Matrix factorization is a well established pattern discovery tool that has seen numerous applications in biomedical data analytics, such as gene expression co-clustering, patient stratification, and gene-disease association mining. Matrix factorization learns a latent data model that takes a data matrix and transforms it into a latent feature space enabling generalization, noise removal and feature discovery. However, factorization algorithms are numerically intensive, and hence there is a pressing challenge to scale current algorithms to work with large datasets. Our focus in this paper is matrix tri-factorization, a popular method that is not limited by the assumption of standard matrix factorization about data residing in one latent space. Matrix tri-factorization solves this by inferring a separate latent space for each dimension in a data matrix, and a latent mapping of interactions between the inferred spaces, making the approach particularly suitable for biomedical data mining.We developed a block-wise approach for latent factor learning in matrix tri-factorization. The approach partitions a data matrix into disjoint submatrices that are treated independently and fed into a parallel factorization system. An appealing property of the proposed approach is its mathematical equivalence with serial matrix tri-factorization. In a study on large biomedical datasets we show that our approach scales well on multi-processor and multi-GPU architectures. On a four-GPU system we demonstrate that our approach can be more than 100-times faster than its single-processor counterpart.A general approach for scaling non-negative matrix tri-factorization is proposed. The approach is especially useful parallel matrix factorization implemented in a multi-GPU environment. We expect the new approach will be useful in emerging procedures for latent factor analysis, notably for data integration, where many large data matrices need to be collectively factorized.The online version of this article (doi:10.1186/s13040-017-0160-6) contains supplementary material, which is available to authorized users. Biomedical data are becoming increasingly challenging to analyze due to their sheer volume and complexity. Dimensionality reduction approaches address challenges in modern biomedical data analytics by learning useful projections of data into a smaller, compact and pattern-rich latent space. An especially popular dimensionality reduction approach uses matrix factorization . NumerouX and learns two latent factors, U and V, such that their product UV approximates X, X≈UV, under some criterion of approximation error. One class of non-negative matrix factorization approaches is non-negative matrix tri-factorization, which extends a two-factor model by introducing a third latent factor S, such that X≈USVT [S [X into blocks and then exploit the block-matrix multiplication when learning U and V. However, such a straightforward approach does not apply to matrix tri-factorization because, as we show in the Methods section, the learning of any block of U and V depends on factor S.Non-negative (two-factor) matrix factorization considers as input a data matrix ≈USVT . This reSVT [S . SeveralSVT [S –15. ThesIn this paper, we develop a principled mathematical approach and an algorithmic solution to latent factor learning for non-negative matrix tri-factorization. While there exists an initial solution to speed up the latent factor learning procedure using accelerated matrix operations on a MapReduce cluster , this apThe paper makes the following contributions. We develop a block-wise approach for matrix tri-factorization. The new approach enables fast factorization on concurrent systems, such as multi-processor and multi-GPU architectures. We report on two variants of the approach: one variant for orthogonal matrix factorization  and the We start by describing the notation, factorization model, and matrix tri-factorization algorithm. The algorithm starts by initializing the latent factors, which are then iteratively revised until convergence. We then introduce a block data representation and provide an algorithm for partitioning data matrices into blocks. Finally, we develop the block-wise latent factor update rules and present the block-wise matrix tri-factorization algorithm.n rows typically describe data instances and m columns provide their features. Non-negative matrix tri-factorization (NMTF) learns a decomposition of X into three latent factors U and V are latent vectors and provide the basis of the vector space into which the data  are projected. Factorization ranks k1,k2≪ min are model parameters that specify the number of latent vectors.Consider a non-negative data matrix USVTFro2 , 21. ColF with respect to model parameters U, S, and V and by solving the gradient equations for the model parameters. This procedure results in the following set of update rules [Reconstruction error is typically minimized using the multiplicative update rules . The rulte rules : 1\docuwhere ∘ represents the element-wise product and the division is performed element-wise. The matrix tri-factorization algorithm starts by initializing latent factors using small random values and then iteratively applies the update rules in Eqs. –3 until U) or input data instances (for V) [UTU=I and VTV=I, where I is an identity matrix. Following a similar procedure of gradient computation as described above, we arrive at the following update rules for orthogonal matrix tri-factorization [An often-desired variant  of matri (for V) , 23. Therization : 4\docuX into N×M blocks, Xi,j) GPUs, each with 12 GB of memory. Given We here present results for non-orthogonal block-wise matrix tri-factorization. Results for orthogonal block-wise matrix tri-factorization are qualitatively the same and are provided in the Additional file Figures Efficiency of parallel implementation depends on dataset shape and on chosen block configuration. Measurements illustrating this dependency are shown in Fig. One bottleneck of GPU-based architectures is communication overhead that occurs when copying data between GPU boards. This overhead was also observed in our experiments. For example, up to 50% of time needed to factorize TCGA-BRCA dataset in a 4-GPU environment was spent for communication. On larger datasets, however, this overhead was less pronounced. A detailed analysis is provided in Additional file We also studied algorithm scalability with respect to factorization rank. Figure Using matrix partitioning approach presented in Algorithm 1, we can increase speedup on sparse datasets that have imbalanced distribution of nonzero elements. The approach adapts matrix block size based on the number of nonzero elements. In Additional file Speedup on GPU-architectures is substantial, and pronounced with the dataset size and number of GPUs. For example, factorization on a retina dataset was 150-times faster than that on a single processor. Datasets in Fig. For TCGA-Methyl dataset, the complete data matrix occupies about 19 GBytes of GPU’s memory  and dense datasets  of similar size, the benefits of using sparse data structure are substantial. On a GPU, the factorization time on a sparse dataset (Fetus) is slower than on comparable dense datasets . This is because multiplication with sparse structures requires slower non-sequential memory access .U and V) and encode cluster interactions (matrix S). The analysis of the latent factors can then lead to data interpretation, cluster discovery, and to prediction of new interactions.Matrix factorization methods can be used to gain a better understanding of the data and their relationships as the methods identify cluster structures and detect potential new associations. The latent factors learned by NMTF reveal clusters in each of the two dimensions of the input data  and clusters of cancer types (from matrix U) with highest interaction scores in matrix S. First, we note that factorization revealed related cancer types, with, for example, colon, stomach and rectum adenocarcinoma (Additional file GATA2 was suggested as a prospective indicator for poor prognosis in patients with colorectal cancer [FAT4 functions as a tumor suppressor for stomach cancer [Additional file l cancer , and FATh cancer . Other sTranscriptional silencing by DNA methylation plays an important role in the onset of cancer , 52. It Non-negative matrix tri-factorization is a successful modeling approach that can reveal hidden patterns in biomedical datasets. Current serial factorization approaches take substantial runtime, particularly for larger datasets. We proposed a block-wise approach to speed up matrix tri-factorization through parallel execution. Experiments show the approach easily scales to very large datasets, and can achieve speedups of up to two orders of magnitude on current GPU-based architectures. We anticipate the proposed approach will be important for data integration, where matrix tri-factorization on large collections of data matrices  has alre


To assess whether the cellular proliferation marker Ki67 provides prognostic information and predicts response to radiation therapy fractionation in patients with localized prostate tumors participating in a randomized trial of 3 radiation therapy fractionation schedules (74 Gy/37 fractions vs 60 Gy/20 fractions vs 57 Gy/19 fractions).A matched case–control study design was used; patients with biochemical/clinical failure >2 years after radiation therapy (BCR) were matched 1:1 to patients without recurrence using established prognostic factors  and fractionation schedule. Immunohistochemistry was used to stain diagnostic biopsy specimens for Ki67, which were scored using the unweighted global method. Conditional logistic regression models estimated the prognostic value of mean and maximum Ki67 scores on BCR risk. Biomarker–fractionation interaction terms determined whether Ki67 was predictive of BCR by fractionation.P = .001). Interaction terms between Ki67 and fractionation schedules were not statistically significant.Using 173 matched pairs, the median for mean and maximum Ki67 scores were 6.6%  and 11.0%  respectively. Both scores were significant predictors of BCR in models adjusted for established prognostic factors. Conditioning on matching variables and age, the odds of BCR were estimated to increase by 9% per 1% increase in mean Ki67 score (odds ratio 1.09; 95% confidence interval 1.04-1.15, Diagnostic Ki67 did not predict BCR according to fractionation schedule in CHHiP; however, it was a strong independent prognostic factor for BCR. Radiation therapy is delivered using uniform fractionation for localized prostate tumors despite varying recurrence rates. Biomarkers to guide treatment stratification and predict fraction size sensitivity are needed. This study evaluated Ki67 in localized prostate cancer, for the first time using an internationally validated methodology accounting for intratumoral heterogeneity. Ki67 did not predict recurrence according to fractionation, providing reassurance that hypofractionated schedules can be safely administered in highly proliferative tumors. Ki67 predicted biochemical/clinical recurrence independently of established prognostic factors, including Gleason score.Prostate cancer (PCa) is the second most common cancer worldwide for males; more than 1.11 million new cases were diagnosed in 2012 Recurrence rates after EBRT for localized PCa vary considerably, from approximately 10% to 40-50% In addition, EBRT is delivered using a uniform fractionation schedule for all localized PCa . This is despite a wide variation in the biology of localized PCa There is a tight inverse association between the proliferative indices of normal tissues and fractionation sensitivity. Tissues with high proliferation indices, such as gastrointestinal mucosa and epidermis, are insensitive to fraction size. In contrast, late-reacting normal tissues, such as kidney, have low proliferative indices and are very sensitive to fraction size The CHHiP trial randomly assigned 3216 men to conventional fractionation (74 Gy in 37 fractions over 7.4 weeks) or 1 of 2 hypofractionated schedules (60 Gy in 20 fractions over 4 weeks or 57 Gy in 19 fractions over 3.8 weeks) A matched case–control methodology was used to select study participants. The study was approved by the London Multi-centre Research Ethics Committee 04/MRE02/10) and the local ethics committees of all participating centers. Patients experiencing recurrence (cases) were matched 1:1 to patients without recurrence (controls). Matching criteria included fractionation schedule  and established prognostic factors including PSA (<10/10-20/>20 ng/mL), Gleason grade (3 + 3/3 + 4/4 + 3/≥4 + 4), and T stage (T1/T2/T3). All tissue samples were centrally reviewed by a specialist uropathologist (C.M.C.), including assignment of Gleason grade according to recent International Society of Urological Pathology and World Health Organization recommendations  and the www.redjournal.org). Immunohistochemistry staining methods are outlined in the www.redjournal.org). All slides were scored using bright-field microscopy by 2 independent investigators blinded to recurrence status and fractionation schedule. The CK5/6 basal marker distinguished preinvasive from invasive disease. Prostatic intraepithelial neoplasia and intraductal carcinoma were not scored. A minimum of 100 tumor cells were required to score each case.Full-face sections from the diagnostic biopsy blocks were used for immunohistochemistry staining. This decision followed a pilot study that demonstrated construction of tissue microarray, using the checkerboard technique The unweighted global assessment of Ki67 developed by the International Ki67 Working Group was used to score all prostate biopsies All cases with a discrepancy in initial mean Ki67 score >10% were rescored Mean and maximum Ki67 scores were evaluated. Recurrence was defined as patients with biochemical t tests.Agreement in Ki67 scores between the 2 scoring investigators was assessed using Bland-Altman plots to measure the difference between the scores versus the mean of the mean Ki67 scores www.redjournal.org).Both Ki67 endpoints were analyzed as continuous variables to maximize statistical power All statistical analysis was conducted using STATA version 13.0  and R .A total of 437 cases were assessed by both scoring investigators. Ki67 scores were provided by both investigators in 400 cases; in 37 cases there was insufficient tumor present. The final matched dataset comprised 173 patients with BCR after start of radiation therapy (cases) and 173 patients without recurrence (controls). Matching was achieved to 100% of relevant criteria in all cases analyzed. Fifty-four patients were excluded because they did not have an appropriate match; these were usually controls with no available matching case. Of the total of 400 cases scored by both investigators, in 12 cases (3.0%) the difference in mean Ki67 between the 2 scoring investigators was ≥10% . These were rescored by both scoring investigators. All rescores were within the required <10% discrepancy.www.redjournal.org). The Bland-Altman plots indicate that the difference in score tended to increase as the mean Ki67 score increased. The overall agreement was considered to be good, with a concordance correlation coefficient of 0.74  for the final scores. For the original scores before rescore, the concordance correlation coefficient was 0.63 .Scatter plots comparing each scoring investigator's final scores, and Bland-Altman plots comparing the difference in final score versus the mean Ki67, are shown in www.redjournal.org). For each unit increase in mean Ki67 the odds of BCR is estimated to increase by 9% , having adjusted for matching variables and age. It is clinically relevant that the prediction of recurrence by mean Ki67 is independent of Gleason grade. The lack of correlation between mean Ki67 and Gleason grade is also displayed in the box and whisker plot (P = .006) in the multivariable model.Multivariable conditional logistic regression models using the entire Trans-CHHiP case–control study sample showed that both mean Ki67 and maximum Ki67 were statistically significant predictors of BCR . The distribution of mean and maximum Ki67 scores according to fractionation schedule and recurrence status, including a statistical comparison of the difference between cases and controls within fractionation arms, is shown in www.redjournal.org).The results of interaction tests between either mean or maximum Ki67 and fractionation schedule were not statistically significant for all comparisons , with possible addition of docetaxel or abiraterone Our exclusion of patients with BCR less than 2 years after radiation therapy means the estimates of the predictive value of Ki67 are likely to be conservative. Maximum Ki67 was also a statistically significant predictor of BCR, which is worthy of further study because a single-field assessment of 100 cells is quicker than 4 fields for mean Ki67.The apparent lack of interaction between Ki67 and fractionation schedule also has clinical implications. The range of proliferative indices seen indicates that the predominantly intermediate-risk PCa included in the trial are usually slowly proliferative. However, when including those cancers showing relatively high proliferation rates, there was no suggestion of a detriment using hypofractionated radiation therapy schedules giving 3 Gy per fraction. Other tumor types encompass wider ranges in proliferation and show higher average proliferation Of 3216 patients recruited to CHHiP, 3112 (96.7%) were treated with ADT from just after their diagnostic biopsy until completion of radiation therapy. Androgen-deprivation therapy may modulate fraction sensitivity because it can markedly reduce proliferation and affect repair of double-stranded DNA breaks Our results are supported by a recent report by Pollack et al This study assessing Ki67 in patients treated with different radiation therapy fractionation schedules reaches 2 conclusions. First, it does not suggest that there is a detriment to using hypofractionated radiation therapy schedules in PCa showing relatively high proliferation. Second, Ki67 is a highly statistically significant biomarker predicting recurrence, independent of established prognostic factors. Because localized PCa shows diverse clinical outcomes, Ki67 has a potential clinical application to guide treatment stratification.


Drug addiction is a major care and safety challenge in prison context. Nowadays, rehabilitation and specific therapeutic programs are suggested to improve health and well-being of inmates during their detention time and to reduce substance abuse relapse after release from prison. Among these programs, several studies reported the benefits for inmates coming from animal assisted interventions. In this pilot controlled study, we investigated the efficacy of a dog assisted therapy program addressed to 22 drug addicted male inmates housed in an attenuated custody institute in Italy. The study lasted six months, the treated group (12 inmates) was involved once a week for one hour in 20 dog assisted therapy sessions, whereas the control group (10 inmates) followed the standard rehabilitation program. One week before the beginning and one week after the end of the sessions, all inmates involved were submitted to symptom checklist-90-revised and Kennedy axis V. Inmates involved in the dog assisted therapy sessions significantly improved their social skills, reducing craving, anxiety and depression symptoms compared to the control group. Despite the limitation due to the small number of inmates enrolled and to the absence of follow up, we found these results encouraging to the use of dog assisted therapy as co-therapy in drug addicted inmates rehabilitation programs, and we claim the need of more extensive study on this subject. Drug addiction represents a major health care and safety challenge in U.S., Canadian and European prisons. A 2004 survey by the U.S. Department of Justice estimated that about 70% of State and 64% of Federal inmates regularly used drugs before incarceration . A recenDrug addiction arises with physiological, behavioural and cognitive symptoms that find their origin in genetic, biological, psychological and social causes . It starIn the prison context, inmates affected by drug addiction need to comply with detention life, characterized by heavy emotional entailments and by the customs and culture of the correctional facility they must take on. Therefore, in order to adapt to this difficult environment, full of stressors and infightings, they have to develop their own coping strategy, which often results in being dysfunctional because of their addiction ,15. In tThis study was conducted in accordance with the Declaration of Helsinki and the Italian Law on privacy of personal data. All subjects involved gave their written informed consent for the inclusion in the study. The protocol was approved by the Scientific and Ethics Committee of the Istituto Zooprofilattico Sperimentale delle Venezie (Project Identification Code: 8/14).We used an unmatched controlled study design  that is appropriate to investigate the effects of a specific health intervention like D.A.T. in a population, in our case a cohort of drug addicted male inmates. This study design needs to answer a practical question of whether D.A.T., which was added to the standard rehabilitation program of the attenuated custody institute thanks to a limited regional funding, provided more beneficial results compared to the standard program. This approach ensured benefits to all participants of the study without the risk of patients receiving a new treatment of unknown utility . The D.AThe attenuated custody institute of the Italian prison “Due Palazzi” in Padua  houses 35 male inmates affected by drug addiction. It provides programs to rehabilitate them towards psychological, educational and medical support, in a secure environment. The health care taker staff includes medical doctors, psychotherapists and psychologists working in partnership with educators to assure that all social and health problems of inmates are faced properly. The institute has its own rehabilitation program that aims to manage inmates effectively, reducing the risk of re-offending behaviour and facilitating their reintegration in the society. The program includes educational and working activities as well as psychodiagnostic and therapeutic ones .selection of inmates with the suitable features to be involved in the program by the prison health care unit and the prison administration;subscription of the “therapeutic-rehabilitative agreement” by the inmate;observation and psycho-diagnostic evaluation of the inmate by the clinical and functional point of view, taking into consideration his personal resources;planning of the “individual therapeutic program” (I.T.P.);integration of the patient in care and rehabilitative activities;evaluation of results reached by the patient compared to the fixed aims.The program takes place in prearranged phases:✓individual interviews with a psychotherapist once a week (1 h or more according to patients’ needs);✓psychotherapy sessions in small group focused on emotion control and assertiveness ;✓relaxation techniques and stress management course ;✓educational activities: design and painting course, theatre course ;✓sport activities (rugby), .The standard program is comprehensive of the following activities:Recently, D.A.T. sessions have been added to the standard rehabilitation program as an additional co-therapy to which inmates can choose to take part.The D.A.T. sessions we considered in this study were performed following the Italian National Guidelines for animal assisted interventions , which eDogs involved in the D.A.T. program were selected after a clinical and behavioural examination performed by a veterinarian with expertise in animal assisted interventions. They were all adult animals, belonging to medium-big size breeds, in good health condition, well socialized and specifically trained to perform dog assisted interventions with various kinds of patients. Health and welfare conditions of dogs were monitored by the veterinarian of the team (in collaboration with dog handlers) during the whole project.Thanks to periodic team meetings, before and during the study, dog handlers received instructions from the psychotherapist and the medical doctor on activities to perform with dogs during the sessions and feedback about their performances.Treated group was divided in four small sub-groups of three people and each sub-group was randomly assigned to a dog-handler couple. Each group was involved in a 60’ session of D.A.T., once a week for six months. Every session followed a standard scheme: an introduction phase during which the psychotherapist introduced the theme and patients were engaged in observational activities; afterwards, a phase in which they actively experienced the interaction with the dog and they were involved in management and performance activities; finally, the elaboration of the experience with the support of the psychotherapist. The psychotherapist previously set all of the activities performed with the dog handlers. They were analogous for all the sub-groups and they were structured following the Maslow’s hierarchy of needs, also known as the Maslow’s Pyramid . At the Our study population was an open cohort composed of 20–40 year old male inmates, coming from Italy, North Africa or Eastern Europe. They were all naturalized Italian citizens living in Veneto region sentenced to short prison terms (not less than one year and not more than four years) to spend in the attenuated custody institute of the Italian prison “Due Palazzi” in Padua . All of them were diagnosed for substance-related and addictive disorders as defined by DSM-5. They had no other mental nor physical deficiency, and they were HIV negative with a good clinical status. Their violent or illegal behaviour were linked to the search for substances; therefore, in such a population, social and health problems were clearly prevalent than the criminal attitude. All inmates were involved in the standard rehabilitation program described above.Recruitment of inmates for D.A.T. program was on a voluntary basis with the following limitations: they needed to be declared free of allergies towards dog fur, they should not be affected by dog phobia, and they must be free of religious or social prejudices against these animals and without pending accuse of animal abuse. In addition, they should have entered the institute since at least six months ago. The control group was composed without applying any matching, enrolling on voluntary basis inmates (of the cohort population considered) who had entered the institute since at least six months like the treated group and who were not interested in taking part to the D.A.T. program. The control group followed the standard rehabilitation program described above that did not include D.A.T. sessions.Twenty-two inmates were selected among 35 people. The sample size was limited by the number of prisoners with eligibility criteria who agreed to take part in the study and by the small size of the D.A.T. program, which could involve a maximum of 12 inmates.T0) and one week after the end (T1) of the D.A.T. program cases and controls were submitted to two psychological tests: Symptom checklist-90-revised (SCL-90-R) and Kennedy Axis V, used in the psychodiagnostic profiling activities provided by the rehabilitation program.One week before the beginning .To evaluate the association between categorical variables , a chi-square test was used, or a Fisher's exact test if one of the expected cells is below 5.T0-T1, SCL-90-R data not being normally distributed , after having evaluated the omoschedasticity through a non-parametric Levene’s test (W50 > 0.05). For Kennedy data that followed, instead, the normal distribution, Student’s t-test for two independent samples was used, after having evaluated the omoschedasticity trough parametric Bartlett’s test . Wilcoxon signed-ranks test or Student’s t-test for matched data were performed to evaluate differences between pre-post data .To compare quantitative variables between two independent samples (D.A.T. vs. standard program), the non-parametric Wilcoxon rank-sum (Mann–Whitney) test was used on the differences p > 0.05) .Among the 35 inmates evaluated, only 24 satisfied eligibility criteria. Twenty-two of them were accepted to take part in the study. Twelve inmates were enrolled for D.A.T. sessions and 10 composed the control group. Not all inmates enrolled in the treated group completed the D.A.T. program: three of them left the attenuated custody institute before the end of the study; two obtained the home confinement and one was moved in a drug rehabilitation centre. Moreover, one of the inmates enrolled in the control group was excluded from statistical analysis because data collected resulted in being an outlier for most parameters considered . The dem0T and 1T in the treated group  except for three subscales: phobic anxiety , hostility  and interpersonal sensitivity    . In the  = 0.04) .p-value = 0.063). In particular, as reported in p-value < 0.05, anxiety and psychoticism with p-value < 0.10  test for two independent samples pointed out a reduction of symptoms significantly different between treated and control group for the global severity index   , Table 6t-test for two independent samples, finding that the enhancement of patients involved in D.A.T. was significantly higher than in the control group for psychological impairment and social skills   .The purpose of this study was to explore the potential effect and efficacy of a D.A.T. program as co-therapy to enhance the standard rehabilitation program directed to detained drug users of the attenuated custody institute of “Due Palazzi” prison in Padua . Our findings suggest that D.A.T. strengthens the therapeutic impact of the standard rehabilitation program on mood and behaviour of inmates, improving their psychological functioning and reducing some dysfunctional symptoms.Strong associations between substance abuse and social alienation and personality disorders concerning social behaviour are documented by several studies ,38,39,40Much research in both human and animal models of addiction highlighted that the transition from controlled to compulsive drug seeking and taking is strongly conditioned by craving ,8,48,49.The positive impact of animal assisted therapy on outcomes like major depression and anxiety symptoms were frequently highlighted on different kinds of patients: children ,59, psycOur findings, deriving from the analysis of Kennedy Axis V results, confirmed a positive decrease in anxiety as well as the depression of inmates involved in the D.A.T. program. Differences were significant compared to the control group and were confirmed by SCL-90-R results. They also pointed out a strong reduction in sleep disorders, symptoms considered strictly related to depression and anxiety. These results are particularly interesting considering that they were reached despite the prison context. These positive findings are probably due to two D.A.T. mechanisms. Indeed, the human-animal relationship improves both the perceived social support ,72,73,74Randomized control trials (R.C.T.) are the gold standard to determine the effect of an animal-assisted intervention on a certain population and a certain outcome ,82, but The limited financial support ensured to have a D.A.T. program of six months with possible extension year by year according to financial means. Therefore, D.A.T. was included in the rehabilitation program as an optional co-therapy. It is quite well known that psychological treatments are most successful when patients can choose them because they are more motivated to comply with treatments they prefer  and thisWe are aware that our results can’t be generalized and there is a lack of external validity; indeed, our statistical power is only 0.25 for a SCL-90-R test but almost 0.80 for the Kennedy axis V; therefore, some non-significant results could become statistically significant testing a bigger number of inmates. Anyway, we think that these data have ecological validity considering the study design and the methods applied.Finally, we consider the absence of follow up on another critical point of our study, but most of the inmates involved left the institute in a short time after the end of D.A.T. sessions, making the follow up unachievable; therefore, we can’t determine if changes in outcomes led to long-term benefits for patients involved.This pilot study results extend previous findings on D.A.T. effects on a specific population, drug addicted male inmates, showing the useful and significant support of D.A.T. in enhancing their social skills, reducing distress levels and, as a consequence, depression and anxiety symptoms in a highly stressing environment like prison. Despite the small sample size, the absence of randomization and the lack of follow up, the encouraging results that we obtained suggest to us to keep the mainstreaming of our standard rehabilitation program with a structured D.A.T. program in the perspective to collect additional data to support our preliminary findings. We conclude that larger and multicentre studies with follow-up assessment are needed to more definitively explore the beneficial and long-lasting effects of D.A.T. on this target population.


Infant feeding practices, including breastfeeding and optimal formula feeding practices, can play a role in the prevention of childhood obesity. The ubiquity of smartphone ownership among women of childbearing age provides important opportunities for the delivery of low-cost, broad reach parenting interventions delivered by mobile phone . Little is known about how parents engage with mHealth programs targeting infant feeding and how such programs might influence infant feeding practices.The objectives of this study were to explore participant views on (1) factors influencing engagement with the Growing healthy program, an mHealth program targeting healthy infant feeding practices from birth to 9 months of age, and (2) the ways in which the program influenced behavioral determinants of capability, opportunity, and motivation for breastfeeding and optimal formula feeding behaviors.Semistructured, telephone interviews were conducted with a purposeful sample (n=24) of mothers participating in the Growing healthy program. Interviews explored participants’ views about engagement with the program and its features, and the ways the program influenced determinants of infant feeding behaviors related to breastfeeding and optimal formula feeding. The interview schedule was informed by the Capability, Opportunity, Motivation, and Behavior (COM-B) model.Participants reported that engagement fluctuated depending on need and the degree to which the program was perceived to fit with existing parenting beliefs and values. Participants identified that the credibility of the program source, the user friendly interface, and tailoring of content and push notifications to baby’s age and key transition points promoted engagement, whereas technical glitches were reported to reduce engagement. Participants discussed that the program increased confidence in feeding decisions. For breastfeeding mothers, this was achieved by helping them to overcome doubts about breast milk supply, whereas mothers using formula reported feeling more confident to feed to hunger and satiety cues rather than encouraging infants to finish the bottle. Participants discussed that the program provided around-the-clock, readily accessible, nonjudgmental information and support on infant feeding and helped to reinforce information received by health professionals or encouraged them to seek additional help if needed. Participants reflected that their plans for feeding were typically made before joining the program, limiting the potential for the program to influence this aspect of motivation. Rather, the program provided emotional reassurance to continue with current feeding plans.Our findings suggest that engagement with the program was influenced by an interplay between the program features and needs of the user. Participants reported that the program enhanced confidence in feeding decisions by providing a 24/7 accessible, expert, nonjudgmental support for infant feeding that complemented health professional advice. It is likely that interventions need to commence during pregnancy to maximize the impact on breastfeeding intentions and plans. Childreor obese . Infantsor obese ,4. Infanor obese  and how or obese -9. Austror obese . Similaror obese . This clMobile health  interventions present an appealing new avenue to support parents with infant feeding. Smartphone ownership is increasing worldwide , with AuEarly research on the efficacy of mHealth interventions in changing health behavior is promising -25; howeThe same review  reportedWe have recently developed the Growing healthy program, an mHealth intervention for parents of young infants, which encourages healthy infant feeding practices across the first 9 months of life, with a focus on socioeconomically disadvantaged parents. Details about the program and its development have been published elsewhere . BrieflyThe development of the program was guided by the Behavior Change Wheel framework, a well-recognized approach to developing behavioral interventions that takes into account the context in which behaviors occur . To undeThis qualitative study aimed to explore participant views on (1) factors influencing engagement with the Growing healthy program and (2) the ways in which the program influenced behavioral determinants of capability, opportunity, and motivation for breastfeeding and optimal formula feeding behaviors. The findings from this study will provide important new insights to guide the development of future mHealth interventions targeting infant feeding to maximize behavior change and effectiveness.A feasibility study of the Growing healthy program has been conducted to examine the acceptability and preliminary effectiveness using a quasi-experimental design, with an mHealth intervention group and a concurrent nonrandomized comparison group . ParticiFor this qualitative substudy, Growing healthy participants (n=301) were purposefully selected from those expressing interest in participating in an interview about their experiences of using the program when their infants were between 6 and 9 months old. From those who expressed interest (n=67), participants were purposefully sampled to recruit mothers with a range of feeding modes, including breastfeeding, formula feeding, and mixed feeding (combining both breastfeeding and formula feeding) and those who were university or nonuniversity educated. Purposefully selected individuals (n=39) were invited by email to participate. Nonresponders were sent a reminder email 1 week following the initial invitation, and if they were unresponsive, participants were called 1 week later to confirm their interest and to schedule an interview. A total of 24 individuals agreed to take part, the remaining 15 were uncontactable. Data saturation was reached (as determined by no new information emerging) after conducting interviews with all who agreed to participate. Verbal consent to participate was given at the initiation of the interview and a Aus $30 supermarket voucher was provided as compensation for the time taken to complete the interview.The interview schedule consisted of semistructured questions tailored to mothers’ feeding mode and the mode of delivery of the Growing healthy program . The questions were structured to address the 2 aims of the study . First, Transcriptions were de-identified and cross-checked with the audio file for accuracy. Thematic analysis was performed using the methods of Braun and Clarke . This meAn initial coding manual was devised based on a review of 5 interviews and subsequently revised several times during the coding process, adding new codes as needed until no new codes were identified. Three researchers  were involved in developing the coding manual based on reading transcripts individually and meeting to discuss the manual. Upon finalizing the coding manual, all interviews were coded by EL with a subset coded by RL. Minor inconsistencies were identified and were resolved through discussion. The researchers then looked for key themes within the data, and upon reviewing these themes, condensed them where appropriate. Finally, themes were defined and appropriately named. Coding, storing, and sorting of de-identified transcripts was undertaken using QSR NVivo software version 11..Ethics approval was provided by Deakin University 2014-093 and University of Technology Sydney 2014000123 Participant characteristics are shown in Participants in this study reported high engagement with the Growing healthy program. Participants used the program to browse content, to actively search for a particular topic to address an immediate need, or were prompted to use the program from a push notification or text message or email. Most participants indicated that they used the app more than the website because it was more conveniently accessed on their smartphone. Engagement with the program was influenced by a range of factors, including user needs and program features .Engagement with the program fluctuated depending on the mothers’ needs  and on their infant’s stage of development. In particular, participants reported that their engagement was highest when their baby was very young and they were establishing routines  and during times of transition . First-time mothers reported using the program as a learning tool, whereas mothers with older children discussed using the program less frequently, typically to reinforce what they had learned with their older child or children. A number of vulnerable parents  reported referring to the app for tips, resources, and reassurance. Participants reported that for their engagement with the program to be high, the content needed to be consistent with their own parenting beliefs and values. For example, if the content was consistent with their extant beliefs about appropriate ways for infants to sleep and feed, they were more likely to engage with the program. In contrast, if the content did not align with their preexisting parenting beliefs and values, they were less likely to engage with the program.Most participants thought the app was clear, contained sufficient information, was user friendly, and was easy to navigate. Many participants perceived the quality of the program to be high because 2 credible universities designed it. This encouraged feelings of trust and confidence in the information, which participants felt was important in promoting greater app use. The receipt of push notifications, text messages (for Web users), and emails was important in prompting engagement for some participants, particularly when the messages aligned with participants’ experiences and needs. Others reported difficulty with knowing how to retrieve push notifications (even if they were perceived to be relevant) or switching off push notifications because of the large number received from multiple apps. Other technical glitches, including the failure of the app to work at times, were reported to reduce engagement.The key themes arising from participant interviews on how the Growing healthy program influenced capability, opportunity, and motivation for breastfeeding and optimal formula feeding practices are outlined in Many mothers interviewed reported that the Growing healthy program increased their confidence in feeding decisions. Confidence was increased by the reassurance provided by the program that mothers were engaging in feeding behaviors that were healthy for their infant and they were doing the “right thing.” This was evident for the majority of participants interviewed, regardless of their feeding mode . Breastfeeding mothers reported that the program helped confirm they were breastfeeding their baby correctly. These mothers also noted that the program provided them with the confidence to continue breastfeeding, particularly when they doubted their milk supply. Formula and mixed feeding mothers discussed that the app increased their confidence to demand feed following their infants’ hunger and satiety cues rather than encouraging infants to finish the bottle. Confidence was also increased because of the credibility of the information source coming from university experts.Participants discussed that the program provided access to understandable, credible information while also providing social support. Participants particularly commented upon the value of the support provided by the app at times of need such as when they were questioning their milk supply and during times when it was not possible to seek advice from others . Participants who were formula feeding or mixed feeding also indicated that the program provided support without fear of judgment of their decision to use formula. These women reported feeling reluctant to discuss formula use with health professionals because of fear of being judged. Some participants noted that the information in the program reinforced advice provided by others in their social and health networks  particularly with regard to breastfeeding. Mothers who were exclusively breastfeeding at the time of the interview were more likely than formula or mixed feeders in this sample to talk about having sought additional help for infant feeding from a range of sources. That is, the program encouraged them to seek additional help if needed, thus potentially increasing both the advice and support they received (opportunity) as well as their skills, knowledge, and confidence in breastfeeding (capability).Motivation in the form of plans was rarely mentioned as having been influenced by the Growing healthy program. For example, mothers appeared to have set plans for if and how long an infant would be breastfed and desires to introduce formula, and these were reportedly formed before joining the program. Nonetheless, mothers reported that the program influenced their motivation to continue with their current behaviors by providing reassurance that they were doing the “right thing” for their baby, both nutritionally and for nonfeeding-related behaviors, such as sleeping.To our knowledge, this is the first study to explore participant views on factors influencing engagement with an mHealth intervention targeting infant feeding and the ways in which the program reportedly influenced key behavioral determinants of breastfeeding and formula feeding practices. The findings suggest that engagement is influenced by an interplay between the needs of the users, congruence between the program and existing parenting beliefs, and the program features. Participants reported that the program enhanced confidence in feeding decisions by providing an “around-the-clock,” credible, nonjudgmental support for infant feeding that reinforced and complemented information received from social networks and health professionals. Participants reflected that motivation in terms of feeding plans and intentions were rarely influenced by the program because these were generally formed before using the program; rather, the program provided emotional reassurance to continue with current feeding plans.Participants’ use of an mHealth program is critical if participants are to be exposed to the behavior change strategies underpinning the program’s effectiveness. Poor or limited engagement reduces the intervention “dose” received and limits the program’s effectiveness even if the behavior change strategies are sound. Our findings highlight the importance of understanding the unique needs of the intended users and how this might influence the mHealth design and delivery characteristics that are likely to be effective with those particular users. This fits with existing literature on user-centered design principles for developing mHealth programs .Our finding that participants reported engagement with the program fluctuated according to need fits well with our quantitative analysis of predictors of actual app use based on analysis of app analytics . In thisIn line with previous research ,30,47, oParticipants reported that the program increased their confidence in feeding decisions by providing reassurance from a credible and trustworthy source, highlighting the interplay between program features and behavior change. Breastfeeding mothers reported that the program increased their confidence in their milk supply, which is critical given that a perceived lack of milk supply is the most common reason given for giving up breastfeeding in the literature . FormulaOur findings highlight the value of the Growing healthy program in providing an accessible “24/7” source of nonjudgmental support for infant feeding, potentially increasing participants opportunity for achieving optimal infant feeding practices. In particular, some mothers who mixed or formula fed felt that society provided little advice or support regarding how to use formula well. Consistent with our previous qualitative work , particiOur findings suggest that the program was less able to influence motivation in terms of infant feeding plans and intentions as these were reportedly formed before joining the program. It is likely that the timing of program delivery was an important limitation here. The average age of infants at the time of enrollment was 7 weeks, and around one-third of mothers had introduced formula at this time, limiting the ability of the program to influence plans around breastfeeding duration. Evidence suggests that plans about whether a mother will breastfeed and for how long are made antenatally, highlighting the importance of commencing the program before birth to influence goals, plans, and ultimately motivation for breastfeeding. Despite this, our findings suggest that mothers who were breastfeeding were motivated to continue because of the reassurance provided about their milk supply. Mixed feeding and formula feeding mothers were also motivated to practice responsive feeding by the reassurance that they were doing the “right thing.” This highlights the importance of reassurance as a motivator for continuation of desired infant feeding practices.Strengths and LimitationsThis study has a number of strengths and limitations. The use of qualitative methods is a strength in enabling an in-depth exploration of factors influencing engagement with the program, how the program influenced behavioral determinants, and the interplay between engagement and behavior change. However, social desirability bias is a potential issue, as some participants may have been eager to please researchers with positive accounts of the program and its effect and possible overreporting of desirable infant feeding practices. Nevertheless, this risk was minimized by having no contact between researchers and participants during the feasibility study and encouragement to provide their honest feedback to help improve the program. Furthermore, it is possible that those who volunteered to be interviewed were more engaged with and had more positive views about the program than those who declined or were unable to be contacted. However, there was no difference in the sociodemographic characteristics between those who participated and those who were uncontactable, suggesting no systematic bias.Our findings suggest that to maximize parental engagement, an mHealth program targeting infant feeding should come from an expert and credible source; be tailored to specific needs of the target group ; use a combination of engagement strategies such as emails, push notifications, and text messages; and undergo extensive testing and ongoing maintenance to ensure high levels of functionality. Participants reported that the program enhanced confidence in breastfeeding and optimal formula feeding behaviors by providing a “24/7” accessible, expert, nonjudgmental support for infant feeding that complemented health professional advice. To improve the impact of the program on motivation and plans for breastfeeding, the program needs to commence antenatally and include behavior change strategies that specifically target motivation and intentions.


PRAME expression was significantly increased most EOC, regardless of stage and grade. Interestingly, PRAME mRNA expression was associated with improved survival in the HGSC subtype. The PRAME locus was a frequent target for copy number alterations (CNA) in HGSC but most changes were heterozygous losses, indicating that elevated PRAME expression is not typically due to CNA. In contrast, PRAME promoter DNA hypomethylation was very common in EOC and HGSC and correlated with increased PRAME expression. PRAME expression and promoter hypomethylation both correlated with LINE-1 hypomethylation, a biomarker of global DNA hypomethylation. Pharmacologic or genetic disruption of DNA methyltransferase (DNMT) enzymes activated PRAME expression in EOC cells. Immunohistochemistry (IHC) of PRAME in EOC revealed frequent, but low level, protein expression, and expression was confined to epithelial cells and localized to the cytoplasm. Cytoplasmic PRAME expression was positively associated with PRAME mRNA expression and negatively associated with promoter methylation, but the latter correlation was not statistically significant. PRAME protein expression did not correlate with EOC clinicopathology or survival. In summary, PRAME is frequently expressed in EOC at the mRNA and protein levels, and DNA methylation is a key mechanism regulating its expression. These data support PRAME as an immunotherapy target in EOC, and suggest treatment with DNMT inhibitors as a means to augment PRAME immunotherapy.PRAME is a cancer-testis antigen (CTA) and potential immuno-therapeutic target, but has not been well-studied in epithelial ovarian cancer (EOC) or its high grade serous (HGSC) subtype. Compared to normal ovary,  Ovarian cancer is the seventh most common female cancer worldwide and accounts for the fifth most female cancer deaths in the US , 2. ApprPRAME  was identified as a gene encoding an HLA-A24-restricted peptide that stimulated tumor-specific cytotoxic T lymphocytes in a human melanoma cell line  and patient survival data using cBioPortal [We retrieved TCGA HGSC ioPortal , 37. We t-tests as appropriate; all tests were two-sided.Overall Survival (OS) was defined as the time between the date of diagnosis and death. Patients who were alive at the time of analysis were censored at the date of last follow up. Progression-free survival (PFS) was defined as the time between the date of surgery and disease recurrence. Patients who were alive and disease-free were censored at the date of last follow-up and median survival times were estimated from the Kaplan-Meier curve. Association between PRAME H-score and clinical parameters was tested with a combination of chi-square and PRAME mRNA expression data  from cBioPortal.We retrieved TCGA copy number data for HGSC and other tumor types from cBioPortal , 37, andhttps://genome-cancer.soe.ucsc.edu/proj/site/xena/heatmap/). Statistical analysis was performed with Graphpad prism. This data set has been described [The Ovarian Cancer - Australia (OV-AU) DNA methylation (Illumina 450 K methylation) and gene expression (Illumina RNAseq) datasets, both version 2015-07-15, were downloaded from UCSC Xena (http://www.broadinstitute.org/gsea/index.jsp) to test for enrichment of RA pathway network genes  with PRAME expression in EOC (N = 285) or HGSC (N = 218). We used a continuous phenotype model, based on PRAME expression data obtained from Affymetrix U133 Plus 2 arrays (GEO accession GSE9899) [We performed GSEA GSE9899) .p-values are provided in the figures and figure legends.We used Graphpad Prism for standard statistical analyses to compare molecular parameters between sample groups. The statistical test used and


The aim of the current study was to replicate the subjective outcome evaluation based on program implementers in the first year (2006/07 school year) of the Full Implementation Phase (Secondary 1 level) of the Project P.A.T.H.S. . After the completion of the Tier 1 program in the 2007/08 school year, 1324 implementers from 213 schools completed a Subjective Outcome Evaluation Form for instructors in order to assess their views of the program, themselves, and the perceived effectiveness of the program. Reliability test indicated the questionnaire was internally consistent. The results showed that, similar to the first year of implementation, high proportions of the respondents had positive perceptions of the program and their own performance. Regarding the perceived effectiveness of the program, roughly 90% of the respondents thought the program was helpful. A statistically significant increase in positive responses was also found in some items of perceived effectiveness in the second year of implementation. Possible factors contributing to such changes, including accumulation of experience and skill enhancement of the implementers, as well as stronger support from the schools, are discussed.


In mediation analysis if unmeasured confounding is present, the estimates for the direct and mediated effects may be over or under estimated. Most methods for the sensitivity analysis of unmeasured confounding in mediation have focused on the mediator-outcome relationship.The Umediation R package enables the user to simulate unmeasured confounding of the exposure-mediator, exposure-outcome, and mediator-outcome relationships in order to see how the results of the mediation analysis would change in the presence of unmeasured confounding. We apply the Umediation package to the Genetic Epidemiology of Chronic Obstructive Pulmonary Disease (COPDGene) study to examine the role of unmeasured confounding due to population stratification on the effect of a single nucleotide polymorphism (SNP) in the CHRNA5/3/B4 locus on pulmonary function decline as mediated by cigarette smoking.https://github.com/SharonLutz/Umediation A tutorial on how to install and use the Umediation package is available in the Additional file Umediation is a flexible R package that examines the role of unmeasured confounding in mediation analysis allowing for normally distributed or Bernoulli distributed exposures, outcomes, mediators, measured confounders, and unmeasured confounders. Umediation also accommodates multiple measured confounders, multiple unmeasured confounders, and allows for a mediator-exposure interaction on the outcome. Umediation is available as an R package at The online version of this article (doi:10.1186/s12859-017-1749-y) contains supplementary material, which is available to authorized users. CHRNA5/3/B4 locus on chromosome 15q25.1 that is associated with decreased lung function (FEV1)  on FEVts (PCs) . It is pWhile the assumption of no unmeasured confounding is required for mediation analysis, in reality this assumption may often be violated in large population based genetic studies. Thus, it is critical to assess the likely degree of bias introduced by unmeasured confounders within any given study. With the Umediation package, users may examine the hypothetical influence of an unobserved confounding variable on the estimation of direct and mediated effects, in the presence or absence of a statistical interaction between the exposure and mediator variables. Importantly, the package is flexible enough to allow for confounders of the exposure-mediator, mediator-outcome, and exposure-outcome relationships. While the data analysis example focused on population stratification which can confound the SNP-mediator and SNP-outcome associations, the strongest potential for unmeasured confounding is lifestyle and socioeconomic factors of the mediator-outcome association, such as physical activity and education. A strength of the Umediation package is that one can simultaneously account for all of these unmeasured confounders.1) through the mediator cigarettes smoking, the Umediation package is applicable and useful in any scenario where there may be unmeasured confounding of the exposure-mediator-outcome relationship (i.e. the exposure was not completely randomized). For example, Umediation has many practical and clinical uses. A relevant clinical example is the pathway by which maternal preeclampsia contributes to the risk of chronic lung disease in the newborn [While the data analysis example focused on confounding bias due to unobserved population stratification in the decomposition of the total effect of a SNP on lung function  to health outcomes at a later stage of life (such as childhood or adulthood). For example, maternal smoking in pregnancy has been consistently associated with a greater risk of childhood overweight and obesity in the offspring . MaternaUmediation examines the role of unmeasured confounding via simulations studies by running mediation analysis  both witAdditionally, the Umediation package currently assumes no correlation between the measured confounders C and unmeasured confounders U. While this is a reasonable assumption for the data example where the measured and unmeasured confounders are PCs, the investigator needs to determine if this is a reasonable assumption for their particular question of interest. While the Umediation package allows for an exposure-mediator interaction on the outcome of interest, it is important to note that the Umediation package does not allow for interactions of the measured and unmeasured confounders with the exposure or mediator on the outcome of interest. Also, the Umediation package currently only accommodates one mediator of the exposure-outcome relationship.While we have focused on the effect of unmeasured confounding of the exposure-mediator-outcome relationship in mediation analysis, there are methods that allow for unmeasured confounding, such as instrumental variable methods. There have been instrumental variable methods proposed that can be extended to handle mediation analysis for continuous, normally distributed outcomes  and binaUmediation allows investigators to make reasonable quantitative estimates of the magnitude of the effect due to unmeasured confounding of the exposure-mediator, mediator-outcome, or exposure-outcome associations. This R package accommodates multiple unmeasured confounders, which may be either Bernoulli or normally distributed. The utility of Umediation becomes apparent whenever the need arises to examine the impact of unmeasured variables in a mediation analysis: in a post-hoc setting, when data collection and analysis have already been conducted, or in the early stages of study design, when exploring the relative value accrued by collecting data on variables that may be costly or difficult to obtain. By estimating the degree of bias produced at the plausible upper and lower boundaries of the association between each unmeasured confounder and the exposure, mediator, or outcome, investigators will be able to assess whether the mediated or direct effects are likely to be over or under estimated due to unobserved confounders.


This study extends the concept of third places to include community sites where older adults gather, often for meals or companionship. The Consolidated Framework for Implementation Research guided program implementation and evaluation. Depending upon health promotion program needs, the physical infrastructure of a site is important, but a supportive director (champion) can often overcome identified deficits. Senior centers may be locally classified into four types based upon eligibility requirements of residents in affiliated housing and services offered. Participants who attend these centers differ in important ways across types by most sociodemographic as well as certain health and health care characteristics. Throughout its operation, ElderSmile has incorporated a spatial approach for addressing socioeconomic disparities in health for older adults and planning community-based health promotion activities.Throughout the course of conducting this study, all Columbia University, New York University, and University at Buffalo institutional review board and Health Insurance Portability and Accountability Act safeguards were followed.The formation of the ElderSmile network of third places (network), also referred to as prevention centers, emerged because the foremost goal of the program, namely, to enhance the oral health of older adults in northern Manhattan, coincided with the mission of the Columbia University College of Dental Medicine, that is, to improve the oral health of its surrounding neighborhoods . In order to have the greatest community-level impact, the program founders (leaders) aimed to include a group of geographically diverse locations to ensure that the prevention centers were conveniently located within close proximity to most of the places where older adults  lived. Prerequisites for site selection (the inner setting) included the following social and physical infrastructure: (1) the location needed to attract a sufficient number of older adults each day (approximately 25 or more), (2) older adults ought to congregate at the prevention center for an extended period of time , and (3) the site mission and director should express an interest in improving the health and quality of life of older adults. In order to conduct a successful outreach event, a prevention center also needed to have sufficient space and ideally, dedicated rooms in which to host the interactive educational slide deck presentation and perform screenings for oral disease, diabetes, and hypertension. Without sufficient space for these educational and screening activities, the outreach event flow was often hindered, and as a result, fewer participants were able to participate. Finally, the dedicated rooms needed to be well-lit and well-ventilated and provide access to electrical outlets and running water. Although few sites met all of these requirements, the ElderSmile outreach team members  were creative and skilled in ensuring that less than ideal physical infrastructure was nonetheless adequate to host prevention activities.The single most important factor in determining the success of a prevention center event was the support and organization of its director . As a result, the ElderSmile outreach team deliberately sought to develop rapport with prevention center directors toward ensuring the sustainability of the program. Time and again, our experience was that an enthusiastic and engaged center director (champion) could overcome any physical infrastructure deficits, and conversely, a disinterested and uncommitted center director could undermine even ideal physical space. Since senior centers and locations where older adults congregate were not used for the sole purpose of health screenings, other recreational activities, such as domino games and walking outside, often occurred simultaneously with outreach events. A supportive and effective director would encourage older adults to participate in ElderSmile outreach events and request that other competing activities be suspended during the educational slide deck presentation, at a minimum.In summary, ElderSmile events held in locations with supportive leaders resulted in successful outreach activities with high participation rates, while ElderSmile events held in locations with disinterested or absentee leaders resulted in unsuccessful outreach activities with low participation rates. By way of illustration, a particularly frustrating situation occurred when the outreach team arrived at a prevention center only to discover that most of the center regulars left on a bus trip to Atlantic City, NJ. As a result, the outreach event was canceled, even though the ElderSmile outreach staff had confirmed the date multiple times with the center director.,Resources from authoritative governmental and advocacy groups for the aging were consulted in developing a locally relevant method for classifying third places for the ElderSmile network of prevention centers.–,–The individual-level data for this study were provided by self-report of participants or collected by staff and dentists of the ElderSmile program via intake interviews, clinical dental assessments, and measurement of glycosylated hemoglobin (HbA1c) and blood pressure (BP). Details of the ElderSmile clinical program and the primary-care screening enhancements are provided elsewhere.NORC, i.e., a housing complex or neighborhood with residential dwellings that were not purposefully planned for older adults and do not restrict admission to older adults, but which house high concentrations of residents aged 60 years and older of low to moderate income, as residents have aged in place. New York State supports the following two NORC programs: (1) NORC Supportive Service Program, for housing complexes or apartment buildings that were built with government assistance, with 50 % of the units with an elderly occupant or 2500 residents aged 60 years or older, and (2) Neighborhood NORC, for a residential dwelling or group of residential dwellings in a geographically defined area with no more than 2000 people who are aged 60 years or older residing in at least 40 % of the units, made up of low-rise buildings (six stories or less), single or multi-family homes not originally built for older adults.As previously mentioned, a locally relevant method for classifying third places for older adults in urban settings was developed consisting of four center types. The first center type is Section 202, i.e., a US Department of Housing and Urban Development program that offers affordable housing opportunities specifically for low- or moderate-income older adults. This program provides rent subsidies and capital advances, i.e., interest-free grants or loans, for constructing or rehabilitating housing structures. To be eligible for Section 202 housing, one person in the household must be 62 years old at the initial occupancy of the housing unit. Support services such as congregate meals, cleaning, and transportation are provided to facilitate independent living.The second center type is NYCHA, i.e., a public housing authority that offers affordable housing to low- and moderate-income residents in the five boroughs of New York City through the Conventional Public Housing Program or Section 8 Leased Housing Program. Housing developments and buildings exclusively for residents aged 62 years and older are available. Senior centers are located within New York City Housing Authority developments that provide recreational activities and meals for senior residents and community members in the surrounding neighborhoods. These senior centers are operated by or in partnership with New York City Housing Authority, New York City Department for the Aging, and community organizations.The third center type is Community Center. Senior centers provide a range of services to adults typically aged 60 and older, notably health and wellness promotion and education. While senior centers vary in physical setting and size, populations served, services offered, and funding sources, a principal service offered by all senior centers is congregate meals—at least one meal a day, 5 days a week.Finally, a senior center or resource center is a place in the community where older adults can socially interact with others and receive support services, which together comprise the fourth center type, namely, Sociodemographic information on ElderSmile participants was obtained by questionnaire in English or Spanish, according to participant preferences. The data gathered included age, gender, race, Hispanic ethnicity, language spoken at home, place of birth, highest level of education attained, and home address. For the purposes of the analyses presented here, participants were categorized by age as 50–64, 65–74, or 75+ years. Race/ethnicity was categorized as non-Hispanic white, non-Hispanic black, Hispanic, and other. Place of birth was categorized as mainland USA, Dominican Republic, Puerto Rico, and other. The highest level of education attained was categorized as primary school, high school, or some college or more.Health and health care information were collected by self-report or clinical assessments. Self-reported smoking status was characterized as never smoked, former smoker, or current smoker. Participants were asked if they had medical insurance , and if so, what type ; if they had dental insurance , and if so, what type (Medicaid or private); and the times since their last medical and dental visits .n = 0), limited function (n = 1–19), and functional dentition (n = 20–28).Specifically, with regard to oral health, participants assessed the status of their teeth and gums as excellent, good, fair, or poor. A faculty dentist performed a screening assessment on older adults who agreed to participate. Participants were examined for the number and condition of their teeth, and the number of teeth present was categorized as edentulous  as assessed by HbA1c was measured by a point-of-care test using capillary (finger stick) blood via a DCA Vantage Analyzer.Finally, both systolic BP (SBP) and diastolic BP (DBP) were measured using an Omron blood pressure monitor.R.Descriptive statistics for self-reported sociodemographic, health, and health care characteristics of participants at ElderSmile outreach events held between July 2006 and October 2013 by center type were computed in Geosupport Desktop Edition.ArcGIS Desktop.Addresses of third places and ElderSmile participants with addresses in Manhattan and the Bronx were processed with the There were 2026 electronic records available for analysis of participants who attended ElderSmile outreach events between July 2006 and October 2013. Of these, 182 records with self-reported residential addresses that could not be georeferenced to locations in Manhattan or the Bronx, and 21 records from two ElderSmile events where the center type could not be classified with certainty, were excluded. The results presented next are based on 1823 records or 90.0 % of the original 2026 records.n = 711 or 39.0 %), followed by NYCHA, Section 202, and NORC center types , more participants at Community Centers than other center types never smoked (62.3 %), and more participants at NORCs had visited a dentist in the last year (59.8 %) and had functional dentition (47.0 %) than at other center types.Toward understanding where the ElderSmile participants lived and how far they travelled to attend outreach events, the residential locations of participants were mapped and colored to correspond to the center type where they attended an outreach event Fig. . Most ofn = 383) of any center type.The residential locations of ElderSmile participants who attended outreach events at a Community Center and the straight-line paths from their residential locations to the Community Centers where they attended these events are depicted in Fig. The residential locations of ElderSmile participants who attended outreach events at a NORC and the straight-line paths from their residential locations to the NORCs where they attended these events are depicted in Fig. n = 18) than any other center type. NYCHA center services are open to both residents who reside at the sites as well as older adults in nearby and outlying communities.The residential locations of ElderSmile participants who attended outreach events at a NYCHA center and the straight-line paths from their residential locations to the NYCHA centers where they attended these events are depicted in Fig. The residential locations of ElderSmile participants who attended outreach events at a Section 202 center and the straight-line paths from their residential locations to the Section 202 centers where they attended these events are depicted in Fig. A locally relevant method for categorizing third places introduced here proved useful in understanding differences among ElderSmile participants who attended outreach events by the center types they visited. Certain findings confirmed the validity of the locally relevant classification method developed as part of this research. For instance, the highest percentages of participants aged 75 years and older attended outreach events in Section 202 centers (46.6 %) and NORCs (43.8 %), and both of the housing programs with which these center types are affiliated have older age eligibility requirements. Further, the highest percentages of participants with Medicaid coverage attended outreach events in Section 202 centers (64.1 %) and NYCHA centers (53.4 %), and both of the housing programs with which these center types are affiliated have income eligibility requirements.On the other hand, this classification system revealed unanticipated differences among participants by the center types they visited that may be useful in planning future outreach events. Note that the highest percentage of participants who had not visited a dentist for more than 3 years (26.0 %) and were edentulous (24.3 %) or had limited function dentition (47.1 %) attended outreach events at Section 202 centers. Older adults may not be aware that oral health visits are important regardless of the number of teeth they retain (reflecting).The exploratory spatial analyses presented here add value beyond the tabulated differences among ElderSmile participants by characteristics across center types. Clearly, certain centers and types drew larger numbers of participants and had larger catchment areas than others. It is also evident that participants are not necessarily attending outreach events at the centers located closest to their residential locations. Next steps include conducting analyses using the transport network in New York City (including both train and bus routes) to estimate travel time distances for participants attending ElderSmile outreach events (planning).A major strength of this study is that these analyses were conducted in close collaboration with the ElderSmile founders, faculty dentists, and staff (implementation leaders) who had firsthand knowledge of the included centers and their directors (champions and change agents). Further, the geographers who are leaders and members of the research team possess both the expertise to conduct meaningful spatial analyses and the skills to create accessible maps to guide program implementation and evaluation (executing). Notable limitations include that we were unable to account for repeat participants at the centers and were missing essential information for 352 records that were thus not included in the analyses reported here. Further, while the classification system used in this study was locally relevant for northern Manhattan, it would need to be adapted to the context of other geographic areas, where health promotion programs are implemented for older adults. Nonetheless, there may be transferable best principles and best practices to be gleaned from our experience in implementing and evaluating the ElderSmile program.Urban planners and public health practitioners are increasingly as focused on the social aspects of neighborhood environments as they are on the physical ones, including meeting places.,,,Beyond documenting attendance and need, investigators have also conducted research into implementing programs at senior centers and other community sites that address pain,This study adds to the evidence based on evaluating place-based programs for health promotion by using the CFIR to guide program implementation and evaluation and introducing a locally relevant system for classifying center types and incorporating a spatial approach that provides insight into where participants live and how far they travel to attend outreach events at particular centers and types. We agree with Dunn that in the absence of real socioeconomic change for disadvantaged populations , we may continue to be disappointed in the outcomes of place-based interventions.


Aim: Programmatic assessment for learning (PAL) is becoming more and more popular as a concept but its implementation is not without problems. In this paper we describe the design principles behind a PAL program in a general practice training context.Design principles: The PAL program was designed to optimise the meaningfulness of assessment information for the registrar and to make him/her use that information to self regulate their learning. The main principles in the program were cognitivist and transformative. The main cognitive principles we used were fostering the understanding of deep structures and stimulating transfer by making registrars constantly connect practice experiences with background knowledge. Ericsson’s deliberate practice approach was built in with regard to the provision of feedback combined with Pintrich’s model of self regulation. Mezirow’s transformative learning and insights from social network theory on collaborative learning were used to support the registrars in their development to become GP professionals. Finally the principal of test enhanced learning was optimised.Epilogue: We have provided this example explain the design decisions behind our program, but not want to present our program as the solution to any given situation. Th. Th5]. Tlearning , 7]..for learIn order for assessment to drive student learning in a more meaningful way, the student has to be enabled to obtain meaningful information about their own performance and use this for their future learning. This is where the programmatic aspect of PAL comes in . Just prAn additional feature of programmatic assessment is the concept of proportionality. This means that the stakes of the decisions made about a student or learner have to be proportional to the credibility of the underlying information. So, single observations or single assessments can be used for feedback but not for high-stakes decisions. In programmatic assessment, all single observations or assessments are collected and collated over time until sufficient information is available to make a high-stakes decision . This agSo logically, programmatic assessment is a longitudinal approach to assessment in which the outcomes of many formal and informal assessments are collected on a continual basis, for example in a portfolio. Typically, the learner and a staff member – often called a mentor or coach – meet at regular intervals to discuss the learner’s progress and their concrete learning goals. And at the end of the study phase, all information is used to decide whether the learner is allowed to progress or not. Importantly, the learner makes an analysis based on all the information available to him or her, and formulates concrete learning goals before meeting with their mentor or coach. As such, the coach is able to give a prognosis during the phase of the most likely outcome. The concept of programmatic assessment has been described in various publications , 7], , .Typically, when the concept of PAL is explained – especially to healthcare providers – it feels intuitively right and people are willing to accept the concept, but implementation is not at all easy. There are several reasons for this. The first and probably most important reason, is the fact that it is a fundamental change in thinking about the role of assessment. Fundamental changes to any discipline just need time to find their way from theory to practice. A conceptually different way of thinking about education, such as problem-based learning, has taken many years and even decades before it has become widely accepted. A second reason concerns the logistical changes needed for the implementation. In PAL the whole assessment program is explicit and therefore the associated investment in time and costs are overt, whereas in many traditional assessment programs costs are generally more covert. That makes a cost comparison quite difficult and easily result in a negative perception towards PAL. The third reason lies most likely in what Vosniadou calls naïve frameworks or naïve theories . ThroughSome of the more intuitive approaches to deal with beliefs and the management of such a change concern careful identification of stakeholders and their roles and careful communication with them. This communication needs to be open and continuous but also agile in that it relates to different stakeholders with different arguments and explanations; ranging from evidence from research to rhetorical conviction. In addition, one of the factors that can help in this process is a description of implementations somewhere else; as a demonstration that the concept can be translated to an actual practice. The purpose of this paper is to provide such a proof of concept. In the Consensus statement and recommendations from the 2010 Ottawa conference  the ideoGP365 is a general practice training program in South Australia and Western Australia, which has been developed by Sturt Fleurieu Education and Training in collaboration with the Flinders University Prideaux Centre for Research in Health Professions Education. It is a one-year curriculum in the context of a three or four-year training program and it is run for all GP registrars in South Australia and Western Australia. During this year, GP registrars (residents) follow the GP365 program which supports them through linking their practice experiences to background knowledge, skills and understanding. During this year, GP365 provides registrars with background reading material, assignments, a supervisor, a medical educator and a peer group to work with. On a continual basis registrars receive feedback from their supervisors, from medical educators and from their peers. In addition, they are given formative tests on relevant knowledge and application of knowledge. During their training registrars build a portfolio which will eventually contain evidence of all feedback from: directly observed patient consultations, reviewed videoed consultations, critical case analysis write-ups, a clinical audit they have performed, professionalism, activities in their peer group, multi-source feedback, mid and end term assessments, the results of their formative tests with their own analyses and written feedback from their medical educator. In total, this program may not seem innovative or different to what is done in many postgraduate training contexts, but there are differences which we will explain below.The most important design principle behind GP365 is the problem of transfer and understanding of the so-called “deep structure” . RegistrThe second design principle is the aggregation of information across different assessment parts. An example of such connection starts with the critical case analysis write-ups. As described above, the registrar receives feedback on all their write-ups which they have to implement and revise. This is an application of Ericsson’s principle of deliberate practice , 18]. T. T18]. TA third principle is an increase in self responsibility for learning. Generally, after graduation learners are expected to be able to take control of their own learning and assessment. Unfortunately, this is not always the case. One of the problems with CME, for example, is that people tend to follow courses in those areas there are already good at . AssessmA fourth principle is the longitudinality of the programme. All the information about the registrar’s performance is collected in a portfolio which is discussed periodically with their supervisor and/or medical educator. Initially, when the information in the portfolio is still ‘thin’ mostly more formative feedback is given, when the information becomes richer serious suggestions for intervention and remedial activities are given and the final decision whether or not the registrar is ready to progress to the next phase is always based on the full and rich information. A final design principle is adaptation of the program to the local context. It is unlikely that any approach in medical education which works well in one country or context could be simply applied in another country. In order for education to be successful it has to link with expectations and cultural determine of its environment. In GP365 it was therefore important to realise that Australia is a vast country with many remote areas. GPs play an important role in the Australian healthcare context and almost always they are the first port of call; moreover, they are often the only port of call. This puts a specific stress on educational programs to educate GPs who are optimally equipped to work individually and safely. Therefore, elements such as self-directed learning, accountability, dealing with uncertainty and tolerance for ambiguity features so prominently in the program, for example like the peer group meetings – the so-called mini releases –, the ongoing feedback on professionalism and the frequent meetings with experienced supervisors and medical educators. This is woven into the program in all kinds of aspects to ensure that the program meets the Colleges’ requirements of “safe independent practitioner” and “college exam readiness”.The program has now been running for two years and it is too soon to provide extensive information as to its success with respect to the quality of graduates. Early results do suggest that the pass rates on fellowship exams are far above the national average but before a clear causal relationship with the PAL approach can be argued for more data are needed. That was not the intent of this paper and although there are anecdotal indications that programmatic assessment for learning is effective, the whole approach is still too young to have produced a sufficiently credible body of evidence. So the jury is still out. Moreover, we feel that any success in our context would not mean that the exact same program would have the same success in another context. That’s why we have focused on providing examples on how the concept of programmatic assessment for learning has influenced design decisions around GP365 assessment program. We hope that our explanation of the underlying principles and the description of how they have influenced our design decisions are helpful for anyone who is considering changing or rebuilding programmatic assessment for learning program. The authors declare that they have no competing interests.