Wellness Promotion; and whether multimedia WORTH was more efficacious in reducing risks when compared to traditional WORTH.Primary outcomes were assessed over the 12-month post-intervention period and included the number of unprotected sex acts, the proportion of protected sex acts, and consistent condom use. At baseline, 77% of participants reported unprotected vaginal or anal sex (n = 237) and 63% (n = 194) had multiple sex partners.Women assigned to traditional or multimedia WORTH were significantly more likely than women assigned to the control condition to report an increase in the proportion of protected sex acts  and a decrease in the number of unprotected sex acts .The promising effects of traditional and multimedia WORTH on increasing condom use and high participation rates suggest that WORTH may be scaled up to redress the concentrated epidemics of HIV/STIs among drug-involved women in the criminal justice system.NCT01784809ClinicalTrials.gov  Community supervision represents the largest segment of the criminal justice system in the U.S. The criminal justice system and HIV/AIDS intersect for drug-using women, particularly those who are low-income Black and Hispanic, who are over-represented in the criminal justice system Drug-involved women under community supervision are at risk for acquiring HIV and sexually transmitted infections (STIs) due to exposure to a spectrum of risk contexts Over the past decade the use of technology-based behavioral HIV prevention strategies has proliferated, including digital media ranging from generic, brief videos to computer-tailored multimedia interventions targeting individual behaviors This randomized controlled trial was designed to test the efficacy of Project WORTH , a four session group-based multimedia HIV/STI prevention intervention for drug-involved female offenders recruited from community supervision settings in New York City. For this trial, 306 women were randomized to either: (1) a four-session traditional group-based HIV/STI intervention ; (2) a four-session multimedia group-based HIV/STI intervention (multimedia WORTH); or (3) a four-session group-based Wellness Promotion intervention that served as an attentional control condition.This study examined two primary hypotheses: (1) ‘‘intervention effect’’ – whether the WORTH HIV/STI risk-reduction intervention delivered by either the traditional or multimedia method would be more efficacious in addressing the following primary outcomes: decreasing the number of self-reported unprotected sex acts, increasing the proportion of protected sex, and increasing consistent condom use, as well as secondary outcomes of reducing the incidence of biologically confirmed STIs over the 12-month follow-up period when compared to the Wellness Promotion control condition; and (2) ‘‘modality effect’’– whether the multimedia HIV/STI risk-reduction intervention would be more efficacious in decreasing the number of unprotected sex acts, increasing the proportion of protected sex, and reducing incidence of biologically confirmed STIs when compared to the traditional method.The protocol for this trial and supporting CONSORT checklist are available as supporting information; see This randomized controlled trial was conducted between November 2009 and January 2012. The Columbia University Institutional Review Board (IRB) and the Center for Court Innovation IRB for community supervision sites approved the study prior to implementation. A total of 1,104 women were screened from community courts and probation sites.Women were eligible to participate in the study if they: (1) were 18 and older and biologically female by birth; (2) had been under community supervision in a community or criminal court, were on probation or parole, were under drug treatment court supervision within 90days; (3) reported one or more incidents of illicit drug use within six months ; (4) had one or more incidents of unprotected vaginal or anal intercourse within 90days; and (5) were HIV positive or had at least one of the following additional HIV/STI risks within six months: (a) had more than one sexual partner; (b) injected drugs; (c) was diagnosed with an STI ; or (e) had unprotected vaginal or anal intercourse with a partner who had HIV or one of following risk factors within six months: (i) had more than one partner, (ii) injected drugs, or (iii) was diagnosed with an STI.Potential participants were considered ineligible if they were unable to complete the informed consent process due to a psychiatric or cognitive impairment, unable to speak English, or if the they were actively trying to become pregnant. Women with pregnancy intentions were excluded due to the intervention’s emphasis on condom use. Women who did not have an address where they could receive mail, lived more than 90 minutes from New York City, or planned to move more than 90 minutes outside of New York City were also excluded. All participants provided written consent to participate in the study.Trained recruitment and retention staff engaged participants, who were assessed with repeated measures at baseline, as well as three-month, six-month, and 12-month post-treatment. Of those who completed the 12-month follow up assessment, 29% reported having been arrested and 35% reported having been incarcerated at some point during the 12 month follow up period. Information on when outcomes were assessed and retention numbers at each assessment is available in the Consort form see . ParticiWe randomly assigned groups of four to nine women to receive one of the three conditions. The computer-generated randomization algorithm was designed to balance the number of women per study arm via an adaptive, biased-coin procedure Traditional WORTH consisted of a four-session, gender-specific group psycho-educational and skills building HIV prevention intervention Multimedia WORTH also consisted of groups that met weekly. Multimedia WORTH covered the same core components as traditional WORTH, with core components translated into interactive computerized games, video enhancements, and interactive visual tools such as individual capacity to respond to video enactments and social support and risk maps The Wellness Promotion arm was designed as an attention control, and was also delivered in a group setting by trained facilitators. Core components of this psycho-educational intervention adapted from an evidence-based wellness promotion intervention During the baseline visit and at each follow-up, participants completed a 1.5-hour computer-assisted self-interview (CASI). Self-report data were examined Chlamydia trachomatis and Neisseria gonorrhea using the Becton Dickinson Probe ET Amplified DNA Assay  and Trichomona vaginalis using a noncommercial real-time PCR assay. We collected oral swabs from participants to test for the presence of HIV 1/2 antibodies using the OraQuick ADVANCE Rapid HIV Test. Participants with positive HIV/STI test results received risk-reduction counseling from the Clinical Research Coordinator and were encouraged to inform their partners and ensure that their partners were treated simultaneously. Participants were then referred to a physician for the appropriate treatment within seven-14 days post baseline. Participants provided verification of treatment by returning a form completed by a medical provider.Data collection included both self-reported data and biological assays. Biological assays were used to detect HIV and three STIs . Women provided a self-collected vaginal swab specimen after completing the CASI at both baseline and 12-month follow up. Specimens were delivered to the Emory University pathology laboratory and assayed for Self-reported information was collected via CASI regarding socio-demographic characteristics including gender, age, ethnicity, marital status, years of education, employment, monthly income, and homelessness (having no regular place to sleep during the past 90days).Measures of legal history included the number of times the participant had been arrested and/or incarcerated, and whether arrests were drug-related.The Risk Behavior Assessment Intention-to-treat analyses were used to estimate the following effects derived from the hypotheses of the study: (1) the intervention effect of assignment to the active treatment condition  versus assignment to the control condition (Wellness Promotion) and (2) within those assigned to the active treatment condition, the modality effect of the delivery method, multimedia versus traditional WORTH. Intention-to-treat analyses included all participants that were randomized, including those who were unavailable for follow-up assessment. All missing data were due to loss to follow-up at post-intervention assessments.Multiple imputation (MI) was used to handle missing data Intervention and modality effects were obtained by applying generalized linear models with random effects for repeated measures in the multiple imputed data. Because the models adding randomized groups as another random effects yielded identical or slightly different coefficients and standard errors that concluded the same significant patterns as the models without random effects for randomized groups, and did not improve the model fits, we used more parsimonious models that only included repeated measures as random effects. Random-effects negative binomial regressions were used to estimate effects of the intervention and modality on the number of unprotected sex acts; corresponding effect estimates are reported as incident rate ratios (IRR) and 95% confidence intervals (CIs). Random-effects linear regressions were used to estimate effects on proportion of protected sex acts; corresponding effect estimates are reported as mean difference (b) and 95% CIs. Random-effects logistic regression models were used to estimate effects on consistent condom use and having multiple partners; for these effect estimates, odds ratios and 95% CIs are reported. Orthogonal contrast coding was used to test separately for intervention effect  and modality effect  within one model. To test for an intervention effect, the coding for multimedia WORTH, traditional WORTH, and Wellness Promotion were +1/3, +1/3, and −2/3, respectively. To test for modality effects, the coding for multimedia WORTH, traditional WORTH, and Wellness Promotion were +1/2, −1/2 and 0, respectively. All random-effects regression models included the contrast codes for intervention and modality effects and the baseline measure of the outcome of interest to estimate the effects for the entire follow-up period, and added the follow-up assessment time (in months), and interaction terms between time and contrast codes to yield the effects for each follow-up assessment. Statistical analyses and MI were performed using Stata 12.We estimated that with a sample of 112 women per arm, the study would have 80% statistical power, assuming alpha = .05, two-sided hypothesis testing, no covariance adjustment, intraclass correlations (ICCs) of.05 for the primary behavioral outcomes, and the following minimum effect sizes: an absolute increase in proportion of condom protected sex of 15 percentage points, and an absolute decrease of five acts of unprotected sex (a relative decrease of 20%). Power analyses used high estimates for ICCs and did not account for covariance adjustment to remain conservative.As presented in Of 244 women, two HIV seroconverted by the 12-month follow-up assessment , which translated to 820 per 100,000 people. A total of 47 newly detected STI cases were found at the 12-month follow-up assessment. The incidence for any STI at 12-month follow-up did not significantly differ between the two WORTH conditions and the Wellness Promotion condition.This study addresses a key priority of the National HIV strategy, that of reducing HIV disparities, intensifying prevention efforts in heavily HIV concentrated areas This trial demonstrates that a theory-based, multi-session, gender-specific HIV/STI prevention intervention delivered through multimedia or traditional group-based modalities can reduce self-reported sexual risk behaviors among women in community supervision settings. The intervention had significant effects averaged over the 12-month follow-up period on primary behavioral outcomes including increasing the proportion of condom-protected sex, increasing consistent condom use, and reducing the number of unprotected sex acts with primary and all partners. The magnitude and consistency of findings across sexual behavior outcomes promotes confidence in the efficacy of the interventions. The content of both multimedia and traditional modalities addressed factors that affect sexual risk such as relationship context, partner violence, drug use, communication and problem solving skills, and access to services.Our hypothesis that the multimedia-delivered intervention would have superior outcomes in reducing sexual risk was not supported; however, the multimedia approach was equally effective as the traditional modality. The multimedia modality may be more feasible to implement in community supervision programs as it may require less training and supervision to implement and sustain, may be more cost effective to deliver In contrast to the significant effects on primary sexual risk behavior outcomes, the WORTH intervention did not influence HIV/STI incidence. This may be due to low HIV and STI incidence rates and small sample size.Three study limitations must be mentioned: (1) findings may not be generalizable to all women under community supervision due to non-random sampling procedures and (2) the use of self-report for measuring primary behavioral outcomes may have resulted in biased responses, influenced by social desirability. However, the use of CASI and the emphasis by study personnel on confidentiality and anonymity may have mitigated potential problems with self-report validity. Although women were not recruited randomly, we were able to access a key population of women with high levels of HIV risk, targeting those in most need of prevention services. Lastly, as the multimedia intervention was delivered in a group format, it presents a mixed modality with multimedia self-paced components, but is not solely a multimedia intervention. Despite these limitations, findings have important implications for HIV prevention science. The study demonstrated high participation, attendance, and retention rates indicating a high level of motivation among women in community supervision to participate in HIV prevention and other health promotion programs. More access to evidence-based prevention strategies as well as attention in HIV research is needed among this high-risk population.This study demonstrates the feasibility of recruiting and retaining drug-using, urban women in community supervision settings for a continuum of HIV prevention, testing, and treatment interventions. Findings draw attention to an effective intervention strategy that may be scaled up to curb the continued spread of HIV/STIs among women in a range of criminal justice settings to reduce highly concentrated HIV epidemics in low-income inner-city neighborhoods. This study demonstrates that both the multimedia and traditional modalities of the WORTH HIV/STI intervention are efficacious and add to the compendium of HIV/STI prevention strategies to be disseminated.Figure S1CONSORT Form.(TIF)Click here for additional data file.Figure S2WORTH Intervention Core Components.(TIF)Click here for additional data file.Checklist S1CONSORT Checklist.(DOC)Click here for additional data file.Protocol S1Trial Protocol.(DOCX)Click here for additional data file.