Optimal Partitioning for Linear Mixed Effects Models: Applications to Identifying Placebo Responders

A long-standing problem in clinical research is distinguishing drug treated subjects that respond due to specific effects of the drug from those that respond to non-specific (or placebo) effects of the treatment. Linear mixed effect models are commonly used to model longitudinal clinical trial data. In this paper we present a solution to the problem of identifying placebo responders using an optimal partitioning methodology for linear mixed effects models. Since individual outcomes in a longitudinal study correspond to curves, the optimal partitioning methodology produces a set of prototypical outcome profiles. The optimal partitioning methodology can accommodate both continuous and discrete covariates. The proposed partitioning strategy is compared and contrasted with the growth mixture modelling approach. The methodology is applied to a two-phase depression clinical trial where subjects in a first phase were treated openly for 12 weeks with fluoxetine followed by a double blind discontinuation phase where responders to treatment in the first phase were randomized to either stay on fluoxetine or switched to a placebo. The optimal partitioning methodology is applied to the first phase to identify prototypical outcome profiles. Using time to relapse in the second phase of the study, a survival analysis is performed on the partitioned data. The optimal partitioning results identify prototypical profiles that distinguish whether subjects relapse depending on whether or not they stay on the drug or are randomized to a placebo.     

Longitudinal Changes in Religiosity Among Emerging Adult College Students

Issues of religion are important aspects of the identity process, which for many emerging adults may be intensified by the college experience. This study investigated longitudinal changes in the religiosity of 434 emerging adult college students (52% female) of diverse ethnic backgrounds (32% African American, 29% Latino American, and 39% European American) during the first 3 semesters of university. Results suggest that changes occur throughout this period, but that such changes are not monolithic across dimensions of religiosity. In the aggregate, significant declines in the behavioral aspects of religiosity were observed across semesters. In contrast, importance of religious beliefs remained relatively constant during this time. However, variations in these patterns were observed when considered at the individual level. Findings further demonstrate that heterogeneity in religiosity is also evident based upon gender and religious affiliation, suggesting that it is fruitful to consider the unique ways in which individuals change during this developmental period.     

The Plantation

David Herlihy, Medieval Households (1985), vii + 227 (Harvard University Press, Cambridge, Mass., £23#lb50, paperback £8#lb95).

Peter Blickle, Gemeindereformation. Die Menschen des 16. Jahrhunderts auf dem Weg zum Heil (1985), 234 (Oldenbourg Verlag, Munich, DM 88).

[Communal Reformation. People of the Sixteenth Century on the Road to Salvation.]

Giovanni Levi, L'eredità immateriale: camera di un esorcista nel Piemonte del seicento (1985), 202 (Einaudi, lire 18,000).

Richard B. Sher, Church and University in the Scottish Enlightenment. The Moderate Literati of Edinburgh (1985), xix + 390 (Edinburgh University Press, Edinburgh, £30#lb00).

The English Satirical Print, 1600–1832: John Brewer (ed.), The Common People and Politics, 1750–1790S (1986), 304 + 120 plates (Chadwyck‐Healey, £40#lb00.).

Roger Miller and Torvald Gerger, Social Change in Nineteenth‐century Swedish Agrarian Society (1985), 130 (Acta Universitatis Stockholmiensis, Stockholm Studies in Human Geography, 5, Almqvist and Wicksell International, Stockholm, n.p.).

Peter Scholliers, De Gentse metaalbewerkers in de 19e eeuw: de enquete van L. Varlez (1985), 1 + 185 + appendix (Centrum voor Hedendaagse Sociale Geschiedenis, Vrije Universiteit, Brussels, n.p.).

Annarita Buttafuoco, Le Mariuccine: storia di un istituzione laica, l'Asilo Mariuccia (1985) 491 (Franco Angeli, Milan, lire 28,000).

L. Margaret Barnett, British Food Policy during the First World War (1985), xix + 241 (George Allen &; Unwin, £25#lb00).

Mary Langan and Bill Schwarz (eds), Crises in the British State 1880–1930 (1985), 288 (Hutchinson University Library, paperback £8#lb95).     

Application of Whole-Genome Sequences and Machine Learning in Source Attribution of Salmonella Typhimurium

Prevention of the emergence and spread of foodborne diseases is an important prerequisite for the improvement of public health. Source attribution models link sporadic human cases of a specific illness to food sources and animal reservoirs. With the next generation sequencing technology, it is possible to develop novel source attribution models. We investigated the potential of machine learning to predict the animal reservoir from which a bacterial strain isolated from a human salmonellosis case originated based on whole-genome sequencing. Machine learning methods recognize patterns in large and complex data sets and use this knowledge to build models. The model learns patterns associated with genetic variations in bacteria isolated from the different animal reservoirs. We selected different machine learning algorithms to predict sources of human salmonellosis cases and trained the model with Danish Salmonella Typhimurium isolates sampled from broilers (n = 34), cattle (n = 2), ducks (n = 11), layers (n = 4), and pigs (n = 159). Using cgMLST as input features, the model yielded an average accuracy of 0.783 (95% CI: 0.77–0.80) in the source prediction for the random forest and 0.933 (95% CI: 0.92–0.94) for the logit boost algorithm. Logit boost algorithm was most accurate (valid accuracy: 92%, CI: 0.8706–0.9579) and predicted the origin of 81% of the domestic sporadic human salmonellosis cases. The most important source was Danish produced pigs (53%) followed by imported pigs (16%), imported broilers (6%), imported ducks (2%), Danish produced layers (2%), Danish produced cattle and imported cattle (<1%) while 18% was not predicted. Machine learning has potential for improving source attribution modeling based on sequence data. Results of such models can inform risk managers to identify and prioritize food safety interventions.     

Latest-Late Fertility? Decline and Resurgence of Late Parenthood Across the Low-Fertility Countries

After decades of fertility postponement, we investigate recent changes in late parenthood across low-fertility countries in the light of observations from the past. We use long series of age-specific fertility rates from the Human Fertility Database (1950–2016) for women, and new data covering the period 1990–2016 for men. In 1950, the contribution of births at age 40 and over to female fertility rates ranged from 2.5 to 9 percent, but then fell sharply until the 1980s. From the 1990s, however, the prevalence of late first births increased rapidly, especially so in countries where it was initially lowest. This has produced a late fertility rebound in the last two decades, occurring much faster for women than for men. Comparisons between recent and past extremely late (age 48+) fertility levels confirm that people are now challenging the natural fertility barriers, particularly for a first child.     

Order test for high-dimensional two-sample means

We propose a new method to test the order between two high-dimensional mean curves. The new statistic extends the approach of Follmann (1996) to high-dimensional data by adapting the strategy of Bai and Saranadasa (1996). The proposed procedure is an alternative to the non-negative basis matrix factorization (NBMF) based test of Lee et al. (2008) for the same hypothesis, but it is much easier to implement. We derive the asymptotic mean and variance of the proposed test statistic under the null hypothesis of equal mean curves. Based on theoretical results, we put forward a permutation procedure to approximate the null distribution of the new test statistic. We compare the power of the proposed test with that of the NBMF-based test via simulations. We illustrate the approach by an application to tidal volume traces.     

Assessing Short-Term Fertility Intentions and Their Realisation Using the Generations and Gender Survey: Pitfalls and Challenges

The use of fertility intention questions to study individual childbearing behaviour has developed rapidly in recent decades. In Europe, the Generations and Gender Surveys are the main sources of cross-national data on fertility intentions and their realisation. This study investigates how an inconsistent implementation of a question about wanting a child now affects the cross-country comparability of intentions to have a child within the next three years and their realisation. We conduct our analysis separately for women and men at prime and late reproductive ages in Austria, France, Italy and Poland. The results show that the overall share of respondents intending to have a child at some point in their life is similar in all four analysed countries. However, once the time horizon and the degree of certainty of fertility intentions are included, substantial cross-country differences appear, particularly in terms of proceptive behaviour and, consequently, the realisation of fertility intentions. We conclude that the inconsistent questionnaire adaptation makes it very difficult to assess the role of country context in the realisation of childbearing intentions.     

The prevalence of sexual aggression and victimization among homosexual men

This study examined the prevalence of unwanted sexual contacts among a sample of 310 homosexual men with an average age of 21.8 years recruited in Berlin, Germany. A modified version of the Sexual Experiences Survey was developed to record unwanted contacts involving different means of coercion, sexual acts, and victim‐perpetrator relationships. Reports were elicited about (a) sexual victimization and (b) perpetration of sexually aggressive acts. Three methods of victimization were studied: physical force, exploitation of the victim's incapacitated state, and verbal coercion. Of the 310 respondents, about 15% reported sexual victimization through the use or threat of forcé. Twenty percent were victimized through exploitation of their inability to offer resistance when in an incapacitated state. Ten percent reported victimization through verbal coercion. In terms of being the perpetrator of sexual aggression, over 5% of respondents reported using or threatening to use physical force. Over 16% reported exploiting a person's incapacitated state, and over 6% admitted to the use of verbal coercion. Acceptance of money for sex was identified as a risk factor for both victimization and perpetration. The data show that sexual aggression is a serious problem among homosexual men which requires further exploration.